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Sample records for tapentadol extended release

  1. Tapentadol extended-release for treatment of chronic pain: a review

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    Vadivelu N

    2011-08-01

    Full Text Available Nalini Vadivelu1, Alexander Timchenko1, Yili Huang2, Raymond Sinatra11Department of Anesthesiology, Yale University School of Medicine, New Haven, CT; 2Internal Medicine, North Shore-LIJ Plainview Hospital, Plainview, NY, USAAbstract: Tapentadol is a centrally acting analgesic with a dual mechanism of action of mu receptor agonism and norepinephrine reuptake inhibition. Tapentadol immediate-release is approved by the US Food and Drug Administration for the management of moderate-to-severe acute pain. It was developed to decrease the intolerability issue associated with opioids. Tapentadol extended-release has a 12-hour duration of effect, and has recently been evaluated for pain in patients with chronic osteoarthritis, low back pain, and pain associated with diabetic peripheral neuropathy. Tapentadol extended-release was found to provide safe and highly effective analgesia for the treatment of chronic pain conditions, including moderate-to-severe chronic osteoarthritis pain and low back pain. Initial trials demonstrating efficacy in neuropathic pain suggest that tapentadol has comparable analgesic effectiveness and better gastrointestinal tolerability than opioid comparators, and demonstrates effectiveness in settings of inflammatory, somatic, and neuropathic pain. Gastrointestinal intolerance and central nervous system effects were the major adverse events noted. Tapentadol will need to be rigorously tested in chronic neuropathic pain, cancer-related pain, and cancer-related neuropathic pain.Keywords: osteoarthritis, neuropathic pain, analgesic, opioids, norepinephrine

  2. Tapentadol extended release for the management of chronic neck pain

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    Billeci D

    2017-03-01

    Full Text Available Domenico Billeci,1 Flaminia Coluzzi2 1Division of Neurosurgery, Ca’Foncello Hospital, University of Padova, Treviso, 2Department of Medical and Surgical Sciences and Biotechnologies, Unit of Anaesthesiology, Intensive Care Medicine, and Pain Therapy, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Latina, Italy Background: The role of opioids in the management of chronic neck pain is still poorly investigated. No data are available on tapentadol extended release (ER. In this article, we present 54 patients with moderate-to-severe chronic neck pain treated with tapentadol ER. Patients and methods: Patients received tapentadol ER 100 mg/day; dosage was then adjusted according to clinical needs. The following parameters were recorded: pain; Douleur Neuropathique 4 score; Neck Disability Index score; range of motion; pain-associated sleep interference; quality of life (Short Form [36] Health Survey; Patient Global Impression of Change (PGIC; Clinician GIC; opioid-related adverse effects; and need for other analgesics. Results: A total of 44 of 54 patients completed the 12-week observation. Tapentadol ER daily doses increased from 100 mg/day to a mean (standard deviation dosage of 204.5 (102.8 mg/day at the final evaluation. Mean pain intensity at movement significantly decreased from baseline (8.1 [1.1] to all time points (P<0.01. At baseline, 70% of patients presented a positive neuropathic component. This percentage dropped to 23% after 12 weeks. Tapentadol improved Neck Disability Index scores from 55.6 (18.6 at baseline to 19.7 (20.9 at the final evaluation (P<0.01. Tapentadol significantly improved neck range of motion in all three planes of motion, particularly in lateral flexion. Quality of life significantly improved in all Short Form (36 Health Survey subscales (P<0.01 and in both physical and mental status (P<0.01. Based on PGIC results, approximately 90% of patients rated their overall condition as much/very much

  3. The analgesic agent tapentadol inhibits calcitonin gene-related peptide release from isolated rat brainstem via a serotonergic mechanism.

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    Greco, Maria Cristina; Navarra, Pierluigi; Tringali, Giuseppe

    2016-01-15

    In this study we tested the hypothesis that tapentadol inhibits GGRP release from the rat brainstem through a mechanism mediated by the inhibition of NA reuptake; as a second alternative hypothesis, we investigated whether tapentadol inhibits GGRP release via the inhibition of 5-HT reuptake. Rat brainstems were explanted and incubated in short-term experiments. CGRP released in the incubation medium was taken as a marker of CGRP release from the central terminals of trigeminal neurons within the brainstem. CGRP levels were measured by radioimmunoassay under basal conditions or in the presence of tapentadol; NA, 5-HT, clonidine, yohimbine and ondansetron were used as pharmacological tools to investigate the action mechanism of tapentadol. The α2-antagonist yohimbine failed to counteract the effects of tapentadol. Moreover, neither NA nor the α2-agonist clonidine per se inhibited K(+)-stimulated CGRP release, thereby indicating that the effects of tapentadol are nor mediated through the block of NA reuptake. Further experiments showed that 5-HT and tramadol, which inhibits both NA and 5-HT reuptake, significantly reduced K(+)-stimulated CGRP release. Moreover, the 5-HT3 antagonist ondansetron was able to counteract the effects of tapentadol in this system. This study provided pharmacological evidence that tapentadol inhibits stimulated CGRP release from the rat brainstem in vitro through a mechanism involving an increase in 5-HT levels in the system and the subsequent activation of 5-HT3 receptors. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Direct conversion from tramadol to tapentadol prolonged release for moderate to severe, chronic malignant tumour-related pain.

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    Kress, H G; Koch, E D; Kosturski, H; Steup, A; Karcher, K; Dogan, C; Etropolski, M; Eerdekens, M

    2016-10-01

    A recent randomized-withdrawal, active- and placebo-controlled, double-blind phase 3 study showed that tapentadol prolonged release (PR) was effective and well tolerated for managing moderate to severe, chronic malignant tumour-related pain in patients who were opioid naive or dissatisfied with current treatment (Pain Physician, 2014, 17, 329-343). This post hoc, subgroup analysis evaluated the efficacy and tolerability of tapentadol PR in patients who previously received and were dissatisfied with tramadol for any reason and who had a pain intensity ≥5 (11-point numerical rating scale) before converting directly to tapentadol PR. In the original study, eligible patients had been randomized (2:1) and titrated to their optimal dose of tapentadol PR (100-250 mg bid) or morphine sulphate-controlled release (40-100 mg bid) over 2 weeks. The present report focuses on results during the titration period for a subgroup of patients randomized to tapentadol PR after having been on tramadol treatment prior to randomization in the study (n = 129). Results for this subgroup are compared with results for all 338 patients who received tapentadol PR during titration (overall tapentadol PR group). Responder rates (responders: completed titration, mean pain intensity pain could safely switch from prior treatment with the weak centrally acting analgesic tramadol directly to the strong centrally acting analgesic tapentadol PR, for an improved analgesic therapy for severe pain. WHAT DOES THIS STUDY ADD?: Results of this post hoc analysis show that patients who had received prior tramadol therapy could switch directly to tapentadol PR, with the majority (˜70%) experiencing improved efficacy. © 2016 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

  5. Assessment of Tapentadol API Abuse Liability With the Researched Abuse, Diversion and Addiction-Related Surveillance System.

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    Vosburg, Suzanne K; Severtson, S Geoffrey; Dart, Richard C; Cicero, Theodore J; Kurtz, Steven P; Parrino, Mark W; Green, Jody L

    2018-04-01

    Tapentadol, a Schedule II opioid with a combination of µ-opioid activity and norepinephrine reuptake inhibition, is used for the management of moderate to severe acute and chronic pain. Its dual mechanism of action is thought to reduce opioid-related side effects that can complicate pain management. Since approval, tapentadol has been tracked across multiple outcomes suggesting abuse liability, and a pattern of relatively low, although not absent, abuse liability has been found. This retrospective cohort study further details the abuse liability of tapentadol as an active pharmaceutical ingredient (API) when immediate-release as well as extended-release formulations were on the market together (fourth quarter of 2011 to second quarter of 2016). Tapentadol (API) was compared with tramadol, hydrocodone, morphine, oxycodone, hydromorphone, and oxymorphone across Poison Center, Drug Diversion, and Treatment Center Programs Combined data streams from the Researched Abuse, Diversion and Addiction-Related Surveillance system. Findings suggest the public health burden related to tapentadol to date is low, but present. Event rates of abuse per population-level denominators were significantly lower than all other opioids examined. However, when adjusted for drug availability, event rates of abuse were lower than most Schedule II opioids studied, but were not the lowest. Disentangling these 2 sets of findings further by examining various opioid formulations, such as extended-release and the role of abuse-deterrent formulations, is warranted. This article presents the results from an examination of tapentadol API across the Researched Abuse, Diversion and Addiction-Related Surveillance System: a broad and carefully designed postmarketing mosaic. Data to date from Poison Center, Drug Diversion, and Treatment Centers combined suggest a low, but present public health burden related to tapentadol. Copyright © 2018. Published by Elsevier Inc.

  6. Comparison of opioid doctor shopping for tapentadol and oxycodone: a cohort study.

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    Cepeda, M Soledad; Fife, Daniel; Vo, Lien; Mastrogiovanni, Gregory; Yuan, Yingli

    2013-02-01

    Obtaining opioids from multiple prescribers, known as doctor shopping, is 1 example of opioid abuse and diversion. The dual mechanism of action of tapentadol could make tapentadol less likely to be abused than other opioids. The aim of this retrospective cohort study was to compare the risk of shopping behavior between tapentadol immediate release (IR) and oxycodone IR. Subjects exposed to tapentadol or oxycodone with no recent opioid use were included and followed for 1 year. The primary outcome was the proportion of subjects who developed shopping behavior defined as subjects who had opioid prescriptions written by >1 prescriber with ≥1 day of overlap filled at ≥3 pharmacies. The opioids involved in the shopping episodes were assessed. A total of 112,821 subjects were exposed to oxycodone and 42,940 to tapentadol. Shopping behavior was seen in .8% of the subjects in the oxycodone group and in .2% of the subjects in the tapentadol group, for an adjusted odds ratio of 3.5 (95% confidence interval, 2.8 to 4.4). In the oxycodone group, 28.0% of the shopping events involved exclusively oxycodone, whereas in the tapentadol group, .6% of the shopping events involved exclusively tapentadol. Results suggest that the risk of shopping behavior is substantially lower with tapentadol than with oxycodone. The risk of opioid doctor shopping, ie, obtaining opioid prescriptions from multiple prescribers, is lower with tapentadol than with oxycodone. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

  7. A Randomized Controlled Trial on the Effect of Tapentadol and Morphine on Conditioned Pain Modulation in Healthy Volunteers.

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    Chris Martini

    Full Text Available Modulatory descending pathways, originating at supraspinal sites that converge at dorsal horn neurons, influence pain perception in humans. Defects in descending pain control are linked to chronic pain states and its restoration may be a valuable analgesic tool. Conditioned pain modulation (CPM is a surrogate marker of descending inhibition that reduces the perception of pain from a primary test stimulus during application of a conditioning stimulus. Here the effects of the analgesics tapentadol, a combined mu-opioid receptor agonist and noradrenaline reuptake inhibitor, and morphine, a strong mu-opioid receptor agonist, were tested on CPM in a randomized, double-blind, placebo-controlled crossover trial in 12 healthy pain-free volunteers, to understand possible differences in mechanism of action between these opioids.On three occasions CPM responses were obtained 60-90 and 120-150 min following intake of tapentadol (100 mg immediate release tablet, morphine (40 mg immediate release tablet or placebo. At both time points, CPM was detectable after treatment with placebo and tapentadol (peak pain ratings reduced by 20-30% after application of the conditioning stimulus but not after morphine. Compared to placebo morphine displayed significantly less CPM: mean treatment difference 18.2% (95% CI 3.4 to 32.9% at 60-90 min after drug intake and 19.5% (95% CI 5.7 to 33.2% at 120-150 min after drug intake (p = 0.001. No difference in CPM between placebo and tapentadol was detected: mean treatment difference 1.5% (95% CI -11.6 to 14.6% at 60-90 min after drug intake and 1.5% (95% CI -16.0 to 18.9% at 120-150 min after drug intake (p = 0.60.Our data show that in volunteers morphine affects CPM, while tapentadol was without effect despite identical experimental conditions. These data confirm that tapentadol's main mechanism of action is distinct from that of morphine and likely related to the effect of adrenergic stimulation on descending controls

  8. Comparison of the risks of shopping behavior and opioid abuse between tapentadol and oxycodone and association of shopping behavior and opioid abuse.

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    Cepeda, M Soledad; Fife, Daniel; Kihm, Mary A; Mastrogiovanni, Greg; Yuan, Yingli

    2014-12-01

    This study compared the risks of opioid shopping behavior and opioid abuse between tapentadol immediate release and oxycodone immediate release and, to validate the definition of shopping, examined the association between opioid shopping and opioid abuse further. This retrospective cohort study using linked dispensing and diagnosis databases followed opioid-naive patients for development of shopping behavior and/or opioid abuse during 1 year after initial exposure to tapentadol or oxycodone. Shopping was defined by having overlapping opioid prescriptions from >1 prescriber filled at ≥3 pharmacies; abuse by having International Classification of Diseases, 9th revision diagnoses reflecting opioid abuse, addiction, or dependence. To determine their association, we cross-tabulated shopping and opioid abuse and calculated odds ratios. Risks of developing each outcome were estimated using logistic regression. Among 277,401 participants initiating opioid use with tapentadol (39,524) or oxycodone (237,877), 0.6% developed shopping behavior, 0.75% developed abuse. Higher proportions of patients in the oxycodone group developed shopping behavior and abuse than in the tapentadol group (shopping: adjusted odds ratio [95% confidence interval], 0.45 [0.36-0.55]; abuse: 0.44 [0.37-0.54]). Shopping behavior and abuse were associated; of those with shopping behavior, 6.5% had abuse. Age (18 to 64 y), sex (male), prior benzodiazepine use, paying cash, and history (mood disorders, abuse of nonopioid medications, and back pain) were risk factors for developing either outcome. Shopping behavior and abuse measure complementary, but associated, constructs, which further validates the current definition of shopping. The risk of developing either is lower among patients who initiate opioid use with tapentadol than those who initiate opioid use with oxycodone.

  9. [Conversion to tapentadol PR improves analgesia and quality of life in patients with severe and chronic pain despite using tramadol > 300 mg/d].

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    Richter, Uwe; Waldmann-Rex, Susanne; Lehmann, Ute

    2015-06-01

    This subgroup analysis of a non-interventional study involving general practitioners and internists investigated the administration of tapentadol PR (prolonged release) in patients with widely-utilized tramadol pretreatment in routine clinical practice in Germany. Data of all patients in the study cohort who had tramadol as the only opioid in their previous therapy were included in the analysis (n = 685); among them especially the 99 patients with tramadol dosages exceeding 300 mg/d were focused. Data collection during the 3-month observation period included previous and concomitant analgesic treatment, tapentadol PR dosage, pain intensity, sleep and quality of life parameters, and tolerability of tapentadol PR. Back pain was the most common cause of pain (n = 86/99), other pain diagnoses were (partly additionally) recorded in 68 cases. A mixed type of pain dominated. The previous tramadol therapy was usually combined with non-opioids (n = 74), co-analgesics (n = 44) and analgesic rescue medication (n = 35). Tapentadol PR therapy reduced the mean initial pain intensity of 7.3 ± 1.5 to 3.1 ± 1.8 points (NRS-11, 11-point pain scale, n = 96) at the end of observation, using an average dosage of 218.7 mg/d. Tapentadol PR was finally applied as the sole analgesic in 32/95 patients. 69/96 patients achieved a clinically meaningful pain relief of at least 50 %, while 63 patients gained a pain reduction of ≥ 4 NRS-points. 89/95 patients reached or exceeded their additional individual treatment goal. This was accompanied by a significant decrease in pain-related impairments of daily activities and an improvement in quality of life with an overall good tolerability of tapentadol PR. Treatment with tapentadol PR was assessed positively by physicians and patients. Data analysis shows a clinically relevant benefit in patients unsuccessfully pretreated with tramadol by consecutive conversion to the potent analgesic tapentadol PR.

  10. Is tapentadol different from classical opioids? A review of the evidence.

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    Langford, Richard M; Knaggs, Roger; Farquhar-Smith, Paul; Dickenson, Anthony H

    2016-11-01

    Tapentadol is a single molecule able to deliver analgesia by two distinct mechanisms, a feature which differentiates it from many other analgesics. Pre-clinical data demonstrate two mechanisms of action: mu-opioid receptor agonist activity and noradrenaline re-uptake inhibition. From these, one may predict that tapentadol would be applicable across a broad spectrum of pain from nociceptive to neuropathic. The evidence in animal models suggests that norepinephrine re-uptake inhibition (NRI) is a key mechanism and may even predominate over opioid actions in chronic (and especially neuropathic) pain states, reinforcing that tapentadol is different to classical opioids and may, therefore, be an a priori choice for the treatment of neuropathic and mixed pain. The clinical studies and subsequent practice experience and surveillance support the concept of opioid and non-opioid mechanisms of action. The reduced incidence of some of the typical opioid-induced side effects, compared to equianalgesic doses of classical opioids, supports the hypothesis that tapentadol analgesia is only partially mediated by opioid agonist mechanisms. Both the pre-clinical and clinical profiles appear to be differentiated from those of classical opioids.

  11. Review of Post-Marketing Safety Data on Tapentadol, a Centrally Acting Analgesic.

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    Stollenwerk, Ariane; Sohns, Melanie; Heisig, Fabian; Elling, Christian; von Zabern, Detlef

    2018-01-01

    Tapentadol is a centrally acting analgesic that has been available for the management of acute and chronic pain in routine clinical practice since 2009. This is the first integrated descriptive analysis of post-marketing safety data following the use of tapentadol in a broad range of pain conditions relating to the topics overall safety, dose administration above approved dosages, administration during pregnancy, serotonin syndrome, respiratory depression, and convulsion. The data analyzed pertain to spontaneous reports from healthcare and non-healthcare professionals and were put in the context of safety information known from interventional and non-interventional trials. The first years of routine clinical practice experience with tapentadol have confirmed the tolerability profile that emerged from the clinical trials. Moreover, the reporting of expected side effects such as respiratory depression and convulsion was low and no major risks were identified. The evaluation of available post-marketing data did not confirm the theoretical risk of serotonin syndrome nor did it reveal unexpected side effects with administration of higher than recommended doses. More than 8 years after its first introduction, the favorable overall safety profile of tapentadol in the treatment of various pain conditions is maintained in the general population. Grünenthal GmbH.

  12. Opioid and noradrenergic contributions of tapentadol to the inhibition of locus coeruleus neurons in the streptozotocin rat model of polyneuropathic pain.

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    Torres-Sanchez, Sonia; Borges, Gisela Da Silva; Mico, Juan A; Berrocoso, Esther

    2018-06-01

    Tapentadol is an analgesic that acts as an agonist of µ opioid receptors (MOR) and that inhibits noradrenaline reuptake. Data from healthy rats show that tapentadol inhibits neuronal activity in the locus coeruleus (LC), a nucleus regulated by both the noradrenergic and opioid systems. Thus, we set out to investigate the effect of tapentadol on LC activity in streptozotocin (STZ)-induced diabetic rats, a model of diabetic polyneuropathy, by analyzing single-unit extracellular recordings of LC neurons. Four weeks after inducing diabetes, tapentadol dose-response curves were obtained from animals pre-treated with RX821002 or naloxone (alpha2-adrenoceptors and opioid receptors antagonists, respectively). In STZ rats, the spontaneous activity of LC neurons (0.9 ± 0.1 Hz) was lower than in naïve animals (1.5 ± 0.1 Hz), and tapentadol's inhibitory effect was also weaker. Alpha2-adrenoceptors blockade by RX821002 (100 μg/kg i.v.) in STZ animals significantly increased the spontaneous activity (from 0.8 ± 0.1 to 1.4 ± 0.2 Hz) and it dampened the inhibition of LC neurons produced by tapentadol. However, opioid receptors blockade following naloxone pre-treatment (5 mg/kg i.v.) did not alter the spontaneous firing rate (0.9 ± 0.2 vs 0.9 ± 0.2 Hz) or the inhibitory effect of tapentadol on LC neurons in STZ animals. Thus, diabetic polyneuropathy appears to exert neuroplastic changes in LC neurotransmission, enhancing the sensitivity of alpha2-adrenoceptors and dampening opioid receptors expression. Tapentadol's activity seems to be predominantly mediated through its noradrenergic effects rather than its influence on opioid receptors in the STZ model of diabetic polyneuropathy. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Pain in the Frail or Elderly Patient: Does Tapentadol Have a Role?

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    Veal, Felicity C; Peterson, Gregory M

    2015-06-01

    Persistent pain affects the elderly disproportionally, occurring in 50% of elderly community-dwelling patients and 80% of aged care residents. The management of pain in the elderly and frail patient is complicated because of the risks posed by changes in pharmacokinetics and pharmacodynamics, polypharmacy, and drug-disease interactions. Trials evaluating the efficacy of analgesics have often excluded elderly patients and universally excluded frail patients; therefore, the true efficacy and side-effect profiles in these population groups are largely unknown, especially for long-term use. A stepwise approach is recommended to managing pain, commencing with paracetamol and adding on opioids when needed to manage pain. However, because of the short duration of clinical trials, exclusion of frail patients, and minimal inclusion of elderly patients, the decision as to which opioid should be added on to paracetamol is a difficult one. This article reviews the evidence surrounding a newer opioid, tapentadol. Tapentadol acts on both the mu receptors and on neuronal reuptake of noradrenaline, and has no significant analgesically active metabolites, which theoretically presents some advantages, particularly in comparison with tramadol. However, the evidence to support tapentadol is weak and the trials were often methodologically poor and sponsored almost universally by the drug company. Currently, there is insufficient evidence to support the use of tapentadol over other opioids, which have been on the market longer, are less expensive, and have better established safety profiles. As a first-line agent after the failure of paracetamol alone, morphine, oxycodone, fentanyl, or buprenorphine are still the preferred evidence-based choices for add-on opioid therapy for elderly or frail patients.

  14. Tapentadol in the management of chronic low back pain: a novel approach to a complex condition?

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    Pergolizzi J

    2011-07-01

    Full Text Available Joseph Pergolizzi1, Eli Alon2, Ralf Baron3, Cesare Bonezzi4, Jan Dobrogowski5, Rafael Gálvez6, Troels Jensen7, Hans-Georg Kress8, Marco AE Marcus9, Bart Morlion10, Serge Perrot11, Rolf-Detlef Treede121Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Universitätsspital Zurich, Switzerland; 3Universitätsklinikum Schleswig-Holstein, Kiel, Germany; 4Fondazione Salvatore Maugeri, Pavia, Italy; 5Zaklad Badania i Leczenia Bólu, Kraków, Poland; 6Hospital Universitario Virgen de las Nieves, Granada, Spain; 7Aarhus University, Denmark; 8Medical University of Vienna, Austria; 9Maastricht University Medical Center and University of Muenster, Maastricht, The Netherlands; 10University Hospitals Leuven, Belgium; 11Hôpital Dieu, Paris, France; 12Ruprecht-Karls-University, Heidelberg, GermanyAbstract: Chronic pain affects approximately 1 in 5 people in Europe, and around half of sufferers receive inadequate pain management. The most common location is the lower back. Pharmacological treatment of this condition is challenging because of the range of causative mechanisms and the difficulty of balancing analgesic efficacy and tolerability. An international panel of clinical pain specialists met in September, 2009, to discuss the treatment of chronic low back pain, and to review preclinical and clinical data relating to the new analgesic, tapentadol. A lack of consensus exists on the best treatment for low back pain. The range of regularly prescribed pharmacological agents extends from nonopioids (paracetamol, NSAIDs, and COX-2 inhibitors to opioids, antidepressants and anticonvulsants. Pain relief may be compromised, however, by an undetected neuropathic component or intolerable side effects. Treatment is potentially life-long and effective analgesics are urgently needed, with demonstrable long-term safety. Combining separate agents with different mechanisms of action could overcome the limitations of present

  15. The influence of μ-opioid and noradrenaline reuptake inhibition in the modulation of pain responsive neurones in the central amygdala by tapentadol in rats with neuropathy

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    Gonçalves, Leonor; Friend, Lauren V.; Dickenson, Anthony H.

    2015-01-01

    Treatments for neuropathic pain are either not fully effective or have problematic side effects. Combinations of drugs are often used. Tapentadol is a newer molecule that produces analgesia in various pain models through two inhibitory mechanisms, namely central μ-opioid receptor (MOR) agonism and noradrenaline reuptake inhibition. These two components interact synergistically, resulting in levels of analgesia similar to opioid analgesics such as oxycodone and morphine, but with more tolerable side effects. The right central nucleus of the amygdala (CeA) is critical for the lateral spinal ascending pain pathway, regulates descending pain pathways and is key in the emotional-affective components of pain. Few studies have investigated the pharmacology of limbic brain areas in pain models. Here we determined the actions of systemic tapentadol on right CeA neurones of animals with neuropathy and which component of tapentadol contributes to its effect. Neuronal responses to multimodal peripheral stimulation of animals with spinal nerve ligation or sham surgery were recorded before and after two doses of tapentadol. After the higher dose of tapentadol either naloxone or yohimbine were administered. Systemic tapentadol resulted in dose-dependent decrease in right CeA neuronal activity only in neuropathy. Both naloxone and yohimbine reversed this effect to an extent that was modality selective. The interactions of the components of tapentadol are not limited to the synergy between the MOR and α2-adrenoceptors seen at spinal levels, but are seen at this supraspinal site where suppression of responses may relate to the ability of the drug to alter affective components of pain. PMID:25576174

  16. Design and evaluation of nicorandil extended-release tablet

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    Ju-Young Kim

    2015-04-01

    Full Text Available The aim of this study was to design and evaluate extended-release formulations of a model drug, nicorandil, in order to achieve the desired steady-state plasma concentration of drug in vivo. Simulation was employed to estimate optimum dissolution and absorption rate of nicorandil. The dissolution test was employed using pH 1.2, 4.0, 6.8 buffer solution, or water, to measure the in vitro release behaviors of nicorandil formulations. A single dose (15 mg of each formulation was orally administered to four beagle dogs under fasted conditions, and the pharmacokinetic parameters were calculated. The in vitro/in vivo relationship of the extended-release formulation was confirmed using in vitro dissolution profiles and plasma concentrations of drug in beagle dogs. Nicorandil was released completely within 30 min from the immediate-release tablets and released for 24 h from the extended-release tablets. The nicorandil plasma concentration could be modified by adjusting the drug release rate from the extended-release formulation. The release rate of nicorandil was the rate-limiting step in the overall absorption of drug from the extended-release formulations. These results highlight the potential of a nicorandil extended-release formulation in the treatment of angina pectoris.

  17. Tapentadol versus tramadol in the management of low back pain in the emergency department

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    Guillén-Astete, Carlos A.; Cardona-Carballo, César; de la Casa-Resino, Cristina

    2017-01-01

    Abstract Nontraumatic musculoskeletal disorders are the main reason for presentation to the emergency department (ED), with rachialgia (back pain) being the most common reason to request medical assessment among them. This also generates the highest demand for reassessments due to poor pain control or onset of adverse reactions to the treatment prescribed in the initial assessment. A retrospective observational study based on usual clinical practice was conducted in patients attending the ED due to low back pain during a period of 24 months. The primary objective was to determine the demand for reassessments in the ED by these patients in the following 30 days, according to the type of therapeutic approach used in the initial assessment. A total of 732 patients who requested medical assessment due to back pain in the ED of our hospital were analyzed, 91 of whom were treated with tapentadol whereas 641 received another treatment. In the first month after the initial assessment, reassessments were less common in the tapentadol group; this difference was significant from days 8 to 15 (P = 0.001, odds ratio [OR] 0.252 with 95% confidence interval [CI] 0.100–0.635) and days 15 to 30 (P pain compared to those who did not receive it (P pain, tapentadol shows clear advantages over the other analgesics analyzed, in terms of pain control and less need for reassessments. PMID:29137025

  18. Accelerated in-vitro release testing methods for extended-release parenteral dosage forms.

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    Shen, Jie; Burgess, Diane J

    2012-07-01

    This review highlights current methods and strategies for accelerated in-vitro drug release testing of extended-release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in-situ depot-forming systems and implants. Extended-release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, 'real-time' in-vitro release tests for these dosage forms are often run over a long time period. Accelerated in-vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in-vitro release methods using United States Pharmacopeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended-release parenteral dosage forms, along with the accelerated in-vitro release testing methods currently employed are discussed. Accelerated in-vitro release testing methods with good discriminatory ability are critical for quality control of extended-release parenteral products. Methods that can be used in the development of in-vitro-in-vivo correlation (IVIVC) are desirable; however, for complex parenteral products this may not always be achievable. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  19. Accelerated in vitro release testing methods for extended release parenteral dosage forms

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    Shen, Jie; Burgess, Diane J.

    2012-01-01

    Objectives This review highlights current methods and strategies for accelerated in vitro drug release testing of extended release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in situ depot-forming systems, and implants. Key findings Extended release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, “real-time” in vitro release tests for these dosage forms are often run over a long time period. Accelerated in vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in vitro release methods using United States Pharmacopoeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended release parenteral dosage forms, along with the accelerated in vitro release testing methods currently employed are discussed. Conclusions Accelerated in vitro release testing methods with good discriminatory ability are critical for quality control of extended release parenteral products. Methods that can be used in the development of in vitro-in vivo correlation (IVIVC) are desirable, however for complex parenteral products this may not always be achievable. PMID:22686344

  20. Characterisation of tramadol, morphine and tapentadol in an acute pain model in Beagle dogs.

    Science.gov (United States)

    Kögel, Babette; Terlinden, Rolf; Schneider, Johannes

    2014-05-01

    To evaluate the analgesic potential of the centrally acting analgesics tramadol, morphine and the novel analgesic tapentadol in a pre-clinical research model of acute nociceptive pain, the tail-flick model in dogs. Prospective part-randomized pre-clinical research trial. Fifteen male Beagle dogs (HsdCpb:DOBE), aged 12-15 months. On different occasions separated by at least 1 week, dogs received intravenous (IV) administrations of tramadol (6.81, 10.0 mg kg(-1) ), tapentadol (2.15, 4.64, 6.81 mg kg(-1) ) or morphine (0.464, 0.681, 1.0 mg kg(-1) ) with subsequent measurement of tail withdrawal latencies from a thermal stimulus (for each treatment n = 5). Blood samples were collected immediately after the pharmacodynamic measurements of tramadol to determine pharmacokinetics and the active metabolite O-demethyltramadol (M1). Tapentadol and morphine induced dose-dependent antinociception with ED50-values of 4.3 mg kg(-1) and 0.71 mg kg(-1) , respectively. In contrast, tramadol did not induce antinociception at any dose tested. Measurements of the serum levels of tramadol and the M1 metabolite revealed only marginal amounts of the M1 metabolite, which explains the absence of the antinociceptive effect of tramadol in this experimental pain model in dogs. Different breeds of dogs might not or only poorly respond to treatment with tramadol due to low metabolism of the drug. Tapentadol and morphine which act directly on μ-opioid receptors without the need for metabolic activation are demonstrated to induce potent antinociception in the experimental model used and should also provide a reliable pain management in the clinical situation. The non-opioid mechanisms of tramadol do not provide antinociception in this experimental setting. This contrasts to many clinical situations described in the literature, where tramadol appears to provide useful analgesia in dogs for post-operative pain relief and in more chronically pain states. © 2014 Association of Veterinary

  1. Pramipexole Extended Release: A Novel Treatment Option in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Wolfram Eisenreich

    2010-01-01

    Full Text Available Pramipexole, the most commonly prescribed dopamine agonist worldwide, meanwhile serves as a reference substance for evaluation of new drugs. Based on numerous clinical data and vast experiences, efficacy and safety profiles of this non-ergoline dopamine agonist are well characterized. Since October 2009, an extended-release formulation of pramipexole has been available for symptomatic treatment of Parkinson's disease. Pramipexole administration can be cut down from three times to once a day due to the newly developed extended-release formulation. This is considerable progress in regard to minimizing pill burden and enhancing compliance. Moreover, the 24 h continuous drug release of the once-daily extended-release formulation results in fewer fluctuations in plasma concentrations over time compared to immediate-release pramipexole, given three times daily. The present study summarizes pharmacokinetics and all essential pharmacological and clinical characteristics of the extended-release formulation. In addition, it provides all study data, available so far, with regard to transition and de-novo administration of extended-release formulation for patients with Parkinson's disease. It further compares efficacy and safety data of immediate-release pramipexole with the extended-release formulation of pramipexole.

  2. DOD and VA Health Care: Actions Needed to Help Ensure Appropriate Medication Continuation and Prescribing Practices

    Science.gov (United States)

    2016-01-01

    Hydrocodone ibuprofen 0.1 Oxymorphone 0.1 Meperidinee 0.1 Methadone √ 0.1 Codeine √ 0.1 Tapentadol < 0.1 Oxaprozin < 0.1 Diclofenac misoprostopolf...formulation (e.g., extended or immediate release), salt form (e.g., hydrochloride or sulfate), or strength of the medication. bThis represents the most...form (e.g., liquid or tablet), modified release formulation (e.g., extended or immediate release), salt form (e.g., hydrochloride or sulfate

  3. Structure activity studies of an analgesic drug tapentadol hydrochloride by spectroscopic and quantum chemical methods

    Science.gov (United States)

    Arjunan, V.; Santhanam, R.; Marchewka, M. K.; Mohan, S.; Yang, Haifeng

    2015-11-01

    Tapentadol is a novel opioid pain reliever drug with a dual mechanism of action, having potency between morphine and tramadol. Quantum chemical calculations have been carried out for tapentadol hydrochloride (TAP.Cl) to determine the properties. The geometry is optimised and the structural properties of the compound were determined from the optimised geometry by B3LYP method using 6-311++G(d,p), 6-31G(d,p) and cc-pVDZ basis sets. FT-IR and FT-Raman spectra are recorded in the solid phase in the region of 4000-400 and 4000-100 cm-1, respectively. Frontier molecular orbital energies, LUMO-HOMO energy gap, ionisation potential, electron affinity, electronegativity, hardness and chemical potential are also calculated. The stability of the molecule arising from hyperconjugative interactions and charge delocalisation has been analysed using NBO analysis. The 1H and 13C nuclear magnetic resonance chemical shifts of the molecule are analysed.

  4. Ispaghula Husk-Based Extended Release Tablets of Diclofenac ...

    African Journals Online (AJOL)

    1Vels College of Pharmacy, Pallavaram, Chennai, India, 2Jeffrey Cheah School of Medicine and Health Sciences, Monash University, ... Keywords: Ispaghula husk, Extended release tablet, Diclofenac sodium, Release kinetics. .... release, i.e., Qt vs t, log (Q0-Qt) vs t and Qt vs .... Wallis TE, Textbook of Pharmacognosy, CBS.

  5. Pharmacological and clinical evidence of nevirapine immediate- and extended-release formulations

    Directory of Open Access Journals (Sweden)

    Ena J

    2012-11-01

    Full Text Available Javier Ena, Concepción Amador, Conxa Benito, Francisco PasquauHIV Unit, Hospital Marina Baixa, Villajoyosa, SpainAbstract: We reviewed the current information available on nevirapine immediate- and extended-release formulations and its role in single-dose and combination antiretroviral therapy. Nevirapine was approved in 1996 and was the first non-nucleoside reverse-transcriptase inhibitor available for the treatment of HIV-1 infection. Nevirapine has demonstrated good efficacy and a well-characterized safety profile. A major drawback is the low genetic barrier, allowing the emergence of resistance in the presence of single mutations in the reverse-transcriptase gene. This shortcoming is particularly relevant when nevirapine is administered in a single dose to prevent mother-to-child transmission of HIV-1 infection, compromising the efficacy of future non-nucleoside reverse transcriptase–inhibitor regimens. Studies published recently have probed the noninferiority of nevirapine compared to ritonavir-boosted atazanavir with both tenofovir disoproxil fumarate and emtricitabine in antiretroviral treatment–naïve patients. In 2011, a new formulation of nevirapine (nevirapine extended release that allowed once-daily dosing was approved by the Food and Drug Administration and by the European Medicines Agency. VERxVe, a study comparing nevirapine extended release with nevirapine immediate release in antiretroviral treatment–naïve patients, and TRANxITION, a study carried out in antiretroviral treatment–experienced patients who switched therapy from nevirapine immediate release to nevirapine extended release, provided data on the noninferiority of the new formulation of nevirapine compared with nevirapine immediate release in terms of efficacy and safety. Nevirapine extended release will further increase the durability and persistence of nevirapine-containing antiretroviral therapy, allowing once-daily dosing regimens.Keywords: nevirapine

  6. Tapentadol versus tramadol in the management of low back pain in the emergency department: Impact of use on the need for reassessments.

    Science.gov (United States)

    Guillén-Astete, Carlos A; Cardona-Carballo, César; de la Casa-Resino, Cristina

    2017-11-01

    Nontraumatic musculoskeletal disorders are the main reason for presentation to the emergency department (ED), with rachialgia (back pain) being the most common reason to request medical assessment among them. This also generates the highest demand for reassessments due to poor pain control or onset of adverse reactions to the treatment prescribed in the initial assessment.A retrospective observational study based on usual clinical practice was conducted in patients attending the ED due to low back pain during a period of 24 months. The primary objective was to determine the demand for reassessments in the ED by these patients in the following 30 days, according to the type of therapeutic approach used in the initial assessment.A total of 732 patients who requested medical assessment due to back pain in the ED of our hospital were analyzed, 91 of whom were treated with tapentadol whereas 641 received another treatment. In the first month after the initial assessment, reassessments were less common in the tapentadol group; this difference was significant from days 8 to 15 (P = 0.001, odds ratio [OR] 0.252 with 95% confidence interval [CI] 0.100-0.635) and days 15 to 30 (P pain compared to those who did not receive it (P pain, tapentadol shows clear advantages over the other analgesics analyzed, in terms of pain control and less need for reassessments.

  7. Treatment-Continuity of ADHD Compared Using Immediate-Release and Extended-Release MPH

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-07-01

    Full Text Available The continuity of methylphenidate (MPH therapy for ADHD in young Medicaid beneficiaries (ages 6 to 17 years treated with immediate-release (IR or extended-release (ER MPH formulations was compared in an analysis of statewide California Medicaid claims (2000-2003 conducted at Columbia University, New York; University of Pennsylvania, Philadelphia; and McNeil Pharmaceuticals, Fort Washington, PA.

  8. Features of the extended-release metformin

    Directory of Open Access Journals (Sweden)

    T O Yalochkina

    2013-03-01

    Full Text Available Реферат по материалам статьи Ali S, Fonseca V. Overview of metformin: special focus on metformin extended release. Expert Opin Pharmacother. 2012 Aug;13(12:1797-805.

  9. Extended release formulations for local anaesthetic agents.

    Science.gov (United States)

    Weiniger, C F; Golovanevski, L; Domb, A J; Ickowicz, D

    2012-08-01

    Systemic toxicity through overdose of local anaesthetic agents is a real concern. By encapsulating local anaesthetics in biodegradable carriers to produce a system for prolonged release, their duration of action can be extended. This encapsulation should also improve the safety profile of the local anaesthetic as it is released at a slower rate. Work with naturally occurring local anaestheticss has also shown promise in the area of reducing systemic and neurotoxicity. Extended duration local anaesthetic formulations in current development or clinical use include liposomes, hydrophobic based polymer particles such as Poly(lactic-co-glycolic acid) microspheres, pasty injectable and solid polymers like Poly(sebacic-co-ricinoleic acid) P(SA:RA) and their combination with synthetic and natural local anaesthetic. Their duration of action, rationale and limitations are reviewed. Direct comparison of the different agents is limited by their chemical properties, the drug doses encapsulated and the details of in vivo models described. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

  10. Metoprolol succinate extended release/hydrochlorothiazide combination tablets

    Directory of Open Access Journals (Sweden)

    James W Hainer

    2007-07-01

    Full Text Available James W Hainer, Jennifer SuggAstraZeneca LP, Wilmington, DE, USAAbstract: Lowering elevated blood pressure (BP with drug therapy reduces the risk for catastrophic fatal and nonfatal cardiovascular events such as stroke and myocardial infarction. Given the heterogeneity of hypertension as a disease, the marked variability in an individual patient’s BP response, and low response rates with monotherapy, expert groups such as the Joint National Committee (JNC emphasize the value of combination antihypertensive regimens, noting that combinations, usually of different classes, have additive antihypertensive effects. Metoprolol succinate extended-release tablet is a beta-1 (cardio-selective adrenoceptor-blocking agent formulated to provide controlled and predictable release of metoprolol. Hydrochlorothiazide (HCT is a well-established diuretic and antihypertensive agent, which promotes natruresis by acting on the distal renal tubule. The pharmacokinetics, efficacy, and safety/tolerability of the antihypertensive combination tablet, metoprolol extended release hydrochlorothiazide, essentially reflect the well-described independent characteristics of each of the component agents. Not only is the combination product more effective than monotherapy with the individual components but the combination product allows a low-dose multidrug regimen as an alternative to high-dose monotherapy, thereby, minimizing the likelihood of dose-related side-effects.Keywords: antihypertensive, blood pressure, cardiovascular disease, combination product

  11. A randomized, double-blind study of hydromorphone hydrochloride extended-release tablets versus oxycodone hydrochloride extended-release tablets for cancer pain: efficacy and safety in Japanese cancer patients (EXHEAL: a Phase III study of EXtended-release HydromorphonE for cAncer pain reLief

    Directory of Open Access Journals (Sweden)

    Inoue S

    2017-08-01

    Full Text Available Satoshi Inoue,1 Yoji Saito,2 Satoru Tsuneto,3 Etsuko Aruga,4 Azusa Ide,1 Yasuyuki Kakurai5 1Clinical Development Department, R&D Division, Daiichi Sankyo, Tokyo,2Department of Anesthesiology, Faculty of Medicine, Shimane University, Shimane, 3Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, 4Department of Palliative Medicine, School of Medicine, Teikyo University, Tokyo, 5Biostatistics and Data Management Department, R&D Division, Daiichi Sankyo, Tokyo, Japan Background: In Japan, there are limited options for switching opioid analgesics. Hydromorphone is an opioid analgesic that is routinely used instead of morphine for cancer pain; however, it is not yet available in Japan. The aim of this study was to assess the efficacy and safety of hydromorphone (DS-7113b extended-release tablets in opioid-naïve patients with cancer pain not relieved by non-opioid analgesics.Subjects and methods: This was a multicenter, randomized, double-blind, parallel-group trial. A double-dummy method was used for blinding. Each randomized subject received either hydromorphone extended-release tablets plus placebo oxycodone hydrochloride extended-release tablets 4 mg/day (n=88 or placebo hydromorphone extended-release tablets plus oxycodone hydrochloride extended-release tablets 10 mg/day (n=93 orally for 7 days (once-daily dosing for hydromorphone and twice-daily dosing for oxycodone. The doses were adjusted as necessary. Efficacy was evaluated by change in visual analog scale (VAS score from baseline to completion of treatment.Results: The between-group difference in least squares mean changes in VAS score from baseline to completion or discontinuation of treatment was −0.4 mm (95% CI −5.9 to 5 mm by analysis of covariance where the baseline VAS score was used as a covariate. The upper limit of the 95% CI was below 10 mm, which was predefined as the noninferiority limit. This verified the noninferiority of hydromorphone tablets

  12. 78 FR 66009 - Determination That INVEGA (Paliperidone) Extended-Release Tablet, 12 Milligrams, Was Not...

    Science.gov (United States)

    2013-11-04

    ...] Determination That INVEGA (Paliperidone) Extended-Release Tablet, 12 Milligrams, Was Not Withdrawn From Sale for... Food and Drug Administration (FDA) has determined that INVEGA (paliperidone) extended-release tablet...-release tablet, 12 mg, if all other legal and regulatory requirements are met. FOR FURTHER INFORMATION...

  13. Profile of extended-release oxycodone/acetaminophen for acute pain

    Directory of Open Access Journals (Sweden)

    Bekhit MH

    2015-10-01

    Full Text Available Mary Hanna Bekhit1–51David Geffen School of Medicine, 2Ronald Reagan UCLA Medical Center, 3UCLA Ambulatory Surgery Center, 4UCLA Wasserman Eye Institute, 5UCLA Martin Luther King Community Hospital, University of California Los Angeles, Los Angeles, CA, USA Abstract: This article provides a historical and pharmacological overview of a new opioid analgesic that boasts an extended-release (ER formulation designed to provide both immediate and prolonged analgesia for up to 12 hours in patients who are experiencing acute pain. This novel medication, ER oxycodone/acetaminophen, competes with current US Food and Drug Administration (FDA-approved opioid formulations available on the market in that it offers two benefits concurrently: a prolonged duration of action, and multimodal analgesia through a combination of an opioid (oxycodone with a nonopioid component. Current FDA-approved combination analgesics, such as Percocet (oxycodone/acetaminophen, are available solely in immediate-release (IR formulations. Keywords: opioid, analgesic, xartemis, acute postsurgical pain, substance abuse, acetaminophen, extended release 

  14. Formulation and Evaluation of Extended- Release Tablet of Zolpidem Tartrate by Wet Granulation Technique

    OpenAIRE

    Fatemeh Pourhashem; Mohammad Reza Avadi

    2016-01-01

    The goal of this study was to design and evaluate extended - release system of the hypnotic agent, Zolpidem tartrate usefulness for the treatment of insomnia. The half-life of this drug is about 1.9 - 3 hours that indicating it a candidate for the extended release formulation. Our investigation relates to development of extended drug delivery system based on Hydroxy propyl methyl cellulose (HPMCK4M) as release retardant, polyvinyl pyrrolidone (PVP k30) as binder and Magnesium S...

  15. Ispaghula Husk-Based Extended Release Tablets of Diclofenac ...

    African Journals Online (AJOL)

    Purpose: To formulate extended-release tablets of diclofenac sodium based on ispaghula husk. Methods: Tablets with varying proportions of diclofenac sodium and ispaghula husk were formulated by wet granulation technique at a fixed compression force of 10 kN. The formulated tablets were evaluated for ...

  16. Formulation and Evaluation of Extended- Release Tablet of Zolpidem Tartrate by Wet Granulation Technique

    Directory of Open Access Journals (Sweden)

    Fatemeh Pourhashem

    2016-06-01

    Full Text Available The goal of this study was to design and evaluate extended - release system of the hypnotic agent, Zolpidem tartrate usefulness for the treatment of insomnia. The half-life of this drug is about 1.9 - 3 hours that indicating it a candidate for the extended release formulation. Our investigation relates to development of extended drug delivery system based on Hydroxy propyl methyl cellulose (HPMCK4M as release retardant, polyvinyl pyrrolidone (PVP k30 as binder and Magnesium Stearate using Factorial design. In vitro release study of matrix tablets was carried out in 0.01N HCl for 2 hours. All prepared matrix tablets were evaluated for physicochemical evaluation and drug content. The formulation that had release profile according to United State Pharmacopoeia selected for stability study according to ICH guidelines.

  17. Rhabdomyolysis following Acute Extended-Release Quetiapine Poisoning: A Case Report

    Directory of Open Access Journals (Sweden)

    Antonios Liolios

    2012-01-01

    Full Text Available Background. During the past few years, there have been a number of case reports concerning rhabdomyolysis following quetiapine poisoning; however, there has been none concerning the medication in its extended-release form. Methods. We present the case report of a 48-year-old man presenting a major depressive disorder and borderline personality disorder, who after voluntary intoxication with 12000 mg of quetiapine extended-release developed signs of acute rhabdomyolysis. Results. The rhabdomyolysis was confirmed by the laboratory and the clinical findings, with elevated levels of creatinine, creatine phosphokinase, and CRP. Discussion. We would like to pinpoint the importance of this complication and our concern of prescribing it for psychiatric patients with chronic somatic comorbidities.

  18. Update on prescription extended-release opioids and appropriate patient selection

    Directory of Open Access Journals (Sweden)

    Brennan MJ

    2013-07-01

    Full Text Available Michael J Brennan The Pain Center of Fairfield, Fairfield, CT, USA Abstract: Chronic pain is largely underdiagnosed, often undertreated, and expected to increase as the American population ages. Many patients with chronic pain require long-term treatment with analgesic medications, and pain management may involve use of prescription opioids for patients whose pain is inadequately controlled through other therapies. Yet because of the potential for abuse and addiction, many clinicians hesitate to treat their patients with pain with potentially beneficial agents. Finding the right opioid for the right patient is the first – often complicated – step. Ensuring that patients continue to properly use the medication while achieving therapeutic analgesic effects is the long-term goal. Combined with careful patient selection and ongoing monitoring, new formulations using extended-release technologies incorporating tamper-resistant features may help combat the growing risk of abuse or misuse, which will hopefully reduce individual suffering and the societal burden of chronic pain. The objective of this manuscript is to provide an update on extended-release opioids and to provide clinicians with a greater understanding of which patients might benefit from these new opioid formulations and how to integrate the recommended monitoring for abuse potential into clinical practice. Keywords: chronic pain, opioid analgesics, extended release, abuse prevention

  19. Critical appraisal of extended-release hydrocodone for chronic pain: patient considerations

    Directory of Open Access Journals (Sweden)

    Gould HJ III

    2015-10-01

    Full Text Available Harry J Gould III,1,3–7 Dennis Paul1–8 1Department of Neurology, 2Department of Pharmacology and Experimental Therapeutics, 3Department of Internal Medicine, Section of Physical Medicine and Rehabilitation, 4Department of Anesthesiology, 5Neuroscience Center of Excellence, 6Center of Excellence for Oral and Craniofacial Biology, 7Pain Mastery Center of Louisiana, 8Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, USA Abstract: Opioid analgesics are currently the most effective pharmacologic option for the management of both acute and chronic forms of moderate-to-severe pain. Although the “as-needed” use of immediate-release formulations is considered optimum for treating acute, painful episodes of limited duration, the scheduled dosing of extended-release formulations with immediate-release supplementation for breakthrough pain is regarded to be most effective for managing chronic conditions requiring around-the-clock treatment. The recent introduction of extended-release formulations of the opioid analgesic hydrocodone potentially broadened the possibility of providing pain relief for individuals for whom current formulations are either ineffective or not tolerated. However, reaction to the approval of the new formulations has fueled controversy over the general safety and need for opioid medications, in light of their potential for misuse, abuse, diversion, and addiction. Here, we discuss how the approval of extended-release formulations of hydrocodone and the emotionally charged controversy over their release may affect physician prescribing and the care available to patients in need of chronic opioid therapy for the management of pain. Keywords: opioid analgesics, patient risks, patient benefits, misuse, addiction

  20. Evaluation of chitosan–anionic polymers based tablets for extended-release of highly water-soluble drugs

    Directory of Open Access Journals (Sweden)

    Yang Shao

    2015-02-01

    Full Text Available The objective of this study is to develop chitosan–anionic polymers based extended-release tablets and test the feasibility of using this system for the sustained release of highly water-soluble drugs with high drug loading. Here, the combination of sodium valproate (VPS and valproic acid (VPA were chosen as the model drugs. Anionic polymers studied include xanthan gum (XG, carrageenan (CG, sodium carboxymethyl cellulose (CMC-Na and sodium alginate (SA. The tablets were prepared by wet granulation method. In vitro drug release was carried out under simulated gastrointestinal condition. Drug release mechanism was studied. Compared with single polymers, chitosan–anionic polymers based system caused a further slowdown of drug release rate. Among them, CS–xanthan gum matrix system exhibited the best extended-release behavior and could extend drug release for up to 24 h. Differential scanning calorimetry (DSC and Fourier transform infrared spectroscopy (FTIR studies demonstrated that polyelectrolyte complexes (PECs were formed on the tablet surface, which played an important role on retarding erosion and swelling of the matrix in the later stage. In conclusion, this study demonstrated that it is possible to develop highly water-soluble drugs loaded extended-release tablets using chitosan–anionic polymers based system.

  1. A comparison of the extended-release and standard-release formulations of tacrolimus in de novo kidney transplant recipients: a 12-month outcome study.

    Science.gov (United States)

    Fanous, Helen; Zheng, Rebecca; Campbell, Carolyn; Huang, Michael; Nash, Michelle M; Rapi, Lindita; Zaltzman, Jeffrey S; Prasad, G V Ramesh

    2013-02-01

    BACKGROUND: Limited comparative data are available on the outcomes between extended-release and standard-release tacrolimus when used de novo in kidney transplant recipients (KTRs). METHODS: We identified KTRs transplanted at our institution during 2009-10 routinely prescribed extended-release tacrolimus and compared them with those transplanted during 2008-09 prescribed standard-release tacrolimus. Graft function (eGFR by MDRD-7 equation) at 12 months post-transplant (primary outcome); new-onset diabetes and other cardiovascular risk factors, BK viremia incidence, acute rejection, and graft survival to 12 months (secondary outcomes) were compared by intent-to-treat analysis. Time-to-steady-state concentration and number of dose adjustments required to attain steady state were recorded. RESULTS: There were no important demographic differences between the extended-release (N = 106) and standard-release (N = 95) cohorts. The estimated glomerular filtration rate (eGFR) at 12 months was similar (58.8 ± 17 versus 59.2 ± 18 mL/min/1.73 m(2), P = 0.307). There was no difference in new-onset diabetes (17 versus 20%, P = 0.581), BK viremia (10 versus 7%, P = 0.450), acute rejection (7 versus 16%, P = 0.067) or graft survival (97 versus 95%, P = 0.301). Time-to-steady state was similar (9.2 ± 1.1 versus 8.1 ± 4.7 days, P = 0.490) although extended-release patients required fewer adjustments to attain steady state (1.2 ± 1.7 [0-8] versus 1.7 ± 1.5 [0-7], P = 0.030) but a similar dose (7.2 ± 2.4 [2-17] versus 7 ± 2.7 [2-16] mg/day, P = 0.697). CONCLUSION: De novo KTRs prescribed extended-release or standard-release tacrolimus demonstrate similar 12-month outcomes.

  2. Once daily, extended release ciprofloxacin for complicated urinary tract infections and acute uncomplicated pyelonephritis.

    Science.gov (United States)

    Talan, David A; Klimberg, Ira W; Nicolle, Lindsay E; Song, James; Kowalsky, Steven F; Church, Deborah A

    2004-02-01

    We assessed the efficacy and safety of 1,000 mg extended release ciprofloxacin orally once daily vs conventional 500 mg ciprofloxacin orally twice daily, each for 7 to 14 days, in patients with a complicated urinary tract infection (cUTI) or acute uncomplicated pyelonephritis (AUP). In this prospective, randomized, double-blind, North American multicenter clinical trial adults were stratified based on clinical presentation of cUTI or AUP and randomized to extended release ciprofloxacin or ciprofloxacin twice daily. Efficacy valid patients had positive pretherapy urine cultures (105 or greater cFU/ml) and pyuria within 48 hours of study entry. Bacteriological and clinical outcomes were assessed at the test of cure visit (5 to 11 days after therapy) and the late followup visit (28 to 42 days after therapy). The intent to treat population comprised 1,035 patients (extended release ciprofloxacin in 517 and twice daily in 518), of whom 435 were efficacy valid (cUTI in 343 and AUP in 92). For efficacy valid patients (cUTI and AUP combined) bacteriological eradication rates at test of cure were 89% (183 of 206) vs 85% (195 of 229) (95% CI -2.4%, 10.3%) and clinical cure rates were 97% (198 of 205) vs 94% (211 of 225) (95% CI -1.2%, 6.9%) for extended release vs twice daily ciprofloxacin. Late followup outcomes were consistent with test of cure findings. Eradication rates for Escherichia coli, which accounted for 58% of pathogens, were 97% or greater per group. Drug related adverse event rates were similar for extended release and twice daily ciprofloxacin (13% and 14%, respectively). Extended release ciprofloxacin at a dose of 1,000 mg once daily was as safe and effective as conventional treatment with 500 mg ciprofloxacin twice daily, each given orally for 7 to 14 days in adults with cUTI or AUP. It provides a convenient, once daily, empirical treatment option.

  3. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

    DEFF Research Database (Denmark)

    Sacco, Ralph L; Diener, Hans-Christoph; Yusuf, Salim

    2008-01-01

    BACKGROUND: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. METHODS: In this double-blind, 2-by-2 factorial trial, we randomly...

  4. Extended-release naltrexone for pre-release prisoners: A randomized trial of medical mobile treatment

    Science.gov (United States)

    Gordon, Michael S.; Vocci, Frank J.; Fitzgerald, Terrence T.; O'Grady, Kevin E.; O'Brien, Charles P.

    2017-01-01

    Background Extended-release naltrexone (XR-NTX), is an effective treatment for opioid use disorder but is rarely initiated in US prisons or with criminal justice populations. Mobile treatment for chronic diseases have been implemented in a variety of settings. Mobile treatment may provide an opportunity to expand outreach to parolees to surmount barriers to traditional clinic treatment. Methods Male and female prisoners (240) with pre-incarceration histories of opioid use disorder who are within one month of release from prison will be enrolled in this randomized clinical trial. Participants are randomized to one of two study arms: 1) [XR-NTX-OTx] One injection of long-acting naltrexone in prison, followed by 6 monthly injections post-release at a community opioid treatment program; or 2) [XR-NTX+ MMTx] One injection of long-acting naltrexone in prison followed by 6 monthly injections post-release at the patient's place of residence utilizing mobile medical treatment. The primary outcomes are: treatment adherence; opioid use; criminal activity; re-arrest; reincarceration; and HIV risk-behaviors. Results We describe the background and rationale for the study, its aims, hypotheses, and study design. Conclusions The use of long-acting injectable naltrexone may be a promising form of treatment for pre-release prisoners. Finally, as many individuals in the criminal justice system drop out of treatment, this study will assess whether treatment at their place of residence will improve adherence and positively affect treatment outcomes. PMID:28011389

  5. Extended-release naltrexone for pre-release prisoners: A randomized trial of medical mobile treatment.

    Science.gov (United States)

    Gordon, Michael S; Vocci, Frank J; Fitzgerald, Terrence T; O'Grady, Kevin E; O'Brien, Charles P

    2017-02-01

    Extended-release naltrexone (XR-NTX), is an effective treatment for opioid use disorder but is rarely initiated in US prisons or with criminal justice populations. Mobile treatment for chronic diseases has been implemented in a variety of settings. Mobile treatment may provide an opportunity to expand outreach to parolees to surmount barriers to traditional clinic treatment. Male and female prisoners (240) with pre-incarceration histories of opioid use disorder who are within one month of release from prison will be enrolled in this randomized clinical trial. Participants are randomized to one of two study arms: 1) [XR-NTX-OTx] One injection of long-acting naltrexone in prison, followed by 6 monthly injections post-release at a community opioid treatment program; or 2) [XR-NTX+ MMTx] One injection of long-acting naltrexone in prison followed by 6 monthly injections post-release at the patient's place of residence utilizing mobile medical treatment. The primary outcomes are: treatment adherence; opioid use; criminal activity; re-arrest; reincarceration; and HIV risk-behaviors. We describe the background and rationale for the study, its aims, hypotheses, and study design. The use of long-acting injectable naltrexone may be a promising form of treatment for pre-release prisoners. Finally, as many individuals in the criminal justice system drop out of treatment, this study will assess whether treatment at their place of residence will improve adherence and positively affect treatment outcomes. ClinicalTrials.gov: NCT02867124. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Preparation and scale up of extended-release tablets of bromopride

    Directory of Open Access Journals (Sweden)

    Guilherme Neves Ferreira

    2014-04-01

    Full Text Available Reproducibility of the tablet manufacturing process and control of its pharmaceutics properties depends on the optimization of formulation aspects and process parameters. Computer simulation such as Design of Experiments (DOE can be used to scale up the production of this formulation, in particular for obtaining sustained-release tablets. Bromopride formulations are marketed in the form of extended-release pellets, which makes the product more expensive and difficult to manufacture. The aim of this study was to formulate new bromopride sustained release formulations as tablets, and to develop mathematical models to standardize the scale up of this formulation, controlling weight and hardness of the tablets during manufacture according to the USP 34th edition. DOE studies were conducted using Minitab(tm software. Different excipient combinations were evaluated in order to produce bromopride sustained-release matrix tablets. In the scale-up study, data were collected and variations in tableting machine parameters were measured. Data were processed by Minitab(tm software, generating mathematical equations used for prediction of powder compaction behavior, according to the settings of the tableting machine suitable for scale-up purposes. Bromopride matrix tablets with appropriate characteristics for sustained release were developed. The scale-up of the formulation with the most suitable sustained release profile was established by using mathematical models, indicating that the formulation can be a substitute for the pellets currently marketed.

  7. Risk based In Vitro Performance Assessment of Extended Release Abuse Deterrent Formulations

    Science.gov (United States)

    Xu, Xiaoming; Gupta, Abhay; Al-Ghabeish, Manar; Calderon, Silvia N.; Khan, Mansoor A.

    2016-01-01

    High strength extended release opioid products, which are indispensable tools in the management of pain, are associated with serious risks of unintentional and potentially fatal overdose, as well as of misuse and abuse that might lead to addiction. The issue of drug abuse becomes increasingly prominent when the dosage forms can be readily manipulated to release a high amount of opioid or to extract the drug in certain products or solvents. One approach to deter opioid drug abuse is by providing novel abuse deterrent formulations (ADF), with properties that may be viewed as barriers to abuse of the product. However, unlike regular extended release formulations, assessment of ADF technologies are challenging, in part due to the great variety of formulation designs available to achieve deterrence of abuse by oral, parenteral, nasal and respiratory routes. With limited prior history or literature information, and lack of compendial standards, evaluation and regulatory approval of these novel drug products become increasingly difficult. The present article describes a risk-based standardized in-vitro approach that can be utilized in general evaluation of abuse deterrent features for all ADF products. PMID:26784976

  8. USE OF EXTENDED-RELEASE PRAMIPEXOLE IN EARLY-STAGE PARKINSON’S DISEASE: DESCRIPTION OF A CLINICAL CASE

    Directory of Open Access Journals (Sweden)

    N. V. Fedorova

    2014-11-01

    Full Text Available The paper considers a clinical case of early-stage mixed Parkinson’s disease (PD with significant affective disorders and restless legs syndrome. Once-daily extended-release pramipexole 3 mg significantly improved a patient’s status and led to regression of movement and affective disorders. The paper gives data on the efficacy of dopamine receptor agonists in treating PD and the benefits of their extended-release formulations.

  9. Clonidine Extended-Release Tablets for Pediatric Patients with Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Jain, Rakesh; Segal, Scott; Kollins, Scott H.; Khayrallah, Moise

    2011-01-01

    Objective: This study examined the efficacy and safety of clonidine hydrochloride extended-release tablets (CLON-XR) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Method: This 8-week, placebo-controlled, fixed-dose trial, including 3 weeks of dose escalation, of patients 6 to 17 years old with ADHD evaluated the…

  10. Topiramate Extended-Release Options: A Focus on Efficacy and Safety in Epilepsy and Comorbidities

    Directory of Open Access Journals (Sweden)

    Yuchen Wang

    2017-02-01

    Full Text Available Topiramate (TPM is effective for multiple seizure types and epilepsy syndromes in children and adults. Topiramate has adverse effects (including cognitive, depression, renal stones, but many of these are low incidence when started at a low dose and slowly titrated to 100 to 200 mg/day. Also, TPM has proven benefit for migraine, obesity, eating disorders, and alcohol use disorders, which can be comorbid in patients with epilepsy and may also be effective in subpopulations within specific psychiatric diagnoses. Recently approved extended-release formulations of TPM (Trokendi and Qudexy in the United States have reliable data supporting their safety and efficacy for patients with epilepsy. They have potential for more rapid titration within 1 month to 200 mg/day and have better patient retention than TPM immediate-release, but there are no robust double-blind randomized controlled trials comparing the different formulations. We expect the once per day extended-release formulations to improve medication adherence compared with the twice per day formulations. This has significant potential to improve outcomes in epilepsy and the other TPM-responsive disorders.

  11. Optimization of Melatonin Dissolution from Extended Release Matrices Using Artificial Neural Networking.

    Science.gov (United States)

    Martarelli, D; Casettari, L; Shalaby, K S; Soliman, M E; Cespi, M; Bonacucina, G; Fagioli, L; Perinelli, D R; Lam, J K W; Palmieri, G F

    2016-01-01

    Efficacy of melatonin in treating sleep disorders has been demonstrated in numerous studies. Being with short half-life, melatonin needs to be formulated in extended-release tablets to prevent the fast drop of its plasma concentration. However, an attempt to mimic melatonin natural plasma levels during night time is challenging. In this work, Artificial Neural Networks (ANNs) were used to optimize melatonin release from hydrophilic polymer matrices. Twenty-seven different tablet formulations with different amounts of hydroxypropyl methylcellulose, xanthan gum and Carbopol®974P NF were prepared and subjected to drug release studies. Using dissolution test data as inputs for ANN designed by Visual Basic programming language, the ideal number of neurons in the hidden layer was determined trial and error methodology to guarantee the best performance of constructed ANN. Results showed that the ANN with nine neurons in the hidden layer had the best results. ANN was examined to check its predictability and then used to determine the best formula that can mimic the release of melatonin from a marketed brand using similarity fit factor. This work shows the possibility of using ANN to optimize the composition of prolonged-release melatonin tablets having dissolution profile desired.

  12. Lipids bearing extruded-spheronized pellets for extended release of poorly soluble antiemetic agent-Meclizine HCl.

    Science.gov (United States)

    Qazi, Faaiza; Shoaib, Muhammad Harris; Yousuf, Rabia Ismail; Nasiri, Muhammad Iqbal; Ahmed, Kamran; Ahmad, Mansoor

    2017-04-12

    Antiemetic agent Meclizine HCl, widely prescribed in vertigo, is available only in immediate release dosage forms. The approved therapeutic dose and shorter elimination half-life make Meclizine HCl a potential candidate to be formulated in extended release dosage form. This study was aimed to develop extended release Meclizine HCl pellets by extrusion spheronization using natural and synthetic lipids. Influence of lipid type, drug/lipid ratio and combinations of different lipids on drug release and sphericity of pellets were evaluated. Thirty two formulations were prepared with four different lipids, Glyceryl monostearate (Geleol ® ), Glyceryl palmitostearate (Precirol ® ), Glyceryl behenate (Compritol ® ) and Carnauba wax, utilized either alone or in combinations of drug/lipid ratio of 1:0.5-1:3. Dissolution studies were performed at variable pH and release kinetics were analyzed. Fourier transform infrared spectroscopy was conducted and no drug lipid interaction was found. Sphericity indicated by shape factor (e R ) varied with type and concentration of lipids: Geleol ® (e R  = 0.891-0.997), Precirol ® (e R  = 0.611-0.743), Compritol ® (e R  = 0.665-0.729) and Carnauba wax (e R  = 0.499-0.551). Highly spherical pellets were obtained with Geleol ® (Aspect ratio = 1.005-1.052) whereas irregularly shaped pellets were formed using Carnauba wax (Aspect ratio = 1.153-1.309). Drug release was effectively controlled by three different combinations of lipids: (i) Geleol ® and Compritol ® , (ii) Geleol ® and Carnauba wax and (iii) Geleol ® , Compritol ® and Carnauba wax. Scanning electron microscopy of Compritol ® pellets showed smooth surface with pores, whereas, irregular rough surface with hollow depressions was observed in Carnauba wax pellets. Energy dispersive spectroscopy indicated elemental composition of lipid matrix pellets. Kinetics of (i) Geleol ® and Compritol ® pellets, explained by Korsmeyer-Peppas (R 2  = 0.978-0.993) indicated

  13. Long-Term Effectiveness and Safety of Dexmethylphenidate Extended-Release Capsules in Adult ADHD

    Science.gov (United States)

    Adler, Lenard A.; Spencer, Thomas; McGough, James J.; Jiang, Hai; Muniz, Rafael

    2009-01-01

    Objective: This study evaluates dexmethylphenidate extended release (d-MPH-ER) in adults with ADHD. Method: Following a 5-week, randomized, controlled, fixed-dose study of d-MPH-ER 20 to 40 mg/d, 170 adults entered a 6-month open-label extension (OLE) to assess long-term safety, with flexible dosing of 20 to 40 mg/d. Exploratory effectiveness…

  14. Tamarind seed gum-hydrolyzed polymethacrylamide-g-gellan beads for extended release of diclofenac sodium using 32 full factorial design.

    Science.gov (United States)

    Nandi, Gouranga; Nandi, Amit Kumar; Khan, Najim Sarif; Pal, Souvik; Dey, Sibasish

    2018-07-15

    Development of tamarind seed gum (TSG)-hydrolyzed polymethacrylamide-g-gellan (h-Pmaa-g-GG) composite beads for extended release of diclofenac sodium using 3 2 full factorial design is the main purpose of this study. The ratio of h-Pmaa-g-GG and TSG and concentration of cross-linker CaCl 2 were taken as independent factors with three different levels of each. Effects of polymer ratio and CaCl 2 on drug entrapment efficiency (DEE), drug release, bead size and swelling were investigated. Responses such as DEE and different drug release parameters were statistically analyzed by 3 2 full factorial design using Design-Expert software and finally the formulation factors were optimized to obtain USP-reference release profile. Drug release rate was found to decrease with decrease in the ratio of h-Pmaa-g-GG:TSG and increase in the concentration of Ca 2+ ions in cross-linking medium. The optimized formulation showed DEE of 93.25% and an extended drug release profile over a period of 10h with f 2 =80.13. Kinetic modeling unveiled case-I-Fickian diffusion based drug release mechanism. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. A Controlled Trial of Extended-Release Guanfacine and Psychostimulants for Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Wilens, Timothy E.; Bukstein, Oscar; Brams, Matthew; Cutler, Andrew J.; Childress, Ann; Rugino, Thomas; Lyne, Andrew; Grannis, Kara; Youcha, Sharon

    2012-01-01

    Objective: To examine efficacy, tolerability, and safety of guanfacine extended release (GXR; less than or equal to 4 mg/d) adjunctive to a long-acting psychostimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents 6 to 17 years of age with suboptimal, but partial, response to psychostimulant…

  16. Fission gas release and fuel rod chemistry related to extended burnup

    International Nuclear Information System (INIS)

    1993-04-01

    The purpose of the meeting was to review the state of the art in fission gas release and fuel rod chemistry related to extended burnup. The meeting was held in a time when national and international programmes on water reactor fuel irradiated in experimental reactors were still ongoing or had reached their conclusion, and when lead test assemblies had reached high burnup in power reactors and been examined. At the same time, several out-of-pile experiments on high burnup fuel or with simulated fuel were being carried out. As a result, significant progress has been registered since the last meeting, particularly in the evaluation of fuel temperature, the degradation of the global thermal conductivity with burnup and in the understanding of the impact on fission gas release. Fifty five participants from 16 countries and one international organization attended the meeting. 28 papers were presented. A separate abstract was prepared for each of the papers. Refs, figs, tabs and photos

  17. Update on extended release quetiapine fumarate in schizophrenia and bipolar disorders

    Directory of Open Access Journals (Sweden)

    El-Khalili N

    2012-11-01

    Full Text Available Nizar El-KhaliliAlpine Clinic, Lafayette, IN, USAAbstract: The atypical antipsychotic quetiapine fumarate is available both as an immediate release (IR and as an extended release (XR formulation allowing flexibility of dosing for individual patients. Approved uses of quetiapine XR include the treatment of schizophrenia (including maintenance therapy for prevention of relapse, the treatment of bipolar disorder (manic and depressive episodes, and the prevention of recurrence in patients with bipolar disorder who respond to quetiapine XR. This narrative review provides an update on quetiapine XR in these indications. The pharmacological profile of quetiapine, including a moderate affinity for dopamine D2 receptors and higher affinity for serotonin 5-hydroxytryptophan (5-HT2A receptors, may explain its broad efficacy and low propensity for extrapyramidal symptoms (EPS. The XR formulation has similar bioavailability but prolonged plasma levels compared with the IR formulation, allowing for less frequent (once-daily dosing. Clinical studies have confirmed the efficacy of quetiapine XR in relieving the acute symptoms of schizophrenia during short-term trials, and reducing the risk for relapse in long-term studies. Direct switching from the IR formulation to the same dose of the XR formulation did not reveal any loss of efficacy or tolerability issues, and switching patients to quetiapine XR from conventional or other atypical antipsychotics (for reasons of insufficient efficacy or tolerability also proved to be beneficial and generally well tolerated. In bipolar disorder, quetiapine XR has also proven effective in relieving acute depressive and manic symptoms. Adverse events with quetiapine XR in patients with either schizophrenia or bipolar disorder are similar to those associated with the IR formulation, the most common being sedation, dry mouth, somnolence, dizziness, and headache. The low propensity for EPS is maintained with the XR formulation

  18. Acceptability of Extended-Release Naltrexone by Heroin-Dependent Patients and Addiction Treatment Providers in the Netherlands

    NARCIS (Netherlands)

    Zaaijer, Eline; Goudriaan, Anna E.; Koeter, Maarten W. J.; Booij, Jan; van den Brink, Wim

    2016-01-01

    Background: Extended-release naltrexone (XRNT) was developed to overcome poor treatment compliance with oral naltrexone in alcohol and opioid-dependent patients. XRNT injections are registered in the United States and Russia, but not in The Netherlands. However, XRNT can be obtained for individual

  19. Fission-gas release in fuel performing to extended burnups in Ontario Hydro nuclear generating stations

    International Nuclear Information System (INIS)

    Floyd, M.R.; Novak, J.; Truant, P.T.

    1992-06-01

    The average discharge burnup of CANDU fuel is about 200 MWh/kgU. A significant number of 37-element bundles have achieved burnups in excess of 400 MWh/kgU. Some of these bundles have experienced failures related to their extended operation. To date, hot-cell examinations have been performed on fuel elements from nine 37-element bundles irradiated in Bruce NGS-A that have burnups in the range of 300-800 MWh/kgU. 1 Most of these have declining power histories from peak powers of up to 59 kW/m. Fission-gas releases of up to 26% have been observed and exhibit a strong dependence on fuel power. This obscures any dependence on burnup. The extent of fission-gas release at extended burnups was not predicted by low-burnup code extrapolations. This is attributed primarily to a reduction in fuel thermal conductivity which results in elevated operating temperatures. Reduced conductivity is due, at least in part, to the buildup of fission products in the fuel matrix. Some evidence of hyperstoichiometry exists, although this needs to be further investigated along with any possible relation to CANLUB graphite coating behaviour and sheath oxidation. Residual tensile sheath strains of up to 2% have been observed and can be correlated with fuel power/fission-gas release. SCC 2 -related defects have been observed in the sheath and endcaps of elements from bundles experiencing declining power histories to burnups in excess of 500 MWh/kgU. This indicates that the current recommended burnup limit of 450 MWh/kgU is justified. SCC-related defects have also been observed in ramped bundles having burnups < 450 MWh/kgU. Hence, additional guidelines are in place for power ramping extended-burnup fuel

  20. 76 FR 53908 - Determination That OPANA ER (Oxymorphone Hydrochloride) Extended-Release Tablets, 7.5 Milligrams...

    Science.gov (United States)

    2011-08-30

    ... proceedings that could result in the withdrawal of approval of the ANDAs that refer to the listed drug. OPANA... relief of moderate to severe pain in patients requiring continuous, around-the-clock opioid treatment for... withdrawal of OPANA ER (oxymorphone HCl) extended-release tablets, 7.5 mg and 15 mg, from sale. We have also...

  1. Assessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Levy Juliana

    2010-03-01

    Full Text Available Abstract Aims To determine prospectively the efficacy, tolerability and patient satisfaction of an extended release formulation of metformin (metformin XR in hospital based outpatients with type 2 diabetes mellitus currently treated with standard metformin. Methods Patients on immediate release standard metformin either alone or combined with other oral agents were switched to extended release metformin XR 500 mg tablets and titrated to a maximum dose of 2000 mg/day Measurements to include glucose and lipid control, blood pressure, body weight, waist circumference, C-reactive protein, adverse events and patient satisfaction were recorded at baseline, three and six months. Results Complete data were obtained for 35 of the 61 patients enrolled to the study. At three and six months no changes were reported for any of the cardiovascular risk factors except for lipids where there was a modest rise in plasma triglycerides. These effects were achieved with a reduced dose of metformin XR compared to pre-study dosing with standard metformin (1500 mg +/- 402 vs 1861 +/- 711 p = 0.004. A total of 77% of patients were free of gastrointestinal side effects and 83% of patients stated a preference for metformin XR at the end of the study. Ghost tablets were reported in the faeces by the majority of the patients (54.1%. Conclusions Patients switched to extended release metformin XR derived the same clinical and metabolic benefits as for standard metformin but with reduced dosage, fewer gastrointestinal side effects and a greater sense of well being and satisfaction on medication.

  2. Simulated Driving Changes in Young Adults with ADHD Receiving Mixed Amphetamine Salts Extended Release and Atomoxetine

    Science.gov (United States)

    Kay, Gary G.; Michaels, M. Alex; Pakull, Barton

    2009-01-01

    Background: Psychostimulant treatment may improve simulated driving performance in young adults with attention-deficit/hyperactivity disorder (ADHD). Method: This was a randomized, double-blind, placebo-controlled, crossover study of simulated driving performance with mixed amphetamine salts--extended release (MAS XR) 50 mg/day (Cohort 1) and…

  3. Management of obesity and cardiometabolic risk – role of phentermine/extended release topiramate

    Directory of Open Access Journals (Sweden)

    Sweeting AN

    2014-02-01

    Full Text Available Arianne N Sweeting,1 Eddy Tabet,1 Ian D Caterson,1,2 Tania P Markovic1,2 1Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 2Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, University of Sydney, NSW, Australia Abstract: The US Food and Drug Administration (FDA recently approved lorcaserin and the combination of phentermine and extended release topiramate (phentermine/topiramate ER for the treatment of obesity in conjunction with a lifestyle intervention, expanding the therapeutic options for long-term obesity pharmacotherapy, which was previously limited to orlistat. Combination phentermine/topiramate ER is associated with greater weight loss compared to its constituent monotherapy, with a more favorable adverse effect profile. Phentermine/topiramate ER also appears to have beneficial effects on cardiometabolic risk, although longer-term cardiovascular safety data are required. While there are no head-to-head studies among the currently available obesity pharmacotherapy agents, phentermine/topiramate ER appears to have a superior weight loss profile. This review will discuss the epidemiology, natural history, and cardiometabolic risk associated with obesity, provide an overview on current obesity pharmacotherapy, and summarize the recent clinical efficacy and safety data underpinning the FDA's approval of both phentermine/topiramate ER and lorcaserin as pharmacotherapy for a long-term obesity intervention. Keywords: obesity, phentermine/topiramate extended release, safety and efficacy, review

  4. Direct and indirect effects of paliperidone extended-release tablets on negative symptoms of schizophrenia

    OpenAIRE

    Bossie, Cynthia

    2008-01-01

    Ibrahim Turkoz, Cynthia A Bossie, Bryan Dirks, Carla M CanusoOrtho-McNeil Janssen Scientific Affairs, LLC, Titusville, NJ, USAAbstract: Direct and indirect effects of the new psychotropic paliperidone extended-release (paliperidone ER) tablets on negative symptom improvement in schizophrenia were investigated using path analysis. A post hoc analysis of pooled data from three 6-week, double-blind, placebo-controlled studies of paliperidone ER in patients experiencing acute exacerbation was con...

  5. Effect of food on early drug exposure from extended-release stimulants: results from the Concerta, Adderall XR Food Evaluation (CAFE) Study.

    Science.gov (United States)

    Auiler, J F; Liu, K; Lynch, J M; Gelotte, C K

    2002-01-01

    Stimulant therapy is the mainstay of treatment for children, adolescents and adults with attention-deficit/hyperactivity disorder (ADHD). Once-daily, extended-release oral formulations offer long acting control of symptoms by modifying drug delivery and absorption. In particular, consistency in early drug exposure is important for symptom control during school or work hours. Because these once-daily formulations are usually taken in the morning, the timing of the doses with breakfast is important. This study compared the effect of a high-fat breakfast on early drug exposure from a morning dose of two extended-release stimulant formulations: the osmotic-controlled OROS tablet of methylphenidate HCI (CONCERTA) and the capsule containing extended-release beads of mixed amphetamine salts (ADDERALL XR). The study had a single-dose, open-label, randomised, four-treatment, crossover design in which healthy subjects received either 36 mg CONCERTA or 20 mg ADDERALL XR in the morning after an overnight fast or a high-fat breakfast. Serial blood samples were collected over 28h to determine plasma concentrations of methylphenidate and amphetamine. The food effect on early drug exposure and the pharmacokinetic profiles up to 8 h after dosing of the two extended-release stimulants were directly compared using partial area (AUC(p4h), AUC(p6h) and AUC(p8h)) fed/fasted ratios. Amphetamine concentrations were markedly lower when the subjects had eaten breakfast, resulting in lower early drug exposures (p food, for patients with ADHD.

  6. Tramadol extended-release in the management of chronic pain

    Science.gov (United States)

    McCarberg, Bill

    2007-01-01

    Chronic, noncancer pain such as that associated with osteoarthritis of the hip and knee is typically managed according to American College of Rheumatology guidelines. Patients unresponsive to first-line treatment with acetaminophen receive nonsteroidal antiinflammatory drugs (NSAIDs), including cyclooxygenase-2 (COX-2) inhibitors. However, many patients may have chronic pain that is refractory to these agents, or they may be at risk for the gastrointestinal, renal, and cardiovascular complications associated with their use. Tramadol, a mild opioid agonist and norepinephrine and serotonin reuptake inhibitor, is recommended by current guidelines for the treatment of moderate to moderately severe pain in patients who have not responded to previous oral therapy, or in patients who have contraindications to COX-2 inhibitors and nonselective NSAIDs. An extended-release (ER) formulation of tramadol was approved by the US Food and Drug Administration in September 2005. In contrast with immediate-release (IR) tramadol, this ER formulation allows once-daily dosing, providing around-the-clock analgesia. In clinical studies, tramadol ER has demonstrated a lower incidence of adverse events than that reported for IR tramadol. Unlike nonselective NSAIDs and COX-2 inhibitors, tramadol ER is not associated with gastrointestinal, renal, or cardiovascular complications. Although tramadol is an opioid agonist, significant abuse has not been demonstrated after long-term therapy. It is concluded that tramadol ER has an efficacy and safety profile that warrants its early use for the management of chronic pain, either alone or in conjunction with nonselective NSAIDs and COX-2 inhibitors. PMID:18488071

  7. Two-way pharmacokinetic interaction studies between saxagliptin and cytochrome P450 substrates or inhibitors: simvastatin, diltiazem extended-release, and ketoconazole

    Directory of Open Access Journals (Sweden)

    Patel C

    2011-06-01

    Full Text Available Chirag G Patel, Li Li, Suzette Girgis, David M Kornhauser, Ernest U Frevert, David W BoultonBristol-Myers Squibb, Princeton, NJ, USABackground: Many medicines, including several cholesterol-lowering agents (eg, lovastatin, simvastatin, antihypertensives (eg, diltiazem, nifedipine, verapamil, and antifungals (eg, ketoconazole are metabolized by and/or inhibit the cytochrome P450 (CYP 3A4 metabolic pathway. These types of medicines are commonly coprescribed to treat comorbidities in patients with type 2 diabetes mellitus (T2DM and the potential for drug-drug interactions of these medicines with new medicines for T2DM must be carefully evaluated.Objective: To investigate the effects of CYP3A4 substrates or inhibitors, simvastatin (substrate, diltiazem (moderate inhibitor, and ketoconazole (strong inhibitor on the pharmacokinetics and safety of saxagliptin, a CYP3A4/5 substrate; and the effects of saxagliptin on these agents in three separate studies.Methods: Healthy subjects were administered saxagliptin 10 mg or 100 mg. Simvastatin, diltiazem extended-release, and ketoconazole doses of 40 mg once daily, 360 mg once daily, and 200 mg twice daily, respectively, were used to determine two-way pharmacokinetic interactions.Results: Coadministration of simvastatin, diltiazem extended-release, or ketoconazole increased mean area under the concentration-time curve values (AUC of saxagliptin by 12%, 109%, and 145%, respectively, versus saxagliptin alone. Mean exposure (AUC of the CYP3A4-generated active metabolite of saxagliptin, 5-hydroxy saxagliptin, decreased with coadministration of simvastatin, diltiazem, and ketoconazole by 2%, 34%, and 88%, respectively. All adverse events were considered mild or moderate in all three studies; there were no serious adverse events or deaths.Conclusion: Saxagliptin, when coadministered with simvastatin, diltiazem extended-release, or ketoconazole, was safe and generally well tolerated in healthy subjects. Clinically

  8. 76 FR 68766 - Draft Blueprint for Prescriber Education for Long-Acting/Extended-Release Opioid Class-Wide Risk...

    Science.gov (United States)

    2011-11-07

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0771] Draft Blueprint for Prescriber Education for Long-Acting/ Extended-Release Opioid Class-Wide Risk... announcing the availability of a draft document entitled ``Blueprint for Prescriber Education for the Long...

  9. Quetiapine extended release versus aripiprazole in children and adolescents with first-episode psychosis

    DEFF Research Database (Denmark)

    Pagsberg, Anne Katrine; Jeppesen, Pia; Klauber, Dea Gowers

    2017-01-01

    of quetiapine-extended release (quetiapine-ER) versus aripiprazole in children and adolescents with first-episode psychosis, to determine whether differences between the two treatments were sufficient to guide clinicians in their choice of one drug over the other. METHODS: In this multicentre, double-blind...... (47 [92%] vs 39 [71%]), orthostatic dizziness (42 [78%] vs 46 [81%]), depression (43 [80%] vs 44 [77%]), tension/inner unrest (37 [69%] vs 50 [88%]), failing memory (41 [76%] vs 44 [77%]), and weight gain (46 [87%] vs 38 [68%]). INTERPRETATION: This first head-to-head comparison of quetiapine...

  10. Formulation of Extended-Release Metformin Hydrochloride Matrix ...

    African Journals Online (AJOL)

    Methods: Various metformin hydrochloride formulations containing a hydrophobic carrier (stearic acid) and a hydrophilic polymer (polyethylene oxide) were prepared using a 32 factorial design. ... The release data were subjected to various release kinetic models and also compared with those of a commercial brand.

  11. Guanfacine Extended Release in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Placebo-Controlled Trial

    Science.gov (United States)

    Sallee, Floyd R.; McGough, James; Wigal, Tim; Donahue, Jessica; Lyne, Andrew; Biederman, Joseph

    2009-01-01

    A double-blind, 9-week, randomized trial was done to compare the efficacy of guanfacine extended release (GXR) with a placebo in treating children and adolescents with attention-deficit/hyperactivity disorders (ADHD). Results find a significant reduction in ADHD from baseline to endpoint for all daily doses of GXR which were measured at 1-, 2-,…

  12. The management of schizophrenia: focus on extended-release quetiapine fumarate

    Directory of Open Access Journals (Sweden)

    Peuskens J

    2011-09-01

    Full Text Available Joseph Peuskens Universitair Psychiatrisch Centrum KU Leuven, Campus St Jozef Kortenberg, Kortenberg, Belgium Abstract: Effective management of schizophrenia remains a significant clinical challenge. While antipsychotic medications have proven efficacy in this disease, there remains an opportunity to further improve symptom control and long-term relapse prevention. Also, a number of factors, including tolerability and complex dosing regimens, can result in nonadherence to medication. Quetiapine is an atypical antipsychotic with proven efficacy and an established tolerability profile in schizophrenia. The once-daily extended-release formulation (quetiapine XR offers a simplified dosing regimen and titration schedule. Short-term clinical studies have shown that quetiapine XR (400–800 mg/d is efficacious in the acute treatment of schizophrenia, while a long-term study has shown that quetiapine XR was significantly more effective than placebo at preventing relapse. Furthermore, an investigation in which stable patients switched from the immediate-release formulation (quetiapine IR to quetiapine XR showed that quetiapine XR is generally well tolerated and has no loss of efficacy compared with quetiapine IR. In patients who experienced insufficient efficacy or poor tolerability on their previous antipsychotic, switching to quetiapine XR significantly improved efficacy compared with the previous treatment. In conclusion, quetiapine XR is an effective and generally well tolerated treatment for schizophrenia. Furthermore, once-daily dosing may improve patient adherence, which may impact positively on patient outcomes. Keywords: adherence, atypical antipsychotics, adverse events

  13. Use of partial AUC to demonstrate bioequivalence of Zolpidem Tartrate Extended Release formulations.

    Science.gov (United States)

    Lionberger, Robert A; Raw, Andre S; Kim, Stephanie H; Zhang, Xinyuan; Yu, Lawrence X

    2012-04-01

    FDA's bioequivalence recommendation for Zolpidem Tartrate Extended Release Tablets is the first to use partial AUC (pAUC) metrics for determining bioequivalence of modified-release dosage forms. Modeling and simulation studies were performed to aid in understanding the need for pAUC measures and also the proper pAUC truncation times. Deconvolution techniques, In Vitro/In Vivo Correlations, and the CAT (Compartmental Absorption and Transit) model were used to predict the PK profiles for zolpidem. Models were validated using in-house data submitted to the FDA. Using dissolution profiles expressed by the Weibull model as input for the CAT model, dissolution spaces were derived for simulated test formulations. The AUC(0-1.5) parameter was indicative of IR characteristics of early exposure and effectively distinguished among formulations that produced different pharmacodynamic effects. The AUC(1.5-t) parameter ensured equivalence with respect to the sustained release phase of Ambien CR. The variability of AUC(0-1.5) is higher than other PK parameters, but is reasonable for use in an equivalence test. In addition to the traditional PK parameters of AUCinf and Cmax, AUC(0-1.5) and AUC(1.5-t) are recommended to provide bioequivalence measures with respect to label indications for Ambien CR: onset of sleep and sleep maintenance.

  14. Comparative steady-state pharmacokinetic study of an extended-release formulation of itopride and its immediate-release reference formulation in healthy volunteers

    OpenAIRE

    Yoon, Seonghae; Lee, Howard; Kim, Tae-Eun; Lee, SeungHwan; Chee, Dong-Hyun; Cho, Joo-Youn; Yu, Kyung-Sang; Jang, In-Jin

    2014-01-01

    Seonghae Yoon,1,* Howard Lee,2,* Tae-Eun Kim,1 SeungHwan Lee,1 Dong-Hyun Chee,3 Joo-Youn Cho,1 Kyung-Sang Yu,1 In-Jin Jang1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 2Clinical Trials Center, Seoul National University Hospital, 3AbbVie Ltd., Seoul, Republic of Korea *These authors contributed equally to this work Background: This study was conducted to compare the oral bioavailability of an itopride extended-release (ER...

  15. Paliperidone extended-release: does it have a place in antipsychotic therapy?

    Directory of Open Access Journals (Sweden)

    Carlos Schönfeldt-Lecuona

    2011-03-01

    Full Text Available Maximilian Gahr1,*, Markus A Kölle1,*, Carlos Schönfeldt-Lecuona1, Peter Lepping2, Roland W Freudenmann11Department of Psychiatry and Psychotherapy, University of Ulm, Ulm, Germany; 2Department of Psychiatry, Glyndwr University, Wales, UK *Both authors contributed equally and their order was determined by coin toss.Abstract: Paliperidone (9-hydroxy-risperidone, the active metabolite of risperidone, was approved for treating schizophrenia worldwide in 2006 as paliperidone extended-release (PER, and became the first second-generation antipsychotic specifically licensed for treating schizoaffective disorder in 2009. However, at the same time, its comparatively high cost gave rise to concerns about the cost-effectiveness of PER as compared with its precursor, risperidone. This paper reviews the existing knowledge of the pharmacology, kinetics, efficacy, tolerability, and fields of application of PER, and compares PER with risperidone in order to determine whether it has a place in antipsychotic therapy. An independent assessment of all relevant publications on PER published until July 2010 was undertaken. PER has a unique pharmacological profile, including single dosing, predominantly renal excretion, low drug–drug interaction risk, and differs from risperidone in terms of mode of action and pharmacokinetics. High-level evidence suggests that PER is efficacious and safe in schizophrenia, schizoaffective disorder, and acute manic episodes. There is a striking lack of published head-to-head comparisons between PER and risperidone, irrespective of indication. Low-level evidence shows a lower risk for hyperprolactinemia and higher patient satisfaction with PER than with risperidone. PER adds to the still limited arsenal of second-generation antipsychotics. In the absence of direct comparisons with risperidone, it remains difficult to come to a final verdict on the potential additional therapeutic benefits of PER which would justify its substantially

  16. Opioid rotation with extended-release opioids: where should we begin?

    Directory of Open Access Journals (Sweden)

    Nalamachu S

    2011-12-01

    Full Text Available Srinivas NalamachuInternational Clinical Research Institute and Pain Management Institute, Overland Park, KS, USAAbstract: Opioid rotation is a common and necessary clinical practice in the management of chronic non-cancer pain to improve therapeutic efficacy with the lowest opioid dose. When dose escalations fail to achieve adequate analgesia or are associated with intolerable side effects, a trial of a new opioid should be considered. Much of the scientific rationale of opioid rotation is based on the wide interindividual variability in sensitivity to opioid analgesics and the novel patient response observed when introducing an opioid-tolerant patient to a new opioid. This article discusses patient indicators for opioid rotation, the conversion process between opioid medications, and additional practical considerations for increasing the effectiveness of opioid therapy during a trial of a new opioid. A Patient vignette that demonstrates a step-wise approach to opioid rotation is also presented.Keywords: extended-release opioids, chronic pain, opioid rotation

  17. Pharmacokinetic drug evaluation of extended release lorcaserin for the treatment of obesity.

    Science.gov (United States)

    Hurren, Kathryn M; Dunham, Marissa W

    2017-08-01

    Lorcaserin is a serotonin 2C receptor antagonist that was FDA approved in 2012. Lorcaserin is recently available as an extended-release (ER) formulation for the treatment of obesity as an adjunct to lifestyle modification. Areas covered: The pharmacokinetics, pharmacodynamics, efficacy, and safety of lorcaserin ER will be reviewed. Expert opinion: Lorcaserin ER 20mg daily provides drug exposure bioequivalent to lorcaserin immediate release (IR) 10mg twice daily. Lorcaserin IR is associated with 3.3 and 3.0% placebo-subtracted weight loss in patients without and with diabetes, respectively. A1C was reduced by 0.9% in patients with diabetes. Common side effects include headache, dry mouth, constipation, dizziness, fatigue, and nausea. Lorcaserin provides potential advantages over other antiobesity medications in regards to tolerability and simplicity of medication initiation, but may not be as effective as other options. Lorcaserin ER offers improved ease of administration and anticipated adherence compared to the IR formulation. The place in therapy for lorcaserin ER and other antiobesity medications will be further clarified by results of pending clinical trials addressing cardiovascular outcomes as well as the role pharmacogenomics and comorbid disease states may play in choosing patient-specific therapy.

  18. Comparative steady-state pharmacokinetic study of an extended-release formulation of itopride and its immediate-release reference formulation in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Yoon S

    2014-01-01

    Full Text Available Seonghae Yoon,1,* Howard Lee,2,* Tae-Eun Kim,1 SeungHwan Lee,1 Dong-Hyun Chee,3 Joo-Youn Cho,1 Kyung-Sang Yu,1 In-Jin Jang1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 2Clinical Trials Center, Seoul National University Hospital, 3AbbVie Ltd., Seoul, Republic of Korea *These authors contributed equally to this work Background: This study was conducted to compare the oral bioavailability of an itopride extended-release (ER formulation with that of the reference immediate-release (IR formulation in the fasting state. The effect of food on the bioavailability of itopride ER was also assessed. Methods: A single-center, open-label, randomized, multiple-dose, three-treatment, three-sequence, crossover study was performed in 24 healthy male subjects, aged 22–48 years, who randomly received one of the following treatments for 4 days in each period: itopride 150 mg ER once daily under fasting or fed conditions, or itopride 50 mg IR three times daily in the fasting state. Steady-state pharmacokinetic parameters of itopride, including peak plasma concentration (Cmax and area under the plasma concentration versus time curve over 24 hours after dosing (AUC0–24h, were determined by noncompartmental analysis. The geometric mean ratio of the pharmacokinetic parameters was derived using an analysis of variance model. Results: A total of 24 healthy Korean subjects participated, 23 of whom completed the study. The geometric mean ratio and its 90% confidence interval of once-daily ER itopride versus IR itopride three times a day for AUC0–24h were contained within the conventional bioequivalence range of 0.80–1.25 (0.94 [0.88–1.01], although Cmax was reached more slowly and was lower for itopride ER than for the IR formulation. Food delayed the time taken to reach Cmax for itopride ER, but AUC0–24h was not affected. There were no serious adverse events and both formulations were

  19. Dose comparison and side effect profile of metformin extended release versus metformin immediate release

    International Nuclear Information System (INIS)

    Hameed, M.; Khan, K.; Salman, S.; Mehmood, N.

    2017-01-01

    Diabetes Mellitus type 2 is very common worldwide, with majority of cases in Asia Pacific region. Metformin is the first line therapy, along with lifestyle modification for all type 2 diabetics as recommended by ADA. Metformin is available as conventional Metformin Immediate Release (MIR) and Metformin Extended Release (MXR). Metformin XR has better gastrointestinal tolerability and fewer side effects as compared to Metformin IR, with similar efficacy regarding anti-hyperglycaemic effects. The objective of this study was to determine whether metformin XR is as effective as Metformin IR in maintaining glycaemic control at equivalent doses or even at reduced doses; and to compare the side effect profile of the two preparations. Methods: This randomized control trial was conducted at Medical and Endocrinology OPD of Jinnah Hospital Lahore A total of 90 type 2 diabetics of both genders were recruited using nonprobability purposive sampling. Patients were randomized into 3 groups; 30 in each group. Group 1 received Metformin IR 1000 mg twice daily; group 2 received metformin XR 1000mg twice daily; and group 3 received metformin XR 500 mg twice daily, for a period of three months. HbA1c was done at baseline and after three months of therapy along with fasting blood sugars and random blood sugars weekly. Results: The mean age of patients was 46+-9 years, with 54% being males and 46% being females. There was a 1% reduction in HbA1c in group 1, 0.7% reduction in group 2 and only 0.4% reduction in group 3. Similarly, all three therapies were equally effective in reducing blood sugar fasting and blood sugar random at three months. Side effects namely diarrhoea, dyspepsia and flatulence were greatest with Metformin IR (40%) but less than half with Metformin XR at equivalent dose and negligible at half the dose. Conclusions: All three Metformin groups were effective in reduction of HbA1C and glycaemic control clinically and there is no statistical difference in HbA1c reduction

  20. Review of extended-release formulations of Tramadol for the management of chronic non-cancer pain: focus on marketed formulations

    Science.gov (United States)

    Kizilbash, Arshi; Ngô-Minh, Cường

    2014-01-01

    Patients with chronic non-malignant pain report impairments of physical, social, and psychological well-being. The goal of pain management should include reducing pain and improving quality of life. Patients with chronic pain require medications that are able to provide adequate pain relief, have minimum dosing intervals to maintain efficacy, and avoid breakthrough pain. Tramadol has proven efficacy and a favourable safety profile. The positive efficacy and safety profile has been demonstrated historically in numerous published clinical studies as well as from post-marketing experience. It is a World Health Organization “Step 2” opioid analgesic that has been shown to be effective, well-tolerated, and valuable, where treatment with strong opioids is not required. A number of extended release formulations of Tramadol are available in Canada and the United States. An optimal extended release Tramadol formulation would be expected to provide consistent pain control with once daily dosing, few sleep interruptions, flexible dosing schedules, and no limitation on taking with meals. Appropriate treatment options should be based on the above proposed attributes. A comparative review of available extended release Tramadol formulations shows that these medications are not equivalent in their pharmacokinetic profile and this may have implications for selecting the optimal therapy for patients with pain syndromes where Tramadol is an appropriate analgesic agent. Differences in pharmacokinetics amongst the formulations may also translate into varied clinical responses in patients. Selection of the appropriate formulation by the health care provider should therefore be based on the patient’s chronic pain condition, needs, and lifestyle. PMID:24711710

  1. Single- and multiple-dose pharmacokinetics of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (MNK-155 compared with immediate-release hydrocodone bitartrate/ibuprofen and immediate-release tramadol HCl/acetaminophen

    Directory of Open Access Journals (Sweden)

    Devarakonda K

    2015-09-01

    Full Text Available Krishna Devarakonda,1 Kenneth Kostenbader,2 Michael J Giuliani,3 Jim L Young41Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, 2Mallinckrodt Pharmaceuticals, 3Research and Development, Mallinckrodt Pharmaceuticals, 4Department of Clinical Affairs and Program Management, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USAObjective: To characterize the single-dose and steady-state pharmacokinetics (PK of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (IR/ER HB/APAP, IR HB/ibuprofen, and IR tramadol HCl/APAP.Methods: In this single-center, open-label, randomized, four-period crossover study, healthy participants received four treatments under fasted conditions: 1 a single dose of two IR/ER HB/APAP 7.5/325 mg tablets (15/650 mg total dose on day 1, followed by two tablets every 12 hours (q12h beginning on day 3; 2 a single dose of IR HB/ibuprofen 15/400 mg (divided as one 7.5/200 mg tablet at hour 0 and 6, followed by one tablet every 6 hours (q6h beginning on day 3; 3 a single dose of IR tramadol HCl/APAP 75/650 mg (divided as one 37.5/325 mg tablet at hour 0 and 6, followed by one tablet q6h beginning on day 3; and 4 a single dose of three IR/ER HB/APAP 7.5/325 mg tablets (22.5/975 mg total dose on day 1, a three-tablet initial dose at 48 hours followed by two-tablet doses q12h beginning on day 3. Hydrocodone and APAP single-dose and steady-state PK were assessed. Adverse events were monitored.Results: The PK analysis was carried out on 29 of 48 enrolled participants who completed all treatment periods. Single-dose hydrocodone exposure was similar for IR/ER HB/APAP 22.5/975 mg and IR HB/ibuprofen 15/400 mg; time to maximum observed plasma concentration was shorter and half-life was longer for IR/ER HB/APAP (22.5/975 mg and 15/650 mg vs IR HB/ibuprofen. Single-dose APAP exposure was similar for IR/ER HB/APAP 15/650 mg and IR tramadol HCl/APAP 75/650 mg. Steady-state hydrocodone and APAP exposures

  2. Assessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    S Yu Vorotnikova

    2012-09-01

    Full Text Available Реферат по статье: Assessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus Juliana Levy, Roberta A Cobas, Marilia B Gomes. Diabetol Metab Syndr. 2010 Mar 18; 2:16.

  3. Application of Physiologically Based Absorption Modeling to Characterize the Pharmacokinetic Profiles of Oral Extended Release Methylphenidate Products in Adults.

    Directory of Open Access Journals (Sweden)

    Xiaoxia Yang

    Full Text Available A previously presented physiologically-based pharmacokinetic model for immediate release (IR methylphenidate (MPH was extended to characterize the pharmacokinetic behaviors of oral extended release (ER MPH formulations in adults for the first time. Information on the anatomy and physiology of the gastrointestinal (GI tract, together with the biopharmaceutical properties of MPH, was integrated into the original model, with model parameters representing hepatic metabolism and intestinal non-specific loss recalibrated against in vitro and in vivo kinetic data sets with IR MPH. A Weibull function was implemented to describe the dissolution of different ER formulations. A variety of mathematical functions can be utilized to account for the engineered release/dissolution technologies to achieve better model performance. The physiological absorption model tracked well the plasma concentration profiles in adults receiving a multilayer-release MPH formulation or Metadate CD, while some degree of discrepancy was observed between predicted and observed plasma concentration profiles for Ritalin LA and Medikinet Retard. A local sensitivity analysis demonstrated that model parameters associated with the GI tract significantly influenced model predicted plasma MPH concentrations, albeit to varying degrees, suggesting the importance of better understanding the GI tract physiology, along with the intestinal non-specific loss of MPH. The model provides a quantitative tool to predict the biphasic plasma time course data for ER MPH, helping elucidate factors responsible for the diverse plasma MPH concentration profiles following oral dosing of different ER formulations.

  4. The Direct and Indirect Effects of Paliperidone Extended-release on Depressive Symptoms in Schizoaffective Disorder: A Path Analysis.

    Science.gov (United States)

    Turkoz, Ibrahim; Fu, Dong-Jing; Bossie, Cynthia A; Alphs, Larry

    2015-01-01

    This analysis evaluates improvement in symptoms of depression in patients with schizoaffective disorder administered oral paliperidone extended-release by accounting for the magnitude of direct and indirect (changes in negative and positive symptoms and worsening of extrapyramidal symptoms) treatment effects on depressive symptoms. Data for this post hoc analysis were drawn from two six-week, randomized, placebo-controlled studies of paliperidone extended-release versus placebo in adult subjects with schizoaffective disorder (N=614; NCT00412373, NCT00397033). Subjects with baseline 17-item Hamilton Rating Scale for Depression scores of 16 or greater were included. Structural equation models (path analyses) were used to separate total effects into direct and indirect effects on depressive symptoms. Change from baseline in 17-item Hamilton Rating Scale for Depression score at the Week 6 end point was the dependent variable; changes in Positive and Negative Syndrome Scale positive and negative factors and Simpson-Angus Scale (to evaluate extrapyramidal symptoms) scores were independent variables. At baseline, 332 of 614 (54.1%) subjects had a 17-item Hamilton Rating Scale for Depression score of 16 or greater. Path analysis determined that up to 26.4 percent of the paliperidone extended-release versus placebo effect on depressive symptoms may be attributed to a direct treatment effect, and 45.8 percent and 28.4 percent were mediated indirectly through improvements on positive and negative symptoms, respectively. No effects were identified as mediated through extrapyramidal symptoms changes (-0.7%). RESULTS of this analysis suggest that paliperidone's effect on depressive symptoms in subjects with schizoaffective disorder participating in two six-week, randomized, placebo-controlled studies is mediated through indirect effects (e.g., positive and negative symptom changes) and a direct treatment effect.

  5. Granisetron Extended-Release Injection: A Review in Chemotherapy-Induced Nausea and Vomiting.

    Science.gov (United States)

    Deeks, Emma D

    2016-12-01

    An extended-release (ER) subcutaneously injectable formulation of the first-generation 5-HT 3 receptor antagonist granisetron is now available in the USA (Sustol ® ), where it is indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) following moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide combination chemotherapy regimens in adults. Granisetron ER is administered as a single subcutaneous injection and uses an erosion-controlled drug-delivery system to allow prolonged granisetron release. Primary endpoint data from phase III studies after an initial cycle of chemotherapy indicate that, when used as part of an antiemetic regimen, granisetron ER injection is more effective than intravenous ondansetron in preventing delayed CINV following highly emetogenic chemotherapy (HEC); is noninferior to intravenous palonosetron in preventing both acute CINV following MEC or HEC and delayed CINV following MEC; and is similar, but not superior, to palonosetron in preventing delayed CINV following HEC. The benefits of granisetron ER were seen in various patient subgroups, including those receiving anthracycline plus cyclophosphamide-based HEC, and (in an extension of one of the studies) over multiple MEC or HEC cycles. Granisetron ER injection is generally well tolerated, with an adverse event profile similar to that of ondansetron or palonosetron. Thus, granisetron ER injection expands the options for preventing both acute and delayed CINV in adults with cancer receiving MEC or anthracycline plus cyclophosphamide-based HEC.

  6. Role of paliperidone extended-release in treatment of schizoaffective disorder.

    Science.gov (United States)

    Canuso, Carla M; Turkoz, Ibrahim; Fu, Dong Jing; Bossie, Cynthia A

    2010-10-05

    Schizoaffective disorder is characterized by the presence of symptoms of both schizophrenia and a major mood disorder. The coexistence of these symptoms can be difficult to manage, and these patients are generally treated with antipsychotics as well as mood stabilizers and/or antidepressants. Additionally, no established treatment guidelines exist for this disorder. This review describes the combined results of two international, double-blind, placebo-controlled clinical studies of paliperidone extended-release (ER), an atypical antipsychotic recently approved in the US for the treatment of schizoaffective disorder. Subjects in these six-week trials were aged 18-65 years, had a diagnosis of schizoaffective disorder based on the Structural Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) Disorders, and were experiencing an acute exacerbation. The subjects from these studies had significant symptomatology as evidenced by a mean (standard deviation) baseline Positive and Negative Syndrome Scale total score of 92.8 (13.0). Based on Young Mania Rating Scale and/or a 21-item Hamilton Rating Scale for Depression score of ≥16 at baseline, 79.5% and 66.9% of subjects presented with prominent manic and depressive symptoms, respectively, and 46.4% presented with mixed symptoms. Approximately half (45%) of subjects were taking adjunctive mood stabilizers and/or antidepressants. Paliperidone ER was found to be effective in improving psychotic and mood symptoms in these subjects. Paliperidone ER was also effective as monotherapy or adjunctive to mood stabilizers and/or antidepressants for subjects with prominent manic, depressive, or mixed symptoms at baseline. No new tolerability signals were observed in this population. To the best of our awareness, these pooled data provide the largest data set of patients with schizoaffective disorder, and extend our knowledge of disease characteristics and treatment response.

  7. Switch from Immediate-release Pramipexole to Extended-release Pramipexole: The Safety and Efficacy Characteristics of Sixty-eight Patients

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    Müge Kuzu

    2016-09-01

    Full Text Available Objective: To evaluate the safety and efficacy of switching from immediate-release pramipexole (pex to extended-release pramipexole (pex-ER. Materials and Methods: Pex-ER became available in Turkey about a year ago, since then we documented satisfactory information on patients (26 women; 38% who were switched from pex to pex-ER. We recorded pre- and post-switch pex and levodopa, equivalent doses of other anti-parkinsonian medication, and analyzed the frequency and nature of reported adverse effects. Results: The mean age of the patients was 63.3 years (range, 44-88 years, and the mean disease duration was 7.1 years (range, 1-27 years. The other drugs were levodopa (57 patients, 82.6%, entacapone (24 patients, 34.58%, rasagiline (20 patients, 29%, amantadine (18 patients, 26.1%, and apomorphine (six patients, 8.7%. Switch from pex to pex-ER was uneventful in 62 (91.2% patients. Adverse events were reported in six (8.8% patients: ankle swelling (two patients, nausea (one patient, dyskinesia (one patient, hypersexuality (one patient, and psychosis (one patient. Problems resolved with further medication change in two patients. Four patients preferred to return to pex. Conclusion: The great majority of patients (91.2% switched from three times daily pex to once daily pex-ER uneventfully. A slight increase in pex daily dose, which was tailored according to patients’ symptomatic needs, resulted in an increase in post-switch levodopa equivalent doses. Our experience is compatible with previously reported studies.

  8. Clinical Efficacy of a Single Two Gram Dose of Azithromycin Extended Release for Male Patients with Urethritis

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    Satoshi Takahashi

    2014-04-01

    Full Text Available To clarify the clinical efficacy of a single oral 2 g dose of azithromycin extended-release for heterosexual male patients with urethritis, and the current antimicrobial sensitivity of Neisseria gonorrhoeae to azithromycin, a prospective clinical trial was conducted from 2011–2013. In patients with gonococcal urethritis, the eradication rate was 90.9% (30 of 33. The susceptibility rates of isolated Neisseria gonorrhoeae strains to ceftriaxone, spectinomycin, cefixime and azithromycin were 100%, 100%, 95.3% (41/43 and 37.2% (16/43, respectively. In the patients with nongonococcal urethritis, the eradication rate was 90.0% (45 of 50. The microbiological eradication rates for the pathogens were 90.9% (30/33 for Neisseria gonorrhoeae, 91.5% (43/47 for Chlamydia trachomatis, 71.4% (5/7 for Mycoplasma genitalium, and 100% (13/13 for Ureaplasma urealyticum. The main adverse event was diarrhea and its manifestation rate was 35.2% (32 of 120. The symptom of diarrhea was mostly temporary and resolved spontaneously. The conclusion was that the treatment regimen with a single oral 2 g dose of azithromycin extended-release would be effective for patients with urethritis. However, the antimicrobial susceptibilities of Neisseria gonorrhoeae and Mycoplasma genitalium should be carefully monitored because of possible treatment failure.

  9. Clinical Efficacy of a Single Two Gram Dose of Azithromycin Extended Release for Male Patients with Urethritis.

    Science.gov (United States)

    Takahashi, Satoshi; Kiyota, Hiroshi; Ito, Shin; Iwasawa, Akihiko; Hiyama, Yoshiki; Uehara, Teruhisa; Ichihara, Koji; Hashimoto, Jiro; Masumori, Naoya; Sunaoshi, Kenichi; Takeda, Koichi; Suzuki, Nobukazu; Hosobe, Takahide; Goto, Hirokazu; Suzuki, Hidenori; Onodera, Shoichi

    2014-04-02

    To clarify the clinical efficacy of a single oral 2 g dose of azithromycin extended-release for heterosexual male patients with urethritis, and the current antimicrobial sensitivity of Neisseria gonorrhoeae to azithromycin, a prospective clinical trial was conducted from 2011-2013. In patients with gonococcal urethritis, the eradication rate was 90.9% (30 of 33). The susceptibility rates of isolated Neisseria gonorrhoeae strains to ceftriaxone, spectinomycin, cefixime and azithromycin were 100%, 100%, 95.3% (41/43) and 37.2% (16/43), respectively. In the patients with nongonococcal urethritis, the eradication rate was 90.0% (45 of 50). The microbiological eradication rates for the pathogens were 90.9% (30/33) for Neisseria gonorrhoeae, 91.5% (43/47) for Chlamydia trachomatis, 71.4% (5/7) for Mycoplasma genitalium, and 100% (13/13) for Ureaplasma urealyticum. The main adverse event was diarrhea and its manifestation rate was 35.2% (32 of 120). The symptom of diarrhea was mostly temporary and resolved spontaneously. The conclusion was that the treatment regimen with a single oral 2 g dose of azithromycin extended-release would be effective for patients with urethritis. However, the antimicrobial susceptibilities of Neisseria gonorrhoeae and Mycoplasma genitalium should be carefully monitored because of possible treatment failure.

  10. Extended Release of an Anti–Heparan Sulfate Peptide From a Contact Lens Suppresses Corneal Herpes Simplex Virus-1 Infection

    Science.gov (United States)

    Jaishankar, Dinesh; Buhrman, Jason S.; Valyi-Nagy, Tibor; Gemeinhart, Richard A.; Shukla, Deepak

    2016-01-01

    Purpose To prolong the release of a heparan sulfate binding peptide, G2-C, using a commercially available contact lens as a delivery vehicle and to demonstrate the ability of the released peptide to block herpes simplex virus-1 (HSV-1) infection using in vitro, ex vivo, and in vivo models of corneal HSV-1 infection. Methods Commercially available contact lenses were immersed in peptide solution for 5 days prior to determining the release of the peptide at various time points. Cytotoxicity of the released samples was determined by MTT and cell cycle analysis, and the functional activity of the released samples were assessed by viral entry, and viral spread assay using human corneal epithelial cells (HCE). The ability to suppress infection in human and pig cornea ex vivo and mouse in vivo models were also assessed. Results Peptide G2-C was released through the contact lens. Following release for 3 days, the peptide showed significant activity by inhibiting HSV-1 viral entry and spread in HCE cells. Significant suppression of infection was also observed in the ex vivo and in vivo experiments involving corneas. Conclusions Extended release of an anti–HS peptide through a commercially available contact lens can generate significant anti–HSV-1 activity and provides a new and effective way to control corneal herpes. PMID:26780322

  11. Effects of Vascular and Nonvascular Adverse Events and of Extended-Release Niacin With Laropiprant on Health and Healthcare Costs.

    Science.gov (United States)

    Kent, Seamus; Haynes, Richard; Hopewell, Jemma C; Parish, Sarah; Gray, Alastair; Landray, Martin J; Collins, Rory; Armitage, Jane; Mihaylova, Borislava

    2016-07-01

    Extended-release niacin with laropiprant did not significantly reduce the risk of major vascular events and increased the risk of serious adverse events in Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE), but its net effects on health and healthcare costs are unknown. 25 673 participants aged 50 to 80 years with previous cardiovascular disease were randomized to 2 g of extended-release niacin with 40 mg of laropiprant daily versus matching placebo, in addition to effective statin-based low-density lipoprotein cholesterol-lowering treatment. The net effects of niacin-laropiprant on quality-adjusted life years and hospital care costs (2012 UK £; converted into US $ using purchasing power parity index) during 4 years in HPS2-THRIVE were evaluated using estimates of the impact of serious adverse events on health-related quality of life and hospital care costs. During the study, participants assigned niacin-laropiprant experienced marginally but not statistically significantly lower survival (0.012 fewer years [standard error (SE) 0.007]), fewer quality-adjusted life years (0.023 [SE 0.007] fewer using UK EQ-5D scores; 0.020 [SE 0.006] fewer using US EQ-5D scores) and accrued greater hospital costs (UK £101 [SE £37]; US $145 [SE $53]). Stroke, heart failure, musculoskeletal events, gastrointestinal events, and infections were associated with significant decreases in health-related quality of life in both the year of the event and in subsequent years. All serious vascular and nonvascular events were associated with substantial increases in hospital care costs. In HPS2-THRIVE, the addition of extended-release niacin-laropiprant to statin-based therapy reduced quality of life-adjusted survival and increased hospital costs. URL: http://clinicaltrials.gov. Unique identifier: NCT00461630. © 2016 American Heart Association, Inc.

  12. Tramadol Extended-Release for the Management of Pain due to Osteoarthritis

    Science.gov (United States)

    Guetti, Cristiana; Paladini, Antonella; Varrassi, Giustino

    2013-01-01

    Current knowledge on pathogenesis of osteoarticular pain, as well as the consequent several, especially on the gastrointestinal, renal, and cardiovascular systems, side effects of NSAIDs, makes it difficult to perform an optimal management of this mixed typology of pain. This is especially observable in elderly patients, the most frequently affected by osteoarthritis (OA). Tramadol is an analgesic drug, the action of which has a twofold action. It has a weak affinity to mu opioid receptors and, at the same time, can result in inhibition of the reuptake of noradrenaline and serotonin in nociceptorial descending inhibitory control system. These two mechanisms, “opioidergic” and “nonopioidergic,” are the grounds for contrasting certain types of pain that are generally less responsive to opioids, such as neuropathic pain or mixed OA pain. The extended-release formulation of tramadol has good efficacy and tolerability and acts through a dosing schedule that allows a high level of patients compliance to therapies with a good recovery outcome for the patients' functional status. PMID:27335872

  13. The Effect of a Novel form of Extended-Release Gabapentin on Pain and Sleep in Fibromyalgia Subjects: An Open-Label Pilot Study.

    Science.gov (United States)

    North, James M; Hong, Kyung-Soo J; Rauck, Richard L

    2016-07-01

    We assessed the efficacy and safety of extended-release gabapentin in a 15-week, open-label, single-arm, single-center study in patients with fibromyalgia (FM). Subjects with documented diagnosis of FM were allowed to participate in the study. We opened enrollment to those who have tried and failed gabapentinoids such as gabapentin or pregabalin due to side effects. Subjects with autoimmune conditions, and or taking opioids for management of their FM pain, were excluded from the study. Subjects were given an extended-release gabapentin starter pack and treated for total of 12 weeks. The primary study endpoint of pain relief was measured using Numeric Pain Rating System (NPRS) scores, and secondary study endpoints were measured with Fibromyalgia Impact Questionnaire (FIQ), Patient's Global Impression of Change (PGIC), and Medical Outcome Sleep questionnaires (MOS). A total of 34 subjects were enrolled and 29 subjects completed the starter pack (85%). Patients reported significant pain relief on NPRS by end of 4 weeks (P life by end of 4 weeks on FIQ (P quality. Improvements in primary and secondary measurements were reflected in PGIC, with significant improvement in patient's impression of FM by week 8. Small sample size, geographical bias, relatively short duration of treatment, and single-arm study without control group. Extended-release gabapentin relieved FM pain symptoms and improved quality-of-life for the FM subjects studied. Subjects reported improvements in both quantity and quality of sleep. © 2015 World Institute of Pain.

  14. A flexible-dose dispenser for immediate and extended release 3D printed tablets.

    Science.gov (United States)

    Pietrzak, Katarzyna; Isreb, Abdullah; Alhnan, Mohamed A

    2015-10-01

    The advances in personalised medicine increased the demand for a fast, accurate and reliable production method of tablets that can be digitally controlled by healthcare staff. A flexible dose tablet system is presented in this study that proved to be suitable for immediate and extended release tablets with a realistic drug loading and an easy-to-swallow tablet design. The method bridges the affordable and digitally controlled Fused Deposition Modelling (FDM) 3D printing with a standard pharmaceutical manufacturing process, Hot Melt Extrusion (HME). The reported method was compatible with three methacrylic polymers (Eudragit RL, RS and E) as well as a cellulose-based one (hydroxypropyl cellulose, HPC SSL). The use of a HME based pharmaceutical filament preserved the linear relationship between the mass and printed volume and was utilized to digitally control the dose via an input from computer software with dose accuracy in the range of 91-95%. Higher resolution printing quality doubled the printing time, but showed a little effect on in vitro release pattern of theophylline and weight accuracy. Physical characterization studies indicated that the majority of the model drug (theophylline) in the 3D printed tablet exists in a crystal form. Owing to the small size, ease of use and the highly adjustable nature of FDM 3D printers, the method holds promise for future individualised treatment. Copyright © 2015. Published by Elsevier B.V.

  15. Film Coating of Nifedipine Extended Release Pellets in a Fluid Bed Coater with a Wurster Insert

    Directory of Open Access Journals (Sweden)

    Luciane Franquelin Gomes de Souza

    2014-01-01

    Full Text Available The objective of this work was to study the coating process of nifedipine extended release pellets using Opadry and Opadry II, in a fluid bed coater with a Wurster insert. The coating process was studied using a complete experimental design of two factors at two levels for each polymer. The variables studied were the inlet air temperature and the coating suspension flow rate. The agglomerate fraction and coating efficiency were the analyzed response variables. The air temperature was the variable that most influenced the coating efficiency for both polymers. In addition, a study of the dissolution profiles of coated and uncoated pellets using 0.5% sodium lauryl sulfate in simulated gastric fluid without enzymes (pH 1.2 was conducted. The results showed a prolonged release profile for the coated and uncoated pellets that was very similar to the standards established by the U.S. Pharmacopoeia. The drug content and the release profiles were not significantly affected by storage at 40°C and 75% relative humidity. However, when exposed to direct sunlight and fluorescent light (light from fluorescent bulbs, the coated pellets lost only 5% of the drug content, while the uncoated ones lost more than 35%; furthermore, the dissolution profile of the uncoated pellets was faster.

  16. Film Coating of Nifedipine Extended Release Pellets in a Fluid Bed Coater with a Wurster Insert

    Science.gov (United States)

    de Souza, Luciane Franquelin Gomes; Nitz, Marcello; Taranto, Osvaldir Pereira

    2014-01-01

    The objective of this work was to study the coating process of nifedipine extended release pellets using Opadry and Opadry II, in a fluid bed coater with a Wurster insert. The coating process was studied using a complete experimental design of two factors at two levels for each polymer. The variables studied were the inlet air temperature and the coating suspension flow rate. The agglomerate fraction and coating efficiency were the analyzed response variables. The air temperature was the variable that most influenced the coating efficiency for both polymers. In addition, a study of the dissolution profiles of coated and uncoated pellets using 0.5% sodium lauryl sulfate in simulated gastric fluid without enzymes (pH 1.2) was conducted. The results showed a prolonged release profile for the coated and uncoated pellets that was very similar to the standards established by the U.S. Pharmacopoeia. The drug content and the release profiles were not significantly affected by storage at 40°C and 75% relative humidity. However, when exposed to direct sunlight and fluorescent light (light from fluorescent bulbs), the coated pellets lost only 5% of the drug content, while the uncoated ones lost more than 35%; furthermore, the dissolution profile of the uncoated pellets was faster. PMID:24772426

  17. Extended-Release Once-Daily Formulation of Tofacitinib: Evaluation of Pharmacokinetics Compared With Immediate-Release Tofacitinib and Impact of Food.

    Science.gov (United States)

    Lamba, Manisha; Wang, Rong; Fletcher, Tracey; Alvey, Christine; Kushner, Joseph; Stock, Thomas C

    2016-11-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. An extended-release (XR) formulation has been designed to provide a once-daily (QD) dosing option to patients to achieve comparable pharmacokinetic (PK) parameters to the twice-daily immediate-release (IR) formulation. We conducted 2 randomized, open-label, phase 1 studies in healthy volunteers. Study A characterized single-dose and steady-state PK of tofacitinib XR 11 mg QD and intended to demonstrate equivalence of exposure under single-dose and steady-state conditions to tofacitinib IR 5 mg twice daily. Study B assessed the effect of a high-fat meal on the bioavailability of tofacitinib from the XR formulation. Safety and tolerability were monitored in both studies. In study A (N = 24), the XR and IR formulations achieved time to maximum plasma concentration at 4 hours and 0.5 hours postdose, respectively; terminal half-life was 5.9 hours and 3.2 hours, respectively. Area under plasma concentration-time curve (AUC) and maximum plasma concentration (C max ) after single- and multiple-dose administration were equivalent between the XR and IR formulations. In study B (N = 24), no difference in AUC was observed for fed vs fasted conditions. C max increased by 27% under the fed state. On repeat administration, negligible accumulation (Tofacitinib administration as an XR or IR formulation was generally well tolerated in these studies. © 2016, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  18. Differential scanning calorimetry as a screening technique in compatibility studies of acyclovir extended release formulations

    International Nuclear Information System (INIS)

    Barboza, Fernanda M.; Vecchia, Debora D.; Tagliari, Monika P.; Ferreira, Andrea Granada; Silva, Marcos A.S.; Stulzer, Hellen K.

    2009-01-01

    Acyclovir (ACV) has been investigated during the past years, mainly due to its antiviral activity. Assessment of possible incompatibility between an active component and different excipients along with the evaluation of thermal stability are crucial parts of a normal study prior to the final formulation setting of a medicine. Thermal analysis studies were used as important and complementary tools during pre-formulation to determine the compatibility of drug excipients with the purpose of developing an acyclovir extended release formulation. Fourier transform infrared spectroscopy and X-ray powder diffraction analyses were also realized. The results showed that ACV only exhibited interaction which could influence the stability of the product in the binary mixtures of ACV/magnesium stearate. (author)

  19. Analgesic Efficacy of a New Immediate-Release/Extended-Release Formulation of Ibuprofen: Results From Single- and Multiple-Dose Postsurgical Dental Pain Studies.

    Science.gov (United States)

    Christensen, Steven; Paluch, Ed; Jayawardena, Shyamalie; Daniels, Stephen; Meeves, Suzanne

    2017-05-01

    Analgesic effects of ibuprofen immediate-release/extended-release (IR/ER) 600-mg tablets were evaluated in 2 randomized, double-blind, placebo-controlled dental pain studies. Patients 16-40 years old with moderate-severe pain following third-molar extraction received single-dose ibuprofen 600 mg IR/ER (formulation A or B), naproxen sodium 220 mg, or placebo (2:2:2:1; study 1) or 4 doses of ibuprofen 600 mg IR/ER (formulation A) or placebo (1:1; study 2). In study 1 (n = 196), mean (standard deviation [SD]) time-weighted sum of pain intensity difference scores for placebo, ibuprofen IR/ER A, ibuprofen IR/ER B, and naproxen, respectively, were 0.05 (9.2), 16.87 (9.4), 17.34 (10.5), and 12.66 (10.0) over 0-12 hours and -0.03 (4.1), 6.57 (4.4), 7.14 (5.2), and 5.14 (5.0) over 8-12 hours (all P ibuprofen IR/ER, respectively (P ibuprofen. Gastrointestinal adverse events predominated with placebo both after study medication administration and after rescue medication use, if applicable. Ibuprofen 600 mg IR/ER provided safe and effective analgesia after single and multiple doses. © 2016, The American College of Clinical Pharmacology.

  20. APF530 (granisetron injection extended-release) in a three-drug regimen for delayed CINV in highly emetogenic chemotherapy.

    Science.gov (United States)

    Schnadig, Ian D; Agajanian, Richy; Dakhil, Christopher; Gabrail, Nashat Y; Smith, Robert E; Taylor, Charles; Wilks, Sharon T; Schwartzberg, Lee S; Cooper, William; Mosier, Michael C; Payne, J Yvette; Klepper, Michael J; Vacirca, Jeffrey L

    2016-06-01

    APF530, extended-release granisetron, provides sustained release for ≥5 days for acute- and delayed-phase chemotherapy-induced nausea and vomiting (CINV). We compared efficacy and safety of APF530 versus ondansetron for delayed CINV after highly emetogenic chemotherapy (HEC), following a guideline-recommended three-drug regimen. HEC patients received APF530 500 mg subcutaneously or ondansetron 0.15 mg/kg intravenously, with dexamethasone and fosaprepitant. Primary end point was delayed-phase complete response (no emesis or rescue medication). A higher percentage of APF530 versus ondansetron patients had delayed-phase complete response (p = 0.014). APF530 was generally well tolerated; treatment-emergent adverse event incidence was similar across arms, mostly mild-to-moderate injection-site reactions. APF530 versus the standard three-drug regimen provided superior control of delayed-phase CINV following HEC. ClinicalTrials.gov : NCT02106494.

  1. A Randomized, Placebo-Controlled Trial of Guanfacine Extended Release in Adolescents With Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Wilens, Timothy E; Robertson, Brigitte; Sikirica, Vanja; Harper, Linda; Young, Joel L; Bloomfield, Ralph; Lyne, Andrew; Rynkowski, Gail; Cutler, Andrew J

    2015-11-01

    Despite the continuity of attention-deficit/hyperactivity disorder (ADHD) into adolescence, little is known regarding use of nonstimulants to treat ADHD in adolescents. This phase 3 trial evaluated the safety and efficacy of guanfacine extended release (GXR) in adolescents with ADHD. This 13-week, multicenter, randomized, double-blind, placebo-controlled trial evaluated once-daily GXR (1-7 mg per day) in adolescents with ADHD aged 13 to 17 years. The primary endpoint was the change from baseline in the ADHD Rating Scale-IV (ADHD-RS-IV) total score; key secondary endpoints included scores from the Clinical Global Impressions-Severity of Illness (CGI-S), and Learning and School domain and Family domain scores from the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) at week 13. A total of 314 participants were randomized (GXR, n = 157; placebo, n = 157). The majority of participants received optimal doses of 3, 4, 5, or 6 mg (30 [22.9%], 26 [19.8%], 27 [20.6%], or 24 [18.3%] participants, respectively), with 46.5% of participants receiving an optimal dose above the currently approved maximum dose limit of 4 mg. Participants receiving GXR showed improvement in ADHD-RS-IV total score compared with placebo (least-squares mean score change, -24.55 [GXR] versus -18.53 [placebo]; effect size, 0.52; p ADHD symptoms in adolescents. GXR was well tolerated, with no new safety signals reported. Dose-Optimization in Adolescents Aged 13-17 Diagnosed With Attention-Deficit/Hyperactivity Disorder (ADHD) Using Extended-Release Guanfacine HCl; http://ClinicalTrials.gov/; NCT01081132. Copyright © 2015. Published by Elsevier Inc.

  2. Cost-effectiveness of extended-release methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder sub-optimally treated with immediate release methylphenidate.

    Directory of Open Access Journals (Sweden)

    Jurjen van der Schans

    Full Text Available Attention-Deficit/Hyperactivity Disorder (ADHD is a common psychiatric disorder in children and adolescents. Immediate-release methylphenidate (IR-MPH is the medical treatment of first choice. The necessity to use several IR-MPH tablets per day and associated potential social stigma at school often leads to reduced compliance, sub-optimal treatment, and therefore economic loss. Replacement of IR-MPH with a single-dose extended release (ER-MPH formulation may improve drug response and economic efficiency.To evaluate the cost-effectiveness from a societal perspective of a switch from IR-MPH to ER-MPH in patients who are sub-optimally treated.A daily Markov-cycle model covering a time-span of 10 years was developed including four different health states: (1 optimal response, (2 sub-optimal response, (3 discontinued treatment, and (4 natural remission. ER-MPH options included methylphenidate osmotic release oral system (MPH-OROS and Equasym XL/Medikinet CR. Both direct costs and indirect costs were included in the analysis, and effects were expressed as quality-adjusted life years (QALYs. Univariate, multivariate as well as probabilistic sensitivity analysis were conducted and the main outcomes were incremental cost-effectiveness ratios.Switching sub-optimally treated patients from IR-MPH to MPH-OROS or Equasym XL/Medikinet CR led to per-patient cost-savings of €4200 and €5400, respectively, over a 10-year treatment span. Sensitivity analysis with plausible variations of input parameters resulted in cost-savings in the vast majority of estimations.This study lends economic support to switching patients with ADHD with suboptimal response to short-acting IR-MPH to long-acting ER-MPH regimens.

  3. Development and validation of an in vitro–in vivo correlation (IVIVC model for propranolol hydrochloride extended-release matrix formulations

    Directory of Open Access Journals (Sweden)

    Chinhwa Cheng

    2014-06-01

    Full Text Available The objective of this study was to develop an in vitro–in vivo correlation (IVIVC model for hydrophilic matrix extended-release (ER propranolol dosage formulations. The in vitro release characteristics of the drug were determined using USP apparatus I at 100 rpm, in a medium of varying pH (from pH 1.2 to pH 6.8. In vivo plasma concentrations and pharmacokinetic parameters in male beagle dogs were obtained after administering oral, ER formulations and immediate-release (IR commercial products. The similarity factor f2 was used to compare the dissolution data. The IVIVC model was developed using pooled fraction dissolved and fraction absorbed of propranolol ER formulations, ER-F and ER-S, with different release rates. An additional formulation ER-V, with a different release rate of propranolol, was prepared for evaluating the external predictability. The results showed that the percentage prediction error (%PE values of Cmax and AUC0–∞ were 0.86% and 5.95%, respectively, for the external validation study. The observed low prediction errors for Cmax and AUC0–∞ demonstrated that the propranolol IVIVC model was valid.

  4. Extended release of hyaluronic acid from hydrogel contact lenses for dry eye syndrome.

    Science.gov (United States)

    Maulvi, Furqan A; Soni, Tejal G; Shah, Dinesh O

    2015-01-01

    Current dry eye treatment includes delivering comfort enhancing agents to the eye via eye drops, but low residence time of eye drops leads to low bioavailability. Frequent administration leads to incompliance in patients, so there is a great need for medical device such as contact lenses to treat dry eye. Studies in the past have demonstrated the efficacy of hyaluronic acid (HA) in the treatment of dry eyes using eye drops. In this paper, we present two methods to load HA in hydrogel contact lenses, soaking method and direct entrapment. The contact lenses were characterized by studying their optical and physical properties to determine their suitability as extended wear contact lenses. HA-laden hydrogel contact lenses prepared by soaking method showed release up to 48 h with acceptable physical and optical properties. Hydrogel contact lenses prepared by direct entrapment method showed significant sustained release in comparison to soaking method. HA entrapped in hydrogels resulted in reduction in % transmittance, sodium ion permeability and surface contact angle, while increase in % swelling. The impact on each of these properties was proportional to HA loading. The batch with 200-μg HA loading showed all acceptable values (parameters) for contact lens use. Results of cytotoxicity study indicated the safety of hydrogel contact lenses. In vivo pharmacokinetics studies in rabbit tear fluid showed dramatic increase in HA mean residence time and area under the curve with lenses in comparison to eye drop treatment. The study demonstrates the promising potential of delivering HA through contact lenses for the treatment of dry eye syndrome.

  5. A long-term, open-label safety study of single-entity hydrocodone bitartrate extended release for the treatment of moderate to severe chronic pain

    Directory of Open Access Journals (Sweden)

    Nalamachu S

    2014-11-01

    Full Text Available Srinivas Nalamachu,1,2 Richard L Rauck,3 Martin E Hale,4 Orlando G Florete Jr,5 Cynthia Y Robinson,6 Stephen J Farr,6 1International Clinical Research Institute, Overland Park, KS, USA; 2Kansas University Medical Center, Kansas City, KS, USA; 3Carolinas Pain Institute, Center for Clinical Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA; 4Gold Coast Research, LLC, Weston, FL, USA; 5Institute of Pain Management, Jacksonville, FL, USA; 6Zogenix, Inc., Emeryville, CA, USA Objective: To evaluate the long-term safety, tolerability, and effectiveness of single-entity extended-release hydrocodone in opioid-experienced subjects with moderate to severe chronic pain not receiving adequate pain relief or experiencing intolerable side effects from their current opioid. Methods: This multicenter, open-label study started with a conversion/titration phase (≤6 weeks where subjects (n=638 were converted to individualized doses (range 20–300 mg of extended-release hydrocodone dosed every 12 hours, followed by a 48-week maintenance phase (n=424. The primary objective (safety and tolerability and the secondary objective (long-term efficacy as measured by change in average pain score; 0= no pain, 10= worst imaginable pain were monitored throughout the study. Results: Subjects were treated for a range of chronic pain etiologies, including osteoarthritis, low back pain, and neuropathic and musculoskeletal conditions. The mean hydrocodone equivalent dose at screening was 68.9±62.2 mg/day and increased to 139.5±81.7 mg/day at the start of the maintenance phase. Unlimited dose adjustments were permitted at the investigator's discretion during the maintenance phase, reflecting typical clinical practice. No unexpected safety issues were reported. Common adverse events during the conversion/titration and maintenance phases, respectively, were constipation (11.3% and 12.5%, nausea (10.7% and 9.9%, vomiting (4.1% and 9.7%, and somnolence (7

  6. A Double-Blind, Randomized, Placebo-Controlled Trial of Divalproex Extended-Release in the Treatment of Bipolar Disorder in Children and Adolescents

    Science.gov (United States)

    Wagner, Karen Dineen; Redden, Laura; Kowatch, Robert A.; Wilens, Timothy E.; Segal, Scott; Chang, Kiki; Wozniak, Patricia; Vigna, Namita V.; Abi-Saab, Walid; Saltarelli, Mario

    2009-01-01

    A double-blind study that involves 150 patients aged 10-17 on the effect of divalproex extended-release in the treatment of bipolar disorder shows that the drug was similar to placebo based on adverse events and that no treatment effect was observed in the drug. The drug is not suitable for treatment of youths with bipolar I disorder, mixed or…

  7. Pharmaceutical Product Lead Optimization for Better In vivo Bioequivalence Performance: A case study of Diclofenac Sodium Extended Release Matrix Tablets.

    Science.gov (United States)

    Shahiwala, Aliasgar; Zarar, Aisha

    2018-01-01

    In order to prove the validity of a new formulation, a considerable amount of effort is required to study bioequivalence, which not only increases the burden of carrying out a number of bioequivalence studies but also eventually increases the cost of the optimization process. The aim of the present study was to develop sustained release matrix tablets containing diclofenac sodium using natural polymers and to demonstrate step by step process of product development till the prediction of in vivo marketed product equivalence of the developed product. Different batches of tablets were prepared by direct compression. In vitro drug release studies were performed as per USP. The drug release data were assessed using model-dependent, modelindependent and convolution approaches. Drug release profiles showed that extended release action were in the following order: Gum Tragacanth > Sodium Alginate > Gum Acacia. Amongst the different batches prepared, only F1 and F8 passed the USP criteria of drug release. Developed formulas were found to fit Higuchi kinetics model with Fickian (case I) diffusion-mediated release mechanism. Model- independent kinetics confirmed that total of four batches were passed depending on the similarity factors based on the comparison with the marketed Diclofenac. The results of in vivo predictive convolution model indicated that predicted AUC, Cmax and Tmax values for batch F8 were similar to that of marketed product. This study provides simple yet effective outline of pharmaceutical product development process that will minimize the formulation development trials and maximize the product success in bioequivalence studies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Bilayer tablets of Paliperidone for Extended release osmotic drug delivery

    Science.gov (United States)

    Chowdary, K. Sunil; Napoleon, A. A.

    2017-11-01

    The purpose of this study is to develop and optimize the formulation of paliperidone bilayer tablet core and coating which should meet in vitro performance of trilayered Innovator sample Invega. Optimization of core formulations prepared by different ratio of polyox grades and optimization of coating of (i) sub-coating build-up with hydroxy ethyl cellulose (HEC) and (ii).enteric coating build-up with cellulose acetate (CA). Some important influence factors such as different core tablet compositions and different coating solution ingredients involved in the formulation procedure were investigated. The optimization of formulation and process was conducted by comparing different in vitro release behaviours of Paliperidone. In vitro dissolution studies of Innovator sample (Invega) with formulations of different release rate which ever close release pattern during the whole 24 h test is finalized.

  9. The changing landscape of opioid prescribing: long-acting and extended-release opioid class-wide Risk Evaluation and Mitigation Strategy

    Directory of Open Access Journals (Sweden)

    Gudin JA

    2012-05-01

    Full Text Available Jeffrey A GudinEnglewood Hospital and Medical Center, Englewood, NJ, USAAbstract: Prescriptions for opioid analgesics to manage moderate-to-severe chronic noncancer pain have increased markedly over the last decade, as have postmarketing reports of adverse events associated with opioids. As an unintentional consequence of greater prescription opioid utilization, there has been the parallel increase in misuse, abuse, and overdose, which are serious risks associated with all opioid analgesics. In response to these concerns, the Food and Drug Administration announced the requirement for a class-wide Risk Evaluation and Mitigation Strategy (REMS for long-acting and extended-release (ER opioid analgesics in April 2011. An understanding of the details of this REMS will be of particular importance to primary care providers. The class-wide REMS is focused on educating health care providers and patients on appropriate prescribing and safe use of ER opioids. Support from primary care will be necessary for the success of this REMS, as these clinicians are the predominant providers of care and the main prescribers of opioid analgesics for patients with chronic pain. Although currently voluntary, future policy will likely dictate that providers undergo mandatory training to continue prescribing medications within this class. This article outlines the elements of the class-wide REMS for ER opioids and clarifies the impact on primary care providers with regard to training, patient education, and clinical practice.Keywords: long-acting opioid, extended-release opioid, risk, REMS, FDA, primary care

  10. A Randomized Double-blind, Placebo Controlled Trial of Venlafaxine-Extended Release for Co-occurring Cannabis Dependence and Depressive Disorders

    Science.gov (United States)

    Levin, Frances R.; Mariani, John; Brooks, Daniel J.; Pavlicova, Martina; Nunes, Edward V.; Agosti, Vito; Bisaga, Adam; Sullivan, Maria A.; Carpenter, Kenneth M.

    2013-01-01

    Aim To evaluate whether venlafaxine-extended release (VEN-XR) is an effective treatment for cannabis dependence with concurrent depressive disorders. Design This was a randomized, 12 week, double-blind, placebo-controlled trial of outpatients (n = 103) with DSM-IV cannabis dependence and major depressive disorder or dysthymia. Participants received up to 375 mg VEN-XR on a fixed-flexible schedule or placebo. All patients received weekly individual cognitive-behavioral psychotherapy that primarily targeted marijuana use. Settings The trial was conducted at two university research centers in the United States. Participants One hundred and three cannabis dependent adults participated in the trial. Measurements The primary outcome measures were 1) abstinence from marijuana defined as at least two consecutive urine-confirmed abstinent weeks and 2) improvement in depressive symptoms based on the Hamilton Depression Rating Scale. Findings The proportion of patients achieving a clinically significant mood improvement [50% decrease in Hamilton Depression score from baseline] was high and did not differ between groups receiving VEN-XR (63%) and placebo (69%) (X12=0.48, p-value= 0.49). The proportion of patients achieving abstinence was low overall, but was significantly worse on VEN-XR (11.8%) compared to placebo (36.5%) (X12=7.46, p-valuemarijuana use in the placebo group (F1,179=30.49, p-valuedepressed, cannabis-dependent patients, venlafaxine-extended release does not appear to be effective at reducing depression and may lead to an increase in cannabis use. PMID:23297841

  11. Extended release local anesthetic agents in a postoperative arthritic pain model.

    Science.gov (United States)

    Ickowicz, Diana E; Golovanevski, Ludmila; Haze, Amir; Domb, Abraham J; Weiniger, Carolyn F

    2014-01-01

    Local anesthetics play an important role in postoperative pain management in orthopedic joint procedures. The aim of this study was to determine the effect of an intraoperative extra-articular injection of poly(DL-lactic acid co castor oil 3:7), p(DLLA:CO) 3:7 loaded with 15% bupivacaine, for postoperative analgesia following knee arthroplasty. Prolonged release local anesthetic formulation was synthesized by mixing p(DLLA:CO) 3:7 with bupivacaine base. Under anesthesia, the knee joint of Sprague-Dawley rats was exposed, a hole drilled in the femoral trochlea. 0.2 mL of either 15% polymer-bupivacaine formulation or plain bupivacaine (control) was injected locally and compared with a nonsurgery control group. Mechanical hyperalgesia was determined by counting the vocalizations and leg withdrawal after joint squeezing. Behavioral assessments over a day postoperative period revealed a reduction in rearing and ambulation in an open-field apparatus in animals of both experimental groups compared with the nonsurgery control. The vocalizations during the hyperalgesia test increased compared with the control at 24 h. At 48 h, 3.667 ± 0.5138, p = 0.0076 vocalizations were recorded for the plain bupivacaine group versus 1.417 ± 0.5138, p < 0.0001 in the 15% polymer-bupivacaine formulation. Bupivacaine encapsulated in p(DLLA:CO) 3:7 extended the duration of the analgesia compared with plain drug in rats and could represent effective postoperative analgesic in orthopedic joint procedures. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  12. The cost effectiveness of long-acting/extended-release antipsychotics for the treatment of schizophrenia: a systematic review of economic evaluations.

    Science.gov (United States)

    Achilla, Evanthia; McCrone, Paul

    2013-04-01

    Antipsychotic medication is the mainstay of treatment in schizophrenia. Long-acting medication has potential advantages over daily medication in improving compliance and thus reducing hospitalization and relapse rates. The high acquisition and administration costs of such formulations raise the need for pharmacoeconomic evaluation. The aim of this article is to provide a comprehensive review of the available evidence on the cost effectiveness of long-acting/extended-release antipsychotic medication and critically appraise the strength of evidence reported in the studies from a methodological viewpoint. Relevant studies were identified by searching five electronic databases: PsycINFO, MEDLINE, EMBASE, the NHS Economic Evaluation Database and the Health Technology Assessment database (HTA). Search terms included, but were not limited to, 'long-acting injection', 'economic evaluation', 'cost-effectiveness' and 'cost-utility'. No limits were applied for publication dates and language. Full economic evaluations on long-acting/extended-release antipsychotics were eligible for inclusion. Observational studies and clinical trials were also checked for cost-effectiveness information. Conference abstracts and poster presentations on the cost effectiveness of long-acting antipsychotics were excluded. Thirty-two percent of identified studies met the selection criteria. Pertinent abstracts were reviewed independently by two reviewers. Relevant studies underwent data extraction by one reviewer and were checked by a second, with any discrepancies being clarified during consensus meetings. Eligible studies were assessed for methodological quality using the quality checklist for economic studies recommended by the NICE guideline on interventions in the treatment and management of schizophrenia. After applying the selection criteria, the final sample consisted of 28 studies. The majority of studies demonstrated that risperidone long-acting injection, relative to oral or other long

  13. A randomized double-blind, placebo-controlled trial of venlafaxine-extended release for co-occurring cannabis dependence and depressive disorders.

    Science.gov (United States)

    Levin, Frances R; Mariani, John; Brooks, Daniel J; Pavlicova, Martina; Nunes, Edward V; Agosti, Vito; Bisaga, Adam; Sullivan, Maria A; Carpenter, Kenneth M

    2013-06-01

    To evaluate whether venlafaxine-extended release (VEN-XR) is an effective treatment for cannabis dependence with concurrent depressive disorders. This was a randomized, 12-week, double-blind, placebo-controlled trial of out-patients (n = 103) with DSM-IV cannabis dependence and major depressive disorder or dysthymia. Participants received up to 375 mg VEN-XR on a fixed-flexible schedule or placebo. All patients received weekly individual cognitive-behavioral psychotherapy that primarily targeted marijuana use. The trial was conducted at two university research centers in the United States. One hundred and three cannabis-dependent adults participated in the trial. The primary outcome measures were (i) abstinence from marijuana defined as at least two consecutive urine-confirmed abstinent weeks and (ii) improvement in depressive symptoms based on the Hamilton Depression Rating Scale. The proportion of patients achieving a clinically significant mood improvement (50% decrease in Hamilton Depression score from baseline) was high and did not differ between groups receiving VEN-XR (63%) and placebo (69%) (χ1 (2)  = 0.48, P = 0.49). The proportion of patients achieving abstinence was low overall, but was significantly worse on VEN-XR (11.8%) compared to placebo (36.5%) (χ1 (2)  = 7.46, P marijuana use in the placebo group (F1,179  = 30.49, P depressed, cannabis-dependent patients, venlafaxine-extended release does not appear to be effective at reducing depression and may lead to an increase in cannabis use. © 2013 Society for the Study of Addiction.

  14. Randomized, double-blind trial of guanfacine extended release in children with attention-deficit/hyperactivity disorder: morning or evening administration.

    Science.gov (United States)

    Newcorn, Jeffrey H; Stein, Mark A; Childress, Ann C; Youcha, Sharon; White, Carla; Enright, Gail; Rubin, Jonathan

    2013-09-01

    To examine the efficacy and tolerability of guanfacine extended release (GXR) administered in the morning or evening in children with attention-deficit/hyperactivity disorder (ADHD). In this multicenter, double-blind, placebo-controlled, dose-optimization study, children 6 to 12 years of age with ADHD were randomized to receive GXR (1-4 mg/d) in the morning and placebo in the evening (GXR am), placebo in the morning and GXR in the evening (GXR pm), or twice-daily placebo. The primary efficacy measure was the ADHD Rating Scale-IV (ADHD-RS-IV). A total of 333 child participants received study drug in the following cohorts: GXR am (n = 107), GXR pm (n = 114), or placebo (n = 112). Mean (standard deviation) changes from baseline to week 8 (visit 10 or last observation carried forward) in ADHD-RS-IV total scores were significant for both GXR treatment groups combined (GXR all-active: -20.0 [12.97]) and separately (GXR am: -19.8 [12.95]; GXR pm: -20.1 [13.04]) compared with placebo (-11.0 [12.93]; p ADHD symptoms. The levels of response and tolerability observed with GXR were similar regardless of time of dosing (morning versus evening), indicating that once-daily GXR monotherapy is effective whether administered in the morning or evening. Clinical trial registration information-Tolerability and Efficacy of AM and PM Once Daily Dosing With Extended-release Guanfacine Hydrochloride in Children 6-12 With Attention-Deficit/Hyperactivity Disorder (ADHD) (The ADHD Tempo Study. Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. Comparative steady-state pharmacokinetic study of an extended-release formulation of itopride and its immediate-release reference formulation in healthy volunteers.

    Science.gov (United States)

    Yoon, Seonghae; Lee, Howard; Kim, Tae-Eun; Lee, SeungHwan; Chee, Dong-Hyun; Cho, Joo-Youn; Yu, Kyung-Sang; Jang, In-Jin

    2014-01-01

    This study was conducted to compare the oral bioavailability of an itopride extended-release (ER) formulation with that of the reference immediate-release (IR) formulation in the fasting state. The effect of food on the bioavailability of itopride ER was also assessed. A single-center, open-label, randomized, multiple-dose, three-treatment, three-sequence, crossover study was performed in 24 healthy male subjects, aged 22-48 years, who randomly received one of the following treatments for 4 days in each period: itopride 150 mg ER once daily under fasting or fed conditions, or itopride 50 mg IR three times daily in the fasting state. Steady-state pharmacokinetic parameters of itopride, including peak plasma concentration (Cmax) and area under the plasma concentration versus time curve over 24 hours after dosing (AUC(0-24h)), were determined by noncompartmental analysis. The geometric mean ratio of the pharmacokinetic parameters was derived using an analysis of variance model. A total of 24 healthy Korean subjects participated, 23 of whom completed the study. The geometric mean ratio and its 90% confidence interval of once-daily ER itopride versus IR itopride three times a day for AUC(0-24h) were contained within the conventional bioequivalence range of 0.80-1.25 (0.94 [0.88-1.01]), although Cmax was reached more slowly and was lower for itopride ER than for the IR formulation. Food delayed the time taken to reach Cmax for itopride ER, but AUC(0-24h) was not affected. There were no serious adverse events and both formulations were generally well tolerated. At steady state, once-daily itopride ER at 150 mg has a bioavailability comparable with that of itopride IR at 50 mg given three times a day under fasting conditions. Food delayed the absorption of itopride ER, with no marked change in its oral bioavailability.

  16. In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation

    DEFF Research Database (Denmark)

    Franek, F; Jarlfors, A; Larsen, F.

    2015-01-01

    Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step...... not imply low intestinal permeability, as indicated by the BDDCS, merely low duodenal/jejunal permeability....... for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq®, an extended release formulation...

  17. Profile of guanfacine extended release and its potential in the treatment of attention-deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Martinez-Raga J

    2015-05-01

    Full Text Available Jose Martinez-Raga,1,2 Carlos Knecht,3 Raquel de Alvaro4 1Teaching Unit of Psychiatry and Psychological Medicine, University Hospital Doctor Peset, University of Valencia, 2CEU Cardenal Herrera University, 3Área de Salud Mental, Hospital Padre Jofré, Valencia, 4Hospital General, Consorcio Hospitalario Provincial, Castellon, Spain Abstract: The α2-adrenergic receptor agonist guanfacine, in its extended-release formulation (GXR, is the most recent nonstimulant medication approved in several countries for the treatment of attention-deficit hyperactivity disorder (ADHD as monotherapy and as adjunctive pharmacotherapy to stimulants in children and adolescents. The present paper aims to review comprehensively and critically the pharmacodynamic and pharmacokinetic characteristics and the published evidence on the efficacy and safety profile of GXR in the treatment of ADHD. A comprehensive search of relevant databases (PubMed, Embase, and PsycInfo was conducted to identify studies published in peer-reviewed journals until January 15, 2015. Though the precise mechanism of action of guanfacine in the treatment of ADHD is not fully understood, it is thought to act directly by enhancing noradrenaline functioning via α2A-adrenoceptors in the prefrontal cortex. Weight-adjusted doses should be used, with a dosing regime on a milligram per kilogram basis, starting at doses in the range 0.05–0.08 mg/kg/day, up to 0.12 mg/kg/day. As evidenced in short-term randomized controlled trials and in long-term open-label extension studies, GXR has been shown to be effective as monotherapy in the treatment of ADHD. Furthermore, GXR has also been found to be effective as adjunctive therapy to stimulant medications in patients with suboptimal responses to stimulants. Many of the adverse reactions associated with GXR, particularly sedation-related effects, were dose-related, transient, mild to moderate in severity, and did not interfere with attention or overall

  18. Rates of opioid dispensing and overdose after introduction of abuse-deterrent extended-release oxycodone and withdrawal of propoxyphene.

    Science.gov (United States)

    Larochelle, Marc R; Zhang, Fang; Ross-Degnan, Dennis; Wharam, J Frank

    2015-06-01

    In the second half of 2010, abuse-deterrent extended-release oxycodone hydrochloride (OxyContin; Purdue Pharma) was introduced and propoxyphene was withdrawn from the US market. The effect of these pharmaceutical market changes on opioid dispensing and overdose rates is unknown. To evaluate the association between 2 temporally proximate changes in the opioid market and opioid dispensing and overdose rates. Claims from a large national US health insurer were analyzed, using an interrupted time series study design. Participants included an open cohort of 31.3 million commercially insured members aged 18 to 64 years between January 1, 2003, and December 31, 2012, with median follow-up of 20 months (last follow-up, December 31, 2012). Introduction of abuse-deterrent OxyContin (resistant to crushing or dissolving) on August 9, 2010, and market withdrawal of propoxyphene on November 19, 2010. Standardized opioid dispensing rates and prescription opioid and heroin overdose rates were the primary outcomes. We used segmented regression to analyze changes in outcomes from 30 quarters before to 8 quarters after the 2 interventions. Two years after the opioid market changes, total opioid dispensing decreased by 19% from the expected rate (absolute change, -32.2 mg morphine-equivalent dose per member per quarter [95% CI, -38.1 to -26.3]). By opioid subtype, the absolute change in dispensing by milligrams of morphine-equivalent dose per member per quarter at 2 years was -11.3 (95% CI, -12.4 to -10.1) for extended-release oxycodone, 3.26 (95% CI, 1.40 to 5.12) for other long-acting opioids, -8.19 (95% CI, -9.30 to -7.08) for propoxyphene, and -16.2 (95% CI, -18.8 to -13.5) for other immediate-release opioids. Two years after the market changes, the estimated overdose rate attributed to prescription opioids decreased by 20% (absolute change, -1.10 per 100,000 members per quarter [95% CI, -1.47 to -0.74]), but heroin overdose increased by 23% (absolute change, 0.26 per 100

  19. Clinical utility of guanfacine extended release in the treatment of ADHD in children and adolescents

    Directory of Open Access Journals (Sweden)

    Bello NT

    2015-06-01

    Full Text Available Nicholas T Bello Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA Abstract: Attention deficit hyperactivity disorder (ADHD is the most common psychiatric illness in children and adolescents. Several stimulant medications, such as methylphenidate and amphetamine derivatives, are available to treat ADHD in pediatric patients. Nonstimulant medications are more preferred by some parents, other caregivers, and patients because they lack the abuse potential of stimulant medications. In the US, one available nonstimulant option is guanfacine extended release (XR. As a selective α2A adrenergic receptor, guanfacine acts on the central noradrenergic pathways and cortical noradrenergic targets to improve working memory and attention. The XR formulation of guanfacine, compared with the immediate-release formulation, is more effective for the long-term management of ADHD and is associated with fewer adverse effects. Available data also indicate that guanfacine XR is superior to atomoxetine and is as effective as the nonselective α2 adrenergic receptor agonist, clonidine XR. The most common adverse effects associated with guanfacine XR are somnolence, fatigue, bradycardia, and hypotension. Somnolence is the most often cited reason for discontinuation. Guanfacine XR is also labeled for use as an adjuvant to stimulant treatment for ADHD. A similar profile of adverse effects as reported with monotherapy is reported when guanfacine XR is “added on” to stimulant therapy with somnolence as the most commonly reported adverse event. This review discusses the clinical efficacy and patient preference of guanfacine XR based on available published data on the safety, relative effectiveness, and tolerance of this medication to treat ADHD. Keywords: Intuniv, norepinephrine, prefrontal cortex, locus coeruleus, impulsivity, inattentive

  20. The Influence of Polyethylene Glycol Solution on the Dissolution Rate of Sustained Release Morphine.

    Science.gov (United States)

    Hodgman, Michael; Holland, Michael G; Englich, Ulrich; Wojcik, Susan M; Grant, William D; Leitner, Erich

    2016-12-01

    Whole bowel irrigation (WBI) is a management option for overdose of medications poorly adsorbed to activated charcoal, with modified release properties, or for body packers. Polyethylene glycol (PEG) is a mixture of ethylene oxide polymers of varying molecular weight. PEG with an average molecular weight of 3350 g/mol is used for WBI. PEG electrolyte lavage solution has been shown in vitro to hasten the dissolution of acetaminophen. The impact of PEG on the pharmacokinetics of extended release pharmaceuticals is unknown. Lower average molecular weight PEG mixtures are used as solvents and excipients. We sought to investigate the impact of PEG on the release of morphine from several extended release morphine formulations. An in vitro gastric model was developed. To test the validity of our model, we first investigated the previously described interaction of ethanol and Avinza®. Once demonstrated, we then investigated the effect of PEG with several extended release morphine formulations. In the validation portion of our study, we confirmed an ethanol Avinza® interaction. Subsequently, we did not observe accelerated release of morphine from Avinza® or generic extended release morphine in the presence of PEG. The use of PEG for gastric decontamination following ingestion of these extended release morphine formulations is unlikely to accelerate morphine release and aggravate intoxication.

  1. 14 CFR 125.363 - Flight release over water.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Flight release over water. 125.363 Section 125.363 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... Flight release over water. (a) No person may release an airplane for a flight that involves extended...

  2. Dalfampridine extended release tablets: 1 year of postmarketing safety experience in the US

    Directory of Open Access Journals (Sweden)

    Jara M

    2013-03-01

    Full Text Available Michele Jara,1 Graham Barker,2 Herbert R Henney 3rd1 1Acorda Therapeutics, Inc, Ardsley, NY, USA; 2Biogen Idec, Inc, Maidenhead, Berkshire, UK Background: Dalfampridine extended release tablets (dalfampridine-ER; prolonged-, modified, or sustained-release fampridine in some countries were approved in the US to improve walking in patients with multiple sclerosis, as demonstrated by improvement in walking speed. Postmarketing safety experience is available from exposure of approximately 46,000 patients in the US from product approval through March 2011. Objective: To provide a descriptive analysis of all spontaneously reported postmarketing adverse events (AEs for dalfampridine-ER since product launch. Methods: AE data were extracted from the safety database from product launch through March 31, 2011; AEs were classified using the Medical Dictionary for Regulatory Activities. Seizure cases were reviewed for patient demographics, time to event from treatment onset, and presence of additional risk factors. Results: The most frequently reported postmarketing AEs were similar to those reported during clinical development: dizziness, insomnia, balance disorder, headache, nausea, urinary tract infection, asthenia, and back pain (all included in US product labeling. New clinically significant findings are related to lack of efficacy and inappropriate dosing. Of the approximately 46,000 patients exposed, 85 seizures were reported (~5.4/1000 patient-years, of which 82 were reported or confirmed by a health care practitioner (~5.2/1000 patient-years. Beyond the intrinsic multiple sclerosis-related seizure risk, more than half of the 85 cases (62% had an additional potential risk factor for seizure including a previous history of convulsions, renal impairment, incorrect dosing, or use of concurrent medications with a labeled seizure risk. Duration of treatment prior to the seizure ranged from one dose to 365 days; 26/85 (31% patients suffered a seizure

  3. A Simple and Improved HPLC-PDA Method for Simultaneous Estimation of Fexofenadine and Pseudoephedrine in Extended Release Tablets by Response Surface Methodology

    Directory of Open Access Journals (Sweden)

    Ruhul Kayesh

    2017-01-01

    Full Text Available A simple RP-HPLC method has been developed for simultaneous estimation of fexofenadine and pseudoephedrine in their extended release tablet. The method was developed based on statistical design of experiments (DoE and Response Surface Methodology. Separation was achieved on double end-capped C18 column (250 mm × 4 mm, 5 μm. In this experiment, two components of mobile phase, namely, acetonitrile (% v/v and methanol (% v/v, were the factors whereas retention and resolution of the chromatographic peaks were the responses. The effects of different composition of factors on the corresponding responses were investigated. The optimum chromatographic condition for the current case was found as an isocratic mobile phase consisting of 20 mM phosphate buffer (pH 6.8 and acetonitrile and methanol in a ratio of 50 : 36 : 14 (% v/v at a flow rate of 1 mL/min for 7 minutes. The retention of pseudoephedrine and fexofenadine was found to be 2.6 min and 4.7 min, respectively. The method was validated according to the ICH and FDA guidelines and various validation parameters were determined. Also, forced degradation studies in acid, base, oxidation, and reduction media and in thermal condition were performed to establish specificity and stability-indicating property of this method. Practical applicability of this method was checked in extended release tablets available in Bangladeshi market.

  4. A Single-Dose, Single-Period Pharmacokinetic Assessment of an Extended-Release Orally Disintegrating Tablet of Methylphenidate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Childress, Ann; Newcorn, Jeffrey; Stark, Jeffrey G; McMahen, Russ; Tengler, Mark; Sikes, Carolyn

    2016-08-01

    To determine the pharmacokinetic (PK) profile of a proprietary formulation of methylphenidate (MPH) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in a phase 1 study. Methylphenidate extended-release orally disintegrating tablets (MPH XR-ODTs) combine two technologies in a single-tablet formulation-an extended-release profile that was designed for once-daily dosing in an ODT that does not require water or chewing for ingestion. This was a single-dose, open-label, single-period, single-treatment study, in which 32 children with ADHD who were receiving MPH in doses of 40 or 60 mg before beginning the study each received a 60-mg dose (2 × 30 mg) of MPH XR-ODT. The following plasma PK parameters of MPH were determined for participants grouped by age (6-7, 8-9, 10-12, and 13-17 years old): maximum concentration (Cmax), time to maximum concentration (Tmax), elimination half-life (T½), area under the curve from 0 hours to infinity (AUCinf), oral clearance (CL/F), and volume of distribution in the terminal phase (Vz/F). Safety and tolerability were also assessed. A total of 32 participants received the study drug. For all participants, plasma concentration-time profiles of MPH exhibited a broad peak after administration of MPH XR-ODT through ∼8 hours, indicating extended release from the formulation, followed by an apparent first-order elimination phase. As age increased, MPH exposure decreased and mean estimates of CL/F increased; however, weight-normalized CL/F values were comparable across age groups. Similarly, mean estimates of Vz/F increased with age, but weight-normalization decreased differences across age groups, with the exception of the youngest age group, which had higher values. All adverse events (AEs) were mild. This XR-ODT formulation of MPH demonstrated weight-normalized clearance rates that were consistent across all age groups, a PK profile consistent with once-daily dosing, and an AE profile consistent with

  5. Extended latanoprost release from commercial contact lenses: in vitro studies using corneal models.

    Directory of Open Access Journals (Sweden)

    Saman Mohammadi

    Full Text Available In this study, we compared, for the first time, the release of a 432 kDa prostaglandin F2a analogue drug, Latanoprost, from commercially available contact lenses using in vitro models with corneal epithelial cells. Conventional polyHEMA-based and silicone hydrogel soft contact lenses were soaked in drug solution (131 μg = ml solution in phosphate buffered saline. The drug release from the contact lens material and its diffusion through three in vitro models was studied. The three in vitro models consisted of a polyethylene terephthalate (PET membrane without corneal epithelial cells, a PET membrane with a monolayer of human corneal epithelial cells (HCEC, and a PET membrane with stratified HCEC. In the cell-based in vitro corneal epithelium models, a zero order release was obtained with the silicone hydrogel materials (linear for the duration of the experiment whereby, after 48 hours, between 4 to 6 μg of latanoprost (an amount well within the range of the prescribed daily dose for glaucoma patients was released. In the absence of cells, a significantly lower amount of drug, between 0.3 to 0.5 μg, was released, (p <0:001. The difference observed in release from the hydrogel lens materials in the presence and absence of cells emphasizes the importance of using an in vitro corneal model that is more representative of the physiological conditions in the eye to more adequately characterize ophthalmic drug delivery materials. Our results demonstrate how in vitro models with corneal epithelial cells may allow better prediction of in vivo release. It also highlights the potential of drug-soaked silicone hydrogel contact lens materials for drug delivery purposes.

  6. Formulation and Pharmacokinetic Evaluation of Controlled-Release ...

    African Journals Online (AJOL)

    The effect of several formulation variables on in ... The in vivo pharmacokinetics of the optimized formulation was compared ... Results: The core tablets exhibited extended release consisting of drug release from the embedded ... important factor in medical treatment with respect ... The solvents for high-performance liquid.

  7. Drug release kinetic analysis and prediction of release data via polymer molecular weight in sustained release diltiazem matrices.

    Science.gov (United States)

    Adibkia, K; Ghanbarzadeh, S; Mohammadi, G; Khiavi, H Z; Sabzevari, A; Barzegar-Jalali, M

    2014-03-01

    This study was conducted to investigate the effects of HPMC (K4M and K100M) as well as tragacanth on the drug release rate of diltiazem (DLTZ) from matrix tablets prepared by direct compression method.Mechanism of drug transport through the matrices was studied by fitting the release data to the 10 kinetic models. 3 model independent parameters; i. e., mean dissolution time (MDT), mean release rate (MRR) and release rate efficacy (RE) as well as 5 time point approaches were established to compare the dissolution profiles. To find correlation between fraction of drug released and polymer's molecular weight, dissolution data were fitted into two proposed equations.All polymers could sustain drug release up to 10 h. The release data were fitted best to Peppas and Higuchi square root kinetic models considering squared correlation coefficient and mean percent error (MPE). RE and MRR were decreased when polymer to drug ratio was increased. Conversely, t60% was increased with raising polymer /drug ratio. The fractions of drug released from the formulations prepared with tragacanth were more than those formulated using the same amount of HPMC K4M and HPMC K100M.Preparation of DLTZ matrices applying HPMCK4M, HPMC K100M and tragacanth could effectively extend the drug release. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: A two-phase randomized controlled trial*

    Science.gov (United States)

    Lofwall, Michelle R.; Babalonis, Shanna; Nuzzo, Paul A.; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L.

    2013-01-01

    Background Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: 1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and 2) whether cessation of ER tramadol produces opioid withdrawal. Methods Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Results Use of breakthrough withdrawal medication differed significantly (popioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. PMID:23755929

  9. Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: a two-phase randomized controlled trial.

    Science.gov (United States)

    Lofwall, Michelle R; Babalonis, Shanna; Nuzzo, Paul A; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L

    2013-11-01

    Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: (1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and (2) whether cessation of ER tramadol produces opioid withdrawal. Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Use of breakthrough withdrawal medication differed significantly (popioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. Pharmacokinetics of an oral extended-release formulation of doxycycline hyclate containing acrylic acid and polymethacrylate in dogs.

    Science.gov (United States)

    Ruiz, Sara Melisa Arciniegas; Olvera, Lilia Gutiérrez; Chacón, Sara del Carmen Caballero; Estrada, Dinorah Vargas

    2015-04-01

    To determine the pharmacokinetics of doxycycline hyclate administered orally in the form of experimental formulations with different proportions of acrylic acid-polymethacrylate-based matrices. 30 healthy adult dogs. In a crossover study, dogs were randomly assigned (in groups of 10) to receive a single oral dose (20 mg/kg) of doxycycline hyclate without excipients (control) or extended-release formulations (ERFs) containing doxycycline, acrylic acid polymer, and polymethacrylate in the following proportions: 1:0.5:0.0075 (ERF1) or 1:1:0.015 (ERF2). Serum concentrations of doxycycline were determined for pharmacokinetic analysis before and at several intervals after each treatment. Following oral administration to the study dogs, each ERF resulted in therapeutic serum doxycycline concentrations for 48 hours, whereas the control treatment resulted in therapeutic serum doxycycline concentrations for only 24 hours. All pharmacokinetic parameters for ERF1 and ERF2 were significantly different; however, findings for ERF1 did not differ significantly from those for the control treatment. Results indicated that both ERFs containing doxycycline, acrylic acid polymer, and polymethacrylate had an adequate pharmacokinetic-pharmacodynamic relationship for a time-dependent drug and a longer release time than doxycycline alone following oral administration in dogs. Given the minimum effective serum doxycycline concentration of 0.26 μg/mL, a dose interval of 48 hours can be achieved for each tested ERF. This minimum inhibitory concentration has the potential to be effective against several susceptible bacteria involved in important infections in dogs. Treatment of dogs with either ERF may have several benefits over treatment with doxycycline alone.

  11. Safety and Efficacy of Paliperidone Extended-Release in Acute and Maintenance Treatment of Schizophrenia

    Directory of Open Access Journals (Sweden)

    Edoardo Spina

    2011-01-01

    Full Text Available Paliperidone, the major active metabolite of risperidone, is a second-generation antipsychotic that has been developed as an extended-release (ER tablet formulation that minimizes peak-trough fluctuations in plasma concentrations, allowing once-daily administration and constant drug delivery. Paliperidone ER has demonstrated efficacy in the reduction of acute schizophrenia symptoms in 6-week, placebo-controlled, double-blind trials and clinical benefits were maintained in the longer-term according to extension studies of up to 52 weeks in duration. Compared with quetiapine, paliperidone ER was associated with a more rapid symptom improvement. In addition, it was more effective than placebo in the prevention of symptom recurrence. Paliperidone ER is generally well tolerated with a predictable adverse event profile. Like risperidone, it is associated with a dose-dependent risk of extrapyramidal symptoms and prolactin elevation. Short-and longer-term studies have indicated a low liability for paliperidone ER to cause metabolic (ie, weight gain, hyperglycaemia and lipid dysregulation or cardiovascular adverse effects. Available safety data from elderly patients appear to be promising. Due to negligible hepatic biotransformation, paliperidone ER is unlikely to be involved in clinically significant metabolic drug-drug interactions. Additional active comparator trials evaluating efficacy, tolerability and cost-effectiveness are required to better define the role of paliperidone ER in the treatment of schizophrenia in relation to other currently available second-generation antipsychotics, particularly risperidone.

  12. Extended-Release Guanfacine Does Not Show a Large Effect on Tic Severity in Children with Chronic Tic Disorders.

    Science.gov (United States)

    Murphy, Tanya K; Fernandez, Thomas V; Coffey, Barbara J; Rahman, Omar; Gavaletz, Allison; Hanks, Camille E; Tillberg, Caitlin S; Gomez, Laura Ibanez; Sukhodolsky, Denis G; Katsovich, Lily; Scahill, Lawrence

    2017-11-01

    To evaluate the tolerability, safety, and preliminary efficacy of extended-release guanfacine in children with chronic tic disorders, including Tourette's disorder (collectively referred to as CTD). This was a multisite, 8-week, randomized, double-blind, placebo-controlled trial. The primary outcome measure was the Yale Global Tic Severity Scale (YGTSS) total score. Key secondary outcomes included the Improvement item of Clinical Global Impressions-Improvement (CGI-I) scale and the Tic Symptom Self-report (TSSR). Adverse events were monitored at each visit. Thirty-four subjects (23 boys and 11 girls) of ages 6 to 17 years (mean = 11.1 ± 3.1) with CTD were randomly assigned to extended-release guanfacine (n = 16) or placebo (n = 18). At baseline, the mean YGTSS total score was 26.3 ± 6.6 for the guanfacine group versus 27.7 ± 8.7 for the placebo group. Within the guanfacine group (mean final daily dose of 2.6 ± 1.1 mg, n = 14), the mean YGTSS total score declined to 23.6 ± 6.42 [t(15) = 1.84, p = 0.08; effect size = 0.35]. The results were similar in the placebo group with a score of 24.7 ± 10.54 at week 8 [t(17) = 1.83, p = 0.08; effect size = 0.38]. There was no significant difference in the rate of positive response on the CGI-I between the guanfacine group and placebo (19% [3/16] vs. 22% [4/18], p = 1.0). The most common adverse events were fatigue, drowsiness, dry mouth, headache, and irritability. Two subjects in the guanfacine group discontinued early-one because of an adverse event (depressed mood) and one because of lack of efficacy; two subjects in the placebo group discontinued because of lack of efficacy. This pilot study did not confirm a clinically meaningful effect size within the guanfacine group. These results do not support the launch of a larger efficacy trial for tics in children and adolescents with CTD.

  13. Treatment satisfaction with paliperidone extended-release tablets: open-label study in schizophrenia patients dissatisfied with previous antipsychotic medication

    Directory of Open Access Journals (Sweden)

    Yang FD

    2017-04-01

    Full Text Available Fu De Yang,1 Juan Li,1 Yun Long Tan,1 Wei Ye Liang,1 Rongzhen Zhang,1 Ning Wang,1 Wei Feng,1 Shangli Cai,2 Jian Min Zhuo,2 Li Li Zhang2 1Beijing Hui-Long-Guan Hospital, 2Department of Medical Affairs, Xian Janssen Pharmaceutical Ltd, Beijing, People’s Republic of China Objective: The aim of this study was to evaluate the changes in treatment satisfaction after switching to paliperidone extended-release (ER in Chinese schizophrenia patients dissatisfied with their previous antipsychotic treatment.Methods: In this 8-week, open-label, single-arm, multicenter, prospective study, 1,693 patients dissatisfied with previous antipsychotic medication were enrolled and switched to paliperidone ER tablets (3–12 mg/d based on clinical judgment. The primary efficacy end point was change in Medication Satisfaction Questionnaire (MSQ score from baseline to week 8. The secondary end points included percentage of patients with MSQ score ≥4, as well as changes in Clinical Global Improvement-Severity (CGI-S and Personal and Social Performance (PSP scores.Results: MSQ scores increased significantly from baseline (mean [standard deviation {SD}]: 2.48 [0.55] to week 8 (5.47 [0.89], P<0.0001; primary end point, full analysis set. The percentage of patients with MSQ score ≥4 was 95.9% at week 8, indicating that most of the patients were satisfied with their treatment. Significant (P<0.0001 improvements from baseline to week 8 were noted in CGI-S score (2.37 [1.20] and PSP score (25.5 [15.0]. A total of 174 (10.28% patients experienced adverse events (AEs. The most common (>10 patients events were extrapyramidal disorder (n=84, 4.96%, poor quality sleep (n=18, 1.06% and akathisia (n=13, 0.77%. The majority of AEs were mild to moderate in severity. No deaths occurred.Conclusion: Treatment satisfaction improved after switching to paliperidone ER from the previous antipsychotic in Chinese patients with schizophrenia. Keywords: atypical antipsychotics, open label

  14. Combination of niacin extended-release and simvastatin results in a less atherogenic lipid profile than atorvastatin monotherapy

    Directory of Open Access Journals (Sweden)

    William Insull Jr

    2010-11-01

    Full Text Available William Insull Jr1, Peter P Toth2, H Robert Superko3, Roopal B Thakkar4, Scott Krause4, Ping Jiang4, Rhea A Parreno4, Robert J Padley41Baylor College of Medicine and Methodist Hospital, Houston, Texas; 2University of Illinois College of Medicine, Peoria, Illinois; 3Celera, Alameda, California, Mercer University, Atlanta, Georgia; 4Abbott, Abbott Park, Illinois, USAObjective: To compare the effects of combination niacin extended-release + simvastatin (NER/S versus atorvastatin alone on apolipoproteins and lipid fractions in a post hoc analysis from SUPREME, a study which compared the lipid effects of niacin extended-release + simvastatin and atorvastatin in patients with hyperlipidemia or mixed dyslipidemia.Patients and methods: Patients (n = 137 with dyslipidemia (not previously receiving statin therapy or having discontinued any lipid-altering treatment 4–5 weeks prior to the study received NER/S (1000/40 mg/day for four weeks, then 2000/40 mg/day for eight weeks or atorvastatin 40 mg/day for 12 weeks. Median percent changes in apolipoprotein (apo A-1, apo B, and the apo B:A-I ratio, and nuclear magnetic resonance lipoprotein subclasses from baseline to week 12 were compared using the Wilcoxon rank-sum test and Fisher’s exact test.Results: NER/S treatment produced significantly greater percent changes in apo A-I and apo B:A-I, and, at the final visit, apo B <80 mg/dL was attained by 59% versus 33% of patients, compared with atorvastatin treatment (P = 0.003. NER/S treatment resulted in greater percent reductions in calculated particle numbers for low-density lipoprotein (LDL, 52% versus 43%; P = 0.022, small LDL (55% versus 45%; P = 0.011, very low-density lipoprotein (VLDL and total chylomicrons (63% versus 39%; P < 0.001, and greater increases in particle size for LDL (2.7% versus 1.0%; P = 0.007 and VLDL (9.3% versus 0.1%; P < 0.001, compared with atorvastatin.Conclusion: NER/S treatment significantly improved apo A-I levels and the apo

  15. Glycine-extended gastrin enhances somatostatin release from cultured rabbit fundic D-cells [v1; ref status: indexed, http://f1000r.es/8n

    Directory of Open Access Journals (Sweden)

    Ian LP Beales

    2013-02-01

    Full Text Available The role of the peptide hormone gastrin in stimulating gastric acid secretion is well established. Mature amidated gastrin is processed from larger peptide precursor forms. Increasingly these processing intermediates, such as glycine-extended gastrin (G-Gly and progastrin, have been shown to have biological activities of their own, often separate and complementary to gastrin. Although G-Gly is synthesized and secreted by gastric antral G-cells, the physiological functions of this putative mediator are unclear. Gastrin and cholecystokinin (CCK stimulate the secretion of somatostatin from gastric D-cells as part of the feedback control of gastric acid. In this study the effect of G-Gly and gastrin on the release of somatostatin from rabbit fundic D-cells was examined. D-cells were obtained by collagenase-EDTA digestion and elutriation and cultured for 48 hours. With a 2 hour exposure to the peptides, gastrin but not G-Gly stimulated somatostatin release. Treatment of D-cells for 24 hours with gastrin or G-Gly individually, significantly enhanced subsequent basal as well as CCK- and GLP-1-stimulated somatostatin release. Twenty four hours exposure to gastrin combined with G-Gly synergistically enhanced basal and agonist-stimulated somatostatin release and cellular somatostatin content. Gastrin and G-Gly may be important in the longer term regulation of D-cell function.

  16. Potential role of gabapentin and extended- release gabapentin in the management of menopausal hot flashes

    Directory of Open Access Journals (Sweden)

    Yadav M

    2013-08-01

    Full Text Available Manisha Yadav, Judith Volkar Center for Specialized Women’s Health, Cleveland Clinic Foundation, Cleveland, Ohio, USA Abstract: About 80% of postmenopausal women experience vasomotor symptoms, such as hot flashes and night sweats – symptoms that are associated with sleep disruption and can lead to fatigue and mood changes. Moreover, hot flashes can be embarrassing for women, causing difficulties at work and in their social lives. Many therapies have been advocated for relief of vasomotor symptoms, but only hormone therapy has been US Food and Drug Administration approved. However, after the Women's Health Initiative Study suggested that there was a correlation between hormone therapy and increased risk for breast cancer and cardiovascular events, many women stopped taking hormone therapy, and many do not want to initiate it. Hormone therapy is also contraindicated in certain women, such as those with a history of hormone-stimulated cancer like breast and uterine cancer. Gabapentin (Neurontin has shown efficacy in relieving vasomotor symptoms and is used as off-label for this indication. A new extended-release formulation of gabapentin has also shown efficacy in treating hot flashes and improving sleep quality with possibly fewer side effects than regular gabapentin. Keywords: Hot flushes, vasomotor symptoms, postmenopausal, hormone-sensitive cancer, non-hormonal therapy, gastric-retentive, Breeze

  17. Pharmacokinetics of hydrocodone extended-release tablets formulated with different levels of coating to achieve abuse deterrence compared with a hydrocodone immediate-release/acetaminophen tablet in healthy subjects.

    Science.gov (United States)

    Darwish, Mona; Bond, Mary; Tracewell, William; Robertson, Philmore; Yang, Ronghua

    2015-01-01

    A hydrocodone extended-release (ER) formulation employing the CIMA(®) Abuse-Deterrence Technology platform was developed to provide resistance against rapid release of hydrocodone when tablets are comminuted or taken with alcohol. This study evaluated the pharmacokinetics of three hydrocodone ER tablet prototypes with varying levels of polymer coating to identify the prototype expected to have the greatest abuse deterrence potential based on pharmacokinetic characteristics that maintain systemic exposure to hydrocodone comparable to that of a commercially available hydrocodone immediate-release (IR) product. In this four-period crossover study, healthy subjects aged 18-45 years were randomized to receive a single intact, oral 45-mg tablet of one of three hydrocodone ER prototypes (low-, intermediate-, or high-level coating) or an intact, oral tablet of hydrocodone IR/acetaminophen (APAP) 10/325 mg every 6 h until four tablets were administered, with each of the four treatments administered once over the four study periods. Dosing periods were separated by a minimum 5-day washout. Naltrexone 50 mg was administered to block opioid receptors. Blood samples for pharmacokinetic assessments were collected predose and through 72 h postdose. Parameters assessed included maximum observed plasma hydrocodone concentration (C(max)), time to C(max) (t(max)), and area under the concentration-time curve from time 0 to infinity (AUC(0-∞)). Mean C(max) values were 49.2, 32.6, and 28.4 ng/mL for the low-, intermediate-, and high-level coating hydrocodone ER tablet prototypes, respectively, and 37.3 ng/mL for the hydrocodone IR/APAP tablet; respective median t(max) values were 5.9, 8.0, 8.0, and 1.0 h. Total systemic exposure to hydrocodone (AUC(0-∞)) was comparable between hydrocodone ER tablet prototypes (640, 600, and 578 ng·h/mL, respectively) and hydrocodone IR/APAP (581 ng·h/mL). No serious adverse events or deaths were reported. The most common adverse events included

  18. Evaluation of Flexible Tacrolimus Drug Concentration Monitoring Approach in Patients Receiving Extended-Release Once-Daily Tacrolimus Tablets.

    Science.gov (United States)

    Philosophe, Benjamin; Leca, Nicolae; West-Thielke, Patricia M; Horwedel, Timothy; Culkin-Gemmell, Christine; Kistler, Kristin; Stevens, Daniel R

    2018-02-20

    The majority of United States kidney transplant patients are treated with tacrolimus, a drug effective in preventing graft rejection, but with a narrow therapeutic range, necessitating close monitoring to avoid increased risks of transplant rejection or toxicity if the tacrolimus concentration is too low or too high, respectively. The trough drug concentration tests are time sensitive; patients treated on a twice-daily basis have blood draws exactly 12 hours after their previous dose. The schedule's rigidity causes problems for both patients and health care providers. Novel once-daily tacrolimus formulations such as LCPT (an extended-release tablet by Veloxis Pharmaceuticals, Inc., Cary, North Carolina) have allowed for blood draws on a once-daily basis; however, even that schedule can be restrictive. Results from tests taken either before or after that 24-hour target time may be discarded, or worse, may lead to inappropriate dose changes. Data from ASTCOFF, a phase 3B pharmacokinetic clinical trial (NCT02339246), demonstrated that the unique pharmacokinetic curve of LCPT may allow for a therapeutic monitoring window that extends for 3 hours before or after the 24-hour monitoring target. Furthermore, important tools to help clinicians interpret these levels, such as formulas to estimate the 24-hour trough level if an alternative monitoring time is used, were constructed from these data. These study results give treating clinicians access to data that allow them to safely use and monitor LCPT in their patients and expand the body of evidence surrounding differentiation and practical application of the novel LCPT tacrolimus formulation. © 2018, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  19. A REVIEW ON CONTROLLED DRUG RELEASE FORMULATION: SPANSULES

    OpenAIRE

    Rinky Maurya; Dr. Pramod Kumar Sharma; Rishabha Malviya

    2014-01-01

    Spansules are a dosage form which was considered as one of the Advanced Drug Delivery System. Multidrug preparations can be delivered easily by spansules or granules in capsule technology. This type of delivery system designed to release a drug or a medicament at two or more different rates or in different span of time. A quick/slow release system provides an initial release of drug followed by a constant rate of drug release over a extended period or a defined period of time and in slow/quic...

  20. Human Abuse Potential of an Abuse-Deterrent (AD), Extended-Release (ER) Morphine Product Candidate (Morphine-ADER Injection-Molded Tablets) vs Extended-Release Morphine Administered Intranasally in Nondependent Recreational Opioid Users.

    Science.gov (United States)

    Webster, Lynn R; Smith, Michael D; Lawler, John; Lindhardt, Karsten; Dayno, Jeffrey M

    2017-09-01

    To compare the relative human abuse potential after insufflation of manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine ER tablets. A randomized, double-blind, double-dummy, active- and placebo-controlled five-way crossover study was performed with adult volunteers who were experienced, nondependent, recreational opioid users. After intranasal (IN) administration of manipulated high-volume (HV) morphine-ADER-IMT (60 mg), participants were randomized (1:1:1:1) to receive IN manipulated low-volume (LV) morphine ER (60 mg), IN manipulated LV morphine-ADER-IMT, intact oral morphine-ADER-IMT (60 mg), and placebo in crossover fashion. Pharmacodynamic and pharmacokinetic assessments included peak effect of drug liking (E max ; primary endpoint) using drug liking visual analog scale (VAS) score, E max using overall drug liking, and take drug again (TDA) VASs scores, and mean abuse quotient (AQ), a pharmacokinetic parameter associated with drug liking. Forty-six participants completed the study. After insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT, drug liking E max was significantly lower ( P  <   0.0001) compared with IN morphine ER. Overall drug liking and TDA E max values were significantly lower ( P  <   0.0001) after insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT compared with IN morphine ER. Mean AQ was lower after insufflation of HV (9.2) and LV (2.3) morphine-ADER-IMT or ingestion of oral morphine-ADER-IMT (5.5) compared with insufflation of LV morphine ER (37.2). All drug liking, take drug again, and abuse quotient endpoints support a significantly lower abuse potential with insufflation of manipulated morphine-ADER-IMT compared with manipulated and insufflated non-AD ER morphine. © 2016 American Academy of Pain Medicine.

  1. Prevention of organ rejection in renal and liver transplantation with extended release tacrolimus

    Directory of Open Access Journals (Sweden)

    Reschen ME

    2014-09-01

    Full Text Available Michael E Reschen, Christopher A O’Callaghan Henry Wellcome Building, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom Abstract: Tacrolimus is the key immunosuppressant used to prevent allograft rejection in kidney and liver transplant recipients. Despite the efficacy of tacrolimus and adjunctive immunosuppressants, a substantial number of patients experience episodes of acute rejection and late graft loss. Nonadherence is an etiological factor in both acute rejection and graft loss. In 2007, a prolonged release version of tacrolimus became available that allows once daily administration, thus halving the pill burden compared to the standard twice-daily tacrolimus. An increasing number of studies in de novo transplantation and in treatment conversion have evaluated the pharmacokinetic profile, efficacy, and safety of prolonged-release tacrolimus. We have reviewed the literature on the use of prolonged-release tacrolimus and hope that this will be of value in the design of protocols for transplant immunosuppression.Keywords: immunosuppression, kidney, hepatic, allograft, adherence

  2. [Therapeutic effects of venlafaxine extended release for patients with depressive and anxiety disorders in the German outpatient setting - results of 2 observational studies including 8500 patients].

    Science.gov (United States)

    Anghelescu, I-G; Dierkes, W; Volz, H-P; Loeschmann, P-A; Schmitt, A B

    2009-11-01

    The therapeutic effects of venlafaxine extended release have been investigated by two prospective observational studies including 8506 patients in the outpatient setting of office based general practitioners and specialists. The efficacy has been documented by the Clinical Global Impression (CGI) scale and by the Hamilton depression (HAMD-21) scale. The tolerability has been assessed by the documentation of adverse events. About (2/3) of the patients were treated because of depression and about (1/3) mainly because of anxiety disorder. The patients of specialists did receive higher dosages and were more severely affected. The response rate on the CGI scale was 87.4 for the patients of general practitioners and 74.2 % for the patients of specialists. The results of the HAMD-21 scale, which has been used by specialists, showed a response rate of 71.8 and a remission rate of 56.3 %. These positive effects could be demonstrated even for the more severely and chronically affected patients. The incidence of adverse events was low in both studies and comparable to the tolerability profile of randomized studies. Importantly, the good tolerability profile was similar even for patients with concomitant cardiovascular disease. In conclusion, these results confirm the efficacy and good tolerability of venlafaxine extended release in the outpatient setting in Germany. Georg Thieme Verlag KG Stuttgart, New York.

  3. Lithium carbonate as a treatment for paliperidone extended-release-induced leukopenia and neutropenia in a patient with schizoaffective disorder; a case report.

    Science.gov (United States)

    Matsuura, Hiroki; Kimoto, Sohei; Harada, Izumi; Naemura, Satoshi; Yamamuro, Kazuhiko; Kishimoto, Toshifumi

    2016-05-26

    Antipsychotic drug treatment can potentially lead to adverse events such as leukopenia and neutropenia. Although these events are rare, they represent serious and life-threatening hematological side effects. We present a case study of a patient with schizoaffective disorder in a 50-year-old woman. We report a case of paliperidone extended-release (ER)-induced leukopenia and neutropenia in a female patient with schizoaffective disorder. Initiating lithium carbonate treatment and decreasing the dose of valproic acid improved the observed leukopenia and neutropenia. This treatment did not influence psychotic symptoms. The combination of paliperidone ER and valproic acid induces increased paliperidone ER plasma levels. Lithium carbonate was successfully used to treat paliperidone ER-induced leukopenia and neutropenia.

  4. Steady-state pharmacokinetics of fluvastatin in healthy subjects following a new extended release fluvastatin tablet, Lescol XL.

    Science.gov (United States)

    Barilla, Denise; Prasad, Pratapa; Hubert, Martine; Gumbhir-Shah, Kavita

    2004-03-01

    This was an open-label, randomized, three-period, three-treatment, multiple dose, crossover study in 12 healthy male and female subjects. This study evaluated single dose and steady-state pharmacokinetics of fluvastatin following single and multiple dose administrations of a new extended release fluvastatin 8 h matrix tablet, Lescol XL 80 mg and 160 mg doses once a day. The study also included a twice a day administration of an immediate release (IR) form of fluvastatin capsule, Lescol, for comparative purposes. All doses were administered for 7 days. The safety and tolerability were also assessed. The pharmacokinetics of fluvastatin were evaluated on days 1 and 7 following each treatment. Fluvastatin systemic exposure was 50% less when administered as Lescol XL 80 mg qd compared with Lescol IR 40 mg bid. Conversely, fluvastatin systemic exposure was 22% higher when administered as Lescol XL 160 mg qd compared with Lescol IR 40 mg bid. Single doses of Lescol XL 80 mg and 160 mg were dose proportional but, deviation (30%) from dose proportionality was observed for the Lescol XL 160 mg at steady-state. There appeared to be moderate (20%-40%) accumulation of serum fluvastatin maximal concentrations and exposure after multiple doses of Lescol XL tablets. Both Lescol XL 80 mg and 160 mg showed delayed absorption and longer apparent elimination half-life compared with fluvastatin IR capsule. Single and multiple doses of fluvastatin were generally well tolerated in this healthy volunteer population. Adverse event profiles were consistent with the published safety profile of the marketed formulations. Aside from one incidence of creatine phosphokinase (CPK) elevation (following Lescol XL 160 mg qd treatment), there were no safety concerns with any of the treatments when administered acutely (7 days). Copyright 2004 John Wiley & Sons, Ltd.

  5. Oral sustained release tablets of zidovudine using binary blends of natural and synthetic polymers.

    Science.gov (United States)

    Emeje, Martins; Olaleye, Olajide; Isimi, Christiana; Fortunak, Joseph; Byrn, Stephen; Kunle, Olobayo; Ofoefule, Sabinus

    2010-01-01

    Oral sustained release matrix tablets of zidovudine (ZDV) were prepared using different types, proportions and blends of carbopol 71G (C71) and a plant gum obtained from Abelmoschus esculentus (AEG). The effect of various formulation factors like polymer proportion, polymer type and pH of the dissolution medium on the in vitro release of the drug was studied, using the half change technique, in 900 ml of dissolution medium, at 100 rpm. Release kinetics were analyzed using Zero-order, Higuchi's square-root and Ritger-Peppas' empirical equations. In vitro release performance as revealed by the time taken for 70% of the drug to be released (t70%), showed that the release rate decreased with increase in polymer proportion. Matrix tablets containing 10 and 20% AEG were found to exhibit immediate-release characteristics. Matrix tablets containing 30% AEG showed t70% value of 204 min and extended the release up to 5 h, while matrix tablets containing 30% carbopol showed t70% value of 234 min and extended the release up to 6 h. Three blends of AEG and C71 at the ratio of 1:2, 2:1 and 1:3 showed t70% values of 132, 312 and 102 min respectively and extended the release up to 8 h. Mathematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets followed Fickian and anomalous release. Drug release from matrix tablets of zidovudine containing blends of AEG and C71 demonstrates the advantage of blending a natural and synthetic polymer over single polymer use.

  6. Once-Daily Tacrolimus Extended-Release Formulation: 1 Year after Conversion in Stable Pediatric Kidney Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Lars Pape

    2011-01-01

    Full Text Available It is speculated that a once-daily dosage of immunosuppression can increase adherence and thereby graft survival. Until now, there have been no studies on once-daily use of Tacrolimus extended-release formulation (TAC-ER in children following pediatric kidney transplantation. In 11 stable pediatric kidney recipients >10 years, efficacy, safety, and tolerability of a switch to TAC-ER were observed over one year. Adherence was determined by use of the BAASIS-Scale Interview and comparison of individual variability of Tacrolimus trough levels. Over the observation period, two acute rejections were observed in one girl with nonadherence and repeated Tacrolimus trough levels of 0 ng/m. Beside this, there were no acute rejections in this trial. TAC dose was increased in 3/11 patients and decreased in 2/11 patients within the course of the study. Six patients did not require a dose adjustment. All but one patient had a maximum of 1 dose change during therapy. Mean Tacrolimus dose, trough levels, and Glomerular filtration rates were also stable. Adherence, as measured by BAASIS-Scale Interview and coefficient of variation of Tacrolimus trough levels, was good at all times. It is concluded that conversion to Tac-ER is safe in low-risk children following pediatric kidney transplantation.

  7. Rifaximin-extended intestinal release induces remission in patients with moderately active Crohn's disease.

    Science.gov (United States)

    Prantera, Cosimo; Lochs, Herbert; Grimaldi, Maria; Danese, Silvio; Scribano, Maria Lia; Gionchetti, Paolo

    2012-03-01

    Bacteria might be involved in the development and persistence of inflammation in patients with Crohn's disease (CD), and antibiotics could be used in therapy. We performed a clinical phase 2 trial to determine whether a gastroresistant formulation of rifaximin (extended intestinal release [EIR]) induced remission in patients with moderately active CD. We performed a multicenter, randomized, double-blind trial of the efficacy and safety of 400, 800, and 1200 mg rifaximin-EIR, given twice daily to 402 patients with moderately active CD for 12 weeks. Data from patients given rifaximin-EIR were compared with those from individuals given placebo, and collected during a 12-week follow-up period. The primary end point was remission (Crohn's Disease Activity Index <150) at the end of the treatment period. At the end of the 12-week treatment period, 62% of patients who received the 800-mg dosage of rifaximin-EIR (61 of 98) were in remission, compared with 43% of patients who received placebo (43 of 101) (P = .005). A difference was maintained throughout the 12-week follow-up period (45% [40 of 89] vs 29% [28 of 98]; P = .02). Remission was achieved by 54% (56 of 104) and 47% (47 of 99) of the patients given the 400-mg and 1200-mg dosages of rifaximin-EIR, respectively; these rates did not differ from those of placebo. Patients given the 400-mg and 800-mg dosages of rifaximin-EIR had low rates of withdrawal from the study because of adverse events; rates were significantly higher among patients given the 1200-mg dosage (16% [16 of 99]). Administration of 800 mg rifaximin-EIR twice daily for 12 weeks induced remission with few adverse events in patients with moderately active CD. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  8. US Food and Drug Administration's Risk Evaluation and Mitigation Strategy for extended-release and long-acting opioids: pros and cons, and a European perspective.

    Science.gov (United States)

    Mercadante, Sebastiano; Craig, David; Giarratano, Antonello

    2012-12-24

    Prescriptions for opioid analgesics to manage moderate-to-severe chronic non-cancer pain have increased markedly over the last decade. An unintentional consequence of greater prescription opioid utilization has been the parallel increase in misuse, abuse and overdose, which are serious risks associated with all opioid analgesics. In response to disturbing rises in prescription opioid abuse, the US Food and Drug Administration (FDA) has proposed the implementation of aggressive Risk Evaluation and Mitigation Strategies (REMS). While REMS could dramatically change the development, release, marketing and prescription of extended-release opioids, questions remain on how these programmes may influence prescribing practices, patient safety and ultimately patient access to these agents. The extent of the availability and misuse of prescription opioids in Europe is difficult to assess from the data currently available, due in large part to the considerable differences in prescribing patterns and regulations between countries. Balancing the availability of prescription opioids for those patients who have pain, while discouraging illicit use, is a complex challenge and requires effective efforts on many levels, particularly in Europe where policies are quite different between countries.

  9. QUALITY OF LIFE AND COMPLIANCE TO THERAPY IN PATIENTS FOLLOWING SUCCESSFULTRANSLUMINAL CORONARY ANGIOPLASTY, WHO WERE PRESCRIBED FLUVASTATIN EXTENDED RELEASE ADDED TO STANDARD THERAPY. PROTOCOL OF THE OPEN-LABEL OBSERVATIONAL STUDY

    Directory of Open Access Journals (Sweden)

    A. V. Susekov

    2010-01-01

    Full Text Available Aim. To evaluate quality of life changes and compliance to therapy in patients following successful transluminal angioplasty, who have indications for fluvastatin extended release in addition to standard treatment.Material and methods. This is a national observational multicenter study. An inclusion of 60 investigator centers is planned (out-patient medical centers, the total number of patients to be included is 600. Patients (men and women with coronary heart disease following successful transluminal coronary angioplasty, who were prescribed fluvastatinextended release (Lescol Forte, Novartis 80 mg once daily will be included in the observation. The following efficacy and safety parameters will be evaluated: quality of life assessed with SF-36 scale before and during treatment; compliance to therapy; adverse events and serious adverse events. Observation period is planned for 6 months. During this period patient is expected to make 4 visits to treating physician. According to the physician’s decision, observation period can be extended to 12 months.Present study status. The study is completed. 524 patients completed the observation, including 116 patients who were followed up for 12 months. There are 414 men (79% and 110 women (21% among patients enrolled into the study.

  10. Extended high dose letrozole regimen versus short low dose letrozole regimen as an adjuvant to gonadotropin releasing hormone antagonist protocol in poor responders undergoing IVF-ET.

    Science.gov (United States)

    Fouda, Usama M; Sayed, Ahmed M

    2011-12-01

    To compare the efficacy and cost-effectiveness of extended high dose letrozole regimen/HPuFSH-gonadotropin releasing hormone antagonist (GnRHant) protocol with short low dose letrozole regimen/HPuFSH-GnRHant protocol in poor responders undergoing IVF-ET. In this randomized controlled trial, 136 women who responded poorly to GnRH agonist long protocol in their first IVF cycle were randomized into two equal groups using computer generated list and were treated in the second IVF cycle by either extended letrozole regimen (5 mg/day during the first 5 days of cycle and 2.5 mg/day during the subsequent 3 days) combined with HPuFSH-GnRHant protocol or short letrozole regimen (2.5 mg/day from cycle day 3-7) combined with HPuFSH-GnRHant protocol. There were no significant differences between both groups with regard to number of oocytes retrieved and clinical pregnancy rate (5.39 ± 2.08 vs. 5.20 ± 1.88 and 22.06% vs. 16.18%, respectively).The total gonadotropins dose and medications cost per cycle were significantly lower in extended letrozole group (44.87 ± 9.16 vs. 59.97 ± 14.91 ampoules and 616.52 ± 94.97 vs. 746.84 ± 149.21 US Dollars ($), respectively).The cost-effectiveness ratio was 2794 $ in extended letrozole group and 4616 $ in short letrozole group. Extended letrozole regimen/HPuFSH-GnRHant protocol was more cost-effective than short letrozole regimen/HPuFSH-GnRHant protocol in poor responders undergoing IVF-ET.

  11. Hydraulic release oil tool

    International Nuclear Information System (INIS)

    Mims, M.G.; Mueller, M.D.; Ehlinger, J.C.

    1992-01-01

    This patent describes a hydraulic release tool. It comprises a setting assembly; a coupling member for coupling to drill string or petroleum production components, the coupling member being a plurality of sockets for receiving the dogs in the extended position and attaching the coupling member the setting assembly; whereby the setting assembly couples to the coupling member by engagement of the dogs in the sockets of releases from and disengages the coupling member in movement of the piston from its setting to its reposition in response to a pressure in the body in exceeding the predetermined pressure; and a relief port from outside the body into its bore and means to prevent communication between the relief port and the bore of the body axially of the piston when the piston is in the setting position and to establish such communication upon movement of the piston from the setting position to the release position and reduce the pressure in the body bore axially of the piston, whereby the reduction of the pressure signals that the tool has released the coupling member

  12. Development of modified-release tablets of zolpidem tartrate by biphasic quick/slow delivery system.

    Science.gov (United States)

    Mahapatra, Anjan Kumar; Sameeraja, N H; Murthy, P N

    2015-06-01

    Zolpidem tartrate is a non-benzodiazepine analogue of imidazopyridine of sedative and hypnotic category. It has a short half-life with usual dosage regimen being 5 mg, two times a day, or 10 mg, once daily. The duration of action is considered too short in certain circumstances. Thus, it is desirable to lengthen the duration of action. The formulation design was implemented by preparing extended-release tablets of zolpidem tartrate using the biphasic delivery system technology, where sodium starch glycolate acts as a superdisintegrant in immediate-release part and hydroxypropyl methyl cellulose as a release retarding agent in extended-release core. Tablets were prepared by direct compression. Both the core and the coat contained the drug. The pre-compression blends were evaluated for angle of repose, bulk density, and compressibility index. The tablets were evaluated for thickness, hardness, weight variation test, friability, and in vitro release studies. No interaction was observed between zolpidem tartrate and excipients from the Fourier transform infrared spectroscopy and differential scanning calorimetry analysis. The results of all the formulations prepared were compared with reference product Stilnoct®. Optimized formulations showed release patterns that match the United States Pharmacopeia (USP) guidelines for zolpidem tartrate extended-release tablets. The mechanism of drug release was studied using different mathematical models, and the optimized formulation has shown Fickian diffusion. Accelerated stability studies were performed on the optimized formulation.

  13. Effect of PPG-PEG-PPG on the tocopherol-controlled release from films intended for food-packaging applications.

    Science.gov (United States)

    Castro López, María del Mar; Dopico García, Sonia; Ares Pernas, Ana; López Vilariño, José Manuel; González Rodríguez, María Victoria

    2012-08-22

    The feasibility of novel controlled release systems for the delivery of active substances from films intended for food packaging was investigated. Because polyolefins are used highly for food-packaging applications, the reported high retention degree of antioxidants has limited their use for active packaging. Thus, in this study, PP films modified with different chain extenders have been developed to favor and control the release rates of the low molecular weight antioxidant tocopherol. The use of different chain extenders as polymer modifiers (PE-PEG M(w), 575; and PPG-PEG-PPG M(w), 2000) has caused significant changes in tocopherol-specific release properties. High-performance liquid chromatography coupled to PDA-FL and PDA-MS was used to test tocopherol and chain extender migration, respectively. The release of tocopherol from the prepared films with two chain extenders into two food simulants was studied. Different temperatures and storage times were also tested. Varying the structural features of the films with the incorporation of different levels of PPG-PEG-PPG, the release of tocopherol (food-packaging additive) into different ethanolic simulants could be clearly controlled. The effect of the temperature and storage time on the release of the antioxidant has been outstanding as their values increased. The migration of the chain extender, also tested, was well below the limits set by European legislation.

  14. Population pharmacokinetics of methylphenidate hydrochloride extended-release multiple-layer beads in pediatric subjects with attention deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Teuscher NS

    2015-05-01

    Full Text Available Nathan S Teuscher,1 Akwete Adjei,2 Robert L Findling,3,4 Laurence L Greenhill,5 Robert J Kupper,2 Sharon Wigal6 1PK/PD Associates, Trophy Club, TX, 2Rhodes Pharmaceuticals L.P., Coventry, RI, 3Department of Psychiatric Services and Research, Kennedy Krieger Institute, Baltimore, MD, 4Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, 5Department of Psychiatry, Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY, 6AVIDA Inc., Newport Beach, CA, USA Abstract: A new multilayer-bead formulation of extended-release methylphenidate hydrochloride (MPH-MLR has been evaluated in pharmacokinetic studies in healthy adults and in Phase III efficacy/safety studies in children and adolescents with attention deficit hyperactivity disorder (ADHD. Using available data in healthy adults, a two-input, one-compartment, first-order elimination population pharmacokinetic model was developed using nonlinear mixed-effect modeling. The model was then extended to pediatric subjects, and was found to adequately describe plasma concentration–time data for this population. A pharmacokinetic/pharmacodynamic model was also developed using change from baseline in the ADHD Rating Scale (ADHD-RS-IV total scores from a pediatric Phase III trial and simulated plasma concentration–time data. During simulations for each MPH-MLR dose level (10–80 mg, increased body weight resulted in decreased maximum concentration. Additionally, as maximum concentration increased, ADHD-RS-IV total score improved (decreased. Knowledge of the relationship between dose, body weight, and clinical response following the administration of MPH-MLR in children and adolescents may be useful for clinicians selecting initial dosing of MPH-MLR. Additional study is needed to confirm these results. Keywords: population pharmacokinetics, Aptensio XR™, MPH-MLR, methylphenidate

  15. Safety profile of dalfampridine extended release in multiple sclerosis: 5-year postmarketing experience in the United States

    Directory of Open Access Journals (Sweden)

    Jara M

    2015-12-01

    Full Text Available Michele Jara, Thomas Aquilina, Peter Aupperle, Adrian L Rabinowicz Acorda Therapeutics, Inc., Ardsley, NY, USA Background: Dalfampridine extended release tablets (dalfampridine-ER; prolonged-, modified, or sustained-release fampridine outside the US, 10 mg twice daily, was approved by the US Food and Drug Administration (FDA in January 2010 to improve walking in people with multiple sclerosis, as determined by an increase in walking speed. Objective: To provide a descriptive analysis of reported adverse events (AEs for commercially available dalfampridine-ER from March 2010 through March 31, 2015. Methods: Five-year postmarketing data for dalfampridine-ER were available from the exposure of approximately 107,000 patients in the US (103,700 patient-years. Commonly reported AEs (≥2% of all reported AEs and serious AEs were determined. The incidence of reported seizures was determined and the events were further investigated. Results: Among the 107,000 patients exposed to dalfampridine-ER (70% female; mean age 52.1, the most common AEs were dizziness (3.7%, insomnia (3.2%, balance disorder (3%, fall (2.4%, headache (2.4%, nausea (2.1%, and urinary tract infection (2%. Other common AEs were drug ineffectiveness (5.8%, gait disturbance (4.6%, and inappropriate dosing (3.1%. Serious AEs included rare anaphylactic reactions (five cases and drug hypersensitivity reactions (eight cases. A total of 657 seizure cases were reported (6.3/1,000 patient-years; of these, 324 were medically confirmed (3.1/1,000 patient-years. Incidence of reported seizures was stable over time. Duration of treatment prior to a seizure ranged from a single dose to >4 years; 12% of the seizures occurred within a week of starting treatment. Conclusion: The 5-year US postmarketing safety data of dalfampridine-ER is consistent with the safety profile observed in clinical trials. Incidence of reported seizures remained stable over time. Since commercial availability in March 2010, a

  16. Efficacy of extended-release divalproex combined with "condensed" dialectical behavior therapy for individuals with borderline personality disorder.

    Science.gov (United States)

    Moen, Richelle; Freitag, Mary; Miller, Michael; Lee, Susanne; Romine, Ann; Song, Sue; Adityanjee, Adit; Schulz, S Charles

    2012-11-01

    Borderline personality disorder (BPD) is a significant psychiatric illness for which medication treatments are still being explored. The goal of this study was to assess divalproex extended release (ER) vs placebo for patients receiving dialectal behavior therapy (DBT). Patients with BPD received 4 weeks of "condensed DBT." Those with Symptom Checklist-90 (SCL-90) scores >150 after this treatment were then randomly and blindly assigned to placebo or divalproex ER for 12 weeks. Repeated measures analysis of variance utilizing last observation carried forward was used to assess the results. Seventeen participants completed the full assessment. Two patients had a significant decrease in SCL-90 in the first 4 weeks, leaving 15 patients for the medication phase of the trial. There were no significant differences between the participants assigned to divalproex ER compared with placebo. However, there was a significant improvement in both groups from baseline to endpoint (P = .001). The response of 2 of 17 participants in the first 4 weeks prior to medication may point to a practice strategy in approaching outpatients with BPD. Although the patients had a decrease in symptoms during the study, there was no advantage observed for divalproex ER and DBT over placebo and DBT.

  17. Determination of source term for Krsko NPP extended fuel cycle

    International Nuclear Information System (INIS)

    Nemec, T.; Persic, A.; Zagar, T.; Zefran, B.

    2004-01-01

    The activity and composition of the potential radioactive releases (source term) is important in the decision making about off-site emergency measures in case of a release into environment. Power uprate of Krsko NPP during modernization in 2000 as well as changing of the fuel type and the core design have influenced the source term value. In 2003 a project of 'Jozef Stefan' Institute and Slovenian nuclear safety administration determined a plantspecific source term for new conditions of fuel type and burnup for extended fuel cycle. Calculations of activity and isotopic composition of the core have been performed with ORIGEN-ARP program. Results showed that the core activity for extended 15 months fuel cycle is slightly lower than for the 12 months cycles, mainly due to larger share of fresh fuel. (author)

  18. A double-blind, placebo-controlled, multicenter study with alprazolam and extended-release alprazolam in the treatment of panic disorder.

    Science.gov (United States)

    Pecknold, J; Luthe, L; Munjack, D; Alexander, P

    1994-10-01

    This is a double-blind, placebo-controlled, flexible-dose, multicenter, 6-week study comparing regular alprazolam (compressed tablet, CT), given four times per day, and extended release alprazolam (XR), given once in the morning. The aim of the XR preparation is to offer less frequent dosing and to reduce interdose anxiety. Of the intent-to-treat group of 209 patients, 184 completed 3 weeks of medication and were evaluated according to protocol. There was a completer rate for the 6 weeks of 94% (CT), 97% (XR), and 87% (placebo). On global measures, Hamilton Rating Scale for Anxiety, phobia rating, and work disability measures, both active treatment groups were equally effective and significantly more efficacious than the placebo cell on endpoint MANOVA analysis. On analysis of the panic factor with endpoint data, both active treatment groups were equally effective throughout the 6-week trial and significantly more efficacious than the placebo group. Drowsiness occurred more frequently with CT alprazolam (86% of patients) than with the XR preparation (79%) or placebo (49%).

  19. Cost-effectiveness of extended release naltrexone to prevent relapse among criminal justice-involved individuals with a history of opioid use disorder.

    Science.gov (United States)

    Murphy, Sean M; Polsky, Daniel; Lee, Joshua D; Friedmann, Peter D; Kinlock, Timothy W; Nunes, Edward V; Bonnie, Richard J; Gordon, Michael; Chen, Donna T; Boney, Tamara Y; O'Brien, Charles P

    2017-08-01

    Criminal justice-involved individuals are highly susceptible to opioid relapse and overdose-related deaths. In a recent randomized trial, we demonstrated the effectiveness of extended-release naltrexone (XR-NTX; Vivitrol ® ) in preventing opioid relapse among criminal justice-involved US adults with a history of opioid use disorder. The cost of XR-NTX may be a significant barrier to adoption. Thus, it is important to account for improved quality of life and downstream cost-offsets. Our aims were to (1) estimate the incremental cost per quality-adjusted life-year (QALY) gained for XR-NTX versus treatment as usual (TAU) and evaluate it relative to generally accepted value thresholds; and (2) estimate the incremental cost per additional year of opioid abstinence. Economic evaluation of the aforementioned trial from the taxpayer perspective. Participants were randomized to 25 weeks of XR-NTX injections or TAU; follow-up occurred at 52 and 78 weeks. Five study sites in the US Northeast corridor. A total of 308 participants were randomized to XR-NTX (n = 153) or TAU (n = 155). Incremental costs relative to incremental economic and clinical effectiveness measures, QALYs and abstinent years, respectively. The 25-week cost per QALY and abstinent-year figures were $162 150 and $46 329, respectively. The 78-week figures were $76 400/QALY and $16 371/abstinent year. At 25 weeks, we can be 10% certain that XR-NTX is cost-effective at a value threshold of $100 000/QALY and 62% certain at $200 000/QALY. At 78 weeks, the cost-effectiveness probabilities are 59% at $100 000/QALY and 76% at $200 000/QALY. We can be 95% confident that the intervention would be considered 'good value' at $90 000/abstinent year at 25 weeks and $500/abstinent year at 78 weeks. While extended-release naltrexone appears to be effective in increasing both quality-adjusted life-years (QALYs) and abstinence, it does not appear to be cost-effective using generally accepted value

  20. Effects of extended-release niacin with laropiprant in high-risk patients

    DEFF Research Database (Denmark)

    Landray, Martin J; Haynes, Richard; Hopewell, Jemma C

    2014-01-01

    BACKGROUND: Patients with evidence of vascular disease are at increased risk for subsequent vascular events despite effective use of statins to lower the low-density lipoprotein (LDL) cholesterol level. Niacin lowers the LDL cholesterol level and raises the high-density lipoprotein (HDL) choleste......-release niacin-laropiprant to statin-based LDL cholesterol-lowering therapy did not significantly reduce the risk of major vascular events but did increase the risk of serious adverse events. (Funded by Merck and others; HPS2-THRIVE ClinicalTrials.gov number, NCT00461630.)....

  1. The cost-effectiveness of solifenacin vs fesoterodine, oxybutynin immediate-release, propiverine, tolterodine extended-release and tolterodine immediate-release in the treatment of patients with overactive bladder in the UK National Health Service.

    Science.gov (United States)

    Cardozo, Linda; Thorpe, Andrew; Warner, Juliet; Sidhu, Manpreet

    2010-08-01

    To assess the cost-effectiveness of solifenacin vs other antimuscarinic strategies commonly used in UK clinical practice, based on the results of a recent published review. Overactive bladder (OAB) syndrome is characterized by symptoms of urgency, frequency, incontinence and nocturia. Pharmacological treatment comprises oral antimuscarinic agents, which are divided into older-generation treatments, including oxybutynin, and new-generation treatments, comprising solifenacin, tolterodine, darifenacin and fesoterodine. The latter have reduced central nervous system penetration and have better selectivity for the M3 subclass of acetylcholine receptors, resulting in improved tolerability. A recent systematic review and meta-analysis of the efficacy and safety of antimuscarinics provided an opportunity for an economic evaluation of these agents using a rigorous assessment of efficacy. A cost-utility analysis was undertaken using a 1-year decision-tree model. Treatment success was defined separately for urgency, frequency and incontinence, with efficacy data taken from the recent review. Treatment persistence rates were taken from the Information Management System database. Utility values for the calculation of quality-adjusted life-years (QALYs) were taken from published sources. The analysis included costs directly associated with treatment for OAB, i.e. antimuscarinic therapy, consultations with general practitioners, and outpatient contacts. Resource use was based on expert opinion. Costs were reported at 2007/2008 prices. Extensive deterministic and probabilistic analyses were conducted to test the robustness of the base-case results. Solifenacin was associated with the highest QALY gains (per 1000 patients) for all three outcomes of interest, i.e. urgency (712.3), frequency (723.1) and incontinence (695.0). Solifenacin was dominant relative to fesoterodine, tolterodine extended-release (ER) and tolterodine immediate-release (IR), and cost-effective relative to

  2. A single 2 g oral dose of extended-release azithromycin for treatment of gonococcal urethritis.

    Science.gov (United States)

    Yasuda, Mitsuru; Ito, Shin; Kido, Akira; Hamano, Kiminari; Uchijima, Yutaka; Uwatoko, Noriyasu; Kusuyama, Hiroyuki; Watanabe, Akiko; Miyamura, Ryuzou; Miyata, Kazutoyo; Deguchi, Takashi

    2014-11-01

    We treated gonococcal urethritis in men with a single 2 g dose of azithromycin extended-release formulation (azithromycin-SR) to determine its microbiological outcomes and tolerability. We enrolled 189 Japanese men with gonococcal urethritis between April 2009 and December 2013. The patients were given a single 2 g dose of azithromycin-SR. Microbiological efficacy was evaluated by the results of the post-treatment molecular testing of Neisseria gonorrhoeae. MIC testing was performed only for pretreatment isolates of N. gonorrhoeae collected from the patients. We evaluated 130 patients for microbiological outcomes. Of these patients, 122 (93.8%) were judged to be microbiologically cured on the basis of negative test results. All isolates for which the azithromycin MICs were ≤0.25 mg/L were eradicated, whereas 5 of 12 isolates for which the MICs were 1 mg/L persisted after the treatment. Forty-six adverse events occurred in 41 patients. However, all adverse events were classified as mild. The eradication rate of N. gonorrhoeae was 93.8% in men with gonococcal urethritis treated with a single 2 g dose of azithromycin-SR. The breakpoint MIC of a 2 g dose of azithromycin-SR for gonococcal urethritis associated with clinical treatment failures appeared to be 1 mg/L. With regard to side effects of higher doses of azithromycin, the 2 g dose of azithromycin-SR appeared to improve tolerability. However, the widespread use of a high-dose regimen of azithromycin might lead to the development of further resistance to azithromycin. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Model-based computer-aided design for controlled release of pesticides

    DEFF Research Database (Denmark)

    Muro Sunè, Nuria; Gani, Rafiqul; Bell, G.

    2005-01-01

    In the field of controlled release technology for pesticides or active ingredients (AI), models that can predict its delivery during application are important for purposes of design and marketing of the pesticide product. Appropriate models for the controlled release of pesticides, if available, ...... extended models have been developed and implemented into a computer-aided system. The total model consisting of the property models embedded into the release models are then employed to study the release of different combinations of AIs and polymer-based microcapsules.......In the field of controlled release technology for pesticides or active ingredients (AI), models that can predict its delivery during application are important for purposes of design and marketing of the pesticide product. Appropriate models for the controlled release of pesticides, if available...

  4. Low-threshold extended-release naltrexone for high utilizers of public services with severe alcohol use disorder: A pilot study.

    Science.gov (United States)

    Smith-Bernardin, Shannon; Rowe, Chris; Behar, Emily; Geier, Michelle; Washington, Stuart; Santos, Glenn-Milo; Euren, Jason; Martin, Judith; Gleghorn, Alice; Coffin, Phillip O

    2018-02-01

    Extended-release naltrexone (XRNTX) is an effective treatment for alcohol use disorder (AUD). We sought to evaluate the feasibility, acceptability, and preliminary effectiveness and cost-effectiveness of XRNTX delivered as a stand-alone service to persons with severe AUD who are high utilizers of multiple urgent and emergency medical services (HUMS). Of 15 HUMS persons with severe AUD selected based on chart review, 11 agreed to participate. Participants received a mean of 4.5 injections (range 2-7). Modest benefits from XRNTX were observed in terms of patients' Urge-to-Drink Score and the costs of emergency medical services utilized. Though limited by a small sample size, costs including client utilization and study related expenses during the post-enrollment period were less than client utilization costs in the pre-enrollment period. We also observed non-significant improvements in the number of drinking days, but no change in quality of life as measured by the EQ-5D. Eighty-eight percent of participants perceived XRNTX as helping with their drinking. Findings need to be replicated in a larger study, however if replicated, the cost savings could be substantial. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. A dose-finding, placebo-controlled study on extended-release felodipine once daily in treatment of hypertension.

    Science.gov (United States)

    Cambell, L M; Ross, J R; Goves, J R; Lees, C T; McCullagh, A; Barnes, P; Timerick, S J; Richardson, P D

    1989-12-01

    Hypertensive patients received a beta-blocker plus placebo once daily for 4 weeks. If their diastolic blood pressure (DBP) was then 95-115 mm Hg, they were randomized to receive, in addition to the beta-blocker, placebo (n = 36), felodipine-extended release (ER) 10 mg (n = 36), or felodipine-ER 20 mg (n = 37) in a 4-week double-blind parallel-group trial. All medication was administered once daily and, when BP was measured 24 h after the last dose, felodipine-ER 10 mg reduced DBP by 14 +/- 9 mm Hg (mean +/- SD) from a mean of 103 mm Hg and felodipine-ER 20 mg reduced DBP by 18 +/- 9 mm Gg from 101 mm Hg. The reductions in DBP with both doses of felodipine were greater than reductions with placebo (5 +/- 8 mm Hg, from 102 mm Hg--both p less than 0.001). At the end of the study, 21% of patients receiving placebo had a DBP less than or equal to 90 mm Hg. In contrast, 69% of patients receiving felodipine-ER 10 mg and 82% receiving 20 mg attained this level. More than 90% of patients receiving 10 mg felodipine-ER once daily had a reduction in DBP greater than 5 mm Hg 24 h postdose. Felodipine-ER was well tolerated. Felodipine-ER once daily is an effective antihypertensive drug for patients who require therapy in addition to a beta-blocker; the tolerability in this study was good, and a starting dose greater than 10 mg once daily is not indicated.

  6. Cost-effectiveness of lurasidone vs quetiapine extended-release (XR) in patients with bipolar depression.

    Science.gov (United States)

    Rajagopalan, Krithika; Meyer, Kellie; O'Day, Ken; Denno, Melissa; Loebel, Antony

    2015-01-01

    Bipolar disorder imposes a high economic burden on patients and society. Lurasidone and quetiapine extended-release (XR) are atypical antipsychotic agents indicated for monotherapy treatment of bipolar depression. Lurasidone is also indicated as adjunctive therapy with lithium or valproate for depressive episodes associated with bipolar disorder. The objective of this analysis was to estimate the cost-effectiveness of lurasidone and quetiapine XR in patients with bipolar depression. A cost-effectiveness model was developed to compare lurasidone to quetiapine XR. The model was based on a US third-party payer perspective over a 3-month time horizon. The effectiveness measure in the model was the percentage of patients achieving remission (Montgomery-Åsberg Depression Rating Scale [MADRS] total score ≤12 by weeks 6-8). The comparison of remission rates was made through an adjusted indirect treatment comparison of lurasidone and quetiapine XR pivotal trials using placebo as the common comparator. Resource utilization for remission vs no remission was estimated from published expert panel data, and resource costs were obtained from a retrospective database study of bipolar I depression patients. Drug costs were estimated using the mean dose from clinical trials and wholesale acquisition costs. Over the 3-month model time period, lurasidone and quetiapine XR patients, respectively, had similar mean numbers of emergency department visits (0.48 vs 0.50), inpatient days (2.1 vs 2.2), and office visits (9.3 vs 9.6). More lurasidone than quetiapine XR patients achieved remission (52.0% vs 43.2%) with slightly higher total costs ($4982 vs $4676), resulting in an incremental cost-effectiveness ratio of $3474 per remission. The probabilistic sensitivity analysis showed lurasidone had an 86% probability of being cost-effective compared to quetiapine XR at a willingness-to-pay threshold of $10,000 per remission. Lurasidone may be a cost-effective option when compared to

  7. Levomilnacipran Extended-Release Treatment in Patients With Major Depressive Disorder: Improvements in Functional Impairment Categories

    Science.gov (United States)

    Gommoll, Carl P.; Chen, Changzheng; Greenberg, William M.; Ruth, Adam

    2015-01-01

    Objective: In this post hoc analysis, improvement in functional impairment in patients with major depressive disorder (MDD) treated with levomilnacipran extended release (ER) was evaluated by assessing shifts from more severe to less severe functional impairment categories on individual Sheehan Disability Scale (SDS) subscales. Method: SDS data were pooled from 5 phase II/III studies conducted between December 2006 and March 2012 of levomilnacipran ER versus placebo in adult patients with MDD (DSM-IV-TR criteria). Proportions of patients shifting from moderate-extreme baseline impairment (score ≥ 4) to mild-no impairment (score ≤ 3) at end of treatment were assessed for each SDS subscale. Proportions of patients shifting from marked-extreme (score ≥ 7) baseline impairment to moderate-no (score ≤ 6) or mild-no impairment (score ≤ 3) at end of treatment, and shifts in which patients worsened from moderate-no to marked-extreme impairment, were also evaluated. Results: A significantly higher proportion of patients treated with levomilnacipran ER than placebo-treated patients improved from more severe categories of functional impairment at baseline to less severe impairment categories across all SDS subscales: work/school, social life, and family life/home responsibilities (P impairment at baseline improved to mild or no impairment, compared with no more than 40% of placebo patients on any subscale. Almost half (42%–47%) of levomilnacipran ER–treated patients versus only about one-third (29%–34%) of placebo patients improved from marked-extreme to mild or no impairment across functional domains. Conclusions: These results suggest that functional improvement was observed across the SDS functional domains. To our knowledge, this is the first such categorical analysis of functional improvement, as measured by the SDS, for an antidepressant. Trial Registration: ClinicalTrials.gov identifiers: NCT00969709, NCT01377194, NCT00969150, and NCT01034462 and Eudra

  8. Are Branded and Generic Extended-Release Ropinirole Formulations Equally Efficacious? A Rater-Blinded, Switch-Over, Multicenter Study

    Directory of Open Access Journals (Sweden)

    Edit Bosnyák

    2014-01-01

    Full Text Available The aim of this study was to compare the efficacy of the branded and a generic extended-release ropinirole formulation in the treatment of advanced Parkinson’s disease (PD. Of 22 enrolled patients 21 completed the study. A rater blinded to treatment evaluated Unified Parkinson’s Disease Rating Scale, Fahn-Tolosa-Marin Tremor Rating Scale, Nonmotor Symptoms Assessment Scale, and a structured questionnaire on ropinirole side effects. Besides, the patients self-administered EQ-5D, Parkinson’s Disease Sleep Scale (PDSS-2, and Beck Depression Inventories. Branded and generic ropinirole treatment achieved similar scores on all tests measuring severity of motor symptoms (primary endpoint, UPDRS-III: 27.0 versus 28.0 points, P=0.505. Based on patient diaries, the lengths of “good time periods” were comparable (10.5 and 10.0 hours for branded and generic ropinirole, resp., P=0.670. However, generic ropinirole therapy achieved almost 3.0 hours shorter on time without dyskinesia (6.5 versus. 9.5 hours, P<0.05 and 2.5 hours longer on time with slight dyskinesia (3.5 versus. 1.0 hours, P<0.05 than the branded ropinirole did. Except for gastrointestinal problems, nonmotor symptoms were similarly controlled. Patients did not prefer either formulation. Although this study has to be interpreted with limitations, it demonstrated that both generic and branded ropinirole administration can achieve similar control on most symptoms of PD.

  9. Estimating nutrient releases from agriculture in China: An extended substance flow analysis framework and a modeling tool

    International Nuclear Information System (INIS)

    Chen, M.; Chen, J.; Sun, F.

    2010-01-01

    Agriculture related pollution has attracted the attention of policy makers as well as scientists in China as its contribution to water impairment has increased, and quantitative information at the national and regional levels is being sought to support decision making. However, traditional approaches are either time-consuming, expensive (e.g. national surveys) or oversimplified and crude (e.g. coefficient methods). Therefore, this study proposed an extended substance flow analysis (SFA) framework to estimate nutrient releases from agricultural and rural activities in China by depicting the nutrient flows in Chinese agro-ecosystems. The six-step process proposed herein includes: (a) system definition; (b) model development; (c) database development; (d) model validation; (e) results interpretation; and (f) uncertainty analysis. The developed Eubolism (Elementary Unit based nutrient Balance mOdeLIng in agro-ecoSysteM) model combined a nutrient balance module with an emission inventory module to quantify the nutrient flows in the agro-ecosystem. The model was validated and then applied to estimate the total agricultural nutrient loads, identify the contribution of different agricultural and rural activities and different land use types to the total loads, and analyze the spatial pattern of agricultural nutrient emissions in China. These results could provide an entire picture of agricultural pollution at the national level and be used to support policy making. Furthermore, uncertainties associated with the structure of the elementary units, spatial resolution, and inputs/parameters were also analyzed to evaluate the robustness of the model results.

  10. The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment

    Science.gov (United States)

    Abolfathi, Bela; Aguado, D. S.; Aguilar, Gabriela; Allende Prieto, Carlos; Almeida, Andres; Tasnim Ananna, Tonima; Anders, Friedrich; Anderson, Scott F.; Andrews, Brett H.; Anguiano, Borja; Aragón-Salamanca, Alfonso; Argudo-Fernández, Maria; Armengaud, Eric; Ata, Metin; Aubourg, Eric; Avila-Reese, Vladimir; Badenes, Carles; Bailey, Stephen; Balland, Christophe; Barger, Kathleen A.; Barrera-Ballesteros, Jorge; Bartosz, Curtis; Bastien, Fabienne; Bates, Dominic; Baumgarten, Falk; Bautista, Julian; Beaton, Rachael; Beers, Timothy C.; Belfiore, Francesco; Bender, Chad F.; Bernardi, Mariangela; Bershady, Matthew A.; Beutler, Florian; Bird, Jonathan C.; Bizyaev, Dmitry; Blanc, Guillermo A.; Blanton, Michael R.; Blomqvist, Michael; Bolton, Adam S.; Boquien, Médéric; Borissova, Jura; Bovy, Jo; Andres Bradna Diaz, Christian; Nielsen Brandt, William; Brinkmann, Jonathan; Brownstein, Joel R.; Bundy, Kevin; Burgasser, Adam J.; Burtin, Etienne; Busca, Nicolás G.; Cañas, Caleb I.; Cano-Díaz, Mariana; Cappellari, Michele; Carrera, Ricardo; Casey, Andrew R.; Cervantes Sodi, Bernardo; Chen, Yanping; Cherinka, Brian; Chiappini, Cristina; Doohyun Choi, Peter; Chojnowski, Drew; Chuang, Chia-Hsun; Chung, Haeun; Clerc, Nicolas; Cohen, Roger E.; Comerford, Julia M.; Comparat, Johan; Correa do Nascimento, Janaina; da Costa, Luiz; Cousinou, Marie-Claude; Covey, Kevin; Crane, Jeffrey D.; Cruz-Gonzalez, Irene; Cunha, Katia; da Silva Ilha, Gabriele; Damke, Guillermo J.; Darling, Jeremy; Davidson, James W., Jr.; Dawson, Kyle; de Icaza Lizaola, Miguel Angel C.; de la Macorra, Axel; de la Torre, Sylvain; De Lee, Nathan; de Sainte Agathe, Victoria; Deconto Machado, Alice; Dell’Agli, Flavia; Delubac, Timothée; Diamond-Stanic, Aleksandar M.; Donor, John; José Downes, Juan; Drory, Niv; du Mas des Bourboux, Hélion; Duckworth, Christopher J.; Dwelly, Tom; Dyer, Jamie; Ebelke, Garrett; Davis Eigenbrot, Arthur; Eisenstein, Daniel J.; Elsworth, Yvonne P.; Emsellem, Eric; Eracleous, Michael; Erfanianfar, Ghazaleh; Escoffier, Stephanie; Fan, Xiaohui; Fernández Alvar, Emma; Fernandez-Trincado, J. G.; Cirolini, Rafael Fernando; Feuillet, Diane; Finoguenov, Alexis; Fleming, Scott W.; Font-Ribera, Andreu; Freischlad, Gordon; Frinchaboy, Peter; Fu, Hai; Gómez Maqueo Chew, Yilen; Galbany, Lluís; García Pérez, Ana E.; Garcia-Dias, R.; García-Hernández, D. A.; Garma Oehmichen, Luis Alberto; Gaulme, Patrick; Gelfand, Joseph; Gil-Marín, Héctor; Gillespie, Bruce A.; Goddard, Daniel; González Hernández, Jonay I.; Gonzalez-Perez, Violeta; Grabowski, Kathleen; Green, Paul J.; Grier, Catherine J.; Gueguen, Alain; Guo, Hong; Guy, Julien; Hagen, Alex; Hall, Patrick; Harding, Paul; Hasselquist, Sten; Hawley, Suzanne; Hayes, Christian R.; Hearty, Fred; Hekker, Saskia; Hernandez, Jesus; Hernandez Toledo, Hector; Hogg, David W.; Holley-Bockelmann, Kelly; Holtzman, Jon A.; Hou, Jiamin; Hsieh, Bau-Ching; Hunt, Jason A. S.; Hutchinson, Timothy A.; Hwang, Ho Seong; Jimenez Angel, Camilo Eduardo; Johnson, Jennifer A.; Jones, Amy; Jönsson, Henrik; Jullo, Eric; Sakil Khan, Fahim; Kinemuchi, Karen; Kirkby, David; Kirkpatrick, Charles C., IV; Kitaura, Francisco-Shu; Knapp, Gillian R.; Kneib, Jean-Paul; Kollmeier, Juna A.; Lacerna, Ivan; Lane, Richard R.; Lang, Dustin; Law, David R.; Le Goff, Jean-Marc; Lee, Young-Bae; Li, Hongyu; Li, Cheng; Lian, Jianhui; Liang, Yu; Lima, Marcos; Lin, Lihwai; Long, Dan; Lucatello, Sara; Lundgren, Britt; Mackereth, J. Ted; MacLeod, Chelsea L.; Mahadevan, Suvrath; Geimba Maia, Marcio Antonio; Majewski, Steven; Manchado, Arturo; Maraston, Claudia; Mariappan, Vivek; Marques-Chaves, Rui; Masseron, Thomas; Masters, Karen L.; McDermid, Richard M.; McGreer, Ian D.; Melendez, Matthew; Meneses-Goytia, Sofia; Merloni, Andrea; Merrifield, Michael R.; Meszaros, Szabolcs; Meza, Andres; Minchev, Ivan; Minniti, Dante; Mueller, Eva-Maria; Muller-Sanchez, Francisco; Muna, Demitri; Muñoz, Ricardo R.; Myers, Adam D.; Nair, Preethi; Nandra, Kirpal; Ness, Melissa; Newman, Jeffrey A.; Nichol, Robert C.; Nidever, David L.; Nitschelm, Christian; Noterdaeme, Pasquier; O’Connell, Julia; Oelkers, Ryan James; Oravetz, Audrey; Oravetz, Daniel; Aquino Ortíz, Erik; Osorio, Yeisson; Pace, Zach; Padilla, Nelson; Palanque-Delabrouille, Nathalie; Alonso Palicio, Pedro; Pan, Hsi-An; Pan, Kaike; Parikh, Taniya; Pâris, Isabelle; Park, Changbom; Peirani, Sebastien; Pellejero-Ibanez, Marcos; Penny, Samantha; Percival, Will J.; Perez-Fournon, Ismael; Petitjean, Patrick; Pieri, Matthew M.; Pinsonneault, Marc; Pisani, Alice; Prada, Francisco; Prakash, Abhishek; Queiroz, Anna Bárbara de Andrade; Raddick, M. Jordan; Raichoor, Anand; Barboza Rembold, Sandro; Richstein, Hannah; Riffel, Rogemar A.; Riffel, Rogério; Rix, Hans-Walter; Robin, Annie C.; Rodríguez Torres, Sergio; Román-Zúñiga, Carlos; Ross, Ashley J.; Rossi, Graziano; Ruan, John; Ruggeri, Rossana; Ruiz, Jose; Salvato, Mara; Sánchez, Ariel G.; Sánchez, Sebastián F.; Sanchez Almeida, Jorge; Sánchez-Gallego, José R.; Santana Rojas, Felipe Antonio; Santiago, Basílio Xavier; Schiavon, Ricardo P.; Schimoia, Jaderson S.; Schlafly, Edward; Schlegel, David; Schneider, Donald P.; Schuster, William J.; Schwope, Axel; Seo, Hee-Jong; Serenelli, Aldo; Shen, Shiyin; Shen, Yue; Shetrone, Matthew; Shull, Michael; Silva Aguirre, Víctor; Simon, Joshua D.; Skrutskie, Mike; Slosar, Anže; Smethurst, Rebecca; Smith, Verne; Sobeck, Jennifer; Somers, Garrett; Souter, Barbara J.; Souto, Diogo; Spindler, Ashley; Stark, David V.; Stassun, Keivan; Steinmetz, Matthias; Stello, Dennis; Storchi-Bergmann, Thaisa; Streblyanska, Alina; Stringfellow, Guy S.; Suárez, Genaro; Sun, Jing; Szigeti, Laszlo; Taghizadeh-Popp, Manuchehr; Talbot, Michael S.; Tang, Baitian; Tao, Charling; Tayar, Jamie; Tembe, Mita; Teske, Johanna; Thakar, Aniruddha R.; Thomas, Daniel; Tissera, Patricia; Tojeiro, Rita; Tremonti, Christy; Troup, Nicholas W.; Urry, Meg; Valenzuela, O.; van den Bosch, Remco; Vargas-González, Jaime; Vargas-Magaña, Mariana; Vazquez, Jose Alberto; Villanova, Sandro; Vogt, Nicole; Wake, David; Wang, Yuting; Weaver, Benjamin Alan; Weijmans, Anne-Marie; Weinberg, David H.; Westfall, Kyle B.; Whelan, David G.; Wilcots, Eric; Wild, Vivienne; Williams, Rob A.; Wilson, John; Wood-Vasey, W. M.; Wylezalek, Dominika; Xiao, Ting; Yan, Renbin; Yang, Meng; Ybarra, Jason E.; Yèche, Christophe; Zakamska, Nadia; Zamora, Olga; Zarrouk, Pauline; Zasowski, Gail; Zhang, Kai; Zhao, Cheng; Zhao, Gong-Bo; Zheng, Zheng; Zheng, Zheng; Zhou, Zhi-Min; Zhu, Guangtun; Zinn, Joel C.; Zou, Hu

    2018-04-01

    The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014–2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as “The Cannon” and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.

  11. Efficacy of Tramadol Extended-Release for Opioid Withdrawal: A Randomized Clinical Trial.

    Science.gov (United States)

    Dunn, Kelly E; Tompkins, D Andrew; Bigelow, George E; Strain, Eric C

    2017-09-01

    Opioid use disorder (OUD) is a significant public health problem. Supervised withdrawal (ie, detoxification) from opioids using clonidine or buprenorphine hydrochloride is a widely used treatment. To evaluate whether tramadol hydrochloride extended-release (ER), an approved analgesic with opioid and nonopioid mechanisms of action and low abuse potential, is effective for use in supervised withdrawal settings. A randomized clinical trial was conducted in a residential research setting with 103 participants with OUD. Participants' treatment was stabilized with morphine, 30 mg, administered subcutaneously 4 times daily. A 7-day taper using clonidine (n = 36), tramadol ER (n = 36), or buprenorphine (n = 31) was then instituted, and patients were crossed-over to double-blind placebo during a post-taper period. The study was conducted from October 25, 2010, to June 23, 2015. Retention, withdrawal symptom management, concomitant medication utilization, and naltrexone induction. Results were analyzed over time and using area under the curve for the intention-to-treat and completer groups. Of the 103 participants, 88 (85.4%) were men and 43 (41.7%) were white; mean (SD) age was 28.9 (10.4) years. Buprenorphine participants (28 [90.3%]) were significantly more likely to be retained at the end of the taper compared with clonidine participants (22 [61.1%]); tramadol ER retention was intermediate and did not differ significantly from that of the other groups (26 [72.2%]; χ2 = 8.5, P = .01). Time-course analyses of withdrawal revealed significant effects of phase (taper, post taper) for the Clinical Opiate Withdrawal Scale (COWS) score (taper mean, 5.19 [SE, .26]; post-taper mean, 3.97 [SE, .23]; F2,170 = 3.6, P = .03) and Subjective Opiate Withdrawal Scale (SOWS) score (taper mean,8.81 [SE, .40]; post-taper mean, 4.14 [SE, .30]; F2,170 = 15.7, P withdrawal severity between the taper and post-taper periods for clonidine (taper mean, 13.1; post

  12. Long-term tolerability of tolterodine extended release in children 5-11 years of age: results from a 12-month, open-label study

    DEFF Research Database (Denmark)

    Nijman, Rien J M; Borgstein, Niels G; Ellsworth, Pamela

    2007-01-01

    OBJECTIVE: To evaluate the long-term tolerability of tolterodine extended release (ER) in children (aged 5-11 yr) with urgency urinary incontinence (UUI). METHODS: This was a multicenter, open-label extension of a 12-wk, double-blind, placebo-controlled study of tolterodine ER. Patients had UUI...... suggestive of detrusor overactivity (>/=1 diurnal incontinence episode per 24h for >/=5 of 7 d) and >/=6 voids per 24h at baseline and had completed the 12-wk double-blind study. Patients received tolterodine ER (2mg once daily) for 12 mo. The primary end points were the incidence and severity of adverse......-blind tolterodine ER, n=221; placebo, n=97). The majority of patients were white (90%), mean+/-SD age was 7.6+/-1.5 yr, and 54% were boys. Forty-nine percent of patients reported >/=1 AE during the study, similar to that observed in the preceding 12-wk study (42%). The most frequent AEs were urinary tract infection...

  13. Slide release mechanism. [for space shuttle orbiter/external tank connection device

    Science.gov (United States)

    Bunker, J. W.; Ritchie, R. S. (Inventor)

    1985-01-01

    A releasable support device is described which is comprised of a hollow body with a sleeve extending transversely there-through for receiving the end of a support shank. A slider-latch, optionally lubricated, extends through side recesses in the sleeve to straddle the shank, respectively, in latched and released positions. The slider-latch is slid from its latched to its unlatched position by a pressure squib whereupon a spring or other pressure means pushes the shank out of the sleeve. At the same time, a follower element is lodged in and closed the hole in the body wall from which the shank was discharged. The mechanism was designed for the shuttle orbiter/external tank connection device.

  14. A Comparative Risk Assessment of Extended Integrated Leak Rate Testing Intervals

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Ji Yong; Hwang, Seok Won; Lee, Byung Sik [Korea Hydro and Nuclear Power Co., Daejeon (Korea, Republic of)

    2009-10-15

    This paper presents the risk impacts of extending the Integrated Leak Rate Testing (ILRT) intervals (from five years to ten years) of Yonggwang (YGN) Unit 1 and 2. These risk impacts depended on the annual variances of meteorological data and resident population. Main comparisons were performed between the initial risk assessment (2005) for the purpose of extending ILRT interval and risk reassessment (2009) where the changed plant internal configurations (core inventory and radioisotope release fraction) and plant external alterations (wind directions, rainfall and population distributions) were monitored. The reassessment showed that there was imperceptible risk increase when the ILRT interval was extended compared to the initial risk assessment. In addition, the increased value of the Large Early Release Frequency (LERF) also satisfied the acceptance guideline proposed on Reg. Guide 1.174. The MACCS II code was used for evaluating the offsite consequence analysis. The primary risk index were used as the Probabilistic Population Dose (PPD) by considering the early effects within 80 km. The Probabilistic Safety Assessment (PSA) of YGN 1 and 2 was applied to evaluate the accident frequency of each source term category and the used PSA scope was limited to internal event.

  15. COMPARATIVE EFFICАCY AND TOLERABILITY OF MONOTHERAPY WITH DEPAKINE CHRONOSPHERE, DRUGS OF CARBAMAZEPINE GROUP WITH EXTENDED RELEASE AND OXCARBAZEPINE IN SYMPTOMATIC AND CRYPTOGENIC FOCAL EPILEPSY (SVT. LUKA’S INSTITUTE OF CHILD NEUROLOGY AND EPILEPSY

    Directory of Open Access Journals (Sweden)

    K. Yu. Mukhin

    2015-01-01

    Full Text Available Research on comparative efficаcy and tolerability of monotherapy with Depakine chronosphere, drugs of Carbamazepine group with extended release and oxcarbazepine in symptomatic and cryptogenic focal epilepsy has been conducted at Svt. Luka’s Institute of Child Neurology and Epilepsy (ICNE (Moscow. This retrospective study covers a random sample of patients treated in ICNE in the period from December 1, 2013 to September 1, 2014.  The study included 131 patients aged 1 to 18 years with symptomatic and cryptogenic focal epilepsy receiving treatment with one of the study drugs in monotherapy: group 1 – monotherapy with Depakine chronosphere (n = 56; group 2 – monotherapy with drugs of carbamazepine group with extended release (n = 55; group 3 – monotherapy with oxcarbazepine (trileptal (n = 20. The obtained results allow us to conclude that the effectiveness of Depakin chronosphere, carbamazepine with extended release and oxcarbazepine in monotherapy of symptomatic and cryptogenic focal epilepsy was comparable (statistically significant differences in efficacy were not found. However, carbamazepine was awarded the highest frequency of seizures aggravation. Drugs showed approximately same tolerability (statistically significant differences in tolerability were not found. However, withdrawal of the drug due to side effects was the rarest in Depakine (3.5 %, and withdrawal due to intolerance was higher in carbamazepine and oxcarbazepine (5 and 10 % respectively. Depakinum and oxcarbazepine had the best results in the blocking of pathological activity on the electroencephalogram, whereas carbamazepine was clearly inferior to them. In this regard, complete clinical-electroencephalographic remission (lasting 12 months or more was achieved under treatment of Depakine chromosphere in 21.5 % of cases, oxcarbazepi on therapy for 12 months was similar in all study drugs. Considering that the objective of epilepsy treatment is to achieve complete

  16. History of the CERN Web Software Public Releases

    CERN Document Server

    Fluckiger, Francois; CERN. Geneva. IT Department

    2016-01-01

    This note is an extended version of the article “Licencing the Web” (http://home.web.cern.ch/topics/birthweb/licensing-web) published by CERN, Nov 2013, in the “Birth of the Web” series of articles (http://home.cern/topics/birth-web). It describes the successive steps of the public release of the CERN Web software, from public domain to open source, and explains their rationale. It provides in annexes historical documents including release announcement and texts of the licences used by CERN and MIT in public software distributions.

  17. Ramizol® encapsulation into extended release PLGA micro- and nanoparticle systems for subcutaneous and intramuscular administration: in vitro and in vivo evaluation.

    Science.gov (United States)

    Wright, Leah; Rao, Shasha; Thomas, Nicky; Boulos, Ramiz A; Prestidge, Clive A

    2018-04-11

    Novel antibiotic Ramizol ® is advancing to clinical trials for the treatment of gastrointestinal Clostridium difficile associated disease. Despite this, previous studies have shown a rapid plasma clearance upon intravenous administration and low oral bioavailability indicating pure drug is unsuitable for systemic infection treatment following oral dosing. The current study aims to investigate the development of poly-lactic-(co-glycolic) acid (PLGA) particles to overcome this limitation and increase the systemic half-life following subcutaneous and intramuscular dosing. The development of new antibiotic treatments will help in combatting the rising incidence of antimicrobial resistance. Ramizol ® was encapsulated into PLGA nano and microparticles using nanoprecipitation and emulsification solvent evaporation techniques. Formulations were analyzed for particle size, loading level and encapsulation efficiency as well as in vitro drug release profiles. Final formulation was advanced to in vivo pharmacokinetic studies in Sprague-Dawley rats. Formulation technique showed major influence on particle size and loading levels with optimal loading of 9.4% and encapsulation efficiency of 92.06%, observed using emulsification solvent evaporation. Differences in formulation technique were also linked with subsequent differences in release profiles. Pharmacokinetic studies in Sprague-Dawley rats confirmed extended absorption and enhanced bioavailability following subcutaneous and intramuscular dosing with up to an 8-fold increase in T max and T 1/2 when compared to the oral and IV routes. Subcutaneous and intramuscular dosing of PLGA particles successfully increased systemic half-life and bioavailability of Ramizol ® . This formulation will allow further development of Ramizol ® for systemic infection eradication.

  18. The Second Data Release of the Sloan Digital Sky Survey

    CERN Document Server

    Abazajian, Kevork; ̈ueros, Marcel A. Ag; Allam, Sahar S.; Anderson, KurtS. J.; Anderson, Scott F.; Annis, James; Bahcall, Neta A.; Baldry, Ivan K.; StevenBastian; Berlind, Andreas; Bernardi, Mariangela; Blanton, Michael R.; BochanskiJr., John J.; Boroski, William N.; Briggs, John W.; Brinkmann, J.; Brunner, Robert J.; ́ari, Tam ́asBudav; Carey, Larry N.; Carliles, Samuel; Castander, Francisco J.; Connolly, A. J.; Csabai, Istvan; Doi, Mamoru; Dong, Feng; Eisenstein, Daniel J.; Evans, Michael L.; Fan, Xiaohui; Finkbeiner, Douglas P.; Friedman, Scott D.; Frieman, Joshua A.; Fukugita, Masataka; Gal, RoyR.; Gillespie, Bruce; Glazebrook, Karl; Gray, Jim; Grebel, Eva K.; Gunn, James E.; Gurbani, Vijay K.; Hall, Patrick B.; Hamabe, Masaru; Harris, Frederick H.; C.Harris, Hugh; Harvanek, Michael; Heckman, Timothy M.; Hendry, John S.; Hennessy, Gregory S.; Hindsley, Robert B.; Hogan, Craig J.; Hogg, David W.; Holmgren, Donald J.; Ichikawa, Shin-ichi; Ichikawa, Takashi; Ivezic, Zeljko; Jester, Sebastian; Johnston, David E.; Jorgensen, AndersM.; Kent, Stephen M.; Kleinman, S. J.; Knapp, G. R.; Kniazev, Alexei Yu.; Kron, Richard G.; Krzesinski, Jurek; Kunszt, Peter Z.; Kuropatkin, Nickolai; Q.Lamb, Donald; Lampeitl, Hubert; Lee, Brian C.; Leger, R. French; Li, Nolan; Lin, Huan; Loh, Yeong-Shang; Long, Daniel C.; Loveday, Jon; Lupton, Robert H.; Malik, Tanu; BruceMargon; Matsubara, Takahiko; McGehee, Peregrine M.; McKay, Timothy A.; AveryMeiksin; Munn, Jeffrey A.; Nakajima, Reiko; Nash, Thomas; Neilsen, Eric H. Jr.; JoNewberg, Heidi; Newman, Peter R.; Nichol, Robert C.; Nicinski, Tom; Nieto-Santisteban, Maria; Nitta, Atsuko; Okamura, Sadanori; O'Mullane, William; Ostriker, Jeremiah P.; Owen, Russell; Padmanabhan, Nikhil; Peoples, John; Pier, Jeffrey R.; Pope, Adrian C.; Quinn, Thomas R.; Richards, Gordon T.; Richmond, Michael W.; Rix, Hans-Walter; Rockosi, Constance M.; Schlegel, David J.; Schneider, Donald P.; Scranton, Ryan; Sekiguchi, Maki; Seljak, Uros; Sergey, Gary; Sesar, Branimir; Sheldon, Erin; Shimasaku, Kazu; Siegmund, Walter A.; Silvestri, Nicole M.; Smith, J. Allyn; ́c, Vernesa Smolči; Snedden, Stephanie A.; AlbertStebbins; Stoughton, Chris; Strauss, Michael A.; SubbaRao, Mark; Szalay, Alexander S.; Szapudi, Istv ́an; Szkody, Paula; Szokoly, Gyula P.; Tegmark, Max; Teodoro, Luis; Thakar, AniruddhaR.; Tremonti, Christy; Tucker, Douglas L.; Uomoto, Alan; Vanden Berk, Daniel E.; Vandenberg, Jan; Vogeley, Michael S.; Voges, Wolfgang; Vogt, Nicole P.; M.Walkowicz, Lucianne; Wang, Shu-i; Weinberg, David H.; West, Andrew A.; White, Simon D.M.; Wilhite, BrianC.; Xu, Yongzhong; Yanny, Brian; Yasuda, Naoki; Yip, Ching-Wa; Yocum, D. R.; York, Donald G.; Zehavi, Idit; Zibetti, Stefano; Zucker, Daniel B.

    2004-01-01

    The Sloan Digital Sky Survey has validated and made publicly available its Second Data Release. This data release consists of 3324 square degrees of five-band (u g r i z) imaging data with photometry for over 88 million unique objects, 367,360 spectra of galaxies, quasars, stars and calibrating blank sky patches selected over 2627 degrees of this area, and tables of measured parameters from these data. The imaging data reach a depth of r ~ 22.2 (95% completeness limit for point sources) and are photometrically and astrometrically calibrated to 2% rms and 100 milli-arcsec rms per coordinate, respectively. The imaging data have all been processed through a new version of the SDSS imaging pipeline, in which the most important improvement since the last data release is fixing an error in the model fits to each object. The result is that model magnitudes are now a good proxy for point spread function (PSF) magnitudes for point sources, and Petrosian magnitudes for extended sources. The spectroscopy extends from 38...

  19. Changes in misuse and abuse of prescription opioids following implementation of Extended-Release and Long-Acting Opioid Analgesic Risk Evaluation and Mitigation Strategy.

    Science.gov (United States)

    Bucher Bartelson, Becki; Le Lait, M Claire; Green, Jody L; Cepeda, M Soledad; Coplan, Paul M; Maziere, Jean-Yves; Wedin, Gregory P; Dart, Richard C

    2017-09-01

    An unintended consequence of extended-release (ER) and long-acting (LA) prescription opioids is that these formulations can be more attractive to abusers than immediate-release (IR) formulations. The US Food and Drug Administration recognized these risks and approved the ER/LA Opioid Analgesic Risk Evaluation and Mitigation Strategy (ER/LA REMS), which has a goal of reducing opioid misuse and abuse and their associated consequences. The primary objective of this analysis is to determine whether ER/LA REMS implementation was associated with decreased reports of misuse and abuse. Data from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS(R)) System Poison Center Program were utilized. Poison center cases are assigned a reason for exposure, a medical outcome, and a level of health care received. Rates adjusted for population and drug utilization were analyzed over time. RADARS System Poison Center Program data indicate a notable decrease in ER/LA opioid rates of intentional abuse and misuse as well as major medical outcomes or hospitalizations following implementation of the ER/LA REMS. While similar decreases were observed for the IR prescription opioid group, the decreasing rate for the ER/LA opioids exceeded the decreasing rates for the IR prescription opioids and was distinctly different than that for the prescription stimulants, indicating that the ER/LA REMS program may have had an additional effect on decreases in opioid abuse and intentional misuse beyond secular trends. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Evaluation of extended-life pheromone formulations used with and without dichlorvos for boll weevil (Coleoptera: Curculionidae) trapping.

    Science.gov (United States)

    Armstrong, J Scott; Greenberg, Shoil M

    2008-04-01

    Boll weevil traps baited with a ComboLure (25 of mg grandlure + 30 mg of eugenol + 90 of mg dichlorvos [DDVP]), an extended-release lure (25 mg of grandlure + 30 mg of eugenol + 60 of mg DDVP kill-strip), and extended-release lure with no DDVP were evaluated for boll weevil, Anthonomus grandis grandis Boheman (Coleoptera: Curculionidae), captures in South Texas cotton, Gossypium hirsutum L., fields during February-March 2005 and March-April 2006. The traps were serviced once a week for five consecutive weeks by using the same methodology as active boll weevil eradication programs. Mean captured boll weevils from extended-release lures with no DDVP were significantly higher in five of 10 trapping weeks compared with captures of the ComboLure and extended lure. Weekly mortality of boll weevils captured was similar for the ComboLure (72.6 +/- 4.7%) and extended lure + DDVP (73.5 +/- 4.0%), and both were significantly higher than the extended lure (32.8 +/- 5.0%) with no DDVP. The presence or absence of DDVP did not significantly affect the sex ratio of field-captured boll weevils. We found no functional reasoning for using DDVP in large scale trapping of boll weevils regardless of the formulation or presentation in the trap. We conducted two additional trapping evaluations after the 2005 and 2006 studies, but the numbers of boll weevils captured were too low for statistical comparisons, indicating that boll weevil eradication is reducing populations in the Rio Grande Valley of Texas.

  1. Atmospheric Release Advisory Capability

    International Nuclear Information System (INIS)

    Dickerson, M.H.; Gudiksen, P.H.; Sullivan, T.J.

    1983-02-01

    The Atmospheric Release Advisory Capability (ARAC) project is a Department of Energy (DOE) sponsored real-time emergency response service available for use by both federal and state agencies in case of a potential or actual atmospheric release of nuclear material. The project, initiated in 1972, is currently evolving from the research and development phase to full operation. Plans are underway to expand the existing capability to continuous operation by 1984 and to establish a National ARAC Center (NARAC) by 1988. This report describes the ARAC system, its utilization during the past two years, and plans for its expansion during the next five to six years. An integral part of this expansion is due to a very important and crucial effort sponsored by the Defense Nuclear Agency to extend the ARAC service to approximately 45 Department of Defense (DOD) sites throughout the continental US over the next three years

  2. 77 FR 4227 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor Analog...

    Science.gov (United States)

    2012-01-27

    ... Factor Analog-Diphtheria Toxoid Conjugate AGENCY: Food and Drug Administration, HHS. ACTION: Final rule... extends the slaughter interval for intact male swine injected with gonadotropin releasing factor analog...-322 for IMPROVEST (gonadotropin releasing factor analog-diphtheria toxoid conjugate) Sterile Solution...

  3. The 'sniffer-patch' technique for detection of neurotransmitter release.

    Science.gov (United States)

    Allen, T G

    1997-05-01

    A wide variety of techniques have been employed for the detection and measurement of neurotransmitter release from biological preparations. Whilst many of these methods offer impressive levels of sensitivity, few are able to combine sensitivity with the necessary temporal and spatial resolution required to study quantal release from single cells. One detection method that is seeing a revival of interest and has the potential to fill this niche is the so-called 'sniffer-patch' technique. In this article, specific examples of the practical aspects of using this technique are discussed along with the procedures involved in calibrating these biosensors to extend their applications to provide quantitative, in addition to simple qualitative, measurements of quantal transmitter release.

  4. Cost-Effectiveness of Extended-Release Methylphenidate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder Sub-Optimally Treated with Immediate Release Methylphenidate

    NARCIS (Netherlands)

    van der Schans, Jurjen; Kotsopoulos, Niko; Hoekstra, Pieter J.; Hak, Eelko; Postma, Maarten J.

    2015-01-01

    BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common psychiatric disorder in children and adolescents. Immediate-release methylphenidate (IR-MPH) is the medical treatment of first choice. The necessity to use several IR-MPH tablets per day and associated potential social stigma at

  5. Post-marketing experience with nevirapine extended release (XR) tablets: effectiveness and tolerability in a population-based cohort in British Columbia, Canada.

    Science.gov (United States)

    Lepik, Katherine J; Yip, Benita; McGovern, Rachel A; Ding, Erin; Nohpal, Adriana; Watson, Birgit E; Toy, Junine; Akagi, Linda; Harrigan, P Richard; Moore, David M; Hogg, Robert S; Montaner, Julio S G; Barrios, Rolando

    2015-01-01

    Nevirapine 400 mg extended release tablets (nevirapine-XR) are a once-daily alternative to nevirapine 200 mg immediate release tablets (nevirapine-IR). Study objectives were to describe the effectiveness and tolerability of nevirapine-XR in clinical practice and, for patients who switched from once daily 2×200 mg nevirapine-IR to nevirapine-XR, compare virological suppression and plasma nevirapine concentrations during each treatment period. HIV-1-infected adults entered the study cohort if they initiated nevirapine-XR in British Columbia (BC) Canada between 1 April 2012 and 30 September 2012 and were followed until 30 September 2013. Demographic and clinical variables were abstracted from the BC Centre for Excellence in HIV/AIDS databases. Patients who switched from once daily nevirapine-IR to nevirapine-XR were monitored for 6 months pre- and post-switch with comparison of virological suppression (McNeamer's test) and median random plasma nevirapine concentrations (Wilcoxon-Mann-Whitney test) in each period. The 536 nevirapine-XR-treated patients were 96% male, median (IQR) age 49.9 (44.0-56.9) years. Median follow-up was 15.6 (14.7-16.5) months, with 474/536 (88%) maintaining virological suppression. Emergent drug resistance developed in 5/536 (1%), adverse drug reactions in 17/536 (3%) and, although 31/536 (6%) reported 'whole' tablets in their stools, this was not associated with adverse outcomes. Among the 305 patients who switched from nevirapine-IR to nevirapine-XR, median (IQR) random plasma nevirapine concentration was higher during nevirapine-IR 5,000 (3,690-6,090) ng/ml than nevirapine-XR 3,930 (3,050-5,150) ng/ml (Pmarketing study affirms the effectiveness and tolerability of nevirapine-XR as an alternative to nevirapine-IR in adults.

  6. Patient preferences and extended-release naltrexone: A new opportunity to treat opioid use disorders in Ukraine.

    Science.gov (United States)

    Marcus, Ruthanne; Makarenko, Iuliia; Mazhnaya, Alyona; Zelenev, Alexei; Polonsky, Maxim; Madden, Lynn; Filippovych, Sergii; Dvoriak, Sergii; Springer, Sandra A; Altice, Frederick L

    2017-10-01

    Scaling up HIV prevention for people who inject drugs (PWID) using opioid agonist therapies (OAT) in Ukraine has been restricted by individual and structural factors. Extended-release naltrexone (XR-NTX), however, provides new opportunities for treating opioid use disorders (OUDs) in this region, where both HIV incidence and mortality continue to increase. Survey results from 1613 randomly selected PWID from 5 regions in Ukraine who were currently, previously or never on OAT were analyzed for their preference of pharmacological therapies for treating OUDs. For those preferring XR-NTX, independent correlates of their willingness to initiate XR-NTX were examined. Among the 1613 PWID, 449 (27.8%) were interested in initiating XR-NTX. Independent correlates associated with interest in XR-NTX included: being from Mykolaiv (AOR=3.7, 95% CI=2.3-6.1) or Dnipro (AOR=1.8, 95% CI=1.1-2.9); never having been on OAT (AOR=3.4, 95% CI=2.1-5.4); shorter-term injectors (AOR=0.9, 95% CI 0.9-0.98); and inversely for both positive (AOR=0.8, CI=0.8-0.9), and negative attitudes toward OAT (AOR=1.3, CI=1.2-1.4), respectively. In the context of Eastern Europe and Central Asia where HIV is concentrated in PWID and where HIV prevention with OAT is under-scaled, new options for treating OUDs are urgently needed. here suggest that XR-NTX could become an option for addiction treatment and HIV prevention especially for PWID who have shorter duration of injection and who harbor negative attitudes to OAT. Decision aids that inform patient preferences with accurate information about the various treatment options are likely to guide patients toward better, patient-centered treatments and improve treatment entry and retention. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. How controlled release technology can aid gene delivery.

    Science.gov (United States)

    Jo, Jun-Ichiro; Tabata, Yasuhiko

    2015-01-01

    Many types of gene delivery systems have been developed to enhance the level of gene expression. Controlled release technology is a feasible gene delivery system which enables genes to extend the expression duration by maintaining and releasing them at the injection site in a controlled manner. This technology can reduce the adverse effects by the bolus dose administration and avoid the repeated administration. Biodegradable biomaterials are useful as materials for the controlled release-based gene delivery technology and various biodegradable biomaterials have been developed. Controlled release-based gene delivery plays a critical role in a conventional gene therapy and genetic engineering. In the gene therapy, the therapeutic gene is released from biodegradable biomaterial matrices around the tissue to be treated. On the other hand, the intracellular controlled release of gene from the sub-micro-sized matrices is required for genetic engineering. Genetic engineering is feasible for cell transplantation as well as research of stem cells biology and medicine. DNA hydrogel containing a sequence of therapeutic gene and the exosome including the individual specific nucleic acids may become candidates for controlled release carriers. Technologies to deliver genes to cell aggregates will play an important role in the promotion of regenerative research and therapy.

  8. The effect of extended release tolterodine used for overactive bladder treatment on female sexual function

    Directory of Open Access Journals (Sweden)

    Athanasios Zachariou

    Full Text Available ABSTRACT Introduction Overactive bladder (OAB is a common condition, especially in middle aged women, requiring long term therapy with anticholinergics to maintain symptoms relief. The aim of the study was to determine the effect of tolterodine extended release (ER used for OAB treatment on the sexual function of women. Materials and Methods Between August 2010 and August 2014, 220 women with confirmed OAB, attended Urogynecology Outpatient Clinic and were prospectively enrolled in this study. 158 women were evaluated, with a comprehensive history, physical examination, urodynamic studies and Female Sexual Function Index (FSFI questionnaire. 73 patients of group A (control group received no treatment and 85 patients of group B received an anticholinergic regimen – tolterodine ER 4mg once daily. Data were evaluated again in accordance with FSFI after three months, using SPSS software. Results A statistically significant increase was noted in group B in domains of desire (pre-treatment 2.5±0.2 to 4.5±0.2 post-treatment, arousal (3.1±0.2 to 3.1±0.2 respectively, lubrication (3.4±0.3 to 4.3±0.3 respectively, orgasm (3.5±0.3 to 4.5±0.3 respectively, satisfaction (2.6±0.2 to 4.2±0.3 respectively and pain (2.4±0.2 to 4.6±0.4 respectively after three months treatment with tolterodine ER. In group A there were no statistically significant changes in pre and post treatment values (p>0.05. Total FSFI score for group B was significantly higher after tolterodine treatment (26.5±1.5 compared to pre-treatment values (17.4±1.4, p0,05 respectively. Conclusions This preliminary study demonstrates that treatment of OAB with tolterodine ER was found to have positive effect on sexual function of patients with OAB.

  9. Pharmacokinetics of nalbuphine hydrochloride extended release tablets in hemodialysis patients with exploratory effect on pruritus.

    Science.gov (United States)

    Hawi, Amale; Alcorn, Harry; Berg, Jolene; Hines, Carey; Hait, Howard; Sciascia, Thomas

    2015-04-08

    Uremic pruritus is a common and deleterious condition among hemodialysis (HD) patients. Central gating of μ/κ opiate circuitry plays an important role in mediating and countering pruritogenic sensation. The objective of this study was to assess the safety and pharmacokinetics (PK) of the mixed μ-antagonist/κ-agonist nalbuphine, administered orally as nalbuphine HCl extended release (ER) tablets in HD patients, and explore its effect on pruritus. In this open-label multiple escalating dose study, 15 HD patients with pruritus and 9 matched healthy subjects were enrolled. Nalbuphine HCl ER dose was escalated from 30 mg QD to 240 mg BID over 15 days. A full PK profile was obtained under dialysis and non-dialysis conditions as a function of dose. Clearance during dialysis was determined by sampling dialysate and arterial/venous blood during dialysis. Pruritus severity was assessed twice daily using a Visual Analog Scale (VAS). Safety monitoring included extensive monitoring of EKG, blood pressure, and pulse oximetry. In HD patients, nalbuphine concentration peaked within 4-9 hours and attained steady state within 2-3 days, with no significant accumulation. Mean half-life was 14.2 hours, mean Cmax and AUCtau ranged between 13 and 83 ng/mL and 118 and 761 ng∙h/mL, respectively, with exposure increasing in a nearly dose-proportional fashion. Exposure in HD patients was about 2-fold higher than in healthy subjects. There was no meaningful difference between exposure on dialysis and non-dialysis days with 1% or less of the dose removed by dialysis. Nalbuphine suppressed itch in a dose-dependent manner, reducing mean VAS score from 4.0 to 1.2 at 180 mg and 0.4 at 240 mg. Nalbuphine HCl ER tablets can be safely administered to HD patients without dose adjustment up to 240 mg BID and may hold promise in treating uremic pruritus.

  10. The role of hyaluronan as a drug carrier to enhance the bioavailability of extended release ophthalmic formulations. Hyaluronan-timolol ionic complexes as a model case.

    Science.gov (United States)

    Battistini, F D; Tártara, L I; Boiero, C; Guzmán, M L; Luciani-Giaccobbe, L C; Palma, S D; Allemandi, D A; Manzo, R H; Olivera, M E

    2017-07-15

    The aim of this work was to obtain information concerning the properties of ophthalmic formulations based on hyaluronic-drug ionic complexes, to identify the factors that determine the onset, intensity and duration of the pharmacotherapeutic effect. Dispersions of a complex of 0.5% w/v of sodium hyaluronate (HyNa) loaded with 0.5% w/v of timolol maleate (TM) were obtained and presented a counterionic condensation higher than 75%. For comparison a similar complex obtained with hyaluronic acid (HyH) was also prepared. Although the viscosity of HyNa-TM was significantly higher than that of HyH-TM, in vitro release of TM from both complexes showed a similar extended drug release profile (20-31% over 5h) controlled by diffusion and ionic exchange. Ocular pharmacokinetic study performed in normotensive rabbits showed that HyNa-TM complex exhibited attractive bioavailability properties in the aqueous humor (AUC and Cmax significantly higher and later Tmax) compared to commercial TM eye-drops. Moreover, a more prolonged period of lowered intra-ocular pressure (10h) and a more intense hypotensive activity was observed after instillation of a drop of HyNa-TM as compared to the eye-drops. Such behavior was related to the longer pre-corneal residence times (400%) observed with HyNa-TM complex. No significant changes in rabbit transcorneal permeation were detected upon complexation. These results demonstrate that the ability of HyNa to modulate TM release, together with its mucoadhesiveness related to the viscosity, affected both the pharmacokinetic and pharmacodynamic parameters. The HyNa-TM complex is a potentially useful carrier for ocular drug delivery, which could improve the TM efficacy and reduce the frequency of administration to improve patient compliance. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Formulation and In vitro/In vivo Evaluation of Sustained Release ...

    African Journals Online (AJOL)

    HP

    2013-07-15

    Jul 15, 2013 ... They are generally used to treat high blood pressure ... extending drug release for highly water-soluble drugs is limited ..... by the high water permeability of Kollidon SR while the ... due to the extremely low water solubility of.

  12. Enhancement of ASTEC and COCOSYS regarding fission product release during MCCI

    Energy Technology Data Exchange (ETDEWEB)

    Agethen, Kathrin [Bochum Univ. (Germany). Reactor Simulation and Safety Group

    2016-10-15

    The focus in this paper is on the enhancement of the fission product release model during molten core concrete interaction in the severe accident analysis codes ASTEC and COCOSYS. After both codes are harmonised and the model interaction as well as the input parameters are adapted, extended model approaches are implemented. These lead to an improvement of the release rates for selected semi-volatile species validated against the ACE tests under ex-vessel conditions.

  13. Release of RANKERN 16A

    Directory of Open Access Journals (Sweden)

    Bird Adam

    2017-01-01

    Full Text Available RANKERN 16 is the latest version of the point-kernel gamma radiation transport Monte Carlo code from AMEC Foster Wheeler’s ANSWERS Software Service. RANKERN is well established in the UK shielding community for radiation shielding and dosimetry assessments. Many important developments have been made available to users in this latest release of RANKERN. The existing general 3D geometry capability has been extended to include import of CAD files in the IGES format providing efficient full CAD modelling capability without geometric approximation. Import of tetrahedral mesh and polygon surface formats has also been provided. An efficient voxel geometry type has been added suitable for representing CT data. There have been numerous input syntax enhancements and an extended actinide gamma source library. This paper describes some of the new features and compares the performance of the new geometry capabilities.

  14. Release of RANKERN 16A

    Science.gov (United States)

    Bird, Adam; Murphy, Christophe; Dobson, Geoff

    2017-09-01

    RANKERN 16 is the latest version of the point-kernel gamma radiation transport Monte Carlo code from AMEC Foster Wheeler's ANSWERS Software Service. RANKERN is well established in the UK shielding community for radiation shielding and dosimetry assessments. Many important developments have been made available to users in this latest release of RANKERN. The existing general 3D geometry capability has been extended to include import of CAD files in the IGES format providing efficient full CAD modelling capability without geometric approximation. Import of tetrahedral mesh and polygon surface formats has also been provided. An efficient voxel geometry type has been added suitable for representing CT data. There have been numerous input syntax enhancements and an extended actinide gamma source library. This paper describes some of the new features and compares the performance of the new geometry capabilities.

  15. Single Layer Extended Release Two-in-One Guaifenesin Matrix Tablet: Formulation Method, Optimization, Release Kinetics Evaluation and Its Comparison with Mucinex® Using Box-Behnken Design.

    Science.gov (United States)

    Morovati, Amirhosein; Ghaffari, Alireza; Erfani Jabarian, Lale; Mehramizi, Ali

    2017-01-01

    Guaifenesin, a highly water-soluble active (50 mg/mL), classified as a BCS class I drug. Owing to its poor flowability and compressibility, formulating tablets especially high-dose one, may be a challenge. Direct compression may not be feasible. Bilayer tablet technology applied to Mucinex®, endures challenges to deliver a robust formulation. To overcome challenges involved in bilayer-tablet manufacturing and powder compressibility, an optimized single layer tablet prepared by a binary mixture (Two-in-one), mimicking the dual drug release character of Mucinex ® was purposed. A 3-factor, 3-level Box-Behnken design was applied to optimize seven considered dependent variables (Release "%" in 1, 2, 4, 6, 8, 10 and 12 h) regarding different levels of independent one (X 1 : Cetyl alcohol, X 2 : Starch 1500 ® , X 3 : HPMC K100M amounts). Two granule portions were prepared using melt and wet granulations, blended together prior to compression. An optimum formulation was obtained (X 1 : 37.10, X 2 : 2, X 3 : 42.49 mg). Desirability function was 0.616. F2 and f1 between release profiles of Mucinex® and the optimum formulation were 74 and 3, respectively. An n-value of about 0.5 for both optimum and Mucinex® formulations showed diffusion (Fickian) control mechanism. However, HPMC K100M rise in 70 mg accompanied cetyl alcohol rise in 60 mg led to first order kinetic (n = 0.6962). The K values of 1.56 represented an identical burst drug releases. Cetyl alcohol and starch 1500 ® modulated guaifenesin release from HPMC K100M matrices, while due to their binding properties, improved its poor flowability and compressibility, too.

  16. Design of cellulose ether-based macromolecular prodrugs of ciprofloxacin for extended release and enhanced bioavailability.

    Science.gov (United States)

    Amin, Muhammad; Abbas, Nazia Shahana; Hussain, Muhammad Ajaz; Sher, Muhammad; Edgar, Kevin J

    2018-07-01

    The present study reveals the syntheses of hydroxypropylcellulose‑(HPC) and hydroxyethylcellulose‑(HEC) based macromolecular prodrugs (MPDs) of ciprofloxacin (CIP) using homogeneous reaction methodology. Covalently loaded drug content (DC) of each prodrug was quantified using UV-Vis spectrophotometry to determine degree of substitution (DS). HPC-ciprofloxacin (HPC-CIP) conjugates showed DS of CIP in the range 0.87-1.15 whereas HEC-ciprofloxacin (HEC-CIP) conjugates showed DS range 0.51-0.75. Transmission electron microscopy revealed that HPC-CIP conjugate 2 and HEC-CIP conjugate 6 self-assembled into nanoparticles of 150-300 and 180-250nm, respectively. Size exclusion chromatography revealed HPC-CIP conjugate 2 and HEC-CIP conjugate 6 as monodisperse systems. In vitro drug release studies indicated 15 and 43% CIP release from HPC-CIP conjugate 2 after 6h in simulated gastric and simulated intestinal fluids (SGF and SIF), respectively. HEC-CIP conjugate 6 showed 16% and 46% release after 6h in SGF and SIF, respectively. HPC-CIP conjugate 2 and HEC-CIP conjugate 6 exhibited half-lives of 10.87 and 11.71h, respectively with area under the curve values of 164 and 175hμgmL -1 , respectively, indicating enhanced bioavailability and improved pharmacokinetic profiles in animal model. Equal antibacterial activities to that of unmodified CIP confirmed their competitive efficacies. Cytotoxicity studies supported their non-toxic nature and biocompatibility. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Use of Extended-Release Calcifediol to Treat Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease.

    Science.gov (United States)

    Sprague, Stuart M; Crawford, Paul W; Melnick, Joel Z; Strugnell, Stephen A; Ali, Shaukat; Mangoo-Karim, Roberto; Lee, Sungchun; Petkovich, P Martin; Bishop, Charles W

    2016-01-01

    Vitamin D insufficiency and secondary hyperparathyroidism (SHPT) are associated with increased morbidity and mortality in chronic kidney disease (CKD) and are poorly addressed by current treatments. The present clinical studies evaluated extended-release (ER) calcifediol, a novel vitamin D prohormone repletion therapy designed to gradually correct low serum total 25-hydroxyvitamin D, improve SHPT control and minimize the induction of CYP24A1 and FGF23. Two identical multicenter, randomized, double-blind, placebo-controlled studies enrolled subjects from 89 US sites. A total of 429 subjects, balanced between studies, with stage 3 or 4 CKD, SHPT and vitamin D insufficiency were randomized 2:1 to receive oral ER calcifediol (30 or 60 µg) or placebo once daily at bedtime for 26 weeks. Most subjects (354 or 83%) completed dosing, and 298 (69%) entered a subsequent open-label extension study wherein ER calcifediol was administered without interruption for another 26 weeks. ER calcifediol normalized serum total 25-hydroxyvitamin D concentrations (>30 ng/ml) in >95% of per-protocol subjects and reduced plasma intact parathyroid hormone (iPTH) by at least 10% in 72%. The proportion of subjects receiving ER calcifediol who achieved iPTH reductions of ≥30% increased progressively with treatment duration, reaching 22, 40 and 50% at 12, 26 and 52 weeks, respectively. iPTH lowering with ER calcifediol was independent of CKD stage and significantly greater than with placebo. ER calcifediol had inconsequential impact on serum calcium, phosphorus, FGF23 and adverse events. Oral ER calcifediol is safe and effective in treating SHPT and vitamin D insufficiency in CKD. © 2016 S. Karger AG, Basel.

  18. Kinetic Modelling of Drug Release from Pentoxifylline Matrix Tablets based on Hydrophilic, Lipophilic and Inert Polymers

    Directory of Open Access Journals (Sweden)

    Mircia Eleonora

    2015-12-01

    Full Text Available Pentoxifylline is a xanthine derivative used in the treatment of peripheral vascular disease, which because of its pharmacokinetic and pharmacologic profile is an ideal candidate for the development of extended release formulations. The aim of this study is to present a kinetic analysis of the pentoxifylline release from different extended release tablets formulations, using mechanistic and empirical kinetic models. A number of 28 formulations were prepared and analysed; the analysed formulations differed in the nature of the matrix forming polymers (hydrophilic, lipophilic, inert and in their concentrations. Measurements were conducted in comparison with the reference product Trental 400 mg (Aventis Pharma. The conditions for the dissolution study were according to official regulations of USP 36: apparatus no. 2, dissolution medium water, volume of dissolution medium is 1,000 mL, rotation speed is 50 rpm, spectrophotometric assay at 274 nm. Six mathematical models, five mechanistic (0 orders, 1st-order release, Higuchi, Hopfenberg, Hixson-Crowell and one empirical (Peppas, were fitted to pentoxifylline dissolution profile from each pharmaceutical formulation. The representative model describing the kinetics of pentoxifylline release was the 1st-order release, and its characteristic parameters were calculated and analysed.

  19. An oral multiparticulate, modified-release, hydrocortisone replacement therapy that provides physiological cortisol exposure.

    Science.gov (United States)

    Whitaker, Martin; Debono, Miguel; Huatan, Hiep; Merke, Deborah; Arlt, Wiebke; Ross, Richard J

    2014-04-01

    It is not possible with current hydrocortisone replacement to mimic the diurnal cortisol profile in patients with adrenal insufficiency. Previous attempts with modified-release technology were unsuccessful. Our objective was to develop hydrocortisone formulations that recreate the diurnal cortisol profile using multiparticulate technology. Screening by in vitro dissolution profiles, pharmacokinetic (PK) testing in dexamethasone-suppressed dogs and humans, and comparison with a reference population. Field laboratories and clinical research facility. Formulations were generated using an enteric (delayed release) design configuration with an extended (sustained release) dissolution profile. In vitro dissolution confirmed delayed and sustained hydrocortisone release. However, in dogs and humans, sustained release resulted in reduced bioavailability. A formulation, DIURF-006, was developed that maintained delayed release but omitted the sustained-release functionality. PK characterization of DIURF-006 showed that, despite absence of a sustained-release component, absorption was sufficiently sustained to deliver extended hydrocortisone absorption. In dexamethasone-suppressed volunteers (n = 16) receiving a twice-daily 'toothbrush' regimen (20 mg at 23:00 h and 10 mg at 07:00 h), DIURF-006 gave a similar cortisol profile to physiological cortisol levels: DIURF-006 vs physiological, Geomean AUC 5610 vs 4706 h * nmol/l, Geomean Cmax 665 vs 594 nmol/l and Median Tmax 8·5 h vs clock time 08:12 h for peak cortisol. The relative bioavailability of DIURF-006 vs hydrocortisone was 89%, and cortisol levels increased linearly with doses between 5 and 30 mg. A multiparticulate oral hydrocortisone formulation with only an enteric coat provides delayed and sustained absorption and when given in a 'toothbrush' regimen provides physiological cortisol exposure. © 2013 John Wiley & Sons Ltd.

  20. Effects of compost age on the release of nutrients

    Directory of Open Access Journals (Sweden)

    Bilal B. Al-Bataina

    2016-09-01

    Full Text Available Composted organic materials are applied to help restore disturbed soils, speed revegetation, and control erosion; these changes are generally beneficial for stormwater quality. Ensuring that nutrient release from compost is adequate for plant needs without degrading stormwater quality is important since composts release nitrogen at variable rates (1–3% of total N/yr and the leaching process can extend for many years. The aim of this work was to understand the effect of compost age on the extent and rates of nitrogen release by conducting detailed rainfall simulation studies of one compost type at three different ages. Models describing temporal changes in nitrogen release to runoff during a single storm and across multiple storms were developed and applied to the runoff data. Nitrogen content (% and bulk density of compost increased with the increase in compost age and total nitrogen release decreased with increasing compost age. The three rain simulations (storms performed on each of the three compost ages show that nitrogen release declined each day of the repeated daily storms. A first-order kinetic model was used to estimate the amount of nitrogen remaining on compost after several storms.

  1. Nematode burdens of pastured cattle treated once at turnout with eprinomectin extended-release injection.

    Science.gov (United States)

    Rehbein, S; Baggott, D G; Johnson, E G; Kunkle, B N; Yazwinski, T A; Yoon, S; Cramer, L G; Soll, M D

    2013-03-01

    The efficacy of eprinomectin in an extended-release injection (ERI) formulation was evaluated against infections with third-stage larvae or eggs of gastrointestinal and pulmonary nematodes in cattle under 120-day natural challenge conditions in a series of five studies conducted in the USA (three studies) and in Europe (two studies). For each study, 30 nematode-free (four studies) or 30 cattle harboring naturally acquired nematode infections (one study) were included. The cattle were of various breeds or crosses, weighed 107.5-273 kg prior to treatment and aged approximately 4-11 months. For each study, animals were blocked based on pre-treatment bodyweight and then randomly allocated to treatment: ERI vehicle (control) at 1 mL/50 kg bodyweight or Eprinomectin 5% (w/v) ERI at 1 mL/50 kg bodyweight (1.0 mg eprinomectin/kg) for a total of 15 and 15 animals in each group. Treatments were administered once on Day 0 by subcutaneous injection in front of the shoulder. In each study, all animals grazed one naturally contaminated pasture for 120 days. At regular intervals during the studies, fecal samples from all cattle were examined for nematode egg and larval counts. In four studies pairs of tracer cattle were used to monitor pasture infectivity at 28-day intervals before and/or during the grazing period. All calves were weighed before turnout onto pasture and at regular intervals until housing on Day 120. For parasite recovery, all study animals were humanely euthanized 27-30 days after removal from pasture. Cattle treated with Eprinomectin ERI had significantly (p92%: Dictyocaulus viviparus (adults and fourth-stage larvae (L4), Bunostomum phlebotomum, Cooperia curticei, Cooperia oncophora, Cooperia punctata, Cooperia surnabada, Cooperia spp. inhibited L4, Haemonchus contortus, Haemonchus placei, Haemonchus spp. inhibited L4, Nematodirus helvetianus, Nematodirus spp. inhibited L4, Oesophagostomum radiatum, Oesophagostomum spp. inhibited L4, Ostertagia leptospicularis

  2. 76 FR 72227 - Order Extending Temporary Conditional Exemption for Nationally Recognized Statistical Rating...

    Science.gov (United States)

    2011-11-22

    ... accessed information for [Insert Number] issued securities and money market instruments through Internet... the arranger will, among other things, disclose on a password-protected Internet Web site the... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-65765; File No. S7-04-09] Order Extending...

  3. Review of levetiracetam, with a focus on the extended release formulation, as adjuvant therapy in controlling partial-onset seizures

    Directory of Open Access Journals (Sweden)

    Carol M Ulloa

    2009-09-01

    Full Text Available Carol M Ulloa, Allen Towfigh, Joseph SafdiehDepartment of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, USAAbstract: Levetiracetam is a second-generation antiepileptic drug (AED with a unique chemical structure and mechanism of action. The extended release formulation of levetiracetam (Keppra XR™; UCB Pharma was recently approved by the Food and Drug Administration for adjunctive therapy in the treatment of partial-onset seizures in patients 16 years of age and older with epilepsy. This approval is based on a double-blind, randomized, placebo-controlled, multicenter, multinational trial. Levetiracetam XR allows for once-daily dosing, which may increase compliance and, given the relatively constant plasma concentrations, may minimize concentration-related adverse effects. Levetiracetam’s mode of action is not fully elucidated, but it has been found to target high-voltage, N-type calcium channels as well as the synaptic vesicle protein 2A (SV2A. Levetiracetam has nearly ideal pharmacokinetics. It is rapidly and almost completely absorbed after oral ingestion, is ‹10% protein-bound, demonstrates linear kinetics, is minimally metabolized through a pathway independent of the cytochrome P450 system, has no significant drug–drug interactions, and has a wide therapeutic index. The most common reported adverse events with levetiracetam XR were somnolence, irritability, dizziness, nausea, influenza, and nasopharyngitis. Levetiracetam XR provides an efficacious and well-tolerated treatment option for adjunctive therapy in the treatment of partial-onset seizures.Keywords: levetiracetam, partial-onset seizures, antiepileptic drugs

  4. Improved Methodology of MSLB M/E Release Analysis for OPR1000

    International Nuclear Information System (INIS)

    Park, Seok Jeong; Kim, Cheol Woo; Seo, Jong Tae

    2006-01-01

    A new mass and energy (M/E) release analysis methodology for the equipment environmental qualification (EEQ) on loss-of-coolant accident (LOCA) has been recently developed and adopted on small break LOCA EEQ. The new methodology for the M/E release analysis is extended to the M/E release analysis for the containment design for large break LOCA and the main steam line break (MSLB) accident, and named KIMERA (KOPEC Improved Mass and Energy Release Analysis) methodology. The computer code systems used in this methodology is RELAP5K/CONTEMPT4 (or RELAP5-ME) which couples RELAP5/MOD3.1/K with enhanced M/E model and LOCA long term model, and CONTEMPT4/ MOD5. This KIMERA methodology is applied to the MSLB M/E release analysis to evaluate the validation of KIMERA methodology for MSLB in containment design. The results are compared with the OPR 1000 FSAR

  5. Attention benefits after a single dose of metadoxine extended release in adults with predominantly inattentive ADHD.

    Science.gov (United States)

    Manor, Iris; Rubin, Jonathan; Daniely, Yaron; Adler, Lenard A

    2014-09-01

    To assess the first-dose effectiveness and tolerability of metadoxine extended release (MDX) in adults with predominantly inattentive attention-deficit/hyperactivity disorder (ADHD-PI). In this double-blind, placebo-controlled, crossover study, adults with ADHD-PI were randomized 1:1:1 to receive a single dose of MDX 1400 mg, MDX 700 mg, and placebo (ClinicalTrials.gov identifier: NCT01685281). The primary efficacy end point was the mean change in the Test of Variables of Attention (TOVA) ADHD score from baseline to 3 to 5 hours after drug administration. Secondary assessments included TOVA subscores, TOVA response rates (defined as an increase of 0.8 points in the TOVA ADHD score), and the Cambridge Neuropsychological Automated Test Battery. Safety assessments included adverse events and vital signs. The intention-to-treat population included 36 patients (52.8% men; mean age, 32 years). The efficacy of MDX 1400 mg was demonstrated by a statistically significant difference in the mean (± SD) change in the TOVA ADHD score at baseline to 3 to 5 hours after drug administration compared with placebo (2.0 [4.2]; P = 0.009). The TOVA response time variability subscore was significantly different between MDX 1400 mg and placebo (mean difference, 7.9 [19.2] points; P = 0.022). Significantly more adults responded to single-dose MDX 1400 mg versus placebo (97.1% vs 71.4%, P = 0.006). There were no statistically significant differences between MDX 700 mg and placebo on any measures. Exploratory analyses of the Cambridge Neuropsychological Automated Test Battery did not yield significant findings. Fatigue and headache were the 2 most frequently reported adverse events. There were no clinically significant abnormalities in laboratory values, vital signs measurements, Columbia-Suicide Severity Rating Scale scores, or electrocardiographic parameters. Single-dose MDX 1400 mg significantly improved sustained and selective attention in adults with ADHD-PI as measured by the TOVA

  6. Healthcare utilization in adults with opioid dependence receiving extended release naltrexone compared to treatment as usual.

    Science.gov (United States)

    Soares, William E; Wilson, Donna; Rathlev, Niels; Lee, Joshua D; Gordon, Michael; Nunes, Edward V; O'Brien, Charles P; Friedmann, Peter D

    2018-02-01

    Opioid use disorders have reached epidemic proportions, with overdose now the leading cause of accidental death in the United States. Extended release naltrexone (XR-NTX) has emerged as a medication treatment that reduces opioid use and craving. However, the effect of XR-NTX therapy on acute healthcare utilization, including emergency department visits and inpatient hospitalizations, remains uncertain. The objective of the current study is to evaluate hospital-based healthcare resource utilization in adults involved in the criminal justice system with a history of opioid use disorder randomized to XR-NTX therapy compared with treatment as usual (TAU) during a 6-month treatment phase and 12months post-treatment follow up. This retrospective exploratory analysis uses data collected in a published randomized trial. Comparisons of the number of emergency department visits and hospital admissions (for drug detox, psychiatric care and other medical reasons) were performed using chi square tests for any admission and negative binomial models for number of admissions. Of the 308 participants randomized, 96% had utilization data (76% complete 6months, 67% complete follow up). No significant differences were seen in overall healthcare utilization (IRR=0.88, 95%CI 0.63-1.23, p=0.45), or substance use-related drug detox hospitalizations (IRR=0.83, 95%CI 0.32-2.16, p=0.71). Despite having more participants report chronic medical problems at baseline (43% vs. 32%, p=0.05), those receiving XR-NTX generally experienced equivalent or lower rates of healthcare utilization compared to TAU. The XR-NTX group had significantly lower medical/surgical related hospital admissions (IRR=0.55, 95%CI 0.30-1.00, p=0.05) during the course of the entire study. XR-NTX did not significantly increase rates of healthcare utilization compared to TAU. Provider concerns regarding healthcare utilization should not preclude the consideration of XR-NTX as therapy for opioid use disorders. Copyright © 2018

  7. WIMS-IJSO - An extended version of the WIMS group constant library

    International Nuclear Information System (INIS)

    Trkov, A.; Perdan, A.

    1982-11-01

    WIMS-IJSO is a preliminary extended version of the WIMS library as supplied with the CDC version of the S-WIMS-code. It is a result of the feasibility study of the possibility to update and extend the WIMS library. In the course of its preparation valuable experience was gained in understanding the definitions, the conventions and the structure of the WIMS library. This experience will be used in the preparation of an extended WIMS library for some materials from carefully chosen evaluated data. The library as supplied with the WIMS-D4 package will be used as the basis. The materials added to the library had been tested in reactor calculations and their performance was found to be satisfactory. The aim of releasing the preliminary version of the WIMS library is to allow different users to apply the data to various problems

  8. An oral multi-particulate, modified release, hydrocortisone replacement therapy that provides physiological cortisol exposure

    Science.gov (United States)

    Huatan, Hiep; Merke, Deborah; Arlt, Wiebke; Ross, Richard J.

    2013-01-01

    Objective It is not possible with current hydrocortisone replacement to mimic the diurnal cortisol profile in patients with adrenal insufficiency. Previous attempts with modified release technology were unsuccessful. Our objective was to develop hydrocortisone formulations that recreate the diurnal cortisol profile using multi-particulate technology. Design and Measurements Screening by in-vitro dissolution profiles, pharmacokinetic testing in dexamethasone suppressed dogs and humans, and comparison to a reference population. Setting Field laboratories and clinical research facility. Results Formulations were generated using an enteric (delayed-release) design configuration with an extended (sustained-release) dissolution profile. In-vitro dissolution confirmed delayed and sustained hydrocortisone release. However, in dogs and humans, sustained release resulted in reduced bioavailability. A formulation, DIURF-006, was developed that maintained delayed release but omitted the sustained release functionality. Pharmacokinetic characterisation of DIURF-006 showed that, despite absence of a sustained release component, absorption was sufficiently sustained to deliver extended hydrocortisone absorption. In dexamethasone-suppressed volunteers (n=16) receiving a twice daily ‘toothbrush’ regimen (20mg at 23:00h and 10mg at 07:00h), DIURF-006 gave a similar cortisol profile to physiological cortisol levels: DIURF-006 vs physiological, Geomean AUC 5610 vs 4706 hr*nmol/l, Geomean Cmax 665 vs 594 nmol/l and Median Tmax 8.5h vs clock time 08:12 hours for peak cortisol. The relative bioavailability of DIURF-006 vs hydrocortisone was 89% and cortisol levels increased linearly with doses between 5 and 30mg. Conclusion A multi-particulate oral hydrocortisone formulation with only an enteric coat provides delayed and sustained absorption and when given in a ‘toothbrush’ regimen provides physiological cortisol exposure. PMID:23980724

  9. Release and Degradation of Microencapsulated Spinosad and Emamectin Benzoate.

    Science.gov (United States)

    Huang, Bin Bin; Zhang, Shao Fei; Chen, Peng Hao; Wu, Gang

    2017-09-07

    The dynamics of release and degradation of the microencapsulation formulation containing spinosad (SP) and emamectin benzoate (EM) were evaluated in the present study. SP and EM were microencapsulated using biodegradable poly-lactic acid (PLA) as the wall material. Their release from and degradation within the prepared SP and EM microspheres (SP-EM-microspheres) were studied. It was found that the encapsulation significantly prolonged the insecticide release. The release could be further extended if the external aqueous phase was pre-saturated with the insecticides and the microspheres were additionally coated with gelatin. On the other hand, increasing the water content of the emulsion or the hydrophilic polycaprolactone (PCL) content in the PLA/PCL mixture accelerated the release. Due to the photolysis and hydrolysis of SP and EM by sunlight, the toxicity of the non-encapsulated insecticides in water declined continuously from 0 through the 9 th day (d), and dissipated in 13 d. In contrast, an aqueous suspension containing 5% SP-EM-microspheres maintained a mostly constant toxicity to Plutella xylostella for 17 d. The biodegradable SP-EM-microspheres showed significantly higher long-term toxicity to P. xylostella due to lower release, reduced photolysis and hydrolysis of the encapsulated insecticides, which were affected by the varied preparation conditions.

  10. A Randomized, Single-Blind, Substitution Study of OROS Methylphenidate (Concerta) in ADHD Adults Receiving Immediate Release Methylphenidate

    Science.gov (United States)

    Spencer, Thomas J.; Mick, Eric; Surman, Craig B. H.; Hammerness, Paul; Doyle, Robert; Aleardi, Megan; Kotarski, Meghan; Williams, Courtney G.; Biederman, Joseph

    2011-01-01

    Objective: The main aim of this study was to examine the efficacy, tolerability, and compliance of an extended-release formulation of methylphenidate (OROS-MPH) in adults with ADHD receiving immediate-release methylphenidate (IR-MPH). Method: Participants were outpatient adults with ADHD who were stable on IR-MPH-administered TID. Participants…

  11. Novel Brassinosteroid-Modified Polyethylene Glycol Micelles for Controlled Release of Agrochemicals.

    Science.gov (United States)

    Pérez Quiñones, Javier; Brüggemann, Oliver; Kjems, Jørgen; Shahavi, Mohammad Hassan; Peniche Covas, Carlos

    2018-02-21

    Two synthetic analogues of brassinosteroids (DI31 and S7) exhibit good plant growth enhancer activity. However, their hydrophobicity and quick metabolism in plants have limited their application and benefits in agriculture. Our objective was to prepare novel brassinosteroid-modified polyethylene glycol (PEG) micelles to achieve controlled release with extended stability while retaining agrochemical activity. Spectroscopic studies confirmed quantitative disubstitution of studied PEGs with the brassinosteroids, while elemental analysis assessed purity of the synthesized conjugates. Conjugates were also characterized by X-ray diffraction and thermal analysis. Dynamic and static light scattering showed stable and homogeneous approximately spherical micelles with average hydrodynamic diameters of 22-120 nm and almost neutral ζ potential. Spherical 30-140 nm micelles were observed by electron microscopy. Sustained in vitro releases at pH 5.5 were extended up to 96 h. Prepared PEG micelles showed good agrochemical activity in the radish seed bioassay and no cytotoxicity to the human microvascular endothelial cell line in the MTS test.

  12. 78 FR 5500 - Manufacturer of Controlled Substances; Notice of Registration; Noramco, Inc.

    Science.gov (United States)

    2013-01-25

    ... (9333) II Opium extracts (9610) II Opium fluid extract (9620) II Opium tincture (9630) II Opium, powdered (9639) II Opium, granulated (9640) II Oxymorphone (9652) II Noroxymorphone (9668) II Tapentadol...

  13. 76 FR 7234 - Manufacturer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2011-02-09

    ... (9333) II Opium extracts (9610) II Opium fluid extract (9620) II Opium tincture (9630) II Opium, powdered (9639) II Opium, granulated (9640) II Oxymorphone (9652) II Noroxymorphone (9668) II Tapentadol...

  14. Effects of paliperidone extended release on hostility among Thai patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Jariyavilas A

    2017-01-01

    Full Text Available Apichat Jariyavilas,1 Nuntika Thavichachart,2 Ronnachai Kongsakon,3 Sunanta Chantakarn,4 Suwanna Arunpongpaisal,5 Vasu Chantarasak,6 Piyadit Jaroensook,7 Khanogwan Kittiwattanagul,8 Osot Nerapusee9 1Srithanya Hospital, Department of Mental Health, Ministry of Public Health, Bangkok, 2Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, 3Department of Psychiatry, Faculty of Medicine, Ramathibodi Hospital, Bangkok, 4Department of Psychiatry, Faculty of Medicine, Siriraj Hospital, Bangkok, 5Department of Psychiatry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 6Somdetchaopraya Institute of Psychiatry, Bangkok, 7Prasrimahabhodhi Hospital, Ubon Ratchathani, 8Khon Kaen Rajanagarindra Psychiatric Hospital, Khon Kaen, 9Medical Affairs, Janssen-Cilag, Bangkok, Thailand Objective: This open-label prospective study investigated the effects of paliperidone extended release (ER on hostility in Thai patients with schizophrenia. Background: Patients diagnosed with schizophrenia may be hostile or exhibit aggressive behavior, which can occasion their admission to psychiatric hospital. Antipsychotic medications are often used to treat hostility and aggression in such patients. Paliperidone ER is effective and well tolerated in the treatment of schizophrenia. However, there are no data available for paliperidone ER with regard to its efficacy on hostility and aggression among Thai patients. This study was a part of the PERFEcT study, a 6-month, open-label, multicenter, multicountry, prospective trial to explore the safety, efficacy, and functionality of paliperidone ER tablets. The current study included only the data obtained from Thai participants. Materials and methods: Flexible dosing of paliperidone ER in a range of 3–12 mg/day was used, allowing investigators to adjust the dosage of each subject individually. The 199 Thai patients had a stable Clinical Global Impression – severity score before enrollment. Demographic

  15. 78 FR 70984 - Order Extending Temporary Conditional Exemption for Nationally Recognized Statistical Rating...

    Science.gov (United States)

    2013-11-27

    ... relied upon that the arranger will, among other things, disclose on a password-protected Internet Web... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-70919; File No. S7-04-09] Order Extending... of Rule 17g-5 Under the Securities Exchange Act of 1934 and Request for Comment November 22, 2013. I...

  16. Tracking of fission products release during refueling operations

    International Nuclear Information System (INIS)

    Agarwal, Sharad; Prajapat, M.K.; Vyas, Shyam; Hussain, S.A.

    2001-01-01

    It has been always observed that the release of fission products increase during refueling operations. At RAPP-3 and 4 an attempt has been made to follow-up the change in fission products activity release at each stage of refueling operation and quantification of concentrations of various radionuclides. This exercise was also extended to refueling operation of the channels containing suspected failed fuel. A level of FPNG ( 133 Xe) was observed to increase by a factor of about 10-40 during refueling of failed channel as compared to healthy channel. It can be concluded that by monitoring FPNG levels in exhaust status of the healthiness of spent fuel can be found out. This report discusses in detail the experiment conducted for this purpose. (author)

  17. Evaluation of the Relative Abuse of an OROS® Extended-release Hydromorphone HCI Product: Results from three Post-market Surveillance Studies.

    Science.gov (United States)

    Butler, Stephen F; McNaughton, Emily C; Black, Ryan A; Cassidy, Theresa A

    2018-01-02

    Formulating prescription opioids to limit abuse remains a priority. OROS® extended-release (ER) hydromorphone HCl (EXALGO®) may have low abuse potential. Three post-marketing studies of the relative abuse liability of OROS hydromorphone ER were conducted. Estimates of abuse, unadjusted and adjusted for prescription volume, were generated for OROS hydromorphone ER and comparators from Q2 2010 through Q2 2014 for a high-risk, substance abuse treatment population and the general population using poison control center data. Comparators were selected for compound, market penetration, and route of administration (ROA) profile. ROA comparisons were made among the substance abuse treatment population. Internet discussion was examined to determine abusers' interest in and desire for the OROS formulation. Examination of abuse prevalence among adults within substance abuse treatment, intentional poison exposures and Internet discussion levels generally support the hypothesis that OROS hydromorphone ER may have lower abuse potential than many other opioid products. OROS hydromorphone ER also appears to be abused less often by alternate ROAs (e.g., snorting and injection). Lower levels of online discussion were observed along with relatively low endorsement for abuse. Abuse of OROS hydromorphone ER was observed in high-risk substance abuse and general population samples but at a very low relative prevalence. Evidence suggests it may be less often abused by alternate ROAs than some comparators. Online data did not find evidence of high levels of desire for OROS hydromorphone ER by recreational abusers. Continued monitoring of this product's abuse liability is warranted.

  18. Ecological release in lizard assemblages of neotropical savannas.

    Science.gov (United States)

    Mesquita, Daniel Oliveira; Colli, Guarino Rinaldi; Vitt, Laurie J

    2007-08-01

    We compare lizard assemblages of Cerrado and Amazonian savannas to test the ecological release hypothesis, which predicts that niche dimensions and abundance should be greater in species inhabiting isolated habitat patches with low species richness (Amazonian savannas and isolated Cerrado patches) when compared with nonisolated areas in central Cerrado with greater species richness. We calculated microhabitat and diet niche breadths with data from 14 isolated Cerrado patches and Amazon savanna areas and six central Cerrado populations. Morphological data were compared using average Euclidean distances, and lizard abundance was estimated using the number of lizards captured in pitfall traps over an extended time period. We found no evidence of ecological release with respect to microhabitat use, suggesting that historical factors are better microhabitat predictors than ecological factors. However, data from individual stomachs indicate that ecological release occurs in these areas for one species (Tropidurus) but not others (Ameiva ameiva, Anolis, Cnemidophorus, and Micrablepharus), suggesting that evolutionary lineages respond differently to environmental pressures, with tropidurids being more affected by ecological factors than polychrotids, teiids, and gymnophthalmids. We found no evidence that ecological release occurs in these areas using morphological data. Based on abundance data, our results indicate that the ecological release (density compensation) hypothesis is not supported: lizard species are not more abundant in isolated areas than in nonisolated areas. The ecology of species is highly conservative, varying little from assemblage to assemblage. Nevertheless, increases in niche breadth for some species indicate that ecological release occurs as well.

  19. Efficacy and safety of extended-release oxcarbazepine (Oxtellar XR™) as adjunctive therapy in patients with refractory partial-onset seizures: a randomized controlled trial

    Science.gov (United States)

    French, JA; Baroldi, P; Brittain, ST; Johnson, JK

    2014-01-01

    Objective To evaluate the efficacy, tolerability, and safety of once-daily 1200 mg and 2400 mg SPN-804 (Oxtellar XR™, Supernus Pharmaceuticals), an extended-release tablet formulation of oxcarbazepine (OXC), added to 1-3 concomitant antiepileptic drugs (AEDs) in adults with refractory partial-onset seizures, with or without secondary generalization. Methods The Prospective, Randomized Study of OXC XR in Subjects with Partial Epilepsy Refractory (PROSPER) study was a multinational, randomized, double-blind, parallel-group Phase 3 study. The primary efficacy endpoint was median percent reduction from baseline in monthly (28-day) seizure frequency for the 16-week double-blind treatment period in the intent-to-treat (ITT) population with analyzable seizure data. Other efficacy analyses included proportion of patients with ≥ 50% seizure reduction, proportion of patients seizure free, and the relationship between clinical response and plasma concentration. Results Median percent reduction was -28.7% for placebo, −38.2% (P = 0.08 vs placebo) for once-daily SPN-804 1200 mg, and −42.9% (P = 0.003) for SPN-804 2400 mg. Responder rates were 28.1%, 36.1% (P = 0.08), and 40.7% (P = 0.02); 16-week seizure-free rates in a pragmatic ITT analysis were 3.3%, 4.9% (P = 0.59), and 11.4% (P = 0.008), respectively. When data were analyzed separately for study site clusters, a post hoc analysis demonstrated that both SPN-804 dosages were significantly superior to placebo in median percent seizure reduction (placebo: −13.3%; 1200 mg: −34.5%, P = 0.02; 2400 mg: −52.7%, P = 0.006) in the North American study site cluster. A concentration–response analysis also supported a clinically meaningful effect for 1200 mg. Adverse event types reflected the drug's established profile. Adverse event frequency was consistent with a pharmacokinetic profile in which SPN-804 produces lower peak plasma concentrations vs immediate-release OXC. Once-daily dosing was not

  20. Influence of factors on release of antimicrobials from antimicrobial packaging materials.

    Science.gov (United States)

    Wu, Yu-Mei; Wang, Zhi-Wei; Hu, Chang-Ying; Nerín, Cristina

    2018-05-03

    Antimicrobial packaging materials (films or coatings) (APMs) have aroused great interest among the scientists or the experts specialized in material science, food science, packaging engineering, biology and chemistry. APMs have been used to package the food, such as dairy products, poultry, meat (e.g., beef), salmon muscle, pastry dough, fresh pasta, bakery products, fruits, vegetables and beverages. Some materials have been already commercialized. The ability of APMs to extend the shelf-life of the food depends on the release rate of the antimicrobials (AMs) from the materials to the food. The optimum rate is defined as target release rate (TRR). To achieve TRR, the influencing factors of the release rate should be considered. Herein we reviewed for the first time these factors and their influence on the release. These factors mainly include the AMs, food (or food simulant), packaging materials, the interactions among them, the temperature and environmental relative humidity (RH).

  1. Role of extended release quetiapine in the management of bipolar disorders

    Directory of Open Access Journals (Sweden)

    Rayan K Al Jurdi

    2010-02-01

    Full Text Available Rayan K Al Jurdi1,2, Lena A Dixit1, Martha Sajatovic3 1Baylor College of Medicine, Department of Psychiatry, Houston, Texas, USA; 2South Central Mental Illness Research and Clinical Core, Department of Veterans Affairs, Houston, Texas; 3Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USAAbstract: Atypical antipsychotics have become a widely utilized component of the bipolar disorder treatment armamentarium, with approximately 45% of bipolar patients prescribed atypicals. Over the last decade all atypical drugs except for clozapine have received a Food and Drug Administration (FDA bipolar indication. In October 2008, the FDA approved quetiapine XR monotherapy for the treatment of acute depressive episodes of bipolar disorder and acute manic or mixed episodes in bipolar I disorder based on two placebo-control trials. Quetiapine was also approved as adjunct therapy with lithium and divalproex for the treatment of acute manic or mixed episodes as well as maintenance of bipolar I disorder. In contrast to immediate release quetiapine which may require a twice-daily regimen, the XR formulation is intended for once-daily administration. This drug profile of quetiapine XR will address chemistry, pharmacodynamics, pharmacokinetics, metabolism, safety and tolerability and clinical trials in bipolar disorder.Keywords: quetiapine XR, bipolar disorder

  2. Effectiveness and gastrointestinal tolerability during conversion and titration with once-daily OROS® hydromorphone extended release in opioid-tolerant patients with chronic low back pain

    Directory of Open Access Journals (Sweden)

    Hale ME

    2013-05-01

    Full Text Available Martin E Hale,1 Srinivas R Nalamachu,2 Arif Khan,3 Michael Kutch4,* 1Gold Coast Research, LLC, Weston, FL, USA; 2International Clinical Research Institute, Overland Park, KS, USA; 3MedNorthwest Clinical Research Center, Bellevue, WA, USA; Duke University Medical Center, Durham, NC, USA; 4Applied Clinical Intelligence, LLC, Bala Cynwyd, PA, USA *Affiliation at the time this work was completed. Michael Kutch is currently affiliated with Cytel Inc, Chesterbrook, PA, USA Purpose: To describe the efficacy and safety of hydromorphone extended-release tablets (OROS hydromorphone ER during dose conversion and titration. Patients and methods: A total of 459 opioid-tolerant adults with chronic moderate to severe low back pain participated in an open-label, 2- to 4-week conversion/titration phase of a double-blind, placebo-controlled, randomized withdrawal trial, conducted at 70 centers in the United States. Patients were converted to once-daily OROS hydromorphone ER at 75% of the equianalgesic dose of their prior total daily opioid dose (5:1 conversion ratio, and titrated as frequently as every 3 days to a maximum dose of 64 mg/day. The primary outcome measure was change in pain intensity numeric rating scale; additional assessments included the Patient Global Assessment and the Roland–Morris Disability Questionnaire scores. Safety assessments were performed at each visit and consisted of recording and monitoring all adverse events (AEs and serious AEs. Results: Mean (standard deviation final daily dose of OROS hydromorphone ER was 37.5 (17.8 mg. Mean (standard error of the mean [SEM] numeric rating scale scores decreased from 6.6 (0.1 at screening to 4.3 (0.1 at the final titration visit (mean [SEM] change, -2.3 [0.1], representing a 34.8% reduction. Mean (SEM change in Patient Global Assessment was -0.6 (0.1, and mean change (SEM in the Roland–Morris Disability Questionnaire was -2.8 (0.3. Patients achieving a stable dose showed greater improvement

  3. Extended-release niacin/laropiprant significantly improves lipid levels in type 2 diabetes mellitus irrespective of baseline glycemic control

    Directory of Open Access Journals (Sweden)

    Bays HE

    2015-02-01

    Full Text Available Harold E Bays,1 Eliot A Brinton,2 Joseph Triscari,3 Erluo Chen,3 Darbie Maccubbin,3 Alexandra A MacLean,3 Kendra L Gibson,3 Rae Ann Ruck,3 Amy O Johnson-Levonas,3 Edward A O’Neill,3 Yale B Mitchel3 1Louisville Metabolic & Atherosclerosis Research Center (L-MARC, Louisville, KY, USA; 2Utah Foundation for Biomedical Research, Salt Lake City, UT, USA; 3Merck & Co, Inc., Whitehouse Station, NJ, USA Background: The degree of glycemic control in patients with type 2 diabetes mellitus (T2DM may alter lipid levels and may alter the efficacy of lipid-modifying agents. Objective: Evaluate the lipid-modifying efficacy of extended-release niacin/laropiprant (ERN/LRPT in subgroups of patients with T2DM with better or poorer glycemic control. Methods: Post hoc analysis of clinical trial data from patients with T2DM who were randomized 4:3 to double-blind ERN/LRPT or placebo (n=796, examining the lipid-modifying effects of ERN/LRPT in patients with glycosylated hemoglobin or fasting plasma glucose levels above and below median baseline levels. Results: At Week 12 of treatment, ERN/LRPT significantly improved low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C, non-high-density lipoprotein cholesterol, triglycerides, and lipoprotein (a, compared with placebo, with equal efficacy in patients above or below median baseline glycemic control. Compared with placebo, over 36 weeks of treatment more patients treated with ERN/LRPT had worsening of their diabetes and required intensification of antihyperglycemic medication, irrespective of baseline glycemic control. Incidences of other adverse experiences were generally low in all treatment groups. Conclusion: The lipid-modifying effects of ERN/LRPT are independent of the degree of baseline glycemic control in patients with T2DM (NCT00485758. Keywords: lipid-modifying agents, hyperglycemia, LDL, HDL, triglycerides

  4. Effect of the Glucagon-like Peptide-1 Analogue Exenatide Extended Release in Cats with Newly Diagnosed Diabetes Mellitus.

    Science.gov (United States)

    Riederer, A; Zini, E; Salesov, E; Fracassi, F; Padrutt, I; Macha, K; Stöckle, T M; Lutz, T A; Reusch, C E

    2016-01-01

    Exenatide extended release (ER) is a glucagon-like peptide-1 analogue that increases insulin secretion, inhibits glucagon secretion and induces satiation in humans with type 2 diabetes mellitus. The use of exenatide ER is safe and stimulates insulin secretion in healthy cats. The objective of this study is to assess the safety of exenatide ER and its effect on body weight, remission and metabolic control in newly diagnosed diabetic cats receiving insulin and a low-carbohydrate diet. Thirty client-owned cats. Prospective placebo-controlled clinical trial. Cats were treated with exenatide ER or 0.9% saline, administered SC, once weekly. Both groups received insulin glargine and a low-carbohydrate diet. Exenatide ER was administered for 16 weeks, or in cats that achieved remission it was given for 4 weeks after discontinuing insulin treatment. Nonparametric tests were used for statistical analysis. Cats in the exenatide ER and placebo groups had transient adverse signs including decreased appetite (60% vs. 20%, respectively, P = .06) and vomiting (53% vs. 40%, respectively, P = .715). Body weight increased significantly in the placebo group (P = .002), but not in cats receiving exenatide ER. Cats on exenatide ER achieved remission or good metabolic control in 40% or 89%, respectively, whereas in control cats percentages were 20% or 58% (P = .427 and P = .178, respectively). Exenatide ER is safe in diabetic cats and does not result in weight gain. Our pilot study suggests that, should there be an additional clinically relevant beneficial effect of exenatide ER in insulin-treated cats on rate of remission and good metabolic control, it would likely approximate 20% and 30%, respectively. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  5. A randomized study to compare the efficacy and safety of extended-release and immediate-release tramadol HCl/acetaminophen in patients with acute pain following total knee replacement.

    Science.gov (United States)

    Park, Yong-Beom; Ha, Chul-Won; Cho, Sung-Do; Lee, Myung-Chul; Lee, Ju-Hong; Seo, Seung-Suk; Kang, Seung-Baik; Kyung, Hee-Soo; Choi, Choong-Hyeok; Chang, NaYoon; Rhim, Hyou Young Helen; Bin, Seong-Il

    2015-01-01

    To evaluate the relative efficacy and safety of extended-release tramadol HCl 75 mg/acetaminophen 650 mg (TA-ER) and immediate-release tramadol HCl 37.5 mg/acetaminophen 325 mg (TA-IR) for the treatment of moderate to severe acute pain following total knee replacement. This phase III, double-blind, placebo-controlled, parallel-group study randomized 320 patients with moderate to severe pain (≥4 intensity on an 11 point numeric rating scale) following total knee replacement arthroplasty to receive oral TA-ER (every 12 hours) or TA-IR (every 6 hours) over a period of 48 hours. In the primary analysis, TA-ER was evaluated for efficacy non-inferior to that of TA-IR based on the sum of pain intensity difference (SPID) at 48 hours after the first dose of study drug (SPID48). Secondary endpoints included SPID at additional time points, total pain relief at all on-therapy time points (TOTPAR), sum of SPID and TOTPAR at all on-therapy time points (SPID + TOTPAR), use of rescue medication, subjective pain assessment (PGIC, Patient Global Impression of Change), and adverse events (AEs). Analysis of the primary efficacy endpoint (SPID48) could not establish the non-inferiority of TA-ER to TA-IR. However, a post hoc analysis with a re-defined non-inferiority margin did demonstrate the non-inferiority of TA-ER to TA-IR. No statistically significant difference in SPID at 6, 12, or 24 hours was observed between the TA-ER and TA-IR groups. Similarly, analysis of TOTPAR showed that there were no significant differences between groups at any on-therapy time point, and SPID + TOTPAR at 6 and 48 hours were similar among groups. There was no difference in the mean frequency or dosage of rescue medication required by both groups, and the majority of patients in both the TA-ER and TA-IR groups rated their pain improvement as 'much' or 'somewhat better'. The overall incidence of ≥1 AEs was similar among the TA-ER (88.8%) and TA-IR (89.5%) groups. The most commonly

  6. PolyMorphine: an innovative biodegradable polymer drug for extended pain relief

    OpenAIRE

    Rosario-Meléndez, Roselin; Harris, Carolyn L.; Delgado-Rivera, Roberto; Yu, Lei; Uhrich, Kathryn E.

    2012-01-01

    Morphine, a potent narcotic analgesic used for the treatment of acute and chronic pain, was chemically incorporated into a poly(anhydride-ester) backbone. The polymer termed “PolyMorphine”, was designed to degrade hydrolytically releasing morphine in a controlled manner to ultimately provide analgesia for an extended time period. PolyMorphine was synthesized via melt-condensation polymerization and its structure was characterized using proton and carbon nuclear magnetic resonance spectroscopi...

  7. Efficacy and safety of extended- versus immediate-release pramipexole in Japanese patients with advanced and L-dopa-undertreated Parkinson disease: a double-blind, randomized trial.

    Science.gov (United States)

    Mizuno, Yoshikuni; Yamamoto, Mitsutoshi; Kuno, Sadako; Hasegawa, Kazuko; Hattori, Nobutaka; Kagimura, Tatsuro; Sarashina, Akiko; Rascol, Olivier; Schapira, Anthony H V; Barone, Paolo; Hauser, Robert A; Poewe, Werner

    2012-01-01

    To compare the efficacy, safety, tolerability, and trough plasma levels of pramipexole extended-release (ER) and pramipexole immediate-release (IR), and to assess the effects of overnight switching from an IR to an ER formulation, in L-dopa-treated patients with Parkinson disease (PD). After a 1- to 4-week screening/enrollment, 112 patients who had exhibited L-dopa-related problems or were receiving suboptimal L-dopa dosage were randomized in double-blind, double-dummy, 1:1 fashion to pramipexole ER once daily or pramipexole IR 2 to 3 times daily for 12 weeks, both titrated to a maximum daily dose of 4.5 mg. Successful completers of double-blind treatment were switched to open-label pramipexole ER, beginning with a 4-week dose-adjustment phase. Among the double-blind treatment patients (n = 56 in each group), Unified Parkinson's Disease Rating Scale Parts II+III total scores decreased significantly from baseline and to a similar degree with pramipexole ER and IR formulations. In each group, 47 double-blind patients (83.9%) reported adverse events (AEs), requiring withdrawal of 3 ER patients (5.4%) and 2 IR patients (3.6%). Trough plasma levels at steady state (at the same doses and dose-normalized concentrations) were also similar with both formulations. Among open-label treatment patients (n = 53 from IR to ER), 83% were successfully switched (no worsening of PD symptoms) to pramipexole ER. In L-dopa-treated patients, pramipexole ER and pramipexole IR demonstrated similar efficacy, safety, tolerability, and trough plasma levels. Patients can be safely switched overnight from pramipexole IR to pramipexole ER with no impact on efficacy.

  8. Fission gas release at high burn-up: beyond the standard diffusion model

    International Nuclear Information System (INIS)

    Landskron, H.; Sontheimer, F.; Billaux, M.R.

    2002-01-01

    At high burn-up standard diffusion models describing the release of fission gases from nuclear fuel must be extended to describe the experimental loss of xenon observed in the fuel matrix of the rim zone. Marked improvements of the prediction of integral fission gas release of fuel rods as well as of radial fission gas profiles in fuel pellets are achieved by using a saturation concept to describe fission gas behaviour not only in the pellet rim but also as an additional fission gas path in the whole pellet. (author)

  9. Pharmacokinetics of a once-daily extended-release formulation of pramipexole in healthy male volunteers: three studies.

    Science.gov (United States)

    Jenner, Peter; Könen-Bergmann, Michael; Schepers, Cornelia; Haertter, Sebastian

    2009-11-01

    Pramipexole is a dopamine agonist used in the treatment of Parkinson's disease. The currently available immediate-release (IR) formulation is taken orally 3 times daily. These studies were conducted to evaluate the pharmacokinetic properties of a variety of prototypes for a once-daily extended-release (ER) formulation of pramipexole and to further characterize the prototype whose pharmacokinetics best matched those of the IR formulation. Three Phase I studies were conducted, all in healthy adult men aged food effect. In the third study, steady-state pharmacokinetics of the optimal ER formulation were assessed across a range of pramipexole doses (0.375-4.5 mg/d), including investigation of the food effect at steady state for the highest dose. Tolerability was assessed throughout all studies based on physical examinations, laboratory measurements, and adverse events (AEs). The 3 studies included 18, 15, and 39 subjects, respectively. Among the ER prototypes tested at 0.75 mg once daily in study 1, a matrix tablet had the optimal pharmacokinetic resemblance to IR pramipexole 0.25 mg TID, with a geometric mean AUC(0-24h,ss) of 17.4 ng.h/mL (vs 16.0 ng.h/mL for the IR formulation), C(max,ss) of 0.967 ng/mL (vs 1.09 ng/mL), and C(min,ss) of 0.455 ng/mL (vs 0.383 ng/mL). For single-dose ER 0.375 mg administered in the fasted state in study 2, in vivo bioavailability was predictable from in vitro dissolution data, with internal mean absolute percent prediction errors of 3.18% for AUC(0-30h) and 4.87% for C(max), and external mean absolute prediction errors of 6.61% and 3.34%, respectively, satisfying current guidelines for a level A IVIVC. For single-dose ER 0.375 mg administered in the fed state, the upper bound of the 90% CI for fed:fasted values was 119.8 for AUC(0-30h) (within the bioequivalence limits of 80%-125%) and 134.1 for C(max). At steady state in study 3 (subjects' 5th treatment day), dosing at 0.375 to 4.5 mg in the fasted state was associated with a linear

  10. THE RAVE CATALOG OF STELLAR ELEMENTAL ABUNDANCES: FIRST DATA RELEASE

    International Nuclear Information System (INIS)

    Boeche, C.; Williams, M.; De Jong, R. S.; Steinmetz, M.; Siebert, A.; Bienaymé, O.; Fulbright, J. P.; Ruchti, G. R.; Bland-Hawthorn, J.; Campbell, R.; Freeman, K. C.; Gibson, B. K.; Gilmore, G.; Grebel, E. K.; Helmi, A.; Munari, U.; Navarro, J. F.; Parker, Q. A.; Reid, W.; Seabroke, G. M.

    2011-01-01

    We present chemical elemental abundances for 36,561 stars observed by the RAdial Velocity Experiment (RAVE), an ambitious spectroscopic survey of our Galaxy at Galactic latitudes |b| > 25° and with magnitudes in the range 9 DENIS 2 minimization technique. We plan to extend this pipeline to include estimates for other elements, such as oxygen and sulfur, in future data releases.

  11. Biphasic insulin-releasing effect of BTS 67 582 in rats.

    Science.gov (United States)

    Storey, D A; Bailey, C J

    1998-12-01

    BTS 67 582 (1,1-dimethyl-2(2-morpholinophenyl)guanidine fumarate) is being developed as a short-acting anti-diabetic insulin secretagogue. The effect of BTS 67 582 on the phasic pattern of insulin release was assessed in anaesthetized normal rats by measuring arterial plasma insulin concentrations while arterial glucose concentrations were fixed at 6, 8.5 and 12.5 mM. Intravenous BTS 67 582 (10 mg kg(-1)) induced an immediate but transient increase in insulin concentrations which declined by 10 min (first phase). This was followed by a smaller but sustained increase in insulin concentrations (second phase). The increment from basal to peak insulin release (0-2 min) was independent of glucose, but the first phase was maintained for longer and the second phase was greater at the highest concentration of glucose (12.5 mM). BTS 67 582 also extended the first-phase insulin response to a standard intravenous glucose challenge and enhanced the rate of glucose disappearance by approximately 12%. Thus BTS 67 582 causes biphasic stimulation of insulin release and augments the insulin-releasing effect of glucose.

  12. Use of fibrin sealants for the localized, controlled release of cefazolin

    Science.gov (United States)

    Tredwell, Stephen; Jackson, John K.; Hamilton, Donald; Lee, Vivian; Burt, Helen M.

    2006-01-01

    Background Fibrin sealants are used increasingly in surgery to reduce bleeding and improve wound healing. They have great potential as biocompatible, biodegradable drug delivery systems, because the sealant may adhere to the target tissue and allow controlled release of the drug over an extended period. We investigated the encapsulation, stability and controlled release of erythromycin and cefazolin from Beriplast fibrin sealants (Aventis Behring Canada). Methods Drug-loaded clots were cast in glass vials and allowed to set. We observed the clots for drug precipitation and aggregation, and we assessed the effect of drug encapsulation on clot strength. Drug stability and release from the clots in phosphate buffered saline (PBS) was quantified by ultraviolet and visible violet absorbance spectroscopy and high-performance liquid chromatography. Results Erythromycin was found to release slowly from the fibrin clots over the first 2 hours but then degrade rapidly. Cefazolin was found to be very stable in clots in PBS (97% stable at 2 d and 93% stable at 5 d). The drug released in a controlled manner over 2 days, with most being released during the first day. The dose of drug released could be varied by changing the amount placed in the thrombin solution. Clot thickness had no effect on the rate of cefazolin release. Conclusion Overall, the 2-day release profile and the excellent stability of the drug suggest that cefazolin-loaded fibrin sealants may offer an effective route of postoperative antibiotic delivery. PMID:17152573

  13. Formulation and evaluation of sustained release matrix tablets of pioglitazone hydrochloride using processed Aloe vera mucilage as release modifier

    Directory of Open Access Journals (Sweden)

    Manoj Choudhary

    2015-01-01

    Full Text Available Background: Natural gums and mucilage which hydrates and swells on contact with aqueous media are used as additives in the formulation of hydrophilic drug delivery system. Aim: The purpose of this study was to develop a new monolithic matrix system for complete delivery of Pioglitazone hydrochloride (HCl, in a zero-order manner over an extended time period using processed Aloe vera gel mucilage (PAG as a release modifier. Materials and Methods: The matrices were prepared by dry blending of selected ratios of polymer and ingredients using direct compression technique. Physicochemical properties of dried powdered mucilage of A. vera were studied. Various formulations of pioglitazone HCl and A. vera mucilage were prepared using different drug: Polymer ratios viz., 1:1, 1:2, 1:3, 1:4, 1:5 for PAG by direct compression technique. Results: The formulated matrix tablets were found to have better uniformity of weight and drug content with low statistical deviation. The swelling behavior and in vitro release rate characteristics were also studied. Conclusion: The study proved that the dried A. vera mucilage can be used as a matrix forming material for controlled release of Pioglitazone HCl matrix tablets.

  14. Metformin extended release treatment of adolescent obesity: a 48-week randomized, double-blind, placebo-controlled trial with 48-week follow-up.

    Science.gov (United States)

    Wilson, Darrell M; Abrams, Stephanie H; Aye, Tandy; Lee, Phillip D K; Lenders, Carine; Lustig, Robert H; Osganian, Stavroula V; Feldman, Henry A

    2010-02-01

    Metformin has been proffered as a therapy for adolescent obesity, although long-term controlled studies have not been reported. To test the hypothesis that 48 weeks of daily metformin hydrochloride extended release (XR) therapy will reduce body mass index (BMI) in obese adolescents, as compared with placebo. Multicenter, randomized, double-blind, placebo-controlled clinical trial. The 6 centers of the Glaser Pediatric Research Network from October 2003 to August 2007. Obese (BMI > or = 95th percentile) adolescents (aged 13-18 years) were randomly assigned to the intervention (n = 39) or placebo groups. Intervention Following a 1-month run-in period, subjects following a lifestyle intervention program were randomized 1:1 to 48 weeks' treatment with metformin hydrochloride XR, 2000 mg once daily, or an identical placebo. Subjects were monitored for an additional 48 weeks. Main Outcome Measure Change in BMI, adjusted for site, sex, race, ethnicity, and age and metformin vs placebo. After 48 weeks, mean (SE) adjusted BMI increased 0.2 (0.5) in the placebo group and decreased 0.9 (0.5) in the metformin XR group (P = .03). This difference persisted for 12 to 24 weeks after cessation of treatment. No significant effects of metformin on body composition, abdominal fat, or insulin indices were observed. Metformin XR caused a small but statistically significant decrease in BMI when added to a lifestyle intervention program. clinicaltrials.gov Identifiers: NCT00209482 and NCT00120146.

  15. Optimising pain management- An update

    African Journals Online (AJOL)

    or managing the side-effects of pain medication. This will only be possible .... structure of tapentadol is unlike other opioids such as morphine, but resembles .... together with psychological and rehabilitative modalities.36 This multidimensional ...

  16. Umatilla Satellite and Release Sites Project : Final Siting Report.

    Energy Technology Data Exchange (ETDEWEB)

    Montgomery, James M.

    1992-04-01

    This report presents the results of site analysis for the Umatilla Satellite and Release Sites Project. The purpose of this project is to provide engineering services for the siting and conceptual design of satellite and release facilities for the Umatilla Basin hatchery program. The Umatilla Basin hatchery program consists of artificial production facilities for salmon and steelhead to enhance production in the Umatilla River as defined in the Umatilla master plan approved in 1989 by the Northwest Power Planning Council. Facilities identified in the master plan include adult salmon broodstock holding and spawning facilities, facilities for recovery, acclimation, and/or extended rearing of salmon juveniles, and development of river sites for release of hatchery salmon and steelhead. The historic and current distribution of fall chinook, summer chinook, and coho salmon and steelhead trout was summarized for the Umatilla River basin. Current and future production and release objectives were reviewed. Twenty seven sites were evaluated for the potential and development of facilities. Engineering and environmental attributes of the sites were evaluated and compared to facility requirements for water and space. Site screening was conducted to identify the sites with the most potential for facility development. Alternative sites were selected for conceptual design of each facility type. A proposed program for adult holding facilities, final rearing/acclimation, and direct release facilities was developed.

  17. Drug delivery systems with modified release for systemic and biophase bioavailability.

    Science.gov (United States)

    Leucuta, Sorin E

    2012-11-01

    This review describes the most important new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body. Drug delivery of these pharmaceutical formulations has the benefit of improving product efficacy and safety, as well as patient convenience and compliance. This paper describes the biopharmaceutical, pharmacokinetic, pharmacologic and technological principles in the design of drug delivery systems with modified release as well as the formulation criteria of prolonged and controlled release drug delivery systems. The paper presents pharmaceutical prolonged and controlled release dosage forms intended for different routes of administration: oral, ocular, transdermal, parenteral, pulmonary, mucoadhesive, but also orally fast dissolving tablets, gastroretentive drug delivery systems, colon-specific drug delivery systems, pulsatile drug delivery systems and carrier or ligand mediated transport for site specific or receptor drug targeting. Specific technologies are given on the dosage forms with modified release as well as examples of marketed products, and current research in these areas.

  18. Controlled release of insect sex pheromones from paraffin wax and emulsions.

    Science.gov (United States)

    Atterholt, C A; Delwiche, M J; Rice, R E; Krochta, J M

    1999-02-22

    Paraffin wax and aqueous paraffin emulsions can be used as controlled release carriers for insect sex pheromones for mating disruption of orchard pests. Paraffin can be applied at ambient temperature as an aqueous emulsion, adheres to tree bark or foliage, releases pheromone for an extended period of time, and will slowly erode from bark and biodegrade in soil. Pheromone emulsions can be applied with simple spray equipment. Pheromone release-rates from paraffin were measured in laboratory flow-cell experiments. Pheromone was trapped from an air stream with an adsorbent, eluted periodically, and quantified by gas chromatography. Pheromone release from paraffin was partition-controlled, providing a constant (zero-order) release rate. A typical paraffin emulsion consisted of 30% paraffin, 4% pheromone, 4% soy oil, 1% vitamin E, 2% emulsifier, and the balance water. Soy oil and vitamin E acted as volatility suppressants. A constant release of oriental fruit moth pheromone from paraffin emulsions was observed in the laboratory for more than 100 days at 27 degreesC, with release-rates ranging from 0.4 to 2 mg/day, depending on the concentration and surface area of the dried emulsion. The use of paraffin emulsions is a viable method for direct application of insect pheromones for mating disruption. Sprayable formulations can be designed to release insect pheromones to the environment at a rate necessary for insect control by mating disruption. At temperatures below 38 degreesC, zero-order release was observed. At 38 degreesC and higher, pheromone oxidation occurred. A partition-controlled release mechanism was supported by a zero-order pheromone release-rate, low air/wax partition coefficients, and pheromone solubility in paraffin.

  19. Safety and tolerability of extended-release niacin-laropiprant: Pooled analyses for 11,310 patients in 12 controlled clinical trials.

    Science.gov (United States)

    McKenney, James; Bays, Harold; Gleim, Gilbert; Mitchel, Yale; Kuznetsova, Olga; Sapre, Aditi; Sirah, Waheeda; Maccubbin, Darbie

    2015-01-01

    The Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) showed that adding extended-release niacin-laropiprant (ERN-LRPT) to statin provided no incremental cardiovascular benefit vs placebo (PBO). ERN-LRPT was also associated with an excess of serious adverse experiences (AEs), some of which were unexpected (infections and bleeding). These findings led to the withdrawal of ERN-LRPT from all markets. We examined the safety profile of ERN-LRPT vs the comparators ERN alone and statins in the ERN-LRPT development program to assess whether similar safety signals were observed to those seen in HPS-THRIVE and whether these might be attributed to ERN or LRPT. Postrandomization safety data from 12 clinical studies, 12 to 52 weeks in duration and involving 11,310 patients, were analyzed across 3 treatments: (1) ERN-LRPT; (2) ERN-NSP (ERN, Merck & Co, Inc or Niaspan [NSP], Abbott Laboratories); and (3) statin-PBO (statin or PBO). The safety profiles of ERN-LRPT and ERN-NSP were similar, except for less flushing with ERN-LRPT. Nonflushing AEs reported more frequently with ERN-LRPT or ERN-NSP than with statin-PBO were mostly nonserious and typical of niacin (nausea, diarrhea, and increased blood glucose). There was no evidence for an increased risk of serious AEs related to diabetes, muscle, infection, or bleeding. Pooled data from 11,310 patients revealed that, except for reduced flushing, the safety profile of ERN-LRPT was similar to that of ERN-NSP; LRPT did not appear to adversely affect the side-effect profile of ERN. The inability to replicate the unexpected AE findings in HPS2-THRIVE could be because of the smaller sample size and substantially shorter duration of these studies. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  20. Airborne system for mapping and tracking extended gamma ray sources

    International Nuclear Information System (INIS)

    Stuart, T.P.; Hendricks, T.J.; Wallace, G.G.; Cleland, J.R.

    1976-01-01

    An airborne system was developed for mapping and tracking extended sources of airborne or terrestrially distributed γ-ray emitters. The system records 300 channel γ-ray spectral data every three seconds on magnetic tape. Computer programs have been written to isolate the contribution from the particular radionuclide of interest. Aircraft position as sensed by a microwave ranging system is recorded every second on magnetic tape. Measurements of airborne stack releases of 41 A concentrations versus time or aircraft position agree well with computer code predictions

  1. Risk Metrics and Measures for an Extended PSA

    International Nuclear Information System (INIS)

    Wielenberg, A.; Loeffler, H.; Hasnaoui, C.; Burgazzi, L.; Cazzoli, E.; Jan, P.; La Rovere, S.; Siklossy, T.; Vitazkova, J.; Raimond, E.

    2016-01-01

    This report provides a review of the main used risk measures for Level 1 and Level 2 PSA. It depicts their advantages, limitations and disadvantages and develops some more precise risk measures relevant for extended PSAs and helpful for decision-making. This report does not recommend or suggest any quantitative value for the risk measures. It does not discuss in details decision-making based on PSA results neither. The choice of one appropriate risk measure or a set of risk measures depends on the decision making approach as well as on the issue to be decided. The general approach for decision making aims at a multi-attribute approach. This can include the use of several risk measures as appropriate. Section 5 provides some recommendations on the main risk metrics to be used for an extended PSA. For Level 1 PSA, Fuel Damage Frequency and Radionuclide Mobilization Frequency are recommended. For Level 2 PSA, the characterization of loss of containment function and a total risk measure based on the aggregated activity releases of all sequences rated by their frequencies is proposed. (authors)

  2. Release mechanisms of acetaminophen from polyethylene oxide/polyethylene glycol matrix tablets utilizing magnetic resonance imaging.

    Science.gov (United States)

    Tajiri, Tomokazu; Morita, Shigeaki; Sakamoto, Ryosaku; Suzuki, Masazumi; Yamanashi, Shigeyuki; Ozaki, Yukihiro; Kitamura, Satoshi

    2010-08-16

    Release mechanism of acetaminophen (AAP) from extended-release tablets of hydrogel polymer matrices containing polyethylene oxide (PEO) and polyethylene glycol (PEG) were achieved using flow-through cell with magnetic resonance imaging (MRI). The hydrogel forming abilities are observed characteristically and the layer thickness which is corresponding to the diffusion length of AAP has a good correlation with the drug release profiles. In addition, polymeric erosion contribution to AAP releasing from hydrogel matrix tablets was directly quantified using size-exclusion chromatography (SEC). The matrix erosion profile indicates that the PEG erosion kinetic depends primarily on the composition ratio of PEG to PEO. The present study has confirmed that the combination of in situ MRI and SEC should be well suited to investigate the drug release mechanisms of hydrogel matrix such as PEO/PEG. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  3. The social functional outcome of being naturalistically treated with paliperidone extended-release in patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Nakagawa R

    2015-06-01

    Full Text Available Ryoko Nakagawa,1 Takashi Ohnishi,1 Hisanori Kobayashi,1 Akihide Wakamatsu,2 Ai Tanimura,3 Kazuo Morita,3 Toshio Yamaoka,3 Hideo Usui,3 Yoshimasa Ogawa,3 Akiko Fujino,3 Kazutake Yoshizawa11Evidence Generation Department, Medical Affairs Division, 2Medical Affairs Strategy Department, Medical Affairs Division, 3Drug Safety Surveillance Department, Japan Safety and Surveillance Division, Janssen Pharmaceutical K.K., Tokyo, JapanBackground: Social functioning is an important outcome for patients with schizophrenia. To evaluate the effects of paliperidone extended-release (PAL-ER on social function, symptomatology, and safety in the routine clinical practice, we conducted a 1-year post-marketing surveillance study of PAL-ER. We also explored relationships between symptomatic improvement and socially functional outcome in patients with schizophrenia.Patients and methods: Patients with an established diagnosis of schizophrenia were allowed flexible 3–12 mg/day dosing during the surveillance. Patients were assessed on social functioning using the Social and Occupational Functioning Assessment Scale (SOFAS and on symptomatology using the Clinical Global Impression–Schizophrenia scale. All adverse events (AEs were also collected.Results: A total of 1,429 patients were enrolled in the surveillance study, of whom 1,405 were evaluable for safety and 1,142 were evaluable for efficacy. The treatment discontinuation rate for any reason during the observation period was 34.66%. Significant improvements were observed on both Social and Occupational Functioning Assessment Scale and Clinical Global Impression–Schizophrenia scale during the observation period. The percentage of patients with socially functional remission (SOFAS ≥61 also increased significantly. A significant association between early improvements in positive symptoms, sex, severity of negative symptoms at baseline, and socially functional remission was observed. A total of 33.52% of patients

  4. Burnable absorber rod releasable latching structure

    International Nuclear Information System (INIS)

    Gjertsen, R.K.; Wilson, J.F.

    1987-01-01

    An elongated nuclear reactivity control member, a releasable latching structure useful for releasably attaching the control member at an end to a top nozzle adapter plate of a nuclear fuel assembly is described comprising: (a) a mounting body including an inner plug portion attached to the end of the control member and an outer end portion disposed axially outward from the inner plug portion and the end of the member; and (b) a spring latch disposed about the mounting body and being attached to the outer end portion. The spring latch has at least one latch finger extending toward the inner plug portion of the body and is movable toward and away from the body between an outer latching position in which the finger is adapted to engage a fuel assembly top nozzle adapter plate and retain the elongated member in a stationary relationship with respect to the adapter plate and an inner unlatching position in which the finger is adapted to disengage from the adapter plate and allow removal of the member from the adapter plate

  5. Managing severe pain and abuse potential: the potential impact of a new abuse-deterrent formulation oxycodone/naltrexone extended-release product

    Directory of Open Access Journals (Sweden)

    Pergolizzi, J

    2018-02-01

    Full Text Available Joseph V Pergolizzi, Jr,1 Robert Taylor Jr,1 Jo Ann LeQuang,1 Robert B Raffa2,3 On behalf of the NEMA Research Group 1NEMA Research Inc., Naples, FL, USA; 2University of Arizona College of Pharmacy, Tucson, AZ, USA; 3Temple University School of Pharmacy, Philadelphia, PA, USA Abstract: Proper management of severe pain represents one of the most challenging clinical dilemmas. Two equally important goals must be attained: the humanitarian/medical goal to relieve suffering and the societal/legal goal to not contribute to the drug abuse problem. This is an age-old problem, and the prevailing emphasis placed on one or the other goal has resulted in pendulum swings that have resulted in either undertreatment of pain or the current epidemic of misuse and abuse. In an effort to provide efficacious strong pain relievers (opioids that are more difficult to abuse by the most dangerous routes of administration, pharmaceutical companies are developing products in which the opioid is manufactured in a formulation that is designed to be tamper resistant. Such a product is known as an abuse-deterrent formulation (ADF. ADF opioid products are designed to deter or resist abuse by making it difficult to tamper with the product and extracting the opioid for inhalation or injection. To date, less than a dozen opioid formulations have been approved by the US Food and Drug Administration to carry specific ADF labeling, but this number will likely increase in the coming years. Most of these products are extended-release formulations. Keywords: oxycodone/naltrexone, abuse-deterrent formulation, abuse-deterrent opioid, oxycodone, abuse liability

  6. Effect of Food Intake on the Pharmacokinetics of a Novel Methylphenidate Extended-Release Oral Suspension for Attention Deficit Hyperactivity Disorder.

    Science.gov (United States)

    Sallee, Floyd R; Palumbo, Donna R; Abbas, Richat; Berry, Sally A; Puthli, Shivanand P; Kathala, Kalyan K

    2017-09-01

    We conducted an open-label, single-dose, randomized, crossover study in healthy adults to assess the impact of food on the bioavailability of 60 mg methylphenidate extended-release oral suspension (MEROS; Quillivant XR™)-a long-acting stimulant for the treatment of attention deficit hyperactivity disorder-by comparing the pharmacokinetic parameters under fed and fasting conditions. When MEROS 60 mg was administered under fed conditions compared with fasting conditions, the exposure of methylphenidate (d enantiomer) was higher, with a mean area under the plasma concentration-vs-time curve (AUC) 0-t of 160.2 ng·h/mL vs 140.4 ng·h/mL, and a mean AUC 0-inf of 163.2 ng·h/mL vs 143.7 ng·h/mL, respectively. The ratios of the ln-transformed geometric means for methylphenidate for AUC 0-t and AUC 0-inf were 119.5% (90%CI, 115.7% to 123.5%) and 119.0% (90%CI, 115.2% to 122.8%), respectively, within the standard 80% to 125% bioequivalence acceptance range indicating no food effect on the overall exposure (rate and extent). There was a small increase in the peak plasma concentration (127.6% [90%CI, 119.9% to 135.8%]). However, this effect was small and not likely to be clinically significant. Overall, MEROS 60 mg was safe in both the fed and fasting condition when administered to healthy volunteers in this study. © 2017 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

  7. Treatment of painful diabetic neuropathy

    Science.gov (United States)

    Petropoulos, Ioannis N.; Alam, Uazman; Malik, Rayaz A.

    2015-01-01

    Painful diabetic neuropathy (PDN) is a debilitating consequence of diabetes that may be present in as many as one in five patients with diabetes. The objective assessment of PDN is difficult, making it challenging to diagnose and assess in both clinical practice and clinical trials. No single treatment exists to prevent or reverse neuropathic changes or to provide total pain relief. Treatment of PDN is based on three major approaches: intensive glycaemic control and risk factor management, treatments based on pathogenetic mechanisms, and symptomatic pain management. Clinical guidelines recommend pain relief in PDN through the use of antidepressants such as amitriptyline and duloxetine, the γ-aminobutyric acid analogues gabapentin and pregabalin, opioids and topical agents such as capsaicin. Of these medications, duloxetine and pregabalin were approved by the US Food and Drug Administration (FDA) in 2004 and tapentadol extended release was approved in 2012 for the treatment of PDN. Proposed pathogenetic treatments include α-lipoic acid (stems reactive oxygen species formation), benfotiamine (prevents vascular damage in diabetes) and aldose-reductase inhibitors (reduces flux through the polyol pathway). There is a growing need for studies to evaluate the most potent drugs or combinations for the management of PDN to maximize pain relief and improve quality of life. A number of agents are potential candidates for future use in PDN therapy, including Nav 1.7 antagonists, N-type calcium channel blockers, NGF antibodies and angiotensin II type 2 receptor antagonists. PMID:25553239

  8. Controlled release systems containing solid dispersions: strategies and mechanisms.

    Science.gov (United States)

    Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Park, Jun Bom; Lee, Beom-Jin

    2011-10-01

    In addition to a number of highly soluble drugs, most new chemical entities under development are poorly water-soluble drugs generally characterized by an insufficient dissolution rate and a small absorption window, leading to the low bioavailability. Controlled-release (CR) formulations have several potential advantages over conventional dosage forms, such as providing a uniform and prolonged therapeutic effect to improve patient compliance, reducing the frequency of dosing, minimizing the number of side effects, and reducing the strength of the required dose while increasing the effectiveness of the drug. Solid dispersions (SD) can be used to enhance the dissolution rate of poorly water-soluble drugs and to sustain the drug release by choosing an appropriate carrier. Thus, a CR-SD comprises both functions of SD and CR for poorly water-soluble drugs. Such CR dosage forms containing SD provide an immediately available dose for an immediate action followed by a gradual and continuous release of subsequent doses to maintain the plasma concentration of poorly water-soluble drugs over an extended period of time. This review aims to summarize all currently known aspects of controlled release systems containing solid dispersions, focusing on the preparation methods, mechanisms of action and characterization of physicochemical properties of the system.

  9. A modified SILCS contraceptive diaphragm for long-term controlled release of the HIV microbicide dapivirine.

    Science.gov (United States)

    Major, Ian; Boyd, Peter; Kilbourne-Brook, Maggie; Saxon, Gene; Cohen, Jessica; Malcolm, R Karl

    2013-07-01

    There is considerable interest in developing new multipurpose prevention technologies to address women's reproductive health needs. This study describes an innovative barrier contraceptive device--based on the SILCS diaphragm--that also provides long-term controlled release of the lead candidate anti-HIV microbicide dapivirine. Diaphragm devices comprising various dapivirine-loaded polymer spring cores overmolded with a nonmedicated silicone elastomer sheath were fabricated by injection molding processes. In vitro release testing, thermal analysis and mechanical characterization were performed on the devices. A diaphragm device containing a polyoxymethylene spring core loaded with 10% w/w dapivirine provided continuous and controlled release of dapivirine over a 6-month period, with a mean in vitro daily release rate of 174 mcg/day. The mechanical properties of the new diaphragm were closely matched to the SILCS diaphragm. The study demonstrates proof of concept for a dapivirine-releasing diaphragm with daily release quantities potentially capable of preventing HIV transmission. In discontinuous clinical use, release of dapivirine may be readily extended over 1 or more years. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Acute opioid withdrawal precipitated by ingestion of crushed embeda (morphine extended release with sequestered naltrexone): case report and the focused review of the literature.

    Science.gov (United States)

    Ruan, Xiulu; Chen, Tao; Gudin, Jeff; Couch, John Patrick; Chiravuri, Srinivas

    2010-01-01

    The introduction of newly formulated extended release (ER) morphine with sequestered naltrexone (Embeda) has provided another treatment option for moderate to severe persistent pain. Embeda was designed to be an abuse-deterrent opioid formulation. Naltrexone is a centrally acting opioid receptor antagonist that blocks the action of opioid. When taken as directed, insignificant amount of sequestered naltrexone would reach systemic circulation, but upon tampering, the released naltrexone may blunt the euphoria of opioids, and possibly precipitate opioid withdrawal in opioid-dependent patient. To describe a case report ofa 50-year-old opioid-dependent male who developed acute opioid withdrawal after taking crushed Embeda. A 50-year-old male with severe, chronic low back pain due to degenerative disc disease was referred to our clinic for pain management. He was taking ER oxycodone 80 mg tid and Roxicodone 30 mg qid prn, with inadequate pain relief A trial of ER oxymorphone was decided, at 40 mg 1-2 doses bid. The patient returned to the clinic 1 week early, out of his ER oxymorphone. At this time, the decision to switch him to Embeda was made, at 80 mg/3.2 mg, 1-2 doses bid. The patient and his family members were counseled about risk involved with tampering with Embeda. A few hours later, our clinic was informed that the patient was brought to emergency room by ambulance, in severe opioid withdrawal. He was treated with IV fluid, antiemetics, clonidine, and IV hydromorphone. His condition improved and he was discharged home the next morning. Later on, the patient admitted that he took two prescribed Embeda within half an hour, the 1st one whole and the 2nd one crushed. He further admitted that he did so against our medical advice. CONCLUSION. Taking tampered Embeda may precipitate opioid withdrawal in opioid-tolerant patient. To the best of our knowledge, this is the first report of induced opioid withdrawal following consumption of crushed Embeda.

  11. Injection-induced moment release can also be aseismic

    Science.gov (United States)

    McGarr, Arthur; Barbour, Andrew J.

    2018-01-01

    The cumulative seismic moment is a robust measure of the earthquake response to fluid injection for injection volumes ranging from 3100 to about 12 million m3. Over this range, the moment release is limited to twice the product of the shear modulus and the volume of injected fluid. This relation also applies at the much smaller injection volumes of the field experiment in France reported by Guglielmi, et al. (2015) and laboratory experiments to simulate hydraulic fracturing described by Goodfellow, et al. (2015). In both of these studies, the relevant moment release for comparison with the fluid injection was aseismic and consistent with the scaling that applies to the much larger volumes associated with injection-induced earthquakes with magnitudes extending up to 5.8. Neither the micro-earthquakes, at the site in France, nor the acoustic emission in the laboratory samples contributed significantly to the deformation due to fluid injection.

  12. Development and evaluation of accelerated drug release testing methods for a matrix-type intravaginal ring.

    Science.gov (United States)

    Externbrink, Anna; Eggenreich, Karin; Eder, Simone; Mohr, Stefan; Nickisch, Klaus; Klein, Sandra

    2017-01-01

    Accelerated drug release testing is a valuable quality control tool for long-acting non-oral extended release formulations. Currently, several intravaginal ring candidates designed for the long-term delivery of steroids or anti-infective drugs are being in the developing pipeline. The present article addresses the demand for accelerated drug release methods for these formulations. We describe the development and evaluation of accelerated release methods for a steroid releasing matrix-type intravaginal ring. The drug release properties of the formulation were evaluated under real-time and accelerated test conditions. Under real-time test conditions drug release from the intravaginal ring was strongly affected by the steroid solubility in the release medium. Under sufficient sink conditions that were provided in release media containing surfactants drug release was Fickian diffusion driven. Both temperature and hydro-organic dissolution media were successfully employed to accelerate drug release from the formulation. Drug release could be further increased by combining the temperature effect with the application of a hydro-organic release medium. The formulation continued to exhibit a diffusion controlled release kinetic under the investigated accelerated conditions. Moreover, the accelerated methods were able to differentiate between different prototypes of the intravaginal ring that exhibited different release profiles under real-time test conditions. Overall, the results of the present study indicate that both temperature and hydro-organic release media are valid parameters for accelerating drug release from the intravaginal ring. Variation of either a single or both parameters yielded release profiles that correlated well with real-time release. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. An atomistic methodology of energy release rate for graphene at nanoscale

    International Nuclear Information System (INIS)

    Zhang, Zhen; Lee, James D.; Wang, Xianqiao

    2014-01-01

    Graphene is a single layer of carbon atoms packed into a honeycomb architecture, serving as a fundamental building block for electric devices. Understanding the fracture mechanism of graphene under various conditions is crucial for tailoring the electrical and mechanical properties of graphene-based devices at atomic scale. Although most of the fracture mechanics concepts, such as stress intensity factors, are not applicable in molecular dynamics simulation, energy release rate still remains to be a feasible and crucial physical quantity to characterize the fracture mechanical property of materials at nanoscale. This work introduces an atomistic simulation methodology, based on the energy release rate, as a tool to unveil the fracture mechanism of graphene at nanoscale. This methodology can be easily extended to any atomistic material system. We have investigated both opening mode and mixed mode at different temperatures. Simulation results show that the critical energy release rate of graphene is independent of initial crack length at low temperature. Graphene with inclined pre-crack possesses higher fracture strength and fracture deformation but smaller critical energy release rate compared with the graphene with vertical pre-crack. Owing to its anisotropy, graphene with armchair chirality always has greater critical energy release rate than graphene with zigzag chirality. The increase of temperature leads to the reduction of fracture strength, fracture deformation, and the critical energy release rate of graphene. Also, higher temperature brings higher randomness of energy release rate of graphene under a variety of predefined crack lengths. The energy release rate is independent of the strain rate as long as the strain rate is small enough

  14. Aspirin and Extended-Release Dipyridamole

    Science.gov (United States)

    ... Mobic), nabumetone (Relafen), naproxen (Aleve, Naprosyn), oxaprozin (Daypro), piroxicam (Feldene), rofecoxib (Vioxx) (no longer available in the ... Mobic), nabumetone (Relafen), naproxen (Aleve, Naprosyn), oxaprozin (Daypro), piroxicam (Feldene), sulindac (Clinoril), and tolmetin (Tolectin); phenytoin (Dilantin); ...

  15. Effect of Concomitant Medications on the Safety and Efficacy of Extended-Release Carbidopa-Levodopa (IPX066) in Patients With Advanced Parkinson Disease: A Post Hoc Analysis.

    Science.gov (United States)

    LeWitt, Peter A; Verhagen Metman, Leo; Rubens, Robert; Khanna, Sarita; Kell, Sherron; Gupta, Suneel

    Extended-release (ER) carbidopa-levodopa (CD-LD) (IPX066/RYTARY/NUMIENT) produces improvements in "off" time, "on" time without troublesome dyskinesia, and Unified Parkinson Disease Rating Scale scores compared with immediate-release (IR) CD-LD or IR CD-LD plus entacapone (CLE). Post hoc analyses of 2 ER CD-LD phase 3 trials evaluated whether the efficacy and safety of ER CD-LD relative to the respective active comparators were altered by concomitant medications (dopaminergic agonists, monoamine oxidase B [MAO-B] inhibitors, or amantadine). ADVANCE-PD (n = 393) assessed safety and efficacy of ER CD-LD versus IR CD-LD. ASCEND-PD (n = 91) evaluated ER CD-LD versus CLE. In both studies, IR- and CLE-experienced patients underwent a 6-week, open-label dose-conversion period to ER CD-LD prior to randomization. For analysis, the randomized population was divided into 3 subgroups: dopaminergic agonists, rasagiline or selegiline, and amantadine. For each subgroup, changes from baseline in PD diary measures ("off" time and "on" time with and without troublesome dyskinesia), Unified Parkinson Disease Rating Scale Parts II + III scores, and adverse events were analyzed, comparing ER CD-LD with the active comparator. Concomitant dopaminergic agonist or MAO-B inhibitor use did not diminish the efficacy (improvement in "off" time and "on" time without troublesome dyskinesia) of ER CD-LD compared with IR CD-LD or CLE, whereas the improvement with concomitant amantadine failed to reach significance. Safety and tolerability were similar among the subgroups, and ER CD-LD did not increase troublesome dyskinesia. For patients on oral LD regimens and taking a dopaminergic agonist, and/or a MAO-B inhibitor, changing from an IR to an ER CD-LD formulation provides approximately an additional hour of "good" on time.

  16. How Far Can Extended Knowledge Be Extended?

    DEFF Research Database (Denmark)

    Wray, K. Brad

    2018-01-01

    by an artifact, like a notebook or telescope. The chapter illustrates this by applying Pritchard’s account of extended knowledge to collaborating scientists. The beliefs acquired through collaborative research cannot satisfy both of Pritchard’s conditions of creditability. Further, there is evidence......Duncan Pritchard (2010) has developed a theory of extended knowledge based on the notion of extended cognition initially developed by Clark and Chalmers (1998). Pritchard’s account gives a central role to the notion of creditability, which requires the following two conditions to be met: (i...... that scientists are not prepared to take responsibility for the actions of the scientists with whom they collaborate....

  17. Coupling 3D printing with hot-melt extrusion to produce controlled-release tablets.

    Science.gov (United States)

    Zhang, Jiaxiang; Feng, Xin; Patil, Hemlata; Tiwari, Roshan V; Repka, Michael A

    2017-03-15

    The main objective of this work was to explore the potential of coupling fused deposition modeling in three-dimensional (3D) printing with hot-melt extrusion (HME) technology to facilitate additive manufacturing, in order to fabricate tablets with enhanced extended release properties. Acetaminophen was used as the model drug and different grades and ratios of polymers were used to formulate tablets. Three-point bending and hardness tests were performed to determine the mechanical properties of the filaments and tablets. 3D-printed tablets, directly compressed mill-extruded tablets, and tablets prepared from a physical mixture were evaluated for drug release rates using a USP-II dissolution apparatus. The surface and cross-sectional morphology of the 3D-printed tablets were assessed by scanning electron microscopy. Differential scanning calorimetry and thermogravimetric analysis were used to characterize the crystal states and thermal properties of materials, respectively. The 3D-printed tablets had smooth surfaces and tight structures; therefore, they showed better extended drug release rates than the directly compressed tablets did. Further, this study clearly demonstrated the feasibility of coupling HME with 3D printing technology, which allows for the formulation of drug delivery systems using different grades and ratios of pharmaceutical polymers. In addition, formulations can be made based on the personal needs of patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Long-acting injectable paliperidone palmitate versus oral paliperidone extended release: a comparative analysis from two placebo-controlled relapse prevention studies.

    Science.gov (United States)

    Markowitz, Michael; Fu, Dong-Jing; Levitan, Bennett; Gopal, Srihari; Turkoz, Ibrahim; Alphs, Larry

    2013-07-11

    Increasing availability and use of long-acting injectable antipsychotics have generated a need to compare these formulations with their oral equivalents; however, a paucity of relevant data is available. This post hoc comparison of the long-term efficacy, safety and tolerability of maintenance treatment with paliperidone palmitate (PP) versus oral paliperidone extended release (ER) used data from two similarly designed, randomised, double-blind (DB), placebo-controlled schizophrenia relapse prevention trials. Assessments included measures of time to relapse, symptom changes/functioning and treatment-emergent adverse events (TEAEs). Time to relapse between treatment groups was evaluated using a Cox proportional hazards model. Between-group differences for continuous variables for change scores during the DB phase were assessed using analysis of co-variance models. Categorical variables were evaluated using Chi-square and Fisher's exact tests. No adjustment was made for multiplicity. Approximately 45% of enrolled subjects in both trials were stabilised and randomised to the DB relapse prevention phase. Risk of relapse was higher in subjects treated with paliperidone ER than in those treated with PP [paliperidone ER/PP hazard ratio (HR), 2.52; 95% confidence interval (CI), 1.46-4.35; p 70, both approximately 58.5%; p = 1.000] compared with a 10.9% decrease for paliperidone ER (58.5% vs 47.6%, respectively; p = 0.048). The least squares mean change for Positive and Negative Syndrome Scale (PANSS) total score at DB end point in these previously stabilised subjects was 3.5 points in favour of PP (6.0 vs 2.5; p = 0.025). The rates of TEAEs and AEs of interest appeared similar. This analysis supports maintenance of effect with the injectable compared with the oral formulation of paliperidone in patients with schizophrenia. The safety profile of PP was similar to that of paliperidone ER. Future studies are needed to confirm these findings.

  19. Release and transport of fission product cesium in the TMI-2 accident

    International Nuclear Information System (INIS)

    Lorenz, R.A.; Collins, J.L.

    1986-01-01

    Approximately 50% of the fission product cesium was released from the overheated UO 2 fuel in the TMI-2 accident. Steam that boiled away from a water pool in the bottom of the reactor vessel transported the released fission products throughout the reactor coolant system (RCS). Some fission products passed directly through a leaking valve with steam and water into the containment structure, but most deposited on dry surfaces inside of the RCS before being dissolved or resuspended when the RCS was refilled with water. A cesium transport model was developed that extended measured cesium in the RCS back to the first day of the accident. The model revealed that ∼62% of the released 137 Cs deposited on dry surfaces inside of the RCS before being slowly leached and transported out of the RCS in leaked or letdown water. The leach rates from the model agreed reasonably well with those measured in the laboratory. The chemical behavior of cesium in the TMI-2 accident agreed with that observed in fission product release tests at Oak Ridge National Laboratory (ORNL)

  20. Modeling of molten core-concrete interactions and fission-product release

    International Nuclear Information System (INIS)

    Norkus, J.K.; Corradini, M.L.

    1991-09-01

    The study of molten core-concrete interaction is important in estimating the possible consequences of a severe nuclear reactor accident. CORCON-Mod2 is a computer program which models the thermal, chemical, and physical phenomena associated with molten core-concrete interactions. Models have been added to extend and improve the modeling of these phenomena. An ideal solution chemical equilibrium methodology is presented to predict the fission-product vaporization release. Additional chemical species have been added, and the calculation of chemical equilibrium has been expanded to the oxidic layer and to the mixed layer configuration. Recent experiments performed at Argonne National Laboratory are compared to CORCON predictions of melt temperature, erosion depth, and release fraction of fission products. The results consistently underpredicted the melt temperatures and erosion rates. However, the predictions of release of Te, Ba, Sr, and U were good. A sensitivity study of the effects of initial temperature, concrete type, use of the mixing option, degree of zirconium oxidation, cavity size, and amount of control material on erosion, gas production, and release of radioactive materials was performed for a PWR and a BWR. The initial melt temperature had the greatest effect on the results of interest. Concrete type and cavity size also had important effects. 78 refs., 35 figs., 40 tabs

  1. Development and evaluation of diltiazem hydrochloride controlled-release pellets by fluid bed coating process

    Directory of Open Access Journals (Sweden)

    Mikkilineni Bhanu Prasad

    2013-01-01

    Full Text Available The aim of the present study was to develop controlled-release pellets of diltiazem HCl with ethyl cellulose and hydroxylpropyl methylcellulose phthalate as the release rate retarding polymers by fluid bed coating technique. The prepared pellets were evaluated for drug content, particle size, subjected to Scanning Electron Microscopy (SEM and Differential Scanning Calori metry (DSC, and evaluated for in vitro release. Stability studies were carried out on the optimized formulations for a period of 3 months. The drug content was in the range of 97%-101%. The mean particle size of the drug-loaded pellets was in the range 700-785 μm. The drug release rate decreased as the concentration of ethyl cellulose increased in the pellet formulations. Among the prepared formulations, FDL10 and FDL11 showed 80% drug release in 16 h, matching with USP dissolution test 6 for diltiazem HCl extended-release capsules. SEM photographs confirmed that the prepared formulations were spherical in nature with a smooth surface. The compatibility between drug and polymers in the drug-loaded pellets was confirmed by DSC studies. Stability studies indicated that the pellets were stable.

  2. Radionuclide release rate inversion of nuclear accidents in nuclear facility based on Kalman filter

    International Nuclear Information System (INIS)

    Tang Xiuhuan; Bao Lihong; Li Hua; Wan Junsheng

    2014-01-01

    The rapidly and continually back-calculating source term is important for nuclear emergency response. The Gaussian multi-puff atmospheric dispersion model was used to produce regional environment monitoring data virtually, and then a Kalman filter was designed to inverse radionuclide release rate of nuclear accidents in nuclear facility and the release rate tracking in real time was achieved. The results show that the Kalman filter combined with Gaussian multi-puff atmospheric dispersion model can successfully track the virtually stable, linear or nonlinear release rate after being iterated about 10 times. The standard error of inversion results increases with the true value. Meanwhile extended Kalman filter cannot inverse the height parameter of accident release as interceptive error is too large to converge. Kalman filter constructed from environment monitoring data and Gaussian multi-puff atmospheric dispersion model can be applied to source inversion in nuclear accident which is characterized by static height and position, short and continual release in nuclear facility. Hence it turns out to be an alternative source inversion method in nuclear emergency response. (authors)

  3. An open-label, flexible-dose study of paliperidone extended-release in Chinese patients with first-onset psychosis

    Directory of Open Access Journals (Sweden)

    Si TM

    2015-01-01

    Full Text Available TianMei Si,1 QingRong Tan,2 KeRang Zhang,3 Yang Wang,4 Qing Rui4 1Peking University Institute of Mental health, Key Laboratory of Mental Health, Ministry of Health (Peking University, Beijing, 2Fourth Military Medical University, First Hospital, Xi’an, 3Shanxi Medical University, First Hospital, Shanxi, 4Janssen Research and Development, Beijing, People’s Republic of China Background: Antipsychotic medications facilitate the improvement of psychotic symptoms in patients with first-episode psychosis. Paliperidone extended-release (pali-ER, an atypical anti­psychotic, was assessed for efficacy and safety in Chinese patients with first-episode psychosis. Methods: In this 8-week, open-label, single-arm, multicenter study, patients with first-episode psychosis (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and a Positive and Negative Syndrome Scale (PANSS total score ≥70 were treated with flexible-dose pali-ER tablets (3–12 mg/day. The primary efficacy endpoint was the percentage of patients with an increase of ≥8 points in Personal and Social Performance (PSP score from baseline to day 56 (8 weeks. Secondary endpoints included reduction in PANSS total score, improvement in Clinical Global Impression-Severity score, PSP score, Subjective Well-being under Neuroleptics Scale score, and relationship between duration of untreated psychosis and PANSS or PSP. Incidences of treatment-emergent adverse events were used to evaluate safety.Results: Overall, 283 of 294 patients (96% achieved a ≥8-point increase in PSP (primary endpoint, analysis set. For the secondary efficacy endpoints, 284/306 patients (93% had a ≥30% reduction in PANSS total score; 266/306 patients (87% achieved a ≤3 Clinical Global Impression-Severity scale score, and 218/294 patients (74% had a PSP score ≥71. The Subjective Well-being under Neuroleptics Scale score was improved from a baseline mean of 72.7 to 94.7 at endpoint. There was a

  4. Growth factor delivery: How surface interactions modulate release in vitro and in vivo

    Science.gov (United States)

    King, William J.; Krebsbach, Paul H.

    2013-01-01

    Biomaterial scaffolds have been extensively used to deliver growth factors to induce new bone formation. The pharmacokinetics of growth factor delivery has been a critical regulator of their clinical success. This review will focus on the surface interactions that control the non-covalent incorporation of growth factors into scaffolds and the mechanisms that control growth factor release from clinically relevant biomaterials. We will focus on the delivery of recombinant human bone morphogenetic protein-2 from materials currently used in the clinical practice, but also suggest how general mechanisms that control growth factor incorporation and release delineated with this growth factor could extend to other systems. A better understanding of the changing mechanisms that control growth factor release during the different stages of preclinical development could instruct the development of future scaffolds for currently untreatable injuries and diseases. PMID:22433783

  5. Barrier and operational risk analysis of hydrocarbon releases (BORA-Release)

    International Nuclear Information System (INIS)

    Sklet, Snorre; Vinnem, Jan Erik; Aven, Terje

    2006-01-01

    This paper presents results from a case study carried out on an offshore oil and gas production platform with the purpose to apply and test BORA-Release, a method for barrier and operational risk analysis of hydrocarbon releases. A description of the BORA-Release method is given in Part I of the paper. BORA-Release is applied to express the platform specific hydrocarbon release frequencies for three release scenarios for selected systems and activities on the platform. The case study demonstrated that the BORA-Release method is a useful tool for analysing the effect on the release frequency of safety barriers introduced to prevent hydrocarbon releases, and to study the effect on the barrier performance of platform specific conditions of technical, human, operational, and organisational risk influencing factors (RIFs). BORA-Release may also be used to analyse the effect on the release frequency of risk reducing measures

  6. Add-on-Statin Extended Release Nicotinic Acid/Laropiprant but Not the Switch to High-Dose Rosuvastatin Lowers Blood Pressure: An Open-Label Randomized Study

    Directory of Open Access Journals (Sweden)

    Anastazia Kei

    2011-01-01

    Full Text Available Introduction. Nicotinic acid (NA and statins have been associated with reductions in blood pressure (BP. Patients and Methods. We recruited 68 normotensive and hypertensive dyslipidemic patients who were treated with a conventional statin dose and had not achieved lipid targets. Patients were randomized to switch to high-dose rosuvastatin (40 mg/day or to add-on current statin treatment with extended release (ER NA/laropiprant (1000/20 mg/day for the first 4 weeks followed by 2000/40 mg/day for the next 8 weeks for 3 months. Results. Switching to rosuvastatin 40 mg/day was not associated with significant BP alterations. In contrast, the addition of ER-NA/laropiprant to current statin treatment resulted in a 7% reduction of systolic BP (from 134±12 to 125±10 mmHg, <.001 versus baseline and =.01 versus rosuvastatin group and a 5% reduction of diastolic BP (from 81±9 to 77±6 mmHg, =.009 versus baseline and =.01 versus rosuvastatin group. These reductions were significant only in the subgroup of hypertensives and were independent of the hypolipidemic effects of ER-NA/laropiprant. Conclusions. Contrary to the switch to high-dose rosuvastatin, the addition of ER-NA/laropiprant to statin treatment was associated with significant reductions in both systolic and diastolic BP.

  7. Fabrication of ketoprofen controlled-release tablets using biopolymeric hydrophilic matrices: in-vitro studies

    International Nuclear Information System (INIS)

    Rashid, S.; Khan, B.A.; Khan, G.M.

    2017-01-01

    Ketoprofen is propionic acid derivative and belongs to the Non-Steroidal anti-inflammatory group of drugs. Due to the short half-life, dosage frequency, patient non-compliance and side effects such as gastrointestinal disturbance, peptic ulceration and gastro intest inal bleeding, it is considered to be good candidate for formulation into controlled release dosage forms. Directly compressed controlled released ( CR) tablets using Acrylic acid derivatives were prepared and evaluated. In-Vitro Physicochemical assessment of the formulated tablets were performed using different physicochemical, dimensional and quality control tests such as weight variation, thickness and diameter, hardness test, friability test, content uniformity, disintegration and dissolution testing. Results of all these tests were formed within acceptable range. The effect of carbomer polymers on the tablet characteristics, drug release rates, release patterns and release kinetics were investigated. The F2-metric technique was applied to compare dissolution profiles of ketoprofen and carbopol tablets with ketoprofen SR - tablets taken as standard preparation. Acrylic acid derivatives when used as polymers resulted in an extended release profile of about 12 h. Using Higuchi's model and the Korsmeyer equation, the drug release mechanism from the tablets was found to be an anomalous type involving diffusion and erosion. Controlled- release Ketoprofen tablets appear to be a good choice for the symptomatic treatment of rheumatoid arthritis and osteoarthritis. Convenient once-daily administration may help improve patient's compliance. (author)

  8. Extended objects

    International Nuclear Information System (INIS)

    Creutz, M.

    1976-01-01

    After some disconnected comments on the MIT bag and string models for extended hadrons, I review current understanding of extended objects in classical conventional relativistic field theories and their quantum mechanical interpretation

  9. PolyMorphine: an innovative biodegradable polymer drug for extended pain relief.

    Science.gov (United States)

    Rosario-Meléndez, Roselin; Harris, Carolyn L; Delgado-Rivera, Roberto; Yu, Lei; Uhrich, Kathryn E

    2012-09-28

    Morphine, a potent narcotic analgesic used for the treatment of acute and chronic pain, was chemically incorporated into a poly(anhydride-ester) backbone. The polymer termed "PolyMorphine", was designed to degrade hydrolytically releasing morphine in a controlled manner to ultimately provide analgesia for an extended time period. PolyMorphine was synthesized via melt-condensation polymerization and its structure was characterized using proton and carbon nuclear magnetic resonance spectroscopies, and infrared spectroscopy. The weight-average molecular weight and the thermal properties were determined. The hydrolytic degradation pathway of the polymer was determined by in vitro studies, showing that free morphine is released. In vitro cytocompatibility studies demonstrated that PolyMorphine is non-cytotoxic towards fibroblasts. In vivo studies using mice showed that PolyMorphine provides analgesia for 3 days, 20 times the analgesic window of free morphine. The animals retained full responsiveness to morphine after being subjected to an acute morphine challenge. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Preparation and Characterization of Azadirachtin Alginate-Biosorbent Based Formulations: Water Release Kinetics and Photodegradation Study.

    Science.gov (United States)

    Flores-Céspedes, Francisco; Martínez-Domínguez, Gerardo P; Villafranca-Sánchez, Matilde; Fernández-Pérez, Manuel

    2015-09-30

    The botanical insecticide azadirachtin was incorporated in alginate-based granules to obtain controlled release formulations (CRFs). The basic formulation [sodium alginate (1.47%) - azadirachtin (0.28%) - water] was modified by the addition of biosorbents, obtaining homogeneous hybrid hydrogels with high azadirachtin entrapment efficiency. The effect on azadirachtin release rate caused by the incorporation of biosorbents such as lignin, humic acid, and olive pomace in alginate formulation was studied by immersion of the granules in water under static conditions. The addition of the biosorbents to the basic alginate formulation reduces the rate of release because the lignin-based formulation produces a slower release. Photodegradation experiments showed the potential of the prepared formulations in protecting azadirachtin against simulated sunlight, thus improving its stability. The results showed that formulation prepared with lignin provided extended protection. Therefore, this study provides a new procedure to encapsulate the botanical insecticide azadirachtin, improving its delivery and photostability.

  11. SRTM Data Release for Africa, Colored Height

    Science.gov (United States)

    2004-01-01

    This color shaded relief image shows the extent of digital elevation data for Africa recently released by the Shuttle Radar Topography Mission (SRTM). This release includes data for all of the continent, plus the island of Madagascar and the Arabian Peninsula. SRTM flew on board the Space Shuttle Endeavour in February 2000 and used an interferometric radar system to map the topography of Earth's landmass between latitudes 56 degrees south and 60 degrees north. The data were processed into geographic 'tiles,' each of which represents one by one degree of latitude and longitude. A degree of latitude measures 111 kilometers (69 miles) north-south, and a degree of longitude measures 111 kilometers or less east-west, decreasing away from the equator. The data are being released to the public on a continent-by-continent basis. This Africa segment includes 3256 tiles, almost a quarter of the total data set. Previous releases covered North America, South America and Eurasia. Forthcoming releases will include Australia plus an 'Islands' release for those islands not included in the continental releases. Together these data releases constitute the world's first high-resolution, near-global elevation model. The resolution of the publicly released data is three arcseconds (1/1,200 of a degree of latitude and longitude), which is about 90 meters (295 feet). Coverage in the current data release extends from 35 degrees north latitude at the southern edge of the Mediterranean to the very tip of South Africa, encompassing a great diversity of landforms. The northern part of the continent consists of a system of basins and plateaus, with several volcanic uplands whose uplift has been matched by subsidence in the large surrounding basins. Many of these basins have been infilled with sand and gravel, creating the vast Saharan lands. The Atlas Mountains in the northwest were created by convergence of the African and Eurasian tectonic plates. The geography of the central latitudes of

  12. Measuring the Acoustic Release of a Chemotherapeutic Agent from Folate-Targeted Polymeric Micelles.

    Science.gov (United States)

    Abusara, Ayah; Abdel-Hafez, Mamoun; Husseini, Ghaleb

    2018-08-01

    In this paper, we compare the use of Bayesian filters for the estimation of release and re-encapsulation rates of a chemotherapeutic agent (namely Doxorubicin) from nanocarriers in an acoustically activated drug release system. The study is implemented using an advanced kinetic model that takes into account cavitation events causing the antineoplastic agent's release from polymeric micelles upon exposure to ultrasound. This model is an improvement over the previous representations of acoustic release that used simple zero-, first- and second-order release and re-encapsulation kinetics to study acoustically triggered drug release from polymeric micelles. The new model incorporates drug release and micellar reassembly events caused by cavitation allowing for the controlled release of chemotherapeutics specially and temporally. Different Bayesian estimators are tested for this purpose including Kalman filters (KF), Extended Kalman filters (EKF), Particle filters (PF), and multi-model KF and EKF. Simulated and experimental results are used to verify the performance of the above-mentioned estimators. The proposed methods demonstrate the utility and high-accuracy of using estimation methods in modeling this drug delivery technique. The results show that, in both cases (linear and non-linear dynamics), the modeling errors are expensive but can be minimized using a multi-model approach. In addition, particle filters are more flexible filters that perform reasonably well compared to the other two filters. The study improved the accuracy of the kinetic models used to capture acoustically activated drug release from polymeric micelles, which may in turn help in designing hardware and software capable of precisely controlling the delivered amount of chemotherapeutics to cancerous tissue.

  13. Amorphous Solid Dispersion of Epigallocatechin Gallate for Enhanced Physical Stability and Controlled Release

    Directory of Open Access Journals (Sweden)

    Yizheng Cao

    2017-11-01

    Full Text Available Epigallocatechin gallate (EGCG has been recognized as the most prominent green tea extract due to its healthy influences. The high instability and low bioavailability, however, strongly limit its utilization in food and drug industries. This work, for the first time, develops amorphous solid dispersion of EGCG to enhance its bioavailability and physical stability. Four commonly used polymeric excipients are found to be compatible with EGCG in water-dioxane mixtures via a stepwise mixing method aided by vigorous mechanical interference. The dispersions are successfully generated by lyophilization. The physical stability of the dispersions is significantly improved compared to pure amorphous EGCG in stress condition (elevated temperature and relative humidity and simulated gastrointestinal tract environment. From the drug release tests, one of the dispersions, EGCG-Soluplus® 50:50 (w/w shows a dissolution profile that only 50% EGCG is released in the first 20 min, and the remains are slowly released in 24 h. This sustained release profile may open up new possibilities to increase EGCG bioavailability via extending its elimination time in plasma.

  14. Amorphous Solid Dispersion of Epigallocatechin Gallate for Enhanced Physical Stability and Controlled Release.

    Science.gov (United States)

    Cao, Yizheng; Teng, Jing; Selbo, Jon

    2017-11-09

    Epigallocatechin gallate (EGCG) has been recognized as the most prominent green tea extract due to its healthy influences. The high instability and low bioavailability, however, strongly limit its utilization in food and drug industries. This work, for the first time, develops amorphous solid dispersion of EGCG to enhance its bioavailability and physical stability. Four commonly used polymeric excipients are found to be compatible with EGCG in water-dioxane mixtures via a stepwise mixing method aided by vigorous mechanical interference. The dispersions are successfully generated by lyophilization. The physical stability of the dispersions is significantly improved compared to pure amorphous EGCG in stress condition (elevated temperature and relative humidity) and simulated gastrointestinal tract environment. From the drug release tests, one of the dispersions, EGCG-Soluplus ® 50:50 ( w / w ) shows a dissolution profile that only 50% EGCG is released in the first 20 min, and the remains are slowly released in 24 h. This sustained release profile may open up new possibilities to increase EGCG bioavailability via extending its elimination time in plasma.

  15. Analysis and comparison of extended and unscented Kalman filtering methods for spacecraft attitude determination

    OpenAIRE

    Diaz, Orlando X.

    2010-01-01

    Approved for public release; distribution is unlimited Two methods of estimating the attitude position of a spacecraft are examined in this thesis: the extended Kalman filter (EKF) and the unscented Kalman filter (UKF). In particular, the UnScented QUaternion Estimator (USQUE) derived from [4] is implemented into a spacecraft model. For generalizations about the each of the filters, a simple problem is initially solved. These solutions display typical characteristics of each filter type. T...

  16. Core degradation and fission product release

    International Nuclear Information System (INIS)

    Wright, R.W.; Hagen, S.J.L.

    1992-01-01

    Experiments on core degradation and melt progression in severe LWR accidents have provided reasonable understanding of the principal processes involved in the early phase of melt progression that extends through core degradation and metallic material melting and relocation. A general but not a quantitative understanding of late phase melt progression that involves ceramic material melting and relocation has also been obtained, primarily from the TMI-2 core examination. A summary is given of the current state of knowledge on core degradation and melt progression obtained from these integral experiments and of the principal remaining significant uncertainties. A summary is also given of the principal results on in-vessel fission product release obtained from these experiments. (author). 8 refs, 5 figs, 3 tabs

  17. Poly lactic acid based injectable delivery systems for controlled release of a model protein, lysozyme.

    Science.gov (United States)

    Al-Tahami, Khaled; Meyer, Amanda; Singh, Jagdish

    2006-02-01

    The objective of this study was to evaluate the critical formulation parameters (i.e., polymer concentration, polymer molecular weight, and solvent nature) affecting the controlled delivery of a model protein, lysozyme, from injectable polymeric implants. The conformational stability and biological activity of the released lysozyme were also investigated. Three formulations containing 10%, 20%, and 30% (w/v) poly lactic acid (PLA) in triacetin were investigated. It was found that increasing polymer concentration in the formulations led to a lower burst effect and a slower release rate. Formulation with a high molecular weight polymer showed a greater burst effect as compared to those containing low molecular weight. Conformational stability and biological activity of released samples were studied by differential scanning calorimeter and enzyme activity assay, respectively. The released samples had significantly (P solution kept at same conditions). Increasing polymer concentration increased both the conformational stability and the biological activity of released lysozyme. In conclusion, phase sensitive polymer-based delivery systems were able to deliver a model protein, lysozyme, in a conformationally stable and biologically active form at a controlled rate over an extended period.

  18. The Effect of Acid pH Modifiers on the Release Characteristics of Weakly Basic Drug from Hydrophlilic–Lipophilic Matrices

    OpenAIRE

    Dvořáčková, Kateřina; Doležel, Petr; Mašková, Eliška; Muselík, Jan; Kejdušová, Martina; Vetchý, David

    2013-01-01

    The solubility of weakly basic drugs within passage though GI tract leads to pH-dependent or even incomplete release of these drugs from extended release formulations and consequently to lower drug absorption and bioavailability. The aim of the study was to prepare and evaluate hydrophilic–lipophilic (hypromellose–montanglycol wax) matrix tablets ensuring the pH-independent delivery of the weakly basic drug verapamil-hydrochloride by an incorporation of three organic acidifiers (citric, fumar...

  19. THE EXTENDED VIRGO CLUSTER CATALOG

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Suk; Rey, Soo-Chang; Lee, Youngdae; Chung, Jiwon; Pak, Mina; Yi, Wonhyeong; Lee, Woong [Department of Astronomy and Space Science, Chungnam National University, 99 Daehak-ro, Daejeon 305-764 (Korea, Republic of); Jerjen, Helmut [Research School of Astronomy and Astrophysics, The Australian National University, Cotter Road, Weston, ACT 2611 (Australia); Lisker, Thorsten [Astronomisches Rechen-Institut, Zentrum für Astronomie der Universität Heidelberg (ZAH), Mönchhofstraße 12-14, D-69120 Heidelberg (Germany); Sung, Eon-Chang [Korea Astronomy and Space Science institute, 776 Daedeokdae-ro, Daejeon 305-348 (Korea, Republic of)

    2015-01-01

    We present a new catalog of galaxies in the wider region of the Virgo cluster, based on the Sloan Digital Sky Survey (SDSS) Data Release 7. The Extended Virgo Cluster Catalog (EVCC) covers an area of 725 deg{sup 2} or 60.1 Mpc{sup 2}. It is 5.2 times larger than the footprint of the classical Virgo Cluster Catalog (VCC) and reaches out to 3.5 times the virial radius of the Virgo cluster. We selected 1324 spectroscopically targeted galaxies with radial velocities less than 3000 km s{sup –1}. In addition, 265 galaxies that have been overlooked in the SDSS spectroscopic survey but have available redshifts in the NASA Extragalactic Database are also included. Our selection process secured a total of 1589 galaxies, 676 of which are not included in the VCC. The certain and possible cluster members are defined by means of redshift comparison with a cluster infall model. We employed two independent and complementary galaxy classification schemes: the traditional morphological classification based on the visual inspection of optical images and a characterization of galaxies from their spectroscopic features. SDSS u, g, r, i, and z passband photometry of all EVCC galaxies was performed using Source Extractor. We compare the EVCC galaxies with the VCC in terms of morphology, spatial distribution, and luminosity function. The EVCC defines a comprehensive galaxy sample covering a wider range in galaxy density that is significantly different from the inner region of the Virgo cluster. It will be the foundation for forthcoming galaxy evolution studies in the extended Virgo cluster region, complementing ongoing and planned Virgo cluster surveys at various wavelengths.

  20. Development of sustained release capsules containing "coated matrix granules of metoprolol tartrate".

    Science.gov (United States)

    Siddique, Sabahuddin; Khanam, Jasmina; Bigoniya, Papiya

    2010-09-01

    The objective of this investigation was to prepare sustained release capsule containing coated matrix granules of metoprolol tartrate and to study its in vitro release and in vivo absorption. The design of dosage form was performed by choosing hydrophilic hydroxypropyl methyl cellulose (HPMC K100M) and hydrophobic ethyl cellulose (EC) polymers as matrix builders and Eudragit® RL/RS as coating polymers. Granules were prepared by composing drug with HPMC K100M, EC, dicalcium phosphate by wet granulation method with subsequent coating. Optimized formulation of metoprolol tartrate was formed by using 30% HPMC K100M, 20% EC, and ratio of Eudragit® RS/RL as 97.5:2.5 at 25% coating level. Capsules were filled with free flowing optimized granules of uniform drug content. This extended the release period upto 12 h in vitro study. Similarity factor and mean dissolution time were also reported to compare various dissolution profiles. The network formed by HPMC and EC had been coupled satisfactorily with the controlled resistance offered by Eudragit® RS. The release mechanism of capsules followed Korsemeyer-Peppas model that indicated significant contribution of erosion effect of hydrophilic polymer. Biopharmaceutical study of this optimized dosage form in rabbit model showed 10 h prolonged drug release in vivo. A close correlation (R(2) = 0.9434) was established between the in vitro release and the in vivo absorption of drug. The results suggested that wet granulation with subsequent coating by fluidized bed technique, is a suitable method to formulate sustained release capsules of metoprolol tartrate and it can perform therapeutically better than conventional immediate release dosage form.

  1. Intramuscular administration of paliperidone palmitate extended-release injectable microsuspension induces a subclinical inflammatory reaction modulating the pharmacokinetics in rats.

    Science.gov (United States)

    Darville, Nicolas; van Heerden, Marjolein; Vynckier, An; De Meulder, Marc; Sterkens, Patrick; Annaert, Pieter; Van den Mooter, Guy

    2014-07-01

    The present study aims at elucidating the intricate nature of the drug release and absorption following intramuscular (i.m.) injection of sustained-release prodrug nanocrystals/microcrystals. A paliperidone palmitate (PPP) long-acting suspension was characterized with regard to particle size (Dv,50 = 1.09 μm) and morphology prior to i.m. injection in rats. The local disposition was rigorously investigated by means of (immuno)histochemistry and transmission electron microscopy while the concurrent multiphasic pharmacokinetics was linked to the microanatomy. A transient (24 h) trauma-induced inflammation promptly evolved into a subclinical but chronic granulomatous inflammatory reaction initiated by the presence of solid material. The dense inflammatory envelope (CD68(+) macrophages) led to particle agglomeration with subsequent drop in dissolution rate beyond 24 h postinjection. This was associated with a decrease in apparent paliperidone (PP) absorption (near-zero order) until 96 h and a delayed time of occurrence of observed maximum drug plasma concentration (168 h). The infiltrating macrophages phagocytosed large fractions of the depot, thereby influencing the (pro)drug release. Radial angiogenesis (CD31(+)) was observed throughout the inflammatory rim from 72 h onwards and presumably contributed to the sustained systemic PP concentrations by maintaining a sufficient absorptive capacity. No solid-state transitions of the retrieved formulation were recorded with X-ray diffraction analysis. In summary, the initial formulation-driven prodrug (PPP) dissolution and drug (PP) absorption were followed by a complex phase determined by the relative contribution of formulation factors and dynamic physiological variables. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  2. FRESCO-II: A computer program for analysis of fission product release from spherical HTGR-fuel elements in irradiation and annealing experiments

    International Nuclear Information System (INIS)

    Krohn, H.; Finken, R.

    1983-06-01

    The modular computer code FRESCO has been developed to describe the mechanism of fission product release from a HTGR-Core under accident conditions. By changing some program modules it has been extended to take into account the transport phenomena (i.e. recoil) too, which only occur under reactor operating conditions and during the irradiation experiments. For this report, the release of cesium and strontium from three HTGR-fuel elements has been evaluated and compared with the experimental data. The results show that the measured release can be described by the considered models. (orig.) [de

  3. Perspectives on extended Deterrence

    International Nuclear Information System (INIS)

    Tertrais, Bruno; Yost, David S.; Bunn, Elaine; Lee, Seok-soo; Levite, Ariel e.; Russell, James A.; Hokayem, Emile; Kibaroglu, Mustafa; Schulte, Paul; Thraenert, Oliver; Kulesa, Lukasz

    2010-05-01

    In November 2009, the Foundation for Strategic Research (Fondation pour la recherche strategique, FRS) convened a workshop on 'The Future of extended Deterrence', which included the participation of some of the best experts of this topic, from the United States, Europe, the Middle East and East Asia, as well as French and NATO officials. This document brings together the papers prepared for this seminar. Several of them were updated after the publication in April 2010 of the US Nuclear Posture Review. The seminar was organized with the support of the French Atomic energy Commission (Commissariat a l'energie atomique - CEA). Content: 1 - The future of extended deterrence: a brainstorming paper (Bruno Tertrais); 2 - US extended deterrence in NATO and North-East Asia (David S. Yost); 3 - The future of US extended deterrence (Elaine Bunn); 4 - The future of extended deterrence: a South Korean perspective (Seok-soo Lee); 5 - Reflections on extended deterrence in the Middle East (Ariel e. Levite); 6 - extended deterrence, security guarantees and nuclear weapons: US strategic and policy conundrums in the Gulf (James A. Russell); 7 - extended deterrence in the Gulf: a bridge too far? (Emile Hokayem); 8 - The future of extended deterrence: the case of Turkey (Mustafa Kibaroglu); 9 - The future of extended deterrence: a UK view (Paul Schulte); 10 - NATO and extended deterrence (Oliver Thraenert); 11 - extended deterrence and assurance in Central Europe (Lukasz Kulesa)

  4. Conversion From Twice-Daily Tacrolimus Capsules to Once-Daily Extended-Release Tacrolimus (LCPT): A Phase 2 Trial of Stable Renal Transplant Recipients

    Science.gov (United States)

    Gaber, A. Osama; Alloway, Rita R.; Bodziak, Kenneth; Kaplan, Bruce; Bunnapradist, Suphamai

    2013-01-01

    Background LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Phase 1 studies demonstrated greater bioavailability to twice-daily tacrolimus capsules and no new safety concerns. Methods In this phase 2 study, adult stable kidney transplant patients on tacrolimus capsules (Prograf) twice-daily were converted to tacrolimus tablets (LCP-Tacro) once-daily; patients continued on LCP-Tacro once-daily for days 8 to 21; trough levels were to be maintained between 5 and 15 ng/mL; 24-hr pharmacokinetic assessments were done on days 7 (baseline pre-switch), 14, and 21. Results Forty-seven patients completed LCP-Tacro dosing per protocol. The mean conversion ratio was 0.71. Pharmacokinetic data demonstrated consistent exposure (AUC) at the lower conversion dose. Cmax (P=0.0001), Cmax/Cmin ratio (P<0.001), percent fluctuation (P<0.0001), and swing (P=0.0004) were significantly lower and Tmax significantly (P<0.001) longer for LCP-Tacro versus Prograf. AUC24 and Cmin correlation coefficients after 7 and 14 days of therapy were 0.86 or more, demonstrating a robust correlation between LCP-Tacro tacrolimus exposure and trough levels. There were three serious adverse events; none were related to study drug and all were resolved. Conclusions Stable kidney transplant patients can be safely converted from Prograf twice-daily to LCP-Tacro. The greater bioavailability of LCP-Tacro allows for once-daily dosing and similar (AUC) exposure at a dose approximately 30% less than the total daily dose of Prograf. LCP-Tacro displays flatter kinetics characterized by significantly lower peak-trough fluctuations. PMID:23715050

  5. Employment-based reinforcement of adherence to an FDA approved extended release formulation of naltrexone in opioid-dependent adults: a randomized controlled trial.

    Science.gov (United States)

    DeFulio, Anthony; Everly, Jeffrey J; Leoutsakos, Jeannie-Marie S; Umbricht, Annie; Fingerhood, Michael; Bigelow, George E; Silverman, Kenneth

    2012-01-01

    Naltrexone provides excellent opioid blockade, but its clinical utility is limited because opioid-dependent patients typically refuse it. An injectable suspension of naltrexone for extended release (XR-NTX) was recently approved by the FDA for treatment of opioid dependence. XR-NTX treatment may require concurrent behavioral intervention to maximize adherence and effectiveness, thus we sought to evaluate employment-based reinforcement as a method of improving adherence to XR-NTX in opiate dependent adults. Opioid-dependent adults (n=38) were detoxified and inducted onto oral naltrexone, then randomly assigned to contingency or prescription conditions. Participants received up to six doses of XR-NTX at four-week intervals. All participants could earn vouchers for attendance and performance at a therapeutic workplace. Contingency participants were required to accept XR-NTX injections to access the workplace and earn vouchers. Prescription participants could earn vouchers independent of their acceptance of XR-NTX injections. Contingency participants accepted significantly more naltrexone injections than prescription participants (87% versus 52%, p=.002), and were more likely to accept all injections (74% versus 26%, p=.004). Participants in the two conditions provided similar percentages of samples negative for opiates (72% versus 65%) and for cocaine (58% versus 54%). Opiate positivity was significantly more likely when samples were also cocaine positive, independent of naltrexone blockade (p=.002). Long-term adherence to XR-NTX in unemployed opiate dependent adults is low under usual care conditions. Employment-based reinforcement can maintain adherence to XR-NTX. Ongoing cocaine use appears to interfere with the clinical effectiveness of XR-NTX on opiate use. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. THE RAVE CATALOG OF STELLAR ELEMENTAL ABUNDANCES: FIRST DATA RELEASE

    Energy Technology Data Exchange (ETDEWEB)

    Boeche, C.; Williams, M.; De Jong, R. S.; Steinmetz, M. [Leibniz-Institut fuer Astrophysik Potsdam (AIP), D-14482 Potsdam (Germany); Siebert, A.; Bienayme, O. [Observatoire Astronomique de Strasbourg, Universite de Strasbourg, CNRS, UMR 7550, F-67000 Strasbourg (France); Fulbright, J. P.; Ruchti, G. R. [Department of Physics and Astronomy, Johns Hopkins University, Baltimore, MD 21218 (United States); Bland-Hawthorn, J. [Sydney Institute for Astronomy, School of Physics A28, University of Sydney, NSW 2006 (Australia); Campbell, R. [Department of Physics and Astronomy, Western Kentucky University, Bowling Green, KY (United States); Freeman, K. C. [Research School of Astronomy and Astrophysics, Australia National University, Weston Creek, Canberra ACT 2611 (Australia); Gibson, B. K. [Jeremiah Horrocks Institute, University of Central Lancashire, Preston PR1 2HE (United Kingdom); Gilmore, G. [Institute of Astronomy, University of Cambridge, Madingley Road, Cambridge CB3 0HA (United Kingdom); Grebel, E. K. [Astronomisches Rechen-Institut, Zentrum fuer Astronomie der Universitaet Heidelberg, D-69120 Heidelberg (Germany); Helmi, A. [Kapteyn Astronomical Institute, University of Groningen, 9700 AV Groningen (Netherlands); Munari, U. [INAF Osservatorio Astronomico di Padova, Asiago I-36012 (Italy); Navarro, J. F. [Department of Physics and Astronomy, University of Victoria, Victoria BC V8W 3P6 (Canada); Parker, Q. A.; Reid, W. [Department of Physics and Astronomy, Faculty of Sciences, Macquarie University, Sydney, NSW 2109 (Australia); Seabroke, G. M. [Mullard Space Science Laboratory, University College London, Holmbury, St. Mary RH5 6NT (United Kingdom); and others

    2011-12-15

    We present chemical elemental abundances for 36,561 stars observed by the RAdial Velocity Experiment (RAVE), an ambitious spectroscopic survey of our Galaxy at Galactic latitudes |b| > 25 Degree-Sign and with magnitudes in the range 9 release of the RAVE chemical catalog is complementary to the third RAVE data release of radial velocities and stellar parameters, and it contains chemical abundances for the elements Mg, Al, Si, Ca, Ti, Fe, and Ni, with a mean error of {approx}0.2 dex, as judged from accuracy tests performed on synthetic and real spectra. Abundances are estimated through a dedicated processing pipeline in which the curve of growth of individual lines is obtained from a library of absorption line equivalent widths to construct a model spectrum that is then matched to the observed spectrum via a {chi}{sup 2} minimization technique. We plan to extend this pipeline to include estimates for other elements, such as oxygen and sulfur, in future data releases.

  7. Polyoxometalate coordination induced controllable release of quinolone in hybrid film

    Science.gov (United States)

    Yang, Fan; Li, Yang; Lv, Yu-Guang; Zhou, Shu-Jing; Li, Si; Gao, Guang-Gang; Liu, Hong

    2018-05-01

    Due to some side effects of quinolones in vivo, it is an urgent issue to extend their new applications in vitro. In this paper, structure-determined vanadium-quinolone functionalized polymolybdates of (NH4)2 [(γ-Mo8O26){VO(CF)2}2] (1) and (NH4)2 [(γ-Mo8O26){VO(NF)2}2] (2) (CF = ciprofloxacin; NF = norfloxacin) have been designed and synthesized. Complex 1 or 2 features a γ-type [Mo8O26]4- polyanion functionalized by two monocapped vanadium-quinolone complexes. Different H-bonds and π···π interactions allow 1 or 2 to form a 2D layered structure at solid state. When complex 1 or 2 is transferred into polyvinyl alcohol (PVA) film, its release rate in solution is lower than that of CF- or NF-PVA film and thus forming a novel quinolone delivery system. This is the first time that slow release effect of quinolone is achieved by polyoxometalate coordination effect. The slow release of 1 or 2 in PVA film is mainly ascribed to the coordination of quinolone with polyoxometalate anions.

  8. Extended Emotions

    DEFF Research Database (Denmark)

    Krueger, Joel; Szanto, Thomas

    2016-01-01

    beyond the neurophysiological confines of organisms; some even argue that emotions can be socially extended and shared by multiple agents. Call this the extended emotions thesis (ExE). In this article, we consider different ways of understanding ExE in philosophy, psychology, and the cognitive sciences...

  9. Anchoring cationic amphiphiles for nucleotide delivery: significance of DNA release from cationic liposomes for transfection.

    Science.gov (United States)

    Hirashima, Naohide; Minatani, Kazuhiro; Hattori, Yoshifumi; Ohwada, Tomohiko; Nakanishi, Mamoru

    2007-06-01

    We have designed and synthesized lithocholic acid-based cationic amphiphile molecules as components of cationic liposomes for gene transfection (lipofection). To study the relationship between the molecular structures of those amphiphilic molecules, particularly the extended hydrophobic appendant (anchor) at the 3-hydroxyl group, and transfection efficiency, we synthesized several lithocholic and isolithocholic acid derivatives, and examined their transfection efficiency. We also compared the physico-chemical properties of cationic liposomes prepared from these derivatives. We found that isolithocholic acid derivatives exhibit higher transfection efficiency than the corresponding lithocholic acid derivatives. This result indicates that the orientation and extension of hydrophobic regions influence the gene transfection process. Isolithocholic acid derivatives showed a high ability to encapsulate DNA in a compact liposome-DNA complex and to protect it from enzymatic degradation. Isolithocholic acid derivatives also facilitated the release of DNA from the liposome-DNA complex, which is a crucial step for DNA entry into the nucleus. Our results show that the transfection efficiency is directly influenced by the ability of the liposome complex to release DNA, rather than by the DNA-encapsulating ability. Molecular modeling revealed that isolithocholic acid derivatives take relatively extended conformations, while the lithocholic acid derivatives take folded structures. Thus, the efficiency of release of DNA from cationic liposomes in the cytoplasm, which contributes to high transfection efficiency, appears to be dependent upon the molecular shape of the cationic amphiphiles.

  10. Evaluation of sleep profile in schizophrenia patients treated with extended-release paliperidone: an open-label prospective study in Southeast Asia

    Directory of Open Access Journals (Sweden)

    Kongsakon R

    2017-10-01

    Full Text Available Ronnachai Kongsakon,1 Nuntika Thavichachart,2 Ka Fai Chung,3 Leslie Lim,4 Beverly Azucena,5 Elizabeth Rondain,6 Benson Go,7 Fe Costales,8 Osot Nerapusee9 1Department of Psychiatry, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 2Department of Medicine, Division of Psychiatry, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand; 3Department of Psychiatry, University of Hong Kong, Hong Kong, People’s Republic of China; 4Department of Psychiatry, Singapore General Hospital, Singapore; 5National Center for Mental Health, Mandaluyong, Philippines; 6Makati Medical Center, Makati, Philippines; 7Northern Mindanao Medical Center, Cagayan De Oro, Misamis Oriental, Philippines; 8Perpetual Succour Hospital, Cebu, Philippines; 9Medical Affairs, Janssen‑Cilag, Bangkok, Thailand Objective: To evaluate the effect of 6 months of treatment with paliperidone extended-release (ER tablets on the sleep profile of patients with schizophrenia.Methods: A total of 984 patients meeting the The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV criteria for schizophrenia who switched their antipsychotic to paliperidone ER were recruited from 61 sites in five countries in Southeast Asia. We recorded patient demographics and assessed sleep quality and daytime drowsiness using visual analog scales.Results: Approximately 70% of patients completed the 6-month study. After the use of paliperidone ER, patients reported significantly better sleep quality (76.44 vs 65.48; p<0.001 and less daytime drowsiness compared with their baseline value (23.18 vs 34.22; p<0.001. Factors predicting sleep profile improvement were completion of the study and higher baseline Positive and Negative Syndrome Scale scores.Conclusion: Paliperidone ER can help schizophrenia patients to improve sleep quality and reduce daytime drowsiness; this was seen especially in the patients who completed the 6-month

  11. Joint release rate estimation and measurement-by-measurement model correction for atmospheric radionuclide emission in nuclear accidents: An application to wind tunnel experiments.

    Science.gov (United States)

    Li, Xinpeng; Li, Hong; Liu, Yun; Xiong, Wei; Fang, Sheng

    2018-03-05

    The release rate of atmospheric radionuclide emissions is a critical factor in the emergency response to nuclear accidents. However, there are unavoidable biases in radionuclide transport models, leading to inaccurate estimates. In this study, a method that simultaneously corrects these biases and estimates the release rate is developed. Our approach provides a more complete measurement-by-measurement correction of the biases with a coefficient matrix that considers both deterministic and stochastic deviations. This matrix and the release rate are jointly solved by the alternating minimization algorithm. The proposed method is generic because it does not rely on specific features of transport models or scenarios. It is validated against wind tunnel experiments that simulate accidental releases in a heterogonous and densely built nuclear power plant site. The sensitivities to the position, number, and quality of measurements and extendibility of the method are also investigated. The results demonstrate that this method effectively corrects the model biases, and therefore outperforms Tikhonov's method in both release rate estimation and model prediction. The proposed approach is robust to uncertainties and extendible with various center estimators, thus providing a flexible framework for robust source inversion in real accidents, even if large uncertainties exist in multiple factors. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Investigating the feasibility of temperature-controlled accelerated drug release testing for an intravaginal ring.

    Science.gov (United States)

    Externbrink, Anna; Clark, Meredith R; Friend, David R; Klein, Sandra

    2013-11-01

    The objective of the present study was to investigate if temperature can be utilized to accelerate drug release from Nuvaring®, a reservoir type intravaginal ring based on polyethylene vinyl acetate copolymer that releases a constant dose of contraceptive steroids over a duration of 3 weeks. The reciprocating holder apparatus (USP 7) was utilized to determine real-time and accelerated etonogestrel release from ring segments. It was demonstrated that drug release increased with increasing temperature which can be attributed to enhanced drug diffusion. An Arrhenius relationship of the zero-order release constants was established, indicating that temperature is a valid parameter to accelerate drug release from this dosage form and that the release mechanism is maintained under these accelerated test conditions. Accelerated release tests are particularly useful for routine quality control to assist during batch release of extended release formulations that typically release the active over several weeks, months or even years, since they can increase the product shelf life. The accelerated method should therefore be able to discriminate between formulations with different release characteristics that can result from normal manufacturing variance. In the case of Nuvaring®, it is well known that the process parameters during the extrusion process strongly influence the polymeric structure. These changes in the polymeric structure can affect the permeability which, in turn, is reflected in the release properties. Results from this study indicate that changes in the polymeric structure can lead to a different temperature dependence of the release rate, and as a consequence, the accelerated method can become less sensitive to detect changes in the release properties. When the accelerated method is utilized during batch release, it is therefore important to take this possible restriction into account and to evaluate the accelerated method with samples from non

  13. Niacin extended-release/simvastatin combination therapy produces larger favorable changes in high-density lipoprotein particles than atorvastatin monotherapy

    Directory of Open Access Journals (Sweden)

    Toth PP

    2012-01-01

    Full Text Available Peter P Toth1, Kamlesh M Thakker2, Ping Jiang2, Robert J Padley21University of Illinois College of Medicine, Peoria, and CGH Medical Center, Sterling, 2Abbott, Abbott Park, IL, USABackground: The purpose of this research was to compare the effects of niacin extended-release in combination with simvastatin (NER/S versus atorvastatin monotherapy on high-density lipoprotein (HDL particle number and size in patients with hyperlipidemia or dyslipidemia from the SUPREME study.Methods: This was a post hoc analysis of patients (n = 137 who completed the SUPREME study and who had lipid particle number and size measurements at both baseline and at week 12 by nuclear magnetic resonance spectroscopy. Following ≥4 weeks without lipid-modifying therapy (washout period, the patients received NER/S 1000/40 mg/day for 4 weeks followed by NER/S 2000/40 mg/day for 8 weeks, or atorvastatin 40 mg/day for 12 weeks. Median percent changes in HDL particle number and size from baseline to week 12 were compared between the NER/S and atorvastatin treatment groups using the Wilcoxon rank-sum test. Distribution of HDL particle subclasses at week 12 was compared between the treatment groups using the Cochran–Mantel–Haenszel test.Results: Treatment with NER/S resulted in a significantly greater percent reduction in small HDL particle number at week 12 compared with atorvastatin monotherapy (-1.8% versus 4.2%, P = 0.014, and a numerically greater percent increase in large HDL particle number (102.4% versus 39.2%, P = 0.078 compared with atorvastatin monotherapy. A significantly greater percent increase in HDL particle size from baseline at week 12 was observed with NER/S compared with atorvastatin (6.0% versus 1.3%, P < 0.001. NER/S treatment also resulted in a significant shift in HDL particle size from small and medium at baseline to large at week 12 (P < 0.0001.Conclusion: Treatment with NER/S resulted in larger favorable changes in number and size of HDL particle

  14. Analysis of fuel centre temperatures and fission gas release data from the IFPE Database

    International Nuclear Information System (INIS)

    Schubert, A.; Lassmann, K.; Van Uffelen, P.; Van de Laar, J.; Elenkov, D.; Asenov, S.; Boneva, S.; Djourelov, N.; Georgieva, M.

    2003-01-01

    The present work has continued the analysis of fuel centre temperatures and fission gas release, calculated with standard options of the TRANSURANUS code. The calculations are compared to experimental data from the International Fuel Performance Experiments (IFPE) database. It is reported an analysis regarding UO 2 fuel for Western-type reactors: Fuel centre temperatures measured in the experiments Contact 1 and Contact 2 (in-pile tests of 2 rods performed at the Siloe reactor in Grenoble, France, closely simulating commercial PWR conditions); Fission gas release data derived from post-irradiation examinations of 9 fuel rods belonging to the High-Burnup Effects Programme, task 3 (HBEP3). The results allow for a comparison of predictions by TRANSURANUS for the mentioned Western-type fuels with those done previously for Russian-type WWER fuel. The comparison has been extended to include fuel centre temperatures as well as fission gas release. The present version of TRANSURANUS includes a model that calculates the production of Helium. The amount of produced Helium is compared to the measured and to the calculated release of the fission gases Xenon and Krypton

  15. Efficacy of Guanfacine Extended Release in the Treatment of Combined and Inattentive Only Subtypes of Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Kollins, Scott H.; Wigal, Timothy L.

    2012-01-01

    Abstract Background Extended-release guanfacine (GXR) is approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6–17 years. This post-hoc analysis further examines the effects of GXR on hyperactivity-impulsivity and inattentiveness. Method Data from two large double-blind placebo-controlled pivotal trials of GXR in the treatment of ADHD were analyzed. Using the pooled population to provide sufficient sample size and associated statistical power, the impact of GXR treatment on core ADHD symptoms was examined by comparing ADHD Rating Scale IV (ADHD-RS-IV) total scores in the overall GXR and placebo groups in subjects with each of the three ADHD subtypes. ADHD-RS-IV Hyperactivity-Impulsivity and Inattentiveness subscale scores in the overall study population by randomized dose group (vs. placebo) were also examined. Results The full analysis set included 631 subjects aged 6–17 years (GXR: n=490; placebo: n=141). Among subjects with the predominantly inattentive subtype of ADHD, differences in least squares (LS) mean reductions from baseline in ADHD-RS-IV total scores were significantly greater in GXR-treated subjects (n=127) than in placebo-treated subjects (n=38) at treatment weeks 3 through 5 and end point (p≤0.020). Among subjects with combined type ADHD, differences in LS mean ADHD-RS-IV total score reductions from baseline were significantly greater in the GXR group (n=354) than in the placebo group (n=100) at treatment weeks 1 through 5 and end point (p≤0.011). The dearth of predominantly hyperactive-impulsive type subjects (n=12) precluded analysis of this subgroup. Each randomized GXR dose group in each trial demonstrated significantly greater reductions from baseline in ADHD-RS-IV Hyperactivity-Impulsivity and Inattentiveness subscale scores than did the respective placebo group at end point (p≤0.05 for all). Conclusions The results support the use of GXR in the treatment of core ADHD symptoms

  16. 76 FR 586 - Importer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2011-01-05

    ... importer of the following basic classes of controlled substances: Drug Schedule Opium, raw (9600) II Concentrate of Poppy Straw (9670) II Tapentadol (9780) II The company plans to import the Raw Opium (9600) and... under international treaties, conventions, or protocols in effect on May 1, 1971. DEA has investigated...

  17. 78 FR 17230 - Importer of Controlled Substances, Notice of Registration, Noramco, Inc.

    Science.gov (United States)

    2013-03-20

    ... basic classes of controlled substances: Drug Schedule Phenylacetone (8501) II Opium, raw (9600) II Poppy Straw Concentrate (9670) II Tapentadol (9780) II The company plans to import raw Opium (9600) and Poppy... treaties, conventions, or protocols in effect on May 1, 1971, at this time. DEA has investigated Noramco...

  18. 77 FR 43862 - Importer of Controlled Substances; Notice of Registration; Noramco, Inc.

    Science.gov (United States)

    2012-07-26

    ... basic classes of controlled substances: Drug Schedule Phenylacetone (8501) II Opium, raw (9600) II Poppy Straw Concentrate (9670) II Tapentadol (9780) II The company plans to import the Opium (9600) and Poppy... treaties, conventions, or protocols in effect on May 1, 1971, at this time. DEA has investigated Noramco...

  19. Developments in managing severe chronic pain: role of oxycodone–naloxone extended release

    Directory of Open Access Journals (Sweden)

    Fanelli G

    2015-07-01

    Full Text Available Guido Fanelli,1 Andrea Fanelli2 1Anesthesia and Intensive Care Unit, University of Parma, Parma, 2Anesthesia and Intensive Care Unit, Policlinico S Orsola-Malpighi, Bologna, Italy Abstract: Chronic pain is a highly disabling condition, which can significantly reduce patients’ quality of life. Prevalence of moderate and severe chronic pain is high in the general population, and it increases significantly in patients with advanced cancer and older than 65 years. Guidelines for the management of chronic pain recommend opioids for the treatment of moderate-to-severe pain in patients whose pain is not responsive to initial therapies with paracetamol and/or nonsteroidal anti-inflammatory drugs. Despite their analgesic efficacy being well recognized, adverse events can affect daily functioning and patient quality of life. Opioid-induced constipation (OIC occurs in 40% of opioid-treated patients. Laxatives are the most common drugs used to prevent and treat OIC. Laxatives do not address the underlying mechanisms of OIC; for this reason, they are not really effective in OIC treatment. Naloxone is an opioid receptor antagonist with low systemic bioavailability. When administered orally, naloxone antagonizes the opioid receptors in the gut wall, while its extensive first-pass hepatic metabolism ensures the lack of antagonist influence on the central-mediated analgesic effect of the opioids. A prolonged-release formulation consisting of oxycodone and naloxone in a 2:1 ratio was developed trying to reduce the incidence of OIC maintaining the analgesic effect compared with use of the sole oxycodone. This review includes evidence related to use of oxycodone and naloxone in the long-term management of chronic non-cancer pain and OIC. Keywords: chronic pain, opioid-induced constipation, opioids, oxycodone–naloxone

  20. Cebranopadol, a novel first-in-class analgesic drug candidate: first experience in patients with chronic low back pain in a randomized clinical trial.

    Science.gov (United States)

    Christoph, Annette; Eerdekens, Marie-Henriette; Kok, Maurits; Volkers, Gisela; Freynhagen, Rainer

    2017-09-01

    Chronic low back pain (LBP) is a common condition, usually with the involvement of nociceptive and neuropathic pain components, high economic burden and impact on quality of life. Cebranopadol is a potent, first-in-class drug candidate with a novel mechanistic approach, combining nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. We conducted the first phase II, randomized, double-blind, placebo- and active-controlled trial, evaluating the analgesic efficacy, safety, and tolerability of cebranopadol in patients with moderate-to-severe chronic LBP with and without neuropathic pain component. Patients were treated for 14 weeks with cebranopadol 200, 400, or 600 μg once daily, tapentadol 200 mg twice daily, or placebo. The primary efficacy endpoints were the change from baseline pain to the weekly average 24-hour pain during the entire 12 weeks and during week 12 of the maintenance phase. Cebranopadol demonstrated analgesic efficacy, with statistically significant and clinically relevant improvements over placebo for all doses as did tapentadol. The responder analysis (≥30% or ≥50% pain reduction) confirmed these results. Cebranopadol and tapentadol displayed beneficial effects on sleep and functionality. Cebranopadol treatment was safe, with higher doses leading to higher treatment discontinuations because of treatment-emergent adverse events occurring mostly during titration. Those patients reaching the target doses had an acceptable tolerability profile. The incidence rate of most frequently reported treatment-emergent adverse events during maintenance phase was ≤10%. Although further optimizing the titration scheme to the optimal dose for individual patients is essential, cebranopadol is a new drug candidate with a novel mechanistic approach for potential chronic LBP treatment.

  1. Blind prediction exercise on modeling of PHWR fuel at extended burnup

    International Nuclear Information System (INIS)

    Sah, D.N.; Viswanathan, U.K.; Viswanadham, C.S.; Unnikrishnan, K.; Rath, B.N.

    2008-01-01

    A blind prediction exercise was organised on Indian Pressurised Heavy Water Reactor (PHWR) fuel to investigate the predictive capability of existing codes for their application at extended burnup and to identify areas of improvement. The blind problem for this exercise was based on a PHWR fuel bundle irradiated in Kakrapar Atomic Power Station-I (KAPS-I) up to about 15 000 MWd/tU and subjected to detailed post-irradiation examination (PIE) in the hot cells facility at BARC. Eleven computer codes from seven countries participated in this exercise. The participants provided blind predictions of fuel temperature, fission gas release, internal gas pressure and other performance parameters for the fuel pins. The predictions were compared with the experimental PIE data which included fuel temperature derived from fuel restructuring, fission gas release measured by fuel pin puncturing, internal gas pressure in pin, cladding oxidation and fuel microstructural data. The details of the blind problem and an analysis of the results of blind predictions by the codes vis-a-vis measured data are provided in this paper

  2. Sustained-release progesterone vaginal suppositories 1--development of sustained-release granule--.

    Science.gov (United States)

    Nakayama, Ayako; Sunada, Hisakazu; Okamoto, Hirokazu; Furuhashi, Kaoru; Ohno, Yukiko; Ito, Mikio

    2009-02-01

    Progesterone (P) is an important hormone for the establishment of pregnancy, and its administration is useful for luteal insufficiency. Considering the problems of commercially available oral and injection drugs, hospital-formulated vaginal suppositories are clinically used. However, since the half-life of P suppositories is short, it is difficult to maintain its constant blood concentration. To sustain drug efficacy and prevent side-effects, we are attempting to develop sustained-release suppositories by examining the degree of sustained-release of active ingredients. In this study, we examined the combinations of granulation methods and release systems for the preparation of sustained-release granules of P, and produced 13 types of sustained-release granules. We also examined the diameter, content, and dissolution of each type of granules, and confirmed that the sustained-release of all types of granules was satisfactory. Among the sustained-release granules, we selected granules with a content and a degree of sustained-release suitable for sustained-release suppositories.

  3. Measured tritium in groundwater related to atmospheric releases from the Marcoule nuclear site

    International Nuclear Information System (INIS)

    Levy, F.; Clech, A.; Crochet, P.

    1996-01-01

    Tritium is released into the atmosphere during normal operation from the industrial facilities operated by COGEMA at Marcoule; over a 1 5-year period covered by this study (1979-1994) the quantities ranged from 4940 to 520 TBq·yr -1 . Atmospheric release in rainy weather results in tritium migration into the ground water by a series of mechanisms associated with the water cycle. COGEMA monitors the ground water by means of bore holes. Atmospheric monitoring is also routinely performed; data on the tritium activity concentration in the air and rainwater are available for the same time period. A simplified observation suggests a relation between the atmospheric tritium release and the ground water radioactivity. In 1994, the activity ranged from 100 to 200 Bq·l -1 in the boreholes located 1 km and 2 km downwind from the point of release, diminishing with the distance to less than 20 Bq·l -1 at about 3 km. The authors attempted to model two types of transfers: atmospheric transfer from the release chimney to the borehole, and transfer in the alluvial ground water. The aquifer comprises the alluvial deposits forming the Codolet plain extending to the south of Marcoule, downwind from the point of atmospheric tritium release. The hydrogeology of the entire Marcoule site has been described in previous studies by the French bureau of geological and mineralogical research (BRGM) and ANTEA. (author)

  4. Nitrate capture and slow release in biochar amended compost and soil.

    Directory of Open Access Journals (Sweden)

    Nikolas Hagemann

    Full Text Available Slow release of nitrate by charred organic matter used as a soil amendment (i.e. biochar was recently suggested as potential mechanism of nutrient delivery to plants which may explain some agronomic benefits of biochar. So far, isolated soil-aged and composted biochar particles were shown to release considerable amounts of nitrate only in extended (>1 h extractions ("slow release". In this study, we quantified nitrate and ammonium release by biochar-amended soil and compost during up to 167 h of repeated extractions in up to six consecutive steps to determine the effect of biochar on the overall mineral nitrogen retention. We used composts produced from mixed manures amended with three contrasting biochars prior to aerobic composting and a loamy soil that was amended with biochar three years prior to analysis and compared both to non-biochar amended controls. Composts were extracted with 2 M KCl at 22°C and 65°C, after sterilization, after treatment with H2O2, after removing biochar particles or without any modification. Soils were extracted with 2 M KCl at 22°C. Ammonium was continuously released during the extractions, independent of biochar amendment and is probably the result of abiotic ammonification. For the pure compost, nitrate extraction was complete after 1 h, while from biochar-amended composts, up to 30% of total nitrate extracted was only released during subsequent extraction steps. The loamy soil released 70% of its total nitrate amount in subsequent extractions, the biochar-amended soil 58%. However, biochar amendment doubled the amount of total extractable nitrate. Thus, biochar nitrate capture can be a relevant contribution to the overall nitrate retention in agroecosystems. Our results also indicate that the total nitrate amount in biochar amended soils and composts may frequently be underestimated. Furthermore, biochars could prevent nitrate loss from agroecosystems and may be developed into slow-release fertilizers to

  5. 78 FR 69132 - Manufacturer of Controlled Substances; Notice of Application; Johnson Matthey, Inc.

    Science.gov (United States)

    2013-11-18

    ...; Notice of Application; Johnson Matthey, Inc. Pursuant to Sec. 1301.33(a), Title 21 of the Code of Federal Regulations (CFR), this is notice that on September 5, 2013, Johnson Matthey Inc., Custom Pharmaceuticals... Remifentanil (9739) II Sufentanil (9740) II Tapentadol (9780) II Fentanyl (9801) II The company plans to...

  6. 21 CFR 1308.12 - Schedule II.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Schedule II. 1308.12 Section 1308.12 Food and... 9733 (26) Remifentanil 9739 (27) Sufentanil 9740 (28) Tapentadol 9780 (d) Stimulants. Unless... which contains any quantity of the following substances having a stimulant effect on the central nervous...

  7. Fouling release nanostructured coatings based on PDMS-polyurea segmented copolymers

    KAUST Repository

    Fang, Jason

    2010-05-01

    The bulk and surface characteristics of a series of coatings based on PDMS-polyurea segmented copolymers were correlated to their fouling release performance. Incorporation of polyurea segments to PDMS backbone gives rise to phase separation with the extensively hydrogen bonded hard domains creating an interconnected network that imparts mechanical rigidity. Increasing the compositional complexity of the system by including fluorinated or POSS-functionalized chain extenders or through nanoclay intercalation, confers further thermomechanical improvements. In analogy to the bulk morphology, the surface topography also reflects the compositional complexity of the materials, displaying a wide range of motifs. Investigations on settlement and subsequent removal of Ulva sporelings on those nanostructured surfaces indicate that the work required to remove the microorganisms is significantly lower compared to coatings based on standard PDMS homopolymer. All in all, the series of materials considered in this study demonstrate advanced fouling release properties, while exhibiting superior mechanical properties and, thus, long term durability. © 2010 Elsevier Ltd.

  8. Development and characterization of colloidal silica-based slow-release permanganate gel (SRP-G): laboratory investigations.

    Science.gov (United States)

    Lee, Eung Seok; Gupta, Neha

    2014-08-01

    Slow-release permanganate (MnO4(-)) gel (SRP-G) is a hyper-saline KMnO4 solution that can be used for treating large, dilute, or deep plumes of chlorinated solvents in groundwater. Ideally, the SRP-G injected into aquifers will slowly gelate to form MnO4(-) gel in situ, and the gel will slowly releases MnO4(-). Objectives of this study were to develop SRP-G using colloidal silica as gelling solution, characterize its gelation and release kinetics, and delineate its dynamics in a saturated sandy media. The SRP-G exhibited a two-phase increase in viscosity: a lag phase characterized by little increase in viscosity followed by a short gelation phase. Gelation lag times of SRP-G solutions increased (from 0.5h to 13d) with decreasing KMnO4 concentrations (from 25 to 8 g L(-1)). Permanganate release from gelated SRP-G increased with increasing KMnO4 concentrations, and was characterized as asymptotic release with initial peak (0.9-2.2 mg min(-1)) followed by more attenuated release. Gelation lag times of SRP-G flowing in sands (linear velocity=2.1md(-1)) increased (1, 3, and 6h) with decreasing KMnO4 concentrations (25.0, 23.0, and 22.9 g L(-1)). Permanganate release from gelated SRP-Gs continued for up to 3d and was characterized as asymptotic release with an initial peak release (∼1.2 g min(-1)) followed by more attenuated release over 70h. Dilution of SRP-G by dispersion in porous media affects gelation and release kinetics. Increasing the silica concentration in the SRP-G may facilitate gelation and extend the duration of MnO4(-) release from emplaced SRP-G in porous media. Copyright © 2014. Published by Elsevier Ltd.

  9. "Effects of the novel relatively short-acting kappa opioid receptor antagonist LY2444296 in behaviors observed after chronic extended-access cocaine self-administration in rats".

    Science.gov (United States)

    Valenza, Marta; Butelman, Eduardo R; Kreek, Mary Jeanne

    2017-08-01

    The recruitment of the stress circuitry contributes to a shift from positive to negative reinforcement mechanisms sustaining long-term cocaine addiction. The kappa opioid receptor (KOPr) signaling is upregulated by stress and chronic cocaine exposure. While KOPr agonists induce anhedonia and dysphoria, KOPr antagonists display antidepressant and anxiolytic properties. Most of the knowledge on KOPr antagonism is based on drugs with unusual pharmacokinetic and pharmacodynamic properties, complicating interpretation of results. Here we characterized in vivo behavioral and neuroendocrine effects of the novel relatively short-acting KOPr antagonist LY2444296. To date, no study has investigated whether systemic KOPr blockade reduced anxiety-like and depressive-like behaviors in animals previously exposed to chronic extended access cocaine self-administration. We tested the effect of LY2444296 in blocking KOPr-mediated aversive and neuroendocrine effects. Then, we tested acute systemic LY2444296 in reducing anxiety- and depression-like behaviors, as well as releasing the stress hormone corticosterone (CORT), observed after chronic extended access (18 h/day for 14 days) cocaine self-administration. LY2444296 blocked U69,593-induced place aversion and -reduced motor activity as well as U69,593-induced release of serum CORT, confirming its major site of action, without exerting an effect per se. Acute systemic administration of LY2444296 reduced anxiety-like and depressive-like behaviors, as well as CORT release, in rats tested after chronic extended access cocaine self-administration, but not in cocaine-naïve rats. Results suggest that acute blockade of KOPr by a relatively short-acting antagonist produces therapeutic-like effects selectively in rats with a history of chronic extended access cocaine self-administration.

  10. Nanovesicles released by Dictyostelium cells: a potential carrier for drug delivery.

    Science.gov (United States)

    Lavialle, Françoise; Deshayes, Sophie; Gonnet, Florence; Larquet, Eric; Kruglik, Sergei G; Boisset, Nicolas; Daniel, Régis; Alfsen, Annette; Tatischeff, Irène

    2009-10-01

    Nanovesicles released by Dictyostelium discoideum cells grown in the presence of the DNA-specific dye Hoechst 33342 have been previously shown to mediate the transfer of the dye into the nuclei of Hoechst-resistant cells. The present investigation extends this work by conducting experiments in the presence of hypericin, a fluorescent therapeutic photosensitizer assayed for antitumoral photodynamic therapy. Nanovesicles released by Dictyostelium cells exhibit an averaged diameter between 50 and 150 nm, as measured by transmission cryoelectron microscopy. A proteomic analysis reveals a predominance of actin and actin-related proteins. The detection of a lysosomal membrane protein (LIMP II) indicates that these vesicles are likely generated in the late endosomal compartment. The use of the hypericin-containing nanovesicles as nanodevices for in vitro drug delivery was investigated by fluorescence microscopy. The observed signal was almost exclusively located in the perinuclear area of two human cell lines, skin fibroblasts (HS68) and cervix carcinoma (HeLa) cells. Studies by confocal microscopy with specific markers of cell organelles, provided evidence that hypericin was accumulated in the Golgi apparatus. All these data shed a new light on in vitro drug delivery by using cell-released vesicles as carriers.

  11. Modulation of release of [3H]acetylcholine in the major pelvic ganglion of the rat.

    Science.gov (United States)

    Somogyi, G T; de Groat, W C

    1993-06-01

    Cholinergic modulation of [3H]acetylcholine release evoked by electrical stimulation was studied in the rat major pelvic ganglion, which was prelabeled with [3H]choline. Acetylcholine (ACh) release was independent of the frequency of stimulation; 0.3 Hz produced the same volley output as 10 Hz. Tetrodotoxin (1 microM) or omission of Ca2+ from the medium abolished ACh release. The M1 receptor agonist (4-hydroxy-2-butynyl)-1-trimethylammonium m-chlorocarbanilate chloride (McN-A 343, 50 microM) increased release (by 136%), whereas the M2 muscarinic agonist oxotremorine (1 microM) decreased ACh release (by 22%). The muscarinic antagonists, atropine (1 microM) or pirenzepine (M1 selective, 1 microM), did not change ACh release. However, pirenzepine (1 microM) blocked the facilitatory effect of McN-A 343, and atropine (1 microM) blocked the inhibitory effect of oxotremorine. The cholinesterase inhibitor physostigmine (1-5 microM), the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP, 10 microM), and the nicotinic antagonist D-tubocurarine (50 microM) did not change ACh release. 4-Aminopyridine, a K+ channel blocker, significantly increased the release (by 146%). Seven days after decentralization of the major pelvic ganglion, the evoked release of ACh was abolished. It is concluded that release of ACh occurs from the preganglionic nerve terminals rather than from the cholinergic cell bodies and is not modulated by actions of endogenous ACh on either muscarinic or nicotinic autoreceptors. These data confirm and extend previous electrophysiological findings indicating that synapses in the major pelvic ganglion have primarily a relay function.

  12. Relative oral bioavailability of morphine and naltrexone derived from crushed morphine sulfate and naltrexone hydrochloride extended-release capsules versus intact product and versus naltrexone solution: a single-dose, randomized-sequence, open-label, three-way crossover trial in healthy volunteers.

    Science.gov (United States)

    Johnson, Franklin K; Stark, Jeffrey G; Bieberdorf, Frederick A; Stauffer, Joe

    2010-06-01

    Morphine sulfate/sequestered naltrexone hydrochloride (HCl) (MS-sNT) extended-release fixed-dose combination capsules, approved by the US Food and Drug Administration (FDA) in August 2009 for chronic moderate to severe pain, contain extended-release morphine pellets with a sequestered core of the opioid antagonist naltrexone. MS-sNT was designed so that if the product is tampered with by crushing, the naltrexone becomes bioavailable to mitigate morphine-induced subjective effects, rendering the product less attractive for tampering. The primary aim of this study was to compare the oral bioavailability of naltrexone and its metabolite 6-beta-naltrexol, derived from crushed pellets from MS-sNT capsules, to naltrexone solution. This study also assessed the relative bioavailability of morphine from crushed pellets from MS-sNT capsules and that from the whole, intact product. This single-dose, randomized-sequence, open-label, 3-period, 3-treatment crossover trial was conducted in healthy volunteers. Adults admitted to the study center underwent a 10-hour overnight fast before study drug administration. Each subject received all 3 of the following treatments, 1 per session, separated by a 14-day washout: tampered pellets (crushed for >or=2 minutes with a mortar and pestle) from a 60-mg MS-sNT capsule (60 mg morphine/2.4 mg naltrexone); 60-mg whole, intact MS-sNT capsule; and oral naltrexone HCl (2.4 mg) solution. Plasma concentrations of naltrexone and 6-beta-naltrexol were measured 0 to 168 hours after administration. Morphine pharmaco-kinetics of crushed and whole pellets were determined 0 to 72 hours after administration. The analysis of relative bioavailability was based on conventional FDA criteria for assuming bioequivalence; that is, 90% CIs for ratios of geometric means (natural logarithm [In]-transformed C(max) and AUC) fell within the range of 80% to 125%. Subjects underwent physical examinations, clinical laboratory tests, and ECG at screening and study

  13. Release Notes for Whisper-1.1

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Forrest B. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Rising, Michael Evan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Alwin, Jennifer Louise [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-04-27

    Whisper is a statistical analysis package developed in 2014 to support nuclear criticality safety (NCS) validation [1-3]. It uses the sensitivity profile data for an application as computed by MCNP6 [4-6] along with covariance files [7,8] for the nuclear data to determine a baseline upper-subcritical-limit (USL) for the application. Whisper version 1.0 was first developed and used at LANL in 2014 [3]. During 2015-2016, Whisper was updated to version 1.1 [9] and is to be included with the upcoming release of MCNP6.2. This document describes the Whisper-1.1 package that will be included with the MCNP6.2 release during 2017. Specific details are provided on the computer systems supported, the software quality assurance (SQA) procedures, installation, and testing. This document does not address other important topics, such as the importance of sensitivity-uncertainty (SU) methods to NCS validation, the theory underlying SU methodology, tutorials on the usage of MCNP-Whisper, practical approaches to using SU methodology to support and extend traditional validation, etc. There are over 50 documents included with Whisper-1.1 and available in the MCNP Reference Collection on the MCNP website (mcnp.lanl.gov) that address all of those topics and more. In this document, however, a complete bibliography of relevant MCNP-Whisper references is provided.

  14. Guanfacine extended release for children and adolescents with attention-deficit/hyperactivity disorder: efficacy following prior methylphenidate treatment

    Directory of Open Access Journals (Sweden)

    Huss M

    2016-05-01

    Full Text Available Michael Huss,1 Vanja Sikirica,2 Amaia Hervas,3,4 Jeffrey H Newcorn,5 Valerie Harpin,6 Brigitte Robertson71Child and Adolescent Psychiatry, Johannes Gutenberg University Mainz, Mainz, Germany; 2Global Health Economics, Outcomes Research and Epidemiology, Shire, Wayne, PA, USA; 3Child and Adolescent Mental Health Unit, University Hospital Mútua de Terressa, Barcelona, Spain; 4Developmental Disorders Unit (UETD, Hospital San Juan de Dios, Barcelona, Spain; 5Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 6Ryegate Children’s Centre, Sheffield Children’s NHS Foundation Trust, Sheffield, UK; 7Global Clinical Development, Shire, Wayne, PA, USAAbstract: Guanfacine extended release (GXR and atomoxetine (ATX are nonstimulant treatments for attention-deficit/hyperactivity disorder (ADHD. As nonstimulant treatments are often used after stimulants in ADHD, GXR was assessed relative to prior stimulant treatment in a randomized controlled trial (RCT, in which ATX was included as a reference arm, and in the open-label phase of a randomized-withdrawal study (RWS. Participants were 6–17 years old with ADHD Rating Scale version IV (ADHD-RS-IV scores ≥32 and Clinical Global Impressions – Severity scores ≥4. RCT participants received dose-optimized GXR (1–7 mg/day, ATX (10–100 mg/day, or placebo for 10–13 weeks. RWS participants received dose-optimized GXR (1–7 mg/day for 13 weeks. Participants’ last stimulant medication prior to enrolment, and reasons for stopping this medication, were collected at baseline. Change from baseline ADHD-RS-IV score and the proportion of responders were assessed by prior stimulant exposure. Of 163 RCT and 296 RWS participants who had previously received stimulant treatment, 142 and 224, respectively, had received methylphenidate (MPH; due to the low number of participants and the heterogeneity of non-MPH treatments, we only report data for prior MPH treatment. The most

  15. Extended icosahedral structures

    CERN Document Server

    Jaric, Marko V

    1989-01-01

    Extended Icosahedral Structures discusses the concepts about crystal structures with extended icosahedral symmetry. This book is organized into six chapters that focus on actual modeling of extended icosahedral crystal structures. This text first presents a tiling approach to the modeling of icosahedral quasiperiodic crystals. It then describes the models for icosahedral alloys based on random connections between icosahedral units, with particular emphasis on diffraction properties. Other chapters examine the glassy structures with only icosahedral orientational order and the extent of tra

  16. Released air during vapor and air cavitation

    Energy Technology Data Exchange (ETDEWEB)

    Jablonská, Jana, E-mail: jana.jablonska@vsb.cz; Kozubková, Milada, E-mail: milada.kozubkova@vsb.cz [VŠB-Technical University of Ostrava, Faculty of Mechanical Engineering, Department of Hydromechanics and Hydraulic Equipment, 17. listopadu 15, 708 33 Ostrava-Poruba (Czech Republic)

    2016-06-30

    Cavitation today is a very important problem that is solved by means of experimental and mathematical methods. The article deals with the generation of cavitation in convergent divergent nozzle of rectangular cross section. Measurement of pressure, flow rate, temperature, amount of dissolved air in the liquid and visualization of cavitation area using high-speed camera was performed for different flow rates. The measurement results were generalized by dimensionless analysis, which allows easy detection of cavitation in the nozzle. For numerical simulation the multiphase mathematical model of cavitation consisting of water and vapor was created. During verification the disagreement with the measurements for higher flow rates was proved, therefore the model was extended to multiphase mathematical model (water, vapor and air), due to release of dissolved air. For the mathematical modeling the multiphase turbulence RNG k-ε model for low Reynolds number flow with vapor and air cavitation was used. Subsequently the sizes of the cavitation area were verified. In article the inlet pressure and loss coefficient depending on the amount of air added to the mathematical model are evaluated. On the basis of the approach it may be create a methodology to estimate the amount of released air added at the inlet to the modeled area.

  17. Risk Assessment of Structural Integrity of Transportation Casks after Extended Storage

    Energy Technology Data Exchange (ETDEWEB)

    Ibarra, Luis; Medina, Ricardo; Yang, Haori

    2018-03-23

    This study assessed the risk of loss of structural integrity of transportation casks and fuel cladding after extended storage. Although it is known that fuel rods discharged from NPPs have a small percentage of rod cladding defects, the behavior of fuel cladding and the structural elements of assemblies during transportation after long-term storage is not well understood. If the fuel degrades during extended storage, it could be susceptible to damage from vibration and impact loads during transport operations, releasing fission-product gases into the canister or the cask interior (NWTRB 2010). Degradation of cladding may occur due to mechanisms associated with hydrogen embrittlement, delayed hydride cracking, low temperature creep, and stress corrosion cracking (SCC) that may affect fuel cladding and canister components after extended storage of hundreds of years. Over extended periods at low temperatures, these mechanisms affect the ductility, strength, and fracture toughness of the fuel cladding, which becomes brittle. For transportation purposes, the fuel may be transferred from storage to shipping casks, or dual-purpose casks may be used for storage and transportation. Currently, most of the transportation casks will be the former case. A risk assessment evaluation is conducted based on results from experimental tests and simulations with advanced numerical models. A novel contribution of this study is the evaluation of the combined effect of component aging and vibration/impact loads in transportation scenarios. The expected levels of deterioration will be obtained from previous and current studies on the effect of aging on fuel and cask components. The emphasis of the study is placed on the structural integrity of fuel cladding and canisters.

  18. Nanostructural control of the release of macromolecules from silica sol–gels

    Science.gov (United States)

    Radin, Shula; Bhattacharyya, Sanjib; Ducheyne, Paul

    2013-01-01

    The therapeutic use of biological molecules such as growth factors and monoclonal antibodies is challenging in view of their limited half-life in vivo. This has elicited the interest in delivery materials that can protect these molecules until released over extended periods of time. Although previous studies have shown controlled release of biologically functional BMP-2 and TGF-β from silica sol–gels, more versatile release conditions are desirable. This study focuses on the relationship between room temperature processed silica sol–gel synthesis conditions and the nanopore size and size distribution of the sol–gels. Furthermore, the effect on release of large molecules with a size up to 70 kDa is determined. Dextran, a hydrophilic polysaccharide, was selected as a large model molecule at molecular sizes of 10, 40 and 70 kDa, as it enabled us to determine a size effect uniquely without possible confounding chemical effects arising from the various molecules used. Previously, acid catalysis was performed at a pH value of 1.8 below the isoelectric point of silica. Herein the silica synthesis was pursued using acid catalysis at either pH 1.8 or 3.05 first, followed by catalysis at higher values by adding base. This results in a mesoporous structure with an abundance of pores around 3.5 nm. The data show that all molecular sizes can be released in a controlled manner. The data also reveal a unique in vivo approach to enable release of large biological molecules: the use more labile sol–gel structures by acid catalyzing above the pH value of the isoelectric point of silica; upon immersion in a physiological fluid the pores expand to reach an average size of 3.5 nm, thereby facilitating molecular out-diffusion. PMID:23643607

  19. Estimating the location and spatial extent of a covert anthrax release.

    Directory of Open Access Journals (Sweden)

    Judith Legrand

    2009-01-01

    Full Text Available Rapidly identifying the features of a covert release of an agent such as anthrax could help to inform the planning of public health mitigation strategies. Previous studies have sought to estimate the time and size of a bioterror attack based on the symptomatic onset dates of early cases. We extend the scope of these methods by proposing a method for characterizing the time, strength, and also the location of an aerosolized pathogen release. A back-calculation method is developed allowing the characterization of the release based on the data on the first few observed cases of the subsequent outbreak, meteorological data, population densities, and data on population travel patterns. We evaluate this method on small simulated anthrax outbreaks (about 25-35 cases and show that it could date and localize a release after a few cases have been observed, although misspecifications of the spore dispersion model, or the within-host dynamics model, on which the method relies can bias the estimates. Our method could also provide an estimate of the outbreak's geographical extent and, as a consequence, could help to identify populations at risk and, therefore, requiring prophylactic treatment. Our analysis demonstrates that while estimates based on the first ten or 15 observed cases were more accurate and less sensitive to model misspecifications than those based on five cases, overall mortality is minimized by targeting prophylactic treatment early on the basis of estimates made using data on the first five cases. The method we propose could provide early estimates of the time, strength, and location of an aerosolized anthrax release and the geographical extent of the subsequent outbreak. In addition, estimates of release features could be used to parameterize more detailed models allowing the simulation of control strategies and intervention logistics.

  20. A randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of the extended-release tramadol hydrochloride/acetaminophen fixed-dose combination tablet for the treatment of chronic low back pain.

    Science.gov (United States)

    Lee, Jae Hyup; Lee, Chong-Suh

    2013-11-01

    Chronic low back pain is a common condition that is often difficult to treat. The combination of tramadol hydrochloride and acetaminophen in an extended-release formulation has been shown to provide rapid and long-lasting analgesic effects resulting from the synergistic activity of these 2 active ingredients. The goal of this study was to evaluate the efficacy and safety of extended-release tramadol hydrochloride 75-mg/acetaminophen 650-mg fixed-dose combination tablets (TA-ER) for the treatment of chronic low back pain. This Phase III, double-blind, placebo-controlled, parallel-group study enrolled 245 patients with moderate to severe (≥4 cm on a 10-cm visual analog scale) chronic (≥3 months') low back pain insufficiently controlled by previous NSAIDs or cyclooxygenase-2-selective inhibitors and randomly assigned them to receive 4 weeks of either TA-ER or placebo. The primary efficacy end point was the percentage of patients with a pain intensity change rate ≥30% from baseline to final evaluation. Secondary end points included quality of life (Korean Short Form-36), functionality (Korean Oswestry Disability Index), and adverse events. The percentage of patients with a pain intensity change rate ≥30% was significantly higher (P Pain relief success rate from baseline was significantly higher with TA-ER versus placebo at days 8 and 15 but not at the final visit. Patients in the TA-ER group had significant improvements versus placebo in role-physical, general health, and reported health transition domains of the Korean Short Form-36 and significantly higher functional improvements in the personal care section of the Korean Oswestry Disability Index. Patient assessment of overall pain control as "very good" was also significantly higher with TA-ER than with placebo. Adverse events were reported more frequently with TA-ER than with placebo; the most common adverse events reported were nausea, dizziness, constipation, and vomiting. TA-ER was significantly more

  1. In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation.

    Science.gov (United States)

    Franek, F; Jarlfors, A; Larsen, F; Holm, P; Steffansen, B

    2015-09-18

    Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq(®), an extended release formulation (ERF). Semi-mechanistic models of desvenlafaxine were built (using SimCyp(®)) by combining in vitro data on dissolution and permeation (mechanistic part of model) with clinical data (obtained from literature) on distribution and clearance (non-mechanistic part of model). The model predictions of desvenlafaxine pharmacokinetics after IRF and ERF administration were compared with published clinical data from 14 trials. Desvenlafaxine in vivo dissolution from the IRF and ERF was predicted from in vitro solubility studies and biorelevant dissolution studies (using the USP3 dissolution apparatus), respectively. Desvenlafaxine apparent permeability (Papp) at varying apical pH was investigated using the Caco-2 cell line and extrapolated to effective intestinal permeability (Peff) in human duodenum, jejunum, ileum and colon. Desvenlafaxine pKa-values and octanol-water partition coefficients (Do:w) were determined experimentally. Due to predicted rapid dissolution after IRF administration, desvenlafaxine was predicted to be available for permeation in the duodenum. Desvenlafaxine Do:w and Papp increased approximately 13-fold when increasing apical pH from 5.5 to 7.4. Desvenlafaxine Peff thus increased with pH down the small intestine. Consequently, desvenlafaxine absorption from an IRF appears rate-limited by low Peff in the upper small intestine, which "delays" the predicted

  2. Nitrogen mineralization and volatilization from controlled release urea fertilizers in selected malaysian soils

    International Nuclear Information System (INIS)

    Singh, K.J.K.A.; Yusop, M.K.; Oad, F.C.

    2017-01-01

    Controlled release urea fertilizers are usually used for extended duration in supplying nitrogen. The rate of urea hydrolysis could be efficiently minimized through these fertilizers. Various controlled released fertilizers i.e Uber-10 (30%N), Meister-20 (40%N), Meister-27 (40%N), Humate Coated Urea (45%N), Duration Polymer Coated Urea Type-V (43%N), Gold-N-Sulfur Coated Urea (41%N) and common urea (46%N) were applied to inland soil series of Malaysia. The soil series investigated were: Serdang (Typic Paleudult), Munchong (Typic Hapludox), Segamat (Typic Hapludox), Selangor (Typic Tropaquept), Rengam (Typic Kandiudult) and Holyrood (Typic Kandiudult). The maximum release of ammonium (NH/sub 4/-N) was noted in Gold-N-Sulfur Coated Urea, Humate Coated Urea and common Urea over 8 weeks of incubation. However, the release of NH4-N under the influence of Duration Type-V and Uber-10 took 2nd place. The Meister-20 and Meister-27 had minimum release of NH4-N. Munchong series was efficient in releasing higher NH4-N compared to rest of soils during 8th week of incubation due to higher soil total carbon, low /sub 4/-N and total nitrogen. Ammonia (NH/sub 3/-N) loss progressively increased with unit increase in incubation week and was higher during 6th week of fertilizer application. The higher loss of NH3-N was found in common Urea. However, Meister-20, Meister-27, Duration Polymer Coated Urea Type-V and Uber-10 had lower loss of NH/sub 3/-N due to slow release property and this character could be beneficial for supplying nutrients to next season crop. (author)

  3. News/Press Releases

    Data.gov (United States)

    Office of Personnel Management — A press release, news release, media release, press statement is written communication directed at members of the news media for the purpose of announcing programs...

  4. Matrix and reservoir-type multipurpose vaginal rings for controlled release of dapivirine and levonorgestrel.

    Science.gov (United States)

    Boyd, Peter; Fetherston, Susan M; McCoy, Clare F; Major, Ian; Murphy, Diarmaid J; Kumar, Sandeep; Holt, Jonathon; Brimer, Andrew; Blanda, Wendy; Devlin, Brid; Malcolm, R Karl

    2016-09-10

    A matrix-type silicone elastomer vaginal ring providing 28-day continuous release of dapivirine (DPV) - a lead candidate human immunodeficiency virus type 1 (HIV-1) microbicide compound - has recently demonstrated moderate levels of protection in two Phase III clinical studies. Here, next-generation matrix and reservoir-type silicone elastomer vaginal rings are reported for the first time offering simultaneous and continuous in vitro release of DPV and the contraceptive progestin levonorgestrel (LNG) over a period of between 60 and 180days. For matrix-type vaginal rings comprising initial drug loadings of 100, 150 or 200mg DPV and 0, 16 or 32mg LNG, Day 1 daily DPV release values were between 4132 and 6113μg while Day 60 values ranged from 284 to 454μg. Daily LNG release ranged from 129 to 684μg on Day 1 and 2-91μg on Day 60. Core-type rings comprising one or two drug-loaded cores provided extended duration of in vitro release out to 180days, and maintained daily drug release rates within much narrower windows (either 75-131μg/day or 37-66μg/day for DPV, and either 96-150μg/day or 37-57μg/day for LNG, depending on core ring configuration and ignoring initial lag release effect for LNG) compared with matrix-type rings. The data support the continued development of these devices as multi-purpose prevention technologies (MPTs) for HIV prevention and long-acting contraception. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Inclusion of cefalexin in SBA-15 mesoporus material and release property

    International Nuclear Information System (INIS)

    Zhai, Qing-Zhou

    2012-01-01

    SBA-15 (Santa Barbara Amorphous-15) is a high ordered mesoporous material. It has the advantages of a non-toxic property, good hydrothermal stability and thermal stability, etc. Inside inner surface a lot of silanols exist. Pore diameter size is uniform and pore size distribution is narrow. This structural feature makes SBA-15 have a higher loading drug amount and be able to effectively extend the drug release cycle. In this paper, polyethylene glycol-block-polypropylene glycol-block-polyethylene glycol was used as template and tetraethyl orthosilicate was used as silica source to prepare SBA-15 by hydrothermal synthesis method. Cefalexin was included in SBA-15 and the included cefalexin drug content was 158.72 mg/g. The composite materials were characterized by using chemical analysis, powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), infrared (IR) spectroscopy, and low temperature nitrogen adsorption–desorption. The results showed that cefalexin had been successfully included in host SBA-15 pore channels. Rational analyses of the release processes of cefalexin drug from the pores of SBA-15 to the simulated body fluid, simulated gastric juice and simulated intestinal fluid were made and sustained-release effects of the drug in complex system were studied. The results showed that in simulated body fluid within 1–5 h cefalexin was fast released and the cumulative release reached 50.00% at 5 h. In 15–20 h, the sustained release speed of cefalexin drug in the composite material decreased and the sustained-release cumulative amount reached 99.87% at 20 h. The release of cefalexin was basically complete. In simulated gastric fluid, composite material sustained-release ended at 4 h, the cumulative sustained release ratio reaching 26.10%. In simulated gastric fluid, the sustained-release was complete at 7 h, the cumulative sustained release ratio reaching 32.46%. The composite material of SBA-15 and cefalexin

  6. Formulation and evaluation of sustained release matrix tablet of rabeprazole using wet granulation technique

    Directory of Open Access Journals (Sweden)

    Ruqaiyah Khan

    2014-01-01

    Full Text Available Introduction: Rabeprazole, a member of substituted benzimidazoles, inhibits the final step in gastric acid secretions. This drug claims to cause fastest acid separation (due to higher pKa, and more rapidly converts to the active species to aid gastric mucin synthesis. The most significant pharmacological action of Rabeprazole is dose dependent suppression of gastric acid secretion; without anticholinergic or H2-blocking action. It completely abolishes the hydrochloric acid secretion as it is powerful inhibitor of gastric acid. Rabeprazole is acid labile and hence commonly formulated as an enteric coated tablet. The absorption of rabeprazole occurs rapidly as soon as tablet leaves the stomach. Aim: In the present study an attempt was made to formulate and evaluate Rabeprazole sustained release matrix tablet using wet granulation technique incorporating various polymers like HPMC-E15, Carbopol934, and sodium carboxymethyl cellulose (CMC. Materials and Methods: The Formulated tablets were evaluated for different physicochemical properties like rheological properties, weight variation, thickness, hardness, % friability, in vitro release studies and drug content. Results: Studies revealed that all the physicochemical parameters comply with the official standards. The in vitro release studies exhibits the release up to 90%, over a prolonged period of time which confirms the extended release profile of formulation, having better bioavailability as well as decreased dosing frequency with reduced doses. Conclusion: The sustained release matrix tablets of rabiprazole shown better bioavailability, efficacy and potency, when compared with official standards.

  7. Development and evaluation of new multiple-unit levodopa sustained-release floating dosage forms.

    Science.gov (United States)

    Goole, J; Vanderbist, F; Amighi, K

    2007-04-04

    This work relates to the development and the in vitro evaluation of sustained-release minitablets (MT), prepared by melt granulation and subsequent compression, which are designed to float over an extended period of time. Levodopa was used as a model drug. The importance of the composition and manufacturing parameters of the MT on their floating and dissolution properties was then examined. The investigation showed that MT composition and MT diameter had the greatest influence on drug release, which was sustained for more than 8h. By using the same formulation, the best floating properties were obtained with 3mm MT prepared at low compression forces ranging between 50 and 100N. Their resultant-weight (RW) values were always higher than those obtained with a marketed HBS dosage form within 13h. When they were filled into gelatin capsules, no sticking was observed. By evaluating the dissolution profiles of levodopa at different pH values, it was found that dissolution profiles depend more on the prolonged-release ability of Methocel K15M than on the pH-dependent solubility of levodopa. Finally, the robustness of the floating MT was assessed by testing the drug release variability in function of the stirring conditions during dissolution tests.

  8. Extended thermodynamics

    CERN Document Server

    Müller, Ingo

    1993-01-01

    Physicists firmly believe that the differential equations of nature should be hyperbolic so as to exclude action at a distance; yet the equations of irreversible thermodynamics - those of Navier-Stokes and Fourier - are parabolic. This incompatibility between the expectation of physicists and the classical laws of thermodynamics has prompted the formulation of extended thermodynamics. After describing the motifs and early evolution of this new branch of irreversible thermodynamics, the authors apply the theory to mon-atomic gases, mixtures of gases, relativistic gases, and "gases" of phonons and photons. The discussion brings into perspective the various phenomena called second sound, such as heat propagation, propagation of shear stress and concentration, and the second sound in liquid helium. The formal mathematical structure of extended thermodynamics is exposed and the theory is shown to be fully compatible with the kinetic theory of gases. The study closes with the testing of extended thermodynamics thro...

  9. Extended family medicine training

    Science.gov (United States)

    Slade, Steve; Ross, Shelley; Lawrence, Kathrine; Archibald, Douglas; Mackay, Maria Palacios; Oandasan, Ivy F.

    2016-01-01

    Abstract Objective To examine trends in family medicine training at a time when substantial pedagogic change is under way, focusing on factors that relate to extended family medicine training. Design Aggregate-level secondary data analysis based on the Canadian Post-MD Education Registry. Setting Canada. Participants All Canadian citizens and permanent residents who were registered in postgraduate family medicine training programs within Canadian faculties of medicine from 1995 to 2013. Main outcome measures Number and proportion of family medicine residents exiting 2-year and extended (third-year and above) family medicine training programs, as well as the types and numbers of extended training programs offered in 2015. Results The proportion of family medicine trainees pursuing extended training almost doubled during the study period, going from 10.9% in 1995 to 21.1% in 2013. Men and Canadian medical graduates were more likely to take extended family medicine training. Among the 5 most recent family medicine exit cohorts (from 2009 to 2013), 25.9% of men completed extended training programs compared with 18.3% of women, and 23.1% of Canadian medical graduates completed extended training compared with 13.6% of international medical graduates. Family medicine programs vary substantially with respect to the proportion of their trainees who undertake extended training, ranging from a low of 12.3% to a high of 35.1% among trainees exiting from 2011 to 2013. Conclusion New initiatives, such as the Triple C Competency-based Curriculum, CanMEDS–Family Medicine, and Certificates of Added Competence, have emerged as part of family medicine education and credentialing. In acknowledgment of the potential effect of these initiatives, it is important that future research examine how pedagogic change and, in particular, extended training shapes the care family physicians offer their patients. As part of that research it will be important to measure the breadth and uptake of

  10. Scale-invariant extended inflation

    International Nuclear Information System (INIS)

    Holman, R.; Kolb, E.W.; Vadas, S.L.; Wang, Y.

    1991-01-01

    We propose a model of extended inflation which makes use of the nonlinear realization of scale invariance involving the dilaton coupled to an inflaton field whose potential admits a metastable ground state. The resulting theory resembles the Jordan-Brans-Dicke version of extended inflation. However, quantum effects, in the form of the conformal anomaly, generate a mass for the dilaton, thus allowing our model to evade the problems of the original version of extended inflation. We show that extended inflation can occur for a wide range of inflaton potentials with no fine-tuning of dimensionless parameters required. Furthermore, we also find that it is quite natural for the extended-inflation period to be followed by an epoch of slow-rollover inflation as the dilaton settles down to the minimum of its induced potential

  11. Hydration-Induced Phase Separation in Amphiphilic Polymer Matrices and its Influence on Voclosporin Release

    Energy Technology Data Exchange (ETDEWEB)

    Khan, I. John [The State Univ. of New Jersey, Piscataway, NJ (United States); Murthy, N. Sanjeeva [The State Univ. of New Jersey, Piscataway, NJ (United States); Kohn, Joachim [The State Univ. of New Jersey, Piscataway, NJ (United States)

    2015-10-30

    Voclosporin is a highly potent, new cyclosporine -- a derivative that is currently in Phase 3 clinical trials in the USA as a potential treatment for inflammatory diseases of the eye. Voclosporin represents a number of very sparingly soluble drugs that are difficult to administer. It was selected as a model drug that is dispersed within amphiphilic polymer matrices, and investigated the changing morphology of the matrices using neutron and x-ray scattering during voclosporin release and polymer resorption. The hydrophobic segments of the amphiphilic polymer chain are comprised of desaminotyrosyl-tyrosine ethyl ester (DTE) and desaminotyrosyl-tyrosine (DT), and the hydrophilic component is poly(ethylene glycol) (PEG). Water uptake in these matrices resulted in the phase separation of hydrophobic and hydrophilic domains that are a few hundred Angstroms apart. These water-driven morphological changes influenced the release profile of voclosporin and facilitated a burst-free release from the polymer. No such morphological reorganization was observed in poly(lactide-co-glycolide) (PLGA), which exhibits an extended lag period, followed by a burst-like release of voclosporin when the polymer was degraded. An understanding of the effect of polymer composition on the hydration behavior is central to understanding and controlling the phase behavior and resorption characteristics of the matrix for achieving long-term controlled release of hydrophobic drugs such as voclosporin.

  12. Hydration-Induced Phase Separation in Amphiphilic Polymer Matrices and its Influence on Voclosporin Release

    Directory of Open Access Journals (Sweden)

    Joachim Kohn

    2012-10-01

    Full Text Available Voclosporin is a highly potent, new cyclosporine-A derivative that is currently in Phase 3 clinical trials in the USA as a potential treatment for inflammatory diseases of the eye. Voclosporin represents a number of very sparingly soluble drugs that are difficult to administer. We therefore selected it as a model drug that is dispersed within amphiphilic polymer matrices, and investigated the changing morphology of the matrices using neutron and x-ray scattering during voclosporin release and polymer resorption. The hydrophobic segments of the amphiphilic polymer chain are comprised of desaminotyrosyl-tyrosine ethyl ester (DTE and desaminotyrosyl-tyrosine (DT, and the hydrophilic component is poly(ethylene glycol (PEG. Water uptake in these matrices resulted in the phase separation of hydrophobic and hydrophilic domains that are a few hundred Angstroms apart. These water-driven morphological changes influenced the release profile of voclosporin and facilitated a burst-free release from the polymer. No such morphological reorganization was observed in poly(lactide-co-glycolide (PLGA, which exhibits an extended lag period, followed by a burst-like release of voclosporin when the polymer was degraded. An understanding of the effect of polymer composition on the hydration behavior is central to understanding and controlling the phase behavior and resorption characteristics of the matrix for achieving long-term controlled release of hydrophobic drugs such as voclosporin.

  13. Planck early results. XIII. Statistical properties of extragalactic radio sources in the Planck Early Release Compact Source Catalogue

    DEFF Research Database (Denmark)

    Lähteenmäki, A.; Poutanen, T.; Natoli, P.

    2011-01-01

    The data reported in Planck's Early Release Compact Source Catalogue (ERCSC) are exploited to measure the number counts (dN/dS) of extragalactic radio sources at 30, 44, 70, 100, 143 and 217 GHz. Due to the full-sky nature of the catalogue, this measurement extends to the rarest and brightest sou...

  14. Estimation of in-vivo neurotransmitter release by brain microdialysis: the issue of validity.

    Science.gov (United States)

    Di Chiara, G.; Tanda, G.; Carboni, E.

    1996-11-01

    Although microdialysis is commonly understood as a method of sampling low molecular weight compounds in the extracellular compartment of tissues, this definition appears insufficient to specifically describe brain microdialysis of neurotransmitters. In fact, transmitter overflow from the brain into dialysates is critically dependent upon the composition of the perfusing Ringer. Therefore, the dialysing Ringer not only recovers the transmitter from the extracellular brain fluid but is a main determinant of its in-vivo release. Two types of brain microdialysis are distinguished: quantitative micro-dialysis and conventional microdialysis. Quantitative microdialysis provides an estimate of neurotransmitter concentrations in the extracellular fluid in contact with the probe. However, this information might poorly reflect the kinetics of neurotransmitter release in vivo. Conventional microdialysis involves perfusion at a constant rate with a transmitter-free Ringer, resulting in the formation of a steep neurotransmitter concentration gradient extending from the Ringer into the extracellular fluid. This artificial gradient might be critical for the ability of conventional microdialysis to detect and resolve phasic changes in neurotransmitter release taking place in the implanted area. On the basis of these characteristics, conventional microdialysis of neurotransmitters can be conceptualized as a model of the in-vivo release of neurotransmitters in the brain. As such, the criteria of face-validity, construct-validity and predictive-validity should be applied to select the most appropriate experimental conditions for estimating neurotransmitter release in specific brain areas in relation to behaviour.

  15. Modelling grain growth in the framework of Rational Extended Thermodynamics

    International Nuclear Information System (INIS)

    Kertsch, Lukas; Helm, Dirk

    2016-01-01

    Grain growth is a significant phenomenon for the thermomechanical processing of metals. Since the mobility of the grain boundaries is thermally activated and energy stored in the grain boundaries is released during their motion, a mutual interaction with the process conditions occurs. To model such phenomena, a thermodynamic framework for the representation of thermomechanical coupling phenomena in metals including a microstructure description is required. For this purpose, Rational Extended Thermodynamics appears to be a useful tool. We apply an entropy principle to derive a thermodynamically consistent model for grain coarsening due to the growth and shrinkage of individual grains. Despite the rather different approaches applied, we obtain a grain growth model which is similar to existing ones and can be regarded as a thermodynamic extension of that by Hillert (1965) to more general systems. To demonstrate the applicability of the model, we compare our simulation results to grain growth experiments in pure copper by different authors, which we are able to reproduce very accurately. Finally, we study the implications of the energy release due to grain growth on the energy balance. The present unified approach combining a microstructure description and continuum mechanics is ready to be further used to develop more elaborate material models for complex thermo-chemo-mechanical coupling phenomena. (paper)

  16. Modelling grain growth in the framework of Rational Extended Thermodynamics

    Science.gov (United States)

    Kertsch, Lukas; Helm, Dirk

    2016-05-01

    Grain growth is a significant phenomenon for the thermomechanical processing of metals. Since the mobility of the grain boundaries is thermally activated and energy stored in the grain boundaries is released during their motion, a mutual interaction with the process conditions occurs. To model such phenomena, a thermodynamic framework for the representation of thermomechanical coupling phenomena in metals including a microstructure description is required. For this purpose, Rational Extended Thermodynamics appears to be a useful tool. We apply an entropy principle to derive a thermodynamically consistent model for grain coarsening due to the growth and shrinkage of individual grains. Despite the rather different approaches applied, we obtain a grain growth model which is similar to existing ones and can be regarded as a thermodynamic extension of that by Hillert (1965) to more general systems. To demonstrate the applicability of the model, we compare our simulation results to grain growth experiments in pure copper by different authors, which we are able to reproduce very accurately. Finally, we study the implications of the energy release due to grain growth on the energy balance. The present unified approach combining a microstructure description and continuum mechanics is ready to be further used to develop more elaborate material models for complex thermo-chemo-mechanical coupling phenomena.

  17. To bind or not to bind? Different temporal binding effects from voluntary pressing and releasing actions.

    Science.gov (United States)

    Zhao, Ke; Chen, Yu-Hsin; Yan, Wen-Jing; Fu, Xiaolan

    2013-01-01

    Binding effect refers to the perceptual attraction between an action and an outcome leading to a subjective compression of time. Most studies investigating binding effects exclusively employ the "pressing" action without exploring other types of actions. The present study addresses this issue by introducing another action, releasing action or the voluntary lifting of the finger/wrist, to investigate the differences between voluntary pressing and releasing actions. Results reveal that releasing actions led to robust yet short-lived temporal binding effects, whereas pressing condition had steady temporal binding effects up to super-seconds. The two actions also differ in sensitivity to changes in temporal contiguity and contingency, which could be attributed to the difference in awareness of action. Extending upon current models of "willed action," our results provide insights from a temporal point of view and support the concept of a dual system consisting of predictive motor control and top-down mechanisms.

  18. Rational extended thermodynamics

    CERN Document Server

    Müller, Ingo

    1998-01-01

    Ordinary thermodynamics provides reliable results when the thermodynamic fields are smooth, in the sense that there are no steep gradients and no rapid changes. In fluids and gases this is the domain of the equations of Navier-Stokes and Fourier. Extended thermodynamics becomes relevant for rapidly varying and strongly inhomogeneous processes. Thus the propagation of high­ frequency waves, and the shape of shock waves, and the regression of small-scale fluctuation are governed by extended thermodynamics. The field equations of ordinary thermodynamics are parabolic while extended thermodynamics is governed by hyperbolic systems. The main ingredients of extended thermodynamics are • field equations of balance type, • constitutive quantities depending on the present local state and • entropy as a concave function of the state variables. This set of assumptions leads to first order quasi-linear symmetric hyperbolic systems of field equations; it guarantees the well-posedness of initial value problems and f...

  19. Hydraulic running and release tool with mechanical emergency release

    International Nuclear Information System (INIS)

    Baker, S.F.

    1991-01-01

    This patent describes a setting tool for connection in a well string to position a tubular member in a well bore. It comprises: a mandrel adapted to be connected to the well string; an outer sleeve surrounding the mandrel and releasably secured thereto; a latch nut releasably connected to the outer sleeve; piston means sealingly engaging the mandrel; shear means releasably securing the piston to the latch nut to maintain the latch nut releasably connected to the tubular member; the mandrel having port means for conducting fluid pressure from the well string to release the piston means from and the latch nut; cooperating engageable surfaces on the piston and latch nut to reengage them together after the piston moves a predetermined longitudinal distance relative to the latch nut; and additional cooperating engageable surfaces on the latch nut and the outer sleeve which are engageable when the piston and engaged latch nut are moved a predetermined additional longitudinal distance by fluid pressure to secure the engaged piston and latch nut with the outer sleeve for retrieval along with the mandrel from the well bore

  20. 1995 Toxic chemical release inventory: Emergency Planning and Community Right-to-Know Act of 1986, Section 313

    International Nuclear Information System (INIS)

    Mincey, S.L.

    1996-08-01

    Section 313 of the Emergency Planning and Community Right-To-Know Act (EPCRA) requires the annual submittal of toxic chemical release information to the U.S. Environmental Protection Agency.Executive Order 12856, 'Federal Compliance With Right-to-Know Laws and Pollution Prevention Requirements' extends the requirements of EPCRA to all Federal agencies. The following document is the August 1996 submittal of the Hanford Site Toxic Chemical Release Inventory report. Included is a Form R for ethylene glycol, the sole chemical used in excess of the established regulatory thresholds at the Hanford Site by the U.S. Department of Energy, Richland Operations Office and its contractors during Calendar Year 1995

  1. A randomized, double-blind study of the efficacy and tolerability of extended-release quetiapine fumarate (quetiapine XR monotherapy in patients with major depressive disorder

    Directory of Open Access Journals (Sweden)

    Wang G

    2014-01-01

    Full Text Available Gang Wang,1 Alexander McIntyre,2 Willie R Earley,3 Shane R Raines,3 Hans Eriksson4 1Beijing Anding Hospital, Capital Medical University, Beijing, People's Republic of China; 2Department of Psychiatry, Penticton Regional Hospital, Penticton, BC, Canada; 3AstraZeneca Pharmaceuticals, Wilmington, DE, USA; 4AstraZeneca R&D, Södertälje, Sweden Objectives: To evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR monotherapy in patients with major depressive disorder (MDD. Patients and methods: This was a 10-week (8-week active treatment/2-week post-treatment randomized, double-blind, placebo- and active-controlled study (D1448C00004. Patients received quetiapine XR 150 mg/day, escitalopram 10 mg/day, or placebo; patients with an inadequate response (<20% improvement in Montgomery–Åsberg Depression Rating Scale [MADRS] total score at week two received double-dose treatment. The primary end point was week eight change from randomization in MADRS total score. Secondary end points included MADRS response (≥50% improvement and remission (score ≤8; Hamilton Rating Scale for Depression total and item 1; Hamilton Rating Scale for Anxiety total, psychic, and somatic; Clinical Global Impressions – Severity of Illness total; Pittsburgh Sleep Quality Index (PSQI global; and Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form percentage maximum total scores. Tolerability was assessed throughout. Results: A total of 471 patients was randomized. No significant improvements in MADRS total score were observed at week eight (last observation carried forward with either active treatment (quetiapine XR, -17.21 [P=0.174]; escitalopram, -16.73 [P=0.346] versus placebo (-15.61. There were no significant differences in secondary end points versus placebo, with the exception of week-eight change in PSQI global score (quetiapine XR, -4.96 [P<0.01] versus placebo, -3.37. Mixed-model repeated

  2. Octacosanol educes physico-chemical attributes, release and bioavailability as modified nanocrystals.

    Science.gov (United States)

    Sen Gupta, Surashree; Ghosh, Mahua

    2017-10-01

    Octacosanol is a lesser known nutraceutical with the potential for treatment of several inflammatory diseases, high cholesterol, Parkinson's symptoms and tumour growth along with the capacity to improve athletic performance. But its lipophilicity and large structure inhibits extended solubility in water resulting in poor absorption and a low bioavailability. In the present work, sodium salt of octacosyl sulfate was synthesized. It displayed improved water solubility. Its nanocrystals, synthesized by means of nanoprecipitation technique, enhanced diffusion velocity, antioxidant capacity, shelf-life, penetrability and bioavailability. Particle size of the nanocrystals ranged between 197 and 220nm. Both modified octacosanol and its nanocrystals displayed maximum lipid peroxidation activities at a concentration 1000ppm, but nanocrystals demonstrated higher prevention. From freeze-thaw cycles it was evident that normal octacosanol crystals were far more prone to temperature variations than the nanocrystals. A pronounced increase in release/diffusion rate and bioavailability was observed for the nanocrystals of the modified octacosanol. In vitro release kinetics, bioavailability and bioequivalence were studied. Relative bioavailability for gastric passage and pancreatic passage of nanocrystals was 2.58 times and 1.81 times that of normal crystals respectively. Furthermore the nanocrystals displayed a superior in vitro release rate, while following a non-Fickian mode. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Effect of surfactant chain length on drug release kinetics from microemulsion-laden contact lenses.

    Science.gov (United States)

    Maulvi, Furqan A; Desai, Ankita R; Choksi, Harsh H; Patil, Rahul J; Ranch, Ketan M; Vyas, Bhavin A; Shah, Dinesh O

    2017-05-30

    The effect of surfactant chain lengths [sodium caprylate (C 8 ), Tween 20 (C 12 ), Tween 80 (C 18 )] and the molecular weight of block copolymers [Pluronic F68 and Pluronic F 127] were studied to determine the stability of the microemulsion and its effect on release kinetics from cyclosporine-loaded microemulsion-laden hydrogel contact lenses in this work. Globule size and dilution tests (transmittance) suggested that the stability of the microemulsion increases with increase in the carbon chain lengths of surfactants and the molecular weight of pluronics. The optical transmittance of direct drug-laden contact lenses [DL-100] was low due to the precipitation of hydrophobic drugs in the lenses, while in microemulsion-laden lenses, the transmittance was improved when stability of the microemulsion was achieved. The results of in vitro release kinetics revealed that drug release was sustained to a greater extent as the stability of microemulsion was improved as well. This was evident in batch PF127-T80, which showed sustained release for 15days in comparison to batch DL-100, which showed release up to 7days. An in vivo drug release study in rabbit tear fluid showed significant increase in mean residence time (MRT) and area under curve (AUC) with PF-127-T80 lenses (stable microemulsion) in comparison to PF-68-SC lenses (unstable microemulsion) and DL-100 lenses. This study revealed the correlation between the stability of microemulsion and the release kinetics of drugs from contact lenses. Thus, it was inferred that the stable microemulsion batches sustained the release of hydrophobic drugs, such as cyclosporine from contact lenses for an extended period of time without altering critical lens properties. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Simulation of pellet-cladding thermomechanical interaction and fission gas release

    International Nuclear Information System (INIS)

    Denis, A.; Soba, A.

    2001-01-01

    This paper summarizes the present status of a computer code that describes some of the main phenomena occurring in a nuclear fuel element throughout its life. Temperature distribution, thermal expansion, elastic and plastic strains, creep, mechanical interaction between pellet and cladding, fission gas release, swelling and densification are modelized. The code assumes an axi-symmetric rod and hence, cylindrical finite elements are employed for the discretization. Due to the temperature dependence of the thermal conductivity, the heat conduction problem is non-linear. Thermal expansion gives origin to elastic or plastic strains, which adequately describe the bamboo effect. Plasticity renders the stress-strain problem non linear. The fission gas inventory is calculated by means of a diffusion model, which assumes spherical grains and uses a finite element scheme. In order to reduce the calculation time, the rod is divided into five cylindrical rings where the temperature is averaged. In each ring the gas diffusion problem is solved in one grain and the results are then extended to the whole ring. The pressure, increased by the released gas, interacts with the stress field. Densification and swelling due to solid and gaseous fission products are also considered. Experiments, particularly those of the FUMEX series, are simulated with this code. A good agreement is obtained for the fuel center line temperature, the inside rod pressure and the fractional gas release. (author)

  5. The systems containing clays and clay minerals from modified drug release: a review.

    Science.gov (United States)

    Rodrigues, Luís Alberto de Sousa; Figueiras, Ana; Veiga, Francisco; de Freitas, Rivelilson Mendes; Nunes, Lívio César Cunha; da Silva Filho, Edson Cavalcanti; da Silva Leite, Cleide Maria

    2013-03-01

    Clays are materials commonly used in the pharmaceutical industry, either as ingredients or as active ingredients. It was observed that when they are administered concurrently, they may interact with drugs reducing their absorption. Therefore, such interactions can be used to achieve technological and biopharmaceutical advantages, regarding the control of release. This review summarizes bibliographic (articles) and technological (patents) information on the use of systems containing clays and clay minerals in modified drug delivery. In this area, formulations such natural clay, commercial clay, synthetic clay, composites clay-polymers, nanocomposites clay-polymers, films and hidrogels composites clay-polymers are used to slow/extend or vectorize the release of drugs and consequently they increase their bioavailability. Finally, this review summarizes the fields of technology and biopharmaceutical applications, where clays are applied. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Large scientific releases

    International Nuclear Information System (INIS)

    Pongratz, M.B.

    1981-01-01

    The motivation for active experiments in space is considered, taking into account the use of active techniques to obtain a better understanding of the natural space environment, the utilization of the advantages of space as a laboratory to study fundamental plasma physics, and the employment of active techniques to determine the magnitude, degree, and consequences of artificial modification of the space environment. It is pointed out that mass-injection experiments in space plasmas began about twenty years ago with the Project Firefly releases. Attention is given to mass-release techniques and diagnostics, operational aspects of mass release active experiments, the active observation of mass release experiments, active perturbation mass release experiments, simulating an artificial modification of the space environment, and active experiments to study fundamental plasma physics

  7. Stimulatory effects of neuronally released norepinephrine on renin release in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Matsumura, Yasuo; Kawazoe, Shinka; Ichihara, Toshio; Shinyama, Hiroshi; Kageyama, Masaaki; Morimoto, Shiro (Osaka Univ. of Pharmaceutical Sciences (Japan))

    1988-10-01

    Extracellular high potassium inhibits renin release in vitro by increasing calcium concentrations in the juxtaglomerular cells. The authors found that the decreased response of renin release from rat kidney cortical slices in high potassium solution changed to a strikingly increased one in the presence of nifedipine at doses over 10{sup {minus}6} M. They then examined the stimulatory effect of extracellular high potassium in the presence of nifedipine on renin release. The enhancement of release was significantly suppressed either by propranolol or by metoprolol but not by prazosin. High potassium plus nifedipine-induced increase in renin release was markedly attenuated by renal denervation. The enhancing effect was not observed when the slices were incubated in calcium-free medium. Divalent cations such as Cd{sup 2+}, Co{sup 2+}, and Mn{sup 2+} blocked this enhancement in a concentration-dependent manner. High potassium elicited an increase in {sup 3}H efflux from the slices preloaded with ({sup 3}H)-norepinephrine. The increasing effect was not influenced by nifedipine but was abolished by the removal of extracellular calcium or by the addition of divalent cations. These observations suggest to us that the high potassium plus nifedipine-induced increase in renin release from the slices is mediated by norepinephrine derived from renal sympathetic nerves and that this neuronally released norepinephrine stimulates renin release via activation of {beta}-adrenoceptors.

  8. A model for short and medium range dispersion of radionuclides released to the atmosphere

    International Nuclear Information System (INIS)

    Clarke, R.H.

    1979-09-01

    A Working Group was established to give practical guidance on the estimation of the dispersion of radioactive releases to the atmosphere. The dispersion is estimated in the short and medium range, that is from about 100 m to a few tens of kilometres from the source, and is based upon a Gaussian plume model. A scheme is presented for categorising atmospheric conditions and values of the associated dispersion parameters are given. Typical results are presented for releases in specific meteorological conditions and a scheme is included to allow for durations of release of up to 24 hours. Consideration has also been given to predicting longer term average concentrations, typically annual averages, and results are presented which facilitate site specific calculations. The results of the models are extended to 100 km from the source, but the increasing uncertainty with which results may be predicted beyond a few tens of kilometres from the source is emphasised. Three technical appendices provide some of the rationale behind the decisions made in adopting the various models in the proposed dispersion scheme. (author)

  9. Risk-informed assessment of radionuclide release from dissolution of spent nuclear fuel and high-level waste glass

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Tae M., E-mail: tae.ahn@nrc.gov

    2017-06-15

    Highlights: • Dissolution of HLW waste form was assessed with long-term risk informed approach. • The radionuclide release rate decreases with time from the initial release rate. • Fast release radionuclides can be dispersed with discrete container failure time. • Fast release radionuclides can be restricted by container opening area. • Dissolved radionuclides may be further sequestered by sorption or others means. - Abstract: This paper aims to detail the different parameters to be considered for use in an assessment of radionuclide release. The dissolution of spent nuclear fuel and high-level nuclear waste glass was considered for risk and performance insights in a generic disposal system for more than 100,000 years. The probabilistic performance assessment includes the waste form, container, geology, and hydrology. Based on the author’s previous extended work and data from the literature, this paper presents more detailed specific cases of (1) the time dependence of radionuclide release, (2) radionuclide release coupled with container failure (rate-limiting process), (3) radionuclide release through the opening area of the container and cladding, and (4) sequestration of radionuclides in the near field after container failure. These cases are better understood for risk and performance insights. The dissolved amount of waste form is not linear with time but is higher at first. The radionuclide release rate from waste form dissolution can be constrained by container failure time. The partial opening area of the container surface may decrease radionuclide release. Radionuclides sequestered by various chemical reactions in the near field of a failed container may become stable with time as the radiation level decreases with time.

  10. Women's experiences of recovery from childbirth: focus on pelvis problems that extend beyond the puerperium.

    Science.gov (United States)

    O'Reilly, Rebecca; Peters, Kath; Beale, Barbara; Jackson, Debra

    2009-07-01

    This study aimed to build understandings of women's recovery experiences in the presence of continued pelvic problems extending beyond the puerperium to provide nurses and other health care professionals with information to enhance current practice. Trauma to the pelvic floor during childbirth is a relatively common occurrence and can include damage to structures and nerves. A significant number of women will experience ongoing physical pelvic problems resulting from childbirth that extend past the puerperium; however, little is known about the experiential aspects of recovery for these women. A qualitative, phenomenological study. Narrative data were collected during conversational interviews with 10 mothers who had sustained pelvic injury during the birth process that persisted past the puerperium. Recruitment was via media releases and brochures distributed through childcare facilities. The data was analysed using Van Manen's thematic analysis. The themes that arose from the analysis were: 'fearing intimacy', 'managing an unpredictable body', 'being resigned' and 'feeling devalued and dismissed'. Pelvic injuries that extend beyond the postpartum period are distressing for women. They negatively affect women's views of themselves and have an impact on various aspects of life including intimate relationships and social activities. Currently, postpartum care may have a focus on baby rather than mother and this focus may impede women making full disclosures of ongoing health needs arising from their delivery. Findings of this study suggest that women may have specific needs that extend beyond the puerperium, indicating a need for continued holistic assessments and extending practice to identify and support women experiencing persistent pelvic postpartum complications.

  11. Enhanced drug encapsulation and extended release profiles of calcium-alginate nanoparticles by using tannic acid as a bridging cross-linking agent.

    Science.gov (United States)

    Abulateefeh, Samer R; Taha, Mutasem O

    2015-01-01

    Calcium alginate nanoparticles (NPs) suffer from sub-optimal stability in bio-relevant media leading to low drug encapsulation efficiency and uncontrolled release profiles. To sort out these drawbacks, a novel approach is proposed herein based on introducing tannic acid into these NPs to act as a bridging cross-linking aid agent. Calcium-alginate NPs were prepared by the ionotropic gelation method and loaded with diltiazem hydrochloride as a model drug. These NPs were characterized in terms of particle size, zeta potential, and morphology, and results were explained in accordance with Fourier-transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The incorporation of tannic acid led to more than four folds increase in drug encapsulation efficiency (i.e. from 15.3% to 69.5%) and reduced burst drug release from 44% to around 10% within the first 30 min. These findings suggest the possibility of improving the properties of Ca-alginate NPs by incorporating cross-linking aid agents under mild conditions.

  12. Development of Modified-Release Tablets of Zolpidem Tartrate by Biphasic Quick/Slow Delivery System

    OpenAIRE

    Mahapatra, Anjan Kumar; Sameeraja, N. H.; Murthy, P. N.

    2014-01-01

    Zolpidem tartrate is a non-benzodiazepine analogue of imidazopyridine of sedative and hypnotic category. It has a short half-life with usual dosage regimen being 5 mg, two times a day, or 10 mg, once daily. The duration of action is considered too short in certain circumstances. Thus, it is desirable to lengthen the duration of action. The formulation design was implemented by preparing extended-release tablets of zolpidem tartrate using the biphasic delivery system technology, where sodium s...

  13. PWR-GALE, Radioactive Gaseous Release and Liquid Release from PWR

    International Nuclear Information System (INIS)

    Chandrasekaran, T.; Lee, J.Y.; Willis, C.A.

    1988-01-01

    1 - Description of program or function: The PWR-GALE (Boiling Water Reactor Gaseous and Liquid Effluents) Code is a computerized mathematical model for calculating the release of radioactive material in gaseous and liquid effluents from pressurized water reactors (PWRs). The calculations are based on data generated from operating reactors, field tests, laboratory tests, and plant-specific design considerations incorporated to reduce the quantity of radioactive materials that may be released to the environment. 2 - Method of solution: GALE calculates expected releases based on 1) standardized coolant activities derived from ANS Standards 18.1 Working Group recommendations, 2) release and transport mechanisms that result in the appearance of radioactive material in liquid and gaseous waste streams, 3) plant-specific design features used to reduce the quantities of radioactive materials ultimately released to the environs, and 4) information received on the operation of nuclear power plants. 3 - Restrictions on the complexity of the problem: The liquid release portion of GALE uses subroutines taken from the ORIGEN (CCC-217) to calculate radionuclide buildup and decay during collection, processing, and storage of liquid radwaste. Memory requirements for this part of the program are determined by the large nuclear data base accessed by these subroutines

  14. Regulating Drug Release Behavior and Kinetics from Matrix Tablets Based on Fine Particle-Sized Ethyl Cellulose Ether Derivatives: An In Vitro and In Vivo Evaluation

    Directory of Open Access Journals (Sweden)

    Kifayat Ullah Shah

    2012-01-01

    Full Text Available The design and fabrication of sustained/controlled release dosage forms, employing new excipients capable of extending/controlling the release of drugs from the dosage forms over prolonged periods, has worked well in achieving optimally enhanced therapeutic levels of the drugs. In this sense, the objective of this study was to investigate the suitability of selected cellulose ether derivatives for use in direct compression (DC and as efficient drug release controlling agents. Controlled release matrix tablets of ciprofloxacin were prepared at different drug-to-polymer (D : P ratios by direct compression using a fine particle sized ethylcellulose ether derivative (ETHOCEL Standard Premium 7FP as rate controlling polymer. The tablets obtained were evaluated for various physico-chemical characteristics and in-vitro drug release studies were conducted in phosphate buffer (pH 7.4 using PharmaTest dissolution apparatus at constant temperature of 37∘C±0.1. Similarity factor 2 was employed to the release profiles of test formulations and were compared with marketed ciprofloxacin conventional tablets. Drug release mechanism and the kinetics involved were investigated by fitting the release profile data to various kinetic models. It was found that with increasing the proportion of ethylcellulose ether derivative in the matrix, the drug release was significantly extended up to 24 hours. The tablets exhibited zero order or nearly zero order drug transport mechanism. In vivo drug release performance of the developed controlled release tablets and reference conventional tablets containing ciprofloxacin were determined in rabbit serum according to randomized two-way crossover study design using High Performance Liquid Chromatography. Several bioavailability parameters of both the test tablets and conventional tablets including max, max and AUC0- were compared which showed an optimized max and max (<0.05. A good correlation was obtained between in vitro

  15. Competitive interactions and controlled release of a natural antioxidant from halloysite nanotubes.

    Science.gov (United States)

    Hári, József; Gyürki, Ádám; Sárközi, Márk; Földes, Enikő; Pukánszky, Béla

    2016-01-15

    Halloysite nanotubes used as potential carrier material for a controlled release stabilizer in polyethylene were thoroughly characterized with several techniques including the measurement of specific surface area, pore volume and surface energy. The high surface energy of the halloysite results in the strong bonding of the additive to the surface. Dissolution experiments carried out with eight different solvents for the determination of the effect of solvent characteristics on the amount of irreversibly bonded quercetin proved that adsorption and dissolution depend on competitive interactions prevailing in the system. Solvents with low polarity dissolve only surplus quercetin adsorbed in multilayers. Polyethylene is a very apolar polymer forming weak interactions with every substance; quercetin dissolves into it from the halloysite surface only above a critical surface coverage. Stabilization experiments confirmed that strong adhesion prevents dissolution and results in limited stabilization efficiency. At larger adsorbed amounts better stability and extended effect were measured indicating dissolution and controlled release. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Modelling approach for biological control of insect pest by releasing infected pest

    International Nuclear Information System (INIS)

    Tan Yuanshun; Chen Lansun

    2009-01-01

    Models of biological control have a long history of theoretical development that have focused on the interactions between a predator and a prey. Here we have extended the classical epidemic model to include a continuous and impulsive pest control strategies by releasing the infected pests bred in laboratory. For the continuous model, the results imply that the susceptible pest goes to extinct if the threshold condition R 0 0 > 1, the positive equilibrium of continuous model is globally asymptotically stable. Similarly, the threshold condition which guarantees the global stability of the susceptible pest-eradication periodic solution is obtained for the model with impulsive control strategy. Consequently, based on the results obtained in this paper, the control strategies which maintain the pests below an acceptably low level are discussed by controlling the release rate and impulsive period. Finally, the biological implications of the results and the efficiency of two control strategies are also discussed

  17. Treatment patterns and health care resource utilization associated with dalfampridine extended release in multiple sclerosis: a retrospective claims database analysis

    Directory of Open Access Journals (Sweden)

    Guo A

    2016-05-01

    Full Text Available Amy Guo,1 Michael Grabner,2 Swetha Rao Palli,2 Jessica Elder,1 Matthew Sidovar,1 Peter Aupperle,1 Stephen Krieger3 1Acorda Therapeutics Inc., Ardsley, New York, NY, USA; 2HealthCore Inc., Wilmington, DE, USA; 3Corinne Goldsmith Dickinson Center for MS, Icahn School of Medicine at Mount Sinai, New York, NY, USA Background: Although previous studies have demonstrated the clinical benefits of dalfampridine extended release (D-ER tablets in patients with multiple sclerosis (MS, there are limited real-world data on D-ER utilization and associated outcomes in patients with MS. Purpose: The objective of this study was to evaluate treatment patterns, budget impact, and health care resource utilization (HRU associated with D-ER use in a real-world setting. Methods: A retrospective claims database analysis was conducted using the HealthCore Integrated Research DatabaseSM. Adherence (measured by medication possession ratio, or [MPR] and persistence (measured by days between initial D-ER claim and discontinuation or end of follow-up were evaluated over 1-year follow-up. Budget impact was calculated as cost per member per month (PMPM over the available follow-up period. D-ER and control cohorts were propensity-score matched on baseline demographics, comorbidities, and MS-related resource utilization to compare walking-impairment-related HRU over follow-up. Results: Of the 2,138 MS patients identified, 1,200 were not treated with D-ER (control and 938 were treated with D-ER. Patients were aged 51 years on average and 74% female. Approximately 82.6% of D-ER patients were adherent (MPR >80%. The estimated budget impact range of D-ER was $0.014–$0.026 PMPM. Propensity-score-matched D-ER and controls yielded 479 patients in each cohort. Postmatching comparison showed that the D-ER cohort was associated with fewer physician (21.5% vs 62.4%, P<0.0001 and other outpatient visits (22.8% vs 51.4%, P<0.0001 over the 12-month follow-up. Changes in HRU from follow

  18. Formulation and in vitro evaluation of mucoadhesive controlled release matrix tablets of flurbiprofen using response surface methodology

    Directory of Open Access Journals (Sweden)

    Ikrima Khalid

    2014-09-01

    Full Text Available The objective of the current study was to formulate mucoadhesive controlled release matrix tablets of flurbiprofen and to optimize its drug release profile and bioadhesion using response surface methodology. Tablets were prepared via a direct compression technique and evaluated for in vitro dissolution parameters and bioadhesive strength. A central composite design for two factors at five levels each was employed for the study. Carbopol 934 and sodium carboxymethylcellulose were taken as independent variables. Fourier transform infrared (FTIR spectroscopy studies were performed to observe the stability of the drug during direct compression and to check for a drug-polymer interaction. Various kinetic models were applied to evaluate drug release from the polymers. Contour and response surface plots were also drawn to portray the relationship between the independent and response variables. Mucoadhesive tablets of flurbiprofen exhibited non-Fickian drug release kinetics extending towards zero-order, with some formulations (F3, F8, and F9 reaching super case II transport, as the value of the release rate exponent (n varied between 0.584 and 1.104. Polynomial mathematical models, generated for various response variables, were found to be statistically significant (P<0.05. The study also helped to find the drug's optimum formulation with excellent bioadhesive strength. Suitable combinations of two polymers provided adequate release profile, while carbopol 934 produced more bioadhesion.

  19. Fabrication of monodisperse magnetic nanoparticles released in solution using a block copolymer template

    Science.gov (United States)

    Morcrette, Mélissa; Ortiz, Guillermo; Tallegas, Salomé; Joisten, Hélène; Tiron, Raluca; Baron, Thierry; Hou, Yanxia; Lequien, Stéphane; Bsiesy, Ahmad; Dieny, Bernard

    2017-07-01

    This paper describes a fabrication process of monodisperse magnetic nanoparticles released in solution, based on combined ‘top-down’ and ‘bottom-up’ approaches. The process involves the use of a self-assembled PS-PMMA block copolymer formed on a sacrificial layer. Such an approach was so far mostly explored for the preparation of patterned magnetic media for ultrahigh density magnetic storage. It is here extended to the preparation of released monodisperse nanoparticles for biomedical applications. A special sacrificial layer had to be developed compatible with the copolymer self-organization. The resulting nanoparticles exhibit very narrow size dispersion (≈7%) and can be good candidates as contrast agents for medical imaging i.e. magnetic resonance imaging or magnetic particle imaging. The approach provides a great freedom in the choice of the particles shapes and compositions. In particular, they can be made of biocompatible magnetic material.

  20. Fabrication of monodisperse magnetic nanoparticles released in solution using a block copolymer template

    International Nuclear Information System (INIS)

    Morcrette, Mélissa; Ortiz, Guillermo; Joisten, Hélène; Dieny, Bernard; Tallegas, Salomé; Baron, Thierry; Bsiesy, Ahmad; Tiron, Raluca; Hou, Yanxia; Lequien, Stéphane

    2017-01-01

    This paper describes a fabrication process of monodisperse magnetic nanoparticles released in solution, based on combined ‘top-down’ and ‘bottom-up’ approaches. The process involves the use of a self-assembled PS-PMMA block copolymer formed on a sacrificial layer. Such an approach was so far mostly explored for the preparation of patterned magnetic media for ultrahigh density magnetic storage. It is here extended to the preparation of released monodisperse nanoparticles for biomedical applications. A special sacrificial layer had to be developed compatible with the copolymer self-organization. The resulting nanoparticles exhibit very narrow size dispersion (≈7%) and can be good candidates as contrast agents for medical imaging i.e. magnetic resonance imaging or magnetic particle imaging. The approach provides a great freedom in the choice of the particles shapes and compositions. In particular, they can be made of biocompatible magnetic material. (paper)

  1. Flash release an alternative for releasing complex MEMS devices

    NARCIS (Netherlands)

    Deladi, S.; Krijnen, Gijsbertus J.M.; Elwenspoek, Michael Curt

    2004-01-01

    A novel time-saving and cost-effective release technique has been developed and is described. The physical nature of the process is explained in combination with experimental observations. The results of the flash release process are compared with those of freeze-drying and supercritical CO2

  2. Extended spider cognition.

    Science.gov (United States)

    Japyassú, Hilton F; Laland, Kevin N

    2017-05-01

    There is a tension between the conception of cognition as a central nervous system (CNS) process and a view of cognition as extending towards the body or the contiguous environment. The centralised conception requires large or complex nervous systems to cope with complex environments. Conversely, the extended conception involves the outsourcing of information processing to the body or environment, thus making fewer demands on the processing power of the CNS. The evolution of extended cognition should be particularly favoured among small, generalist predators such as spiders, and here, we review the literature to evaluate the fit of empirical data with these contrasting models of cognition. Spiders do not seem to be cognitively limited, displaying a large diversity of learning processes, from habituation to contextual learning, including a sense of numerosity. To tease apart the central from the extended cognition, we apply the mutual manipulability criterion, testing the existence of reciprocal causal links between the putative elements of the system. We conclude that the web threads and configurations are integral parts of the cognitive systems. The extension of cognition to the web helps to explain some puzzling features of spider behaviour and seems to promote evolvability within the group, enhancing innovation through cognitive connectivity to variable habitat features. Graded changes in relative brain size could also be explained by outsourcing information processing to environmental features. More generally, niche-constructed structures emerge as prime candidates for extending animal cognition, generating the selective pressures that help to shape the evolving cognitive system.

  3. Rapid onset of treatment effects on psychosis, depression, and mania in patients with acute exacerbation of schizoaffective disorder following treatment with oral extended-release paliperidone.

    Science.gov (United States)

    Fu, Dong-Jing; Turkoz, Ibrahim; Bossie, Cynthia A; Patel, Hiren; Alphs, Larry

    2016-03-15

    Patients with schizoaffective disorder (SCA) experience complicated interplays of psychotic, depressive, and manic symptoms. Paliperidone extended-release (pali ER) tablets have been shown to be efficacious in these patients, but treatment response has not been studied relative to the onset of effects for these symptom domains. In a pooled analysis of data from two 6-week, randomized, placebo-controlled studies, the onset of treatment effects with oral pali ER was evaluated by symptom domain (psychosis, depression, mania) in patients with an acute SCA exacerbation. Subjects were categorized as having prominent psychotic (Positive and Negative Syndrome Scale score >70), depressive (Hamilton Rating Scale for Depression-21 score ≥16), or manic (Young Mania Rating Scale score ≥16) symptoms at baseline. Of the 614 patients in these analyses, 597 (97.2%), 411 (66.9%), and 488 (79.5%) had prominent psychotic, depressive, and manic symptoms at baseline, respectively. Pali ER treatment was associated with rapid and significant improvement of all three symptom domains versus placebo within 1 week of initiation, regardless of whether treatment was given as monotherapy or in combination with mood stabilizers and/or antidepressants. Adverse events were similar to those reported in the original published studies. This post hoc analysis of two phase 3 trials requires confirmation in prospective studies. This pooled analysis suggests that treatment with pali ER is associated with rapid control of psychotic, depressive, and manic symptoms in patients with SCA. Its findings support the benefit of pali ER as a primary treatment for the management of SCA. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Extended mind and after: socially extended mind and actor-network.

    Science.gov (United States)

    Kono, Tetsuya

    2014-03-01

    The concept of extended mind has been impressively developed over the last 10 years by many philosophers and cognitive scientists. The extended mind thesis (EM) affirms that the mind is not simply ensconced inside the head, but extends to the whole system of brain-body-environment. Recently, some philosophers and psychologists try to adapt the idea of EM to the domain of social cognition research. Mind is socially extended (SEM). However, EM/SEM theory has problems to analyze the interactions among a subject and its surroundings with opposition, antagonism, or conflict; it also tends to think that the environment surrounding the subject is passive or static, and to neglect the power of non-human actants to direct and regulate the human subject. In these points, actor-network theory (ANT) proposed by Latour and Callon is more persuasive, while sharing some important ideas with EM/SEM theory. Actor-network is a hybrid community which is composed of a series of heterogeneous elements, animate and inanimate for a certain period of time. I shall conclude that EM/SEM could be best analyzed as a special case of actor-network. EM/SEM is a system which can be controlled by a human agent alone. In order to understand collective behavior, philosophy and psychology have to study the actor-network in which human individuals are situated.

  5. Novel Injectable Pentablock Copolymer Based Thermoresponsive Hydrogels for Sustained Release Vaccines.

    Science.gov (United States)

    Bobbala, Sharan; Tamboli, Viral; McDowell, Arlene; Mitra, Ashim K; Hook, Sarah

    2016-01-01

    The need for multiple vaccinations to enhance the immunogenicity of subunit vaccines may be reduced by delivering the vaccine over an extended period of time. Here, we report two novel injectable pentablock copolymer based thermoresponsive hydrogels made of polyethyleneglycol-polycaprolactone-polylactide-polycaprolactone-polyethyleneglycol (PEG-PCL-PLA-PCL-PEG) with varying ratios of polycaprolactone (PCL) and polylactide (PLA), as single shot sustained release vaccines. Pentablock copolymer hydrogels were loaded with vaccine-encapsulated poly lactic-co-glycolic acid nanoparticles (PLGA-NP) or with the soluble vaccine components. Incorporation of PLGA-NP into the thermoresponsive hydrogels increased the complex viscosity of the gels, lowered the gelation temperature, and minimized the burst release of antigen and adjuvants. The two pentablock hydrogels stimulated both cellular and humoral responses. The addition of PLGA-NP to the hydrogels sustained immune responses for up to 49 days. The polymer with a higher ratio of PCL to PLA formed a more rigid gel, induced stronger immune responses, and stimulated effective anti-tumor responses in a prophylactic melanoma tumor model.

  6. Platelet-Released Growth Factors Modulate the Secretion of Cytokines in Synoviocytes under Inflammatory Joint Disease

    Science.gov (United States)

    Rasuo, Biljana; Hock, Jennifer Vanessa Phi; Kweider, Nisreen; Fragoulis, Athanassios; Sönmez, Tolga Taha; Jahr, Holger; Pufe, Thomas; Lippross, Sebastian

    2017-01-01

    The etiology and pathogenesis of rheumatoid arthritis (RA) are marked by a complex interplay of various cell populations and is mediated by different signaling pathways. Traditionally, therapies have primarily focused on pain relief, reducing inflammation and the recovery of joint function. More recently, however, researchers have discussed the therapeutic efficacy of autologous platelet-rich plasma (PRP). The main objective of this work is to examine the influences of platelet-released growth factor (PRGF) on human synoviocytes under inflammatory conditions. Additionally, it is checked to which extend treatment with platelet concentrate influences the release of cytokines form synoviocytes. For this purpose, an in vitro RA model was created by stimulating the cells with the TNF-α. The release of cytokines was measured by ELISA. The cytokine gene expression was analyzed by real-time PCR. It has been observed that the stimulation concentration of 10 ng/ml TNF-α resulted in a significantly increased endogenous secretion and gene expression of IL-6 and TNF-α. The anti-inflammatory effect of PRGF could be confirmed through significant reduction of TNF-α and IL-1β. An induced inflammatory condition seems to cause PRGF to inhibit the release of proinflammatory cytokines. Further study is required to understand the exact effect mechanism of PRGF on synoviocytes. PMID:29348703

  7. Platelet-Released Growth Factors Modulate the Secretion of Cytokines in Synoviocytes under Inflammatory Joint Disease

    Directory of Open Access Journals (Sweden)

    Mersedeh Tohidnezhad

    2017-01-01

    Full Text Available The etiology and pathogenesis of rheumatoid arthritis (RA are marked by a complex interplay of various cell populations and is mediated by different signaling pathways. Traditionally, therapies have primarily focused on pain relief, reducing inflammation and the recovery of joint function. More recently, however, researchers have discussed the therapeutic efficacy of autologous platelet-rich plasma (PRP. The main objective of this work is to examine the influences of platelet-released growth factor (PRGF on human synoviocytes under inflammatory conditions. Additionally, it is checked to which extend treatment with platelet concentrate influences the release of cytokines form synoviocytes. For this purpose, an in vitro RA model was created by stimulating the cells with the TNF-α. The release of cytokines was measured by ELISA. The cytokine gene expression was analyzed by real-time PCR. It has been observed that the stimulation concentration of 10 ng/ml TNF-α resulted in a significantly increased endogenous secretion and gene expression of IL-6 and TNF-α. The anti-inflammatory effect of PRGF could be confirmed through significant reduction of TNF-α and IL-1β. An induced inflammatory condition seems to cause PRGF to inhibit the release of proinflammatory cytokines. Further study is required to understand the exact effect mechanism of PRGF on synoviocytes.

  8. The Extended Enterprise concept

    DEFF Research Database (Denmark)

    Larsen, Lars Bjørn; Vesterager, Johan; Gobbi, Chiara

    1999-01-01

    This paper provides an overview of the work that has been done regarding the Extended Enterprise concept in the Common Concept team of Globeman 21 including references to results deliverables concerning the development of the Extended Enterprise concept. The first section presents the basic concept...... picture from Globeman21, which illustrates the Globeman21 way of realising the Extended Enterprise concept. The second section presents the Globeman21 EE concept in a life cycle perspective, which to a large extent is based on the thoughts and ideas behind GERAM (ISO/DIS 15704)....

  9. Extended Enterprise performance Management

    NARCIS (Netherlands)

    Bobbink, Maria Lammerdina; Hartmann, Andreas

    2014-01-01

    The allegiance of partnering organisations and their employees to an Extended Enterprise performance is its proverbial sword of Damocles. Literature on Extended Enterprises focuses on collaboration, inter-organizational integration and learning to avoid diminishing or missing allegiance becoming an

  10. Costs and effects of paliperidone extended release compared with alternative oral antipsychotic agents in patients with schizophrenia in Greece: a cost effectiveness study.

    Science.gov (United States)

    Geitona, Maria; Kousoulakou, Hara; Ollandezos, Markos; Athanasakis, Kostas; Papanicolaou, Sotiria; Kyriopoulos, Ioannis

    2008-08-28

    To compare the costs and effects of paliperidone extended release (ER), a new pharmaceutical treatment for the management of schizophrenia, with the most frequently prescribed oral treatments in Greece (namely risperidone, olanzapine, quetiapine, aripiprazole and ziprasidone) over a 1-year time period. A decision tree was developed and tailored to the specific circumstances of the Greek healthcare system. Therapeutic effectiveness was defined as the annual number of stable days and the clinical data was collected from international clinical trials and published sources. The study population was patients who suffer from schizophrenia with acute exacerbation. During a consensus panel of 10 psychiatrists and 6 health economists, data were collected on the clinical practice and medical resource utilisation. Unit costs were derived from public sources and official reimbursement tariffs. For the comparators official retail prices were used. Since a price had not yet been granted for paliperidone ER at the time of the study, the conservative assumption of including the average of the highest targeted European prices was used, overestimating the price of paliperidone ER in Greece. The study was conducted from the perspective of the National Healthcare System. The data indicate that paliperidone ER might offer an increased number of stable days (272.5 compared to 272.2 for olanzapine, 265.5 f risperidone, 260.7 for quetiapine, 260.5 for ziprasidone and 258.6 for aripiprazole) with a lower cost compared to the other therapies examined (euro 7,030 compared to euro 7,034 for olanzapine, euro 7,082 for risperidone, euro 8,321 for quetiapine, euro 7,713 for ziprasidone and euro 7,807 for aripiprazole). During the sensitivity analysis, a +/- 10% change in the duration and frequency of relapses and the economic parameters did not lead to significant changes in the results. Treatment with paliperidone ER can lead to lower total cost and higher number of stable days in most of the

  11. Costs and effects of paliperidone extended release compared with alternative oral antipsychotic agents in patients with schizophrenia in Greece: A cost effectiveness study

    Directory of Open Access Journals (Sweden)

    Papanicolaou Sotiria

    2008-08-01

    Full Text Available Abstract Background To compare the costs and effects of paliperidone extended release (ER, a new pharmaceutical treatment for the management of schizophrenia, with the most frequently prescribed oral treatments in Greece (namely risperidone, olanzapine, quetiapine, aripiprazole and ziprasidone over a 1-year time period. Methods A decision tree was developed and tailored to the specific circumstances of the Greek healthcare system. Therapeutic effectiveness was defined as the annual number of stable days and the clinical data was collected from international clinical trials and published sources. The study population was patients who suffer from schizophrenia with acute exacerbation. During a consensus panel of 10 psychiatrists and 6 health economists, data were collected on the clinical practice and medical resource utilisation. Unit costs were derived from public sources and official reimbursement tariffs. For the comparators official retail prices were used. Since a price had not yet been granted for paliperidone ER at the time of the study, the conservative assumption of including the average of the highest targeted European prices was used, overestimating the price of paliperidone ER in Greece. The study was conducted from the perspective of the National Healthcare System. Results The data indicate that paliperidone ER might offer an increased number of stable days (272.5 compared to 272.2 for olanzapine, 265.5 f risperidone, 260.7 for quetiapine, 260.5 for ziprasidone and 258.6 for aripiprazole with a lower cost compared to the other therapies examined (€7,030 compared to €7,034 for olanzapine, €7,082 for risperidone, €8,321 for quetiapine, €7,713 for ziprasidone and €7,807 for aripiprazole. During the sensitivity analysis, a ± 10% change in the duration and frequency of relapses and the economic parameters did not lead to significant changes in the results. Conclusion Treatment with paliperidone ER can lead to lower total cost

  12. Development and validation of stability indicating method for the quantitative determination of venlafaxine hydrochloride in extended release formulation using high performance liquid chromatography

    Directory of Open Access Journals (Sweden)

    Jaspreet Kaur

    2010-01-01

    Full Text Available Objective : Venlafaxine,hydrochloride is a structurally novel phenethyl bicyclic antidepressant, and is usually categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI but it has been referred to as a serotonin-norepinephrine-dopamine reuptake inhibitor. It inhibits the reuptake of dopamine. Venlafaxine HCL is widely prescribed in the form of sustained release formulations. In the current article we are reporting the development and validation of a fast and simple stability indicating, isocratic high performance liquid chromatographic (HPLC method for the determination of venlafaxine hydrochloride in sustained release formulations. Materials and Methods : The quantitative determination of venlafaxine hydrochloride was performed on a Kromasil C18 analytical column (250 x 4.6 mm i.d., 5 μm particle size with 0.01 M phosphate buffer (pH 4.5: methanol (40: 60 as a mobile phase, at a flow rate of 1.0 ml/min. For HPLC methods, UV detection was made at 225 nm. Results : During method validation, parameters such as precision, linearity, accuracy, stability, limit of quantification and detection and specificity were evaluated, which remained within acceptable limits. Conclusions : The method has been successfully applied for the quantification and dissolution profiling of Venlafaxine HCL in sustained release formulation. The method presents a simple and reliable solution for the routine quantitative analysis of Venlafaxine HCL.

  13. The Effect of Nebivolol versus Metoprolol Succinate Extended Release on Asymmetric Dimethylarginine in Hypertension

    Science.gov (United States)

    Kandavar, Ramprasad; Higashi, Yusuke; Chen, Wei; Blackstock, Christopher; Vaughn, Charlotte; Sukhanov, Sergiy; Sander, Gary E.; Roffidal, Louise E.; Delafontaine, Patrice; Giles, Thomas D.

    2011-01-01

    Objectives This study sought to determine if metoprolol succinate ER (MET), and nebivolol (NEB), a β1-AR with increased bioavailability of nitric oxide (NO), would have differing effects on plasma asymmetric dimethylarginine concentration in hypertensives. Background It was hypothesized that NEB, a β1-AR antagonist and β3-AR agonist with NO- releasing properties and MET, only a β1-AR antagonist, would have different effects on plasma ADMA concentration. Methods Forty-one hypertensive subjects randomly received either 50 mg of MET (n = 19) or 5 mg of NEB (n = 22) for 4 weeks followed by 100 mg MET and 10 mg NEB for 4 weeks. ADMA and IGF-1 were measured by ELISA kit; endothelial progenitor cells were estimated using fluorescein-labeled monoclonal antibody to KDR and CD133 receptors; arterial augmentation index was measured by radial tonometry. Results Baseline systolic/diastolic blood pressure was 155.1 ± 18.7/85.3 ± 12.5 mm Hg for MET subjects and 157.6 ± 20.7/87.1 ± 14.0 mm Hg for NEB subjects. Baseline ADMA was 0.32 ± 0.123 μmol/L in the MET group and 0.4035 ± 0.1378 in the NEB group. ADMA increased 44.78% and 72% in the MET group at weeks 4 and 8 (p < 0.05 for both), respectively, without increase in the NEB group. At week 8 augmentation index was increased in the MET group (p<0.05). IGF-1 and EPC were unchanged by treatment. Conclusions Plasma ADMA and augmentation index are increased in a dose-dependent fashion by MET but not with NEB. PMID:21251896

  14. Sustained release nimesulide microparticles: evaluation of release modifying property of ethy

    International Nuclear Information System (INIS)

    Khan, S.A.; Ahmed, M.; Nisar-ur-Rehman; Madni, A.U.; Aamir, M.N.; Murtaza, G.

    2011-01-01

    Microencapsulated controlled-release preparations of nimesulide were formulated. Microparticles were prepared by modified phase separation (non-solvent addition) technique using different ratios of ethylcellulose. The microparticles (M/sub 1/, M/sub 2/, and M/sub 3/) were yellow, free flowing and spherical in shape with the particle size varying from 93.62 +- 14.15 to 104.19 +- 18.15 mu m. The t/sub 60%/of nimesulide release from microparticles was found to be 3 +- 0.6, 5 +- 0.6 and 8 +- 0.8 h for formulations M/sub 1/, M/sub 2/, and M/sub 3/, respectively. FT-IR, XRD, and thermal analysis were done which showed that there is no interaction between the polymer and drug. The mechanism of drug release from nimesulide microparticles was studied by using Higuchi and Korsmeyer-Peppas models. The value of coefficient of determination (R/sup 2/) for M/sub 1/, M/sub 2/, and M/sub 3/ indicates anomalous and case-II transport release mechanism. The dissolution data of designed system verified its ability to maintain plasma concentration without the need of frequent dosing. The Nimesulide microparticles prolonged drug release for 12 hours or longer. Based on the results of release studies, M/sub 3/ was opted as a suitable microparticulate formulation allowing the controlled release of nimesulide over a prolonged period of time. Moreover, its encapsulation efficiency was also comparable to the other two formulations (M/sub 1/ and M/sub 2/). In conclusion, the influence of polymer concentration should be considered during formulation development. (author)

  15. Extended-release hydrocodone – gift or curse?

    Directory of Open Access Journals (Sweden)

    Krashin D

    2013-01-01

    Full Text Available Daniel Krashin,1 Natalia Murinova,2 Andrea M Trescot31Department of Anesthesiology and Pain Medicine, 2Department of Neurology University of Washington, Seattle, WA, USA 3Algone Pain Center, Wasilla, AK, USAAbstract: Hydrocodone is a semisynthetic opioid, which has been used for decades as a short-acting analgesic combined with acetaminophen (or less commonly ibuprofen. Several long-acting, non-acetaminophen-containing hydrocodone formulations are undergoing trials in the US under the auspices of the US Food and Drug Administration, and may be available shortly. This article reviews some of the advantages (including drug familiarity and lack of acetaminophen toxicity and potential disadvantages (including altered use patterns and high morphine equivalent dosing of such a medication formulation. We also discuss the abuse potential of long-acting versus short-acting opioids in general and hydrocodone specifically, as well as the metabolism of hydrocodone.Keywords: hydrocodone, long-acting opioids, opioid abuse, acetaminophen toxicity, tamper-resistant opioids

  16. Locomotor therapy with extended-release crystalline glucocorticoids

    Directory of Open Access Journals (Sweden)

    Vladimir Vasilyevich Badokin

    2013-01-01

    Full Text Available Topical glucocorticoid (GC therapy for locomotor diseases is an extremely important component of a comprehensive program to treat inflammatory and, to a lesser extent, degenerative diseases. It reduces the time of hospitalization by 5—10 days in this category of patients, has a prompt and potent anti-inflammatory effect, and shows predictable efficiency. This therapy shows good tolerability and high safety and prevents serious adverse reactions to GC treatment.

  17. Formulation of Extended-Release Metformin Hydrochloride Matrix ...

    African Journals Online (AJOL)

    Erah

    ... of diclofenac sodium by non-solvent addition technique. Trop J Pharm. Res 2010; 9(2): 187-195. 17. Hadjiioannou TP, Christian GD, Koupparis MA,. Macheras PE. Quantitative Calculations in. Pharmaceutical Practice and Research, VCH. Publishers Inc, New York: 1993; p 345-348. 18. Bourne DWA. Pharmacokinetics.

  18. Investigating the in vitro drug release kinetics from controlled release diclofenac potassium-ethocel matrix tablets and the influence of co-excipients on drug release patterns.

    Science.gov (United States)

    Shah, Shefaat Ullah; Shah, Kifayat Ullah; Rehman, Asimur; Khan, Gul Majid

    2011-04-01

    The objective of the study was to formulate and evaluate controlled release polymeric tablets of Diclofenac Potassium for the release rate, release patterns and the mechanism involved in the release process of the drug. Formulations with different types and grades of Ethyl Cellulose Ether derivatives in several drug-to-polymer ratios (D:P) were compressed into tablets using the direct compression method. In vitro drug release studies were performed in phosphate buffer (pH 7.4) as dissolution medium by using USP Method-1 (Rotating Basket Method). Similarity factor f2 and dissimilarity factor f1 were applied for checking the similarities and dissimilarities of the release profiles of different formulations. For the determination of the release mechanism and drug release kinetics various mathematical/kinetic models were employed. It was found that all of the Ethocel polymers could significantly slow down the drug release rate with Ethocel FP polymers being the most efficient, especially at D:P ratios of 10:03 which lead towards the achievement of zero or near zero order release kinetics.

  19. Protecting privacy in data release

    CERN Document Server

    Livraga, Giovanni

    2015-01-01

    This book presents a comprehensive approach to protecting sensitive information when large data collections are released by their owners. It addresses three key requirements of data privacy: the protection of data explicitly released, the protection of information not explicitly released but potentially vulnerable due to a release of other data, and the enforcement of owner-defined access restrictions to the released data. It is also the first book with a complete examination of how to enforce dynamic read and write access authorizations on released data, applicable to the emerging data outsou

  20. Extending the Lunar Mapping and Modeling Portal - New Capabilities and New Worlds

    Science.gov (United States)

    Day, B. H.; Law, E.; Arevalo, E.; Bui, B.; Chang, G.; Dodge, K.; Kim, R. M.; Malhotra, S.; Sadaqathullah, S.

    2015-12-01

    NASA's Lunar Mapping and Modeling Portal (LMMP) provides a web-based Portal and a suite of interactive visualization and analysis tools to enable mission planners, lunar scientists, and engineers to access mapped lunar data products from past and current lunar missions (http://lmmp.nasa.gov). During the past year, the capabilities and data served by LMMP have been significantly expanded. New interfaces are providing improved ways to access and visualize data. Many of the recent enhancements to LMMP have been specifically in response to the requirements of NASA's proposed Resource Prospector lunar rover, and as such, provide an excellent example of the application of LMMP to mission planning. At the request of NASA's Science Mission Directorate, LMMP's technology and capabilities are now being extended to additional planetary bodies. New portals for Vesta and Mars are the first of these new products to be released. On March 31, 2015, the LMMP team released Vesta Trek (http://vestatrek.jpl.nasa.gov), a web-based application applying LMMP technology to visualizations of the asteroid Vesta. Data gathered from multiple instruments aboard Dawn have been compiled into Vesta Trek's user-friendly set of tools, enabling users to study the asteroid's features. With an initial release on July 1, 2015, Mars Trek replicates the functionality of Vesta Trek for the surface of Mars. While the entire surface of Mars is covered, higher levels of resolution and greater numbers of data products are provided for special areas of interest. Early releases focus on past, current, and future robotic sites of operation. Future releases will add many new data products and analysis tools as Mars Trek has been selected for use in site selection for the Mars 2020 rover and in identifying potential human landing sites on Mars. Other destinations will follow soon. The user community is invited to provide suggestions and requests as the development team continues to expand the capabilities of LMMP

  1. EPICS release 3.11 specific documentation -- EPICS release notes for 3.11

    International Nuclear Information System (INIS)

    1994-01-01

    EPICS release 3.11 is now ready for user testing. A person who wants to set up a simplified application environment to boot an IOC and create databases using R3.11 should follow the directions in Appendix B, page 27, of the EPICS Source/Release Control Manual, Sept. 20, 1993. The R3.11 EPICS path at ANL/APS is /net/phebos/epics/R3.11 so the command to get the new release is /net/phebos/epics/R3.11/Unix/share/bin/getrel /net/phebos/epics/R3.11. An existing R3.8 short form report can be copied to this new directory and used to create a database. ANL/APS is currently testing an Application Developers Source/Release control system. It is not yet ready for general distribution. Attached are the EPICS R3.11 release notes

  2. Experiments to quantify airborne release from packages with dispersible radioactive materials under accident conditions

    Energy Technology Data Exchange (ETDEWEB)

    Martens, R.; Lange, F. [Gesellschaft fuer Anlagen- und Reaktorsicherheit (GRS) mbH, Schwertnergasse 1, 50667 Koeln (Germany); Koch, W.; Nolte, O. [Fraunhofer-Institut fuer Toxikologie und Experimentelle Medizin (ITEM), Nikolai-Fuchs-Str.1, 30625 Hannover (Germany)

    2005-07-01

    For transport or handling accidents involving packages with radioactive materials and the assessment of potential radiological consequences, for the review of current requirements of the IAEA Transport Regulations, and for their possible further development reliable release data following mechanical impact are required. Within this context a research project was carried out which extends the basis for a well-founded examination of the contemporary system of requirements of 'Low Specific Activity' (LSA)-type materials and allows for its further development where appropriate. This project comprises a prior system-analytical examination and an experimental programme aiming at improving the general physical understanding of the release process as well as the quantity and the characteristics of airborne released material for non-fixed dispersible LSA-II material upon mechanical impact. Impaction experiments applying small, medium and real sized specimens of different dispersible materials revealed that the release behaviour of dispersible powders strongly depends upon material properties, e.g. particle size distribution and cohesion forces. The highest experimentally determined release fraction of respirable mass (AED < 10 {mu}m) amounted to about 2 % and was obtained for 2 kg of un-contained easily dispersible pulverized fly ash (PFA). For larger un-contained PFA specimen the release fraction decreases. However, packaging containing powdery material substantially reduces the airborne release fraction. The measured airborne release fractions for a 200 l drum with Type A certificate containing PFA were about a factor of 50 to 100 lower than for un-contained material. For a drop height of 9 m the airborne release fraction amounted to about 4 x 10{sup -5}. This value should be applicable for most of transport and handling accidents with mechanical impact. For a metal container of Type IP-2 or better which contains powder masses of 100 kg or more this release

  3. Development of Novel Protocol for Preclinical Monitoring the Release of Adjuvants Encapsulated Mucosal Delivery Carriers

    Directory of Open Access Journals (Sweden)

    Mohamed Ibrahim-Saeed

    2015-12-01

    Full Text Available This work contributes in vaccines down-stream process by introducing a novel platform for in-vitro monitoring of vaccine-adjuvant delivery profile as a crucial preclinical optimizing step in mucosal vaccines. Nano and micro particles of Calcium phosphate (Cap vaccine-adjuvant were encapsulated in Chitosan and Alginate polymeric carriers. Adjuvants release profiles monitored in a permeable bag at 37°C, pH 2, incubated in isotonic buffer for 96 hours. The released Calcium in the outer buffer was monitored and compared in-addition to the carrier’s swelling and biophysical properties. The adjuvants and carriers did not interfere with the proliferation of cultured hepatocytes an indicator of their safe use; Chitosan’s viscosity and swelling were higher than Alginate. Chitosan’s Zeta-potential was significantly high positive, while Cap and Alginate were negative. The prepared CaP and Chitosan particles were in nano-size, while the ready-made CaP adjuvant and Alginate were in micro-size using zeta-seizer and scanning electron-micrograph. The release of nano-size particle was in ascending, extended and controlled manner compared to micro-size adjuvant. Moreover, nano-adjuvant release profile from Chitosan was superior compared to Alginate. The core controlling factors in vaccine-adjuvant sustained release includes; smaller adjuvant particles (nano-size, carrier’s low swelling, high viscosity and importantly carrier-adjuvant entrapment reversibility. Chitosan offers sustained ascending superior capacity in releasing Nano-Cap adjuvant. This novel in-vitro pre-clinical study answer a crucial downstream preparative step for optimizing mucosal vaccines before their direct routine in-vivo trial on animal regardless of adjuvant’s particle size or delivery kinetics.

  4. Triggered Release from Polymer Capsules

    Energy Technology Data Exchange (ETDEWEB)

    Esser-Kahn, Aaron P. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry; Odom, Susan A. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry; Sottos, Nancy R. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Materials Science and Engineering; White, Scott R. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Aerospace Engineering; Moore, Jeffrey S. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry

    2011-07-06

    Stimuli-responsive capsules are of interest in drug delivery, fragrance release, food preservation, and self-healing materials. Many methods are used to trigger the release of encapsulated contents. Here we highlight mechanisms for the controlled release of encapsulated cargo that utilize chemical reactions occurring in solid polymeric shell walls. Triggering mechanisms responsible for covalent bond cleavage that result in the release of capsule contents include chemical, biological, light, thermal, magnetic, and electrical stimuli. We present methods for encapsulation and release, triggering methods, and mechanisms and conclude with our opinions on interesting obstacles for chemically induced activation with relevance for controlled release.

  5. The symmetric extendibility of quantum states

    International Nuclear Information System (INIS)

    Nowakowski, Marcin L

    2016-01-01

    Studies on the symmetric extendibility of quantum states have become particularly important in the context of the analysis of one-way quantum measures of entanglement, and the distillability and security of quantum protocols. In this paper we analyze composite systems containing a symmetric extendible part, with particular attention devoted to the one-way security of such systems. Further, we introduce a new one-way entanglement monotone based on the best symmetric approximation of a quantum state and the extendible number of a quantum state. We underpin these results with geometric observations about the structures of multi-party settings which posses substantial symmetric extendible components in their subspaces. The impossibility of reducing the maximal symmetric extendibility by means of the one-way local operations and classical communication method is pointed out on multiple copies. Finally, we state a conjecture linking symmetric extendibility with the one-way distillability and security of all quantum states, analyzing the behavior of a private key in the neighborhood of symmetric extendible states. (paper)

  6. Technical basis and radiological release plan for trackhoe number-sign H0-17-5669 at 100 BC-1

    International Nuclear Information System (INIS)

    Wesselman, M.A.

    1996-03-01

    This report documents the development of a method for the radiological release of a tracked heavy equipment vehicle used in the excavation of the 116 C-1 crib at Hanford Reservation, including the technical bases for selection of release criteria and the instrumentation to be used for the surveys. The vehicle is a backhoe with an articulated arm extending from a tracked vehicle body and for ease is called a ''trackhoe''. The trackhoe was used at the 1301N crib to install the initial string of temporary casing. The trackhoe dug into the crib overburden to a depth of about 10 feet and in the process the bucket became contaminated with mixed fission/activation products and plutonium. An attempt was made to decontaminate the bucket, but was only partially successful as the facilities at the work site were not adequate to achieve a complete release. Surveys of the bucket indicated that direct readings for beta-gamma contamination were over 100 times higher than those for alpha contamination

  7. A Three-Pulse Release Tablet for Amoxicillin: Preparation, Pharmacokinetic Study and Physiologically Based Pharmacokinetic Modeling.

    Science.gov (United States)

    Li, Jin; Chai, Hongyu; Li, Yang; Chai, Xuyu; Zhao, Yan; Zhao, Yunfan; Tao, Tao; Xiang, Xiaoqiang

    2016-01-01

    amoxicillin. In vitro release study firstly indicated a three-pulse release profile of the tablet. Later the pulse tablet was found to generate the sustained release of amoxicillin in beagle dogs. Furthermore, the Simcyp® software was used to simulate the in vivo concentration time curve model of the three-pulse release tablet for amoxicillin in both human and beagle dog. The prediction by PBPK model nicely fitted the observation in human and beagle dog. This study has demonstrated the interrelation of factors affecting the pulsatile formulation of amoxicillin using a Box-Behnken design. The three-pulse release tablets of amoxicillin were proven to generate pulsatile release in vitro and sustained release in vivo. This formulation was also found to extend the effective plasma concentration in human compared to the tablet of immediate release based on the simulation data by PBPK modeling. This study provides an example of using PBPK to guide the development of pulsatile dosage forms.

  8. Guidance for Evaluating the Safety of Experimental Releases of Mosquitoes, Emphasizing Mark-Release-Recapture Techniques.

    Science.gov (United States)

    Benedict, Mark Q; Charlwood, J Derek; Harrington, Laura C; Lounibos, L Philip; Reisen, William K; Tabachnick, Walter J

    2018-01-01

    Experimental releases of mosquitoes are performed to understand characteristics of populations related to the biology, ability to transmit pathogens, and ultimately their control. In this article, we discuss considerations related to the safety of experimental releases of living mosquitoes, applying principles of good practice in vector biology that protect human health and comfort. We describe specific factors of experimental releases of mosquitoes that we believe are critical to inform institutional biosafety committees and similar review boards to which proposals to conduct mosquito release experiments have been submitted. In this study, "experimental releases" means those that do not significantly increase vector capacity or nuisance biting relative to the unperturbed natural baseline. This document specifically does not address releases of mosquitoes for ongoing control programs or trials of new control methods for which broader assessments of risk are required. It also does not address releases of transgenic or exotic (non-native) mosquito species, both of which require particular regulatory approval. Experimental releases may include females and males and evaluation must consider their effects based on the number released, their genotype and phenotype, the environment into which they are released, and postrelease collection activities. We consider whether increases of disease transmission and nuisance biting might result from proposed experimental releases against the backdrop of natural population size variation. We recommend that experimental releases be conducted in a manner that can be reasonably argued to have insignificant negative effects. Reviewers of proposals for experimental releases should expect applicants to provide such an argument based on evidence from similar studies and their planned activities. This document provides guidance for creating and evaluating such proposals.

  9. The Pan-STARRS1 Survey Data Release

    Science.gov (United States)

    Chambers, Kenneth C.; Pan-STARRS Team

    2017-01-01

    The first Pan-STARRS1 Science Mission is complete and an initial Data Release 1, or DR1, including a database of measured attributes, stacked images, and metadata of the 3PI Survey, will be available from the STScI MAST archive. This release will contain all stationary objects with mean and stack photometry registered on the GAIA astrometric frame.The characteristics of the Pan-STARRS1 Surveys will be presented, including image quality, depth, cadence, and coverage. Measured attributes include PSF model magnitudes, aperture magnitudes, Kron Magnitudes, radial moments, Petrosian magnitudes, DeVaucoulers, Exponential, and Sersic magnitudes for extended objects. Images include total intensity, variance, and masks.An overview of both DR1 and the second data release DR2, to follow in the spring of 2017, will be presented. DR2 will add all time domain data and individual warped images. We will also report on the status of the Pan-STARRS2 Observatory and ongoing science with Pan-STARRS. The science from the PS1 surveys has included results in many t fields of astronomy from Near Earth Objects to cosmology.The Pan-STARRS1 Surveys have been made possible through contributions of the Institute for Astronomy of the University of Hawaii; the Pan-STARRS Project Office; the Max-Planck Society and its participating institutes: the Max Planck Institute for Astronomy, Heidelberg and the Max Planck Institute for Extraterrestrial Physics, Garching; The Johns Hopkins University; Durham University; the University of Edinburgh; Queen's University Belfast; the Harvard-Smithsonian Center for Astrophysics, the Las Cumbres Observatory Global Telescope Network Incorporated; the National Central University of Taiwan; the Space Telescope Science Institute; the National Aeronautics and Space Administration under Grants No. NNX08AR22G, NNX12AR65G, NNX14AM74G issued through the Planetary Science Division of the NASA Science Mission Directorate; the National Science Foundation under Grant No. AST

  10. A comparison of alternative methods of calculating complementary cumulative distribution functions of health effects following an atmospheric radioactive release

    International Nuclear Information System (INIS)

    Ponting, A.C.; Nair, S.

    1984-04-01

    A concept extensively used in studying the consequences of accidental atmospheric radioactive releases is that of the Complementary Cumulative Distribution Function, CCDF. Various methods of calculating CCDFs have been developed with particular applications in putting degraded core accidents in perspective and in identifying release sequences leading to high risks. This note compares three methods with specific reference to their accuracy and computational efficiency. For two of the methods (that used in the US Reactor Safety Study code CRAC2 and extended version of that method), the effects of varying the sector width and considering site-specific population distributions have been determined. For the third method it is only necessary to consider the effects of site-specific population distributions. (author)

  11. Extended likelihood inference in reliability

    International Nuclear Information System (INIS)

    Martz, H.F. Jr.; Beckman, R.J.; Waller, R.A.

    1978-10-01

    Extended likelihood methods of inference are developed in which subjective information in the form of a prior distribution is combined with sampling results by means of an extended likelihood function. The extended likelihood function is standardized for use in obtaining extended likelihood intervals. Extended likelihood intervals are derived for the mean of a normal distribution with known variance, the failure-rate of an exponential distribution, and the parameter of a binomial distribution. Extended second-order likelihood methods are developed and used to solve several prediction problems associated with the exponential and binomial distributions. In particular, such quantities as the next failure-time, the number of failures in a given time period, and the time required to observe a given number of failures are predicted for the exponential model with a gamma prior distribution on the failure-rate. In addition, six types of life testing experiments are considered. For the binomial model with a beta prior distribution on the probability of nonsurvival, methods are obtained for predicting the number of nonsurvivors in a given sample size and for predicting the required sample size for observing a specified number of nonsurvivors. Examples illustrate each of the methods developed. Finally, comparisons are made with Bayesian intervals in those cases where these are known to exist

  12. The transmembrane collagen COL-99 guides longitudinally extending axons in C. elegans.

    Science.gov (United States)

    Taylor, Jesse; Unsoeld, Thomas; Hutter, Harald

    2018-06-01

    We have identified the transmembrane collagen, COL-99, in a genetic screen for novel genes involved in axon guidance in the nematode C. elegans. COL-99 is similar to transmembrane collagens type XIII, XXIII and XXV in vertebrates. col-99 mutants exhibit guidance defects in axons extending along the major longitudinal axon tracts, most prominently the left ventral nerve cord (VNC). COL-99 is expressed in the hypodermis during the time of axon outgrowth. We provide evidence that a furin cleavage site in COL-99 is essential for function, suggesting that COL-99 is released from the cells producing it. Vertebrate homologs of COL-99 have been shown to be expressed in mammalian nervous systems and linked to various neurological disease but have not been associated with guidance of extending neurons. col-99 acts genetically with the discoidin domain receptors ddr-1 and ddr-2, which are expressed by neurons affected in col-99 mutants. Discoidin domain receptors are activated by collagens in vertebrates. DDR-1 and DDR-2 may function as receptors for COL-99. Our results establish a novel role for a transmembrane collagen in axonal guidance and asymmetry establishment of the VNC. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Extended Year, Extended Contracts: Increasing Teacher Salary Options.

    Science.gov (United States)

    Gandara, Patricia

    1992-01-01

    Reports on an attempt to raise teacher salaries through an extended contract made possible through year-round school schedules. Teacher satisfaction with the 1987 experiment in three California schools (the Orchard Plan) has been high. Elements that have contributed to job satisfaction are discussed. (SLD)

  14. An understanding of modified release matrix tablets behavior during drug dissolution as the key for prediction of pharmaceutical product performance - case study of multimodal characterization of quetiapine fumarate tablets.

    Science.gov (United States)

    Kulinowski, Piotr; Woyna-Orlewicz, Krzysztof; Rappen, Gerd-Martin; Haznar-Garbacz, Dorota; Węglarz, Władysław P; Dorożyński, Przemysław P

    2015-04-30

    Motivation for the study was the lack of dedicated and effective research and development (R&D) in vitro methods for oral, generic, modified release formulations. The purpose of the research was to assess multimodal in vitro methodology for further bioequivalence study risk minimization. Principal results of the study are as follows: (i) Pharmaceutically equivalent quetiapine fumarate extended release dosage form of Seroquel XR was developed using a quality by design/design of experiment (QbD/DoE) paradigm. (ii) The developed formulation was then compared with originator using X-ray microtomography, magnetic resonance imaging and texture analysis. Despite similarity in terms of compendial dissolution test, developed and original dosage forms differed in micro/meso structure and consequently in mechanical properties. (iii) These differences were found to be the key factors of failure of biorelevant dissolution test using the stress dissolution apparatus. Major conclusions are as follows: (i) Imaging methods allow to assess internal features of the hydrating extended release matrix and together with the stress dissolution test allow to rationalize the design of generic formulations at the in vitro level. (ii) Technological impact on formulation properties e.g., on pore formation in hydrating matrices cannot be overlooked when designing modified release dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Innovation of novel 'Tab in Tab' system for release modulation of milnacipran HCl: optimization, formulation and in vitro investigations.

    Science.gov (United States)

    Parejiya, Punit B; Barot, Bhavesh S; Patel, Hetal K; Shelat, Pragna K; Shukla, Arunkumar

    2013-11-01

    The study was aimed toward development of modified release oral drug delivery system for highly water soluble drug, Milnacipran HCl (MH). Novel Tablet in Tablet system (TITs) comprising immediate and extended release dose of MH in different parts was fabricated. The outer shell was composed of admixture of MH, lactose and novel herbal disintegrant obtained from seeds of Lepidium sativum. In the inner core, MH was matrixed with blend of hydrophilic (Benecel®) and hydrophobic (Compritol®) polymers. 3² full factorial design and an artificial neuron network (ANN) were employed for correlating effect of independent variables on dependent variables. The TITs were characterized for pharmacopoeial specifications, in vitro drug release, SEM, drug release kinetics and FTIR study. The release pattern of MH from batch A10 containing 25.17% w/w Benecel® and 8.21% w/w of Compritol® exhibited drug release pattern close proximal to the ideal theoretical profile (t(50%) = 5.92 h, t(75%) = 11.9 h, t(90%) = 18.11 h). The phenomenon of drug release was further explained by concept of percolation and the role of Benecel® and Compritol® in drug release retardation was studied. The normalized error obtained from ANN was less, compared with the multiple regression analysis, and exhibits the higher accuracy in prediction. The results of short-term stability study revealed stable chataracteristics of TITs. SEM study of TITs at different dissolution time points confirmed both diffusion and erosion mechanisms to be operative during drug release from the batch A10. Novel TITs can be a succesful once a day delivery system for highly water soluble drugs.

  16. Evidence for autocrine and paracrine regulation of allergen-induced mast cell mediator release in the guinea pig airways.

    Science.gov (United States)

    Yu, Li; Liu, Qi; Canning, Brendan J

    2018-03-05

    Mast cells play an essential role in immediate type hypersensitivity reactions and in chronic allergic diseases of the airways, including asthma. Mast cell mediator release can be modulated by locally released autacoids and circulating hormones, but surprisingly little is known about the autocrine effects of mediators released upon mast cell activation. We thus set out to characterize the autocrine and paracrine effects of mast cell mediators on mast cell activation in the guinea pig airways. By direct measures of histamine, cysteinyl-leukotriene and thromboxane release and with studies of allergen-evoked contractions of airway smooth muscle, we describe a complex interplay amongst these autacoids. Notably, we observed an autocrine effect of the cysteinyl-leukotrienes acting through cysLT 1 receptors on mast cell leukotriene release. We confirmed the results of previous studies demonstrating a marked enhancement of mast cell mediator release following cyclooxygenase inhibition, but we have extended these results by showing that COX-2 derived eicosanoids inhibit cysteinyl-leukotriene release and yet are without effect on histamine release. Given the prominent role of COX-1 inhibition in aspirin-sensitive asthma, these data implicate preformed mediators stored in granules as the initial drivers of these adverse reactions. Finally, we describe the paracrine signaling cascade leading to thromboxane synthesis in the guinea pig airways following allergen challenge, which occurs indirectly, secondary to cysLT 1 receptor activation on structural cells and/ or leukocytes within the airway wall, and a COX-2 dependent synthesis of the eicosanoid. The results highlight the importance of cell-cell and autocrine interactions in regulating allergic responses in the airways. Copyright © 2017. Published by Elsevier B.V.

  17. A Novel Biped Pattern Generator Based on Extended ZMP and Extended Cart-Table Model

    Directory of Open Access Journals (Sweden)

    Guangbin Sun

    2015-07-01

    Full Text Available This paper focuses on planning patterns for biped walking on complex terrains. Two problems are solved: ZMP (zero moment point cannot be used on uneven terrain, and the conventional cart-table model does not allow vertical CM (centre of mass motion. For the ZMP definition problem, we propose the extended ZMP (EZMP concept as an extension of ZMP to uneven terrains. It can be used to judge dynamic balance on universal terrains. We achieve a deeper insight into the connection and difference between ZMP and EZMP by adding different constraints. For the model problem, we extend the cart-table model by using a dynamic constraint instead of constant height constraint, which results in a mathematically symmetric set of three equations. In this way, the vertical motion is enabled and the resultant equations are still linear. Based on the extended ZMP concept and extended cart-table model, a biped pattern generator using triple preview controllers is constructed and implemented simultaneously to three dimensions. Using the proposed pattern generator, the Atlas robot is simulated. The simulation results show the robot can walk stably on rather complex terrains by accurately tracking extended ZMP.

  18. Extended KN algebras and extended conformal field theories over higher genus Riemann surfaces

    International Nuclear Information System (INIS)

    Ceresole, A.; Huang Chaoshang

    1990-01-01

    A global operator formalism for extended conformal field theories over higher genus Riemann surfaces is introduced and extended KN algebra are obtained by means of the KN bases. The BBSS construction of the spin-3 operator is carried out for Kac-Moody algebra A 2 over a Riemann surface of arbitrary genus. (orig.)

  19. Examination of Zircaloy-clad spent fuel after extended pool storage

    International Nuclear Information System (INIS)

    Bradley, E.R.; Bailey, W.J.; Johnson, A.B. Jr.; Lowry, L.M.

    1981-09-01

    This report presents the results from metallurgical examinations of Zircaloy-clad fuel rods from two bundles (0551 and 0074) of Shippingport PWR Core 1 blanket fuel after extended water storage. Both bundles were exposed to water in the reactor from late 1957 until discharge. The estimated average burnups were 346 GJ/kgU (4000 MWd/MTU) for bundle 0551 and 1550 GJ/kgU (18,000 MWd/MTU) for bundle 0074. Fuel rods from bundle 0551 were stored in deionized water for nearly 21 yr prior to examination in 1980, representing the world's oldest pool-stored Zircaloy-clad fuel. Bundle 0074 has been stored in deionized water since reactor discharge in 1964. Data from the current metallurgical examinations enable a direct assessment of extended pool storage effects because the metallurgical condition of similar fuel rods was investigated and documented soon after reactor discharge. Data from current and past examinations were compared, and no significant degradation of the Zircaloy cladding was indicated after almost 21 yr in water storage. The cladding dimensions and mechanical properties, fission gas release, hydrogen contents of the cladding, and external oxide film thicknesses that were measured during the current examinations were all within the range of measurements made on fuel bundles soon after reactor discharge. The appearance of the external surfaces and the microstructures of the fuel and cladding were also similar to those reported previously. In addition, no evidence of accelerated corrosion or hydride redistribution in the cladding was observed

  20. Sustained Dye Release Using Poly(urea-urethane)/Cellulose Nanocrystal Composite Microcapsules.

    Science.gov (United States)

    Yoo, Youngman; Martinez, Carlos; Youngblood, Jeffrey P

    2017-02-14

    The aim of this study is to develop methods to reinforce polymeric microspheres with cellulose nanocrystals (CNCs) to make eco-friendly microcapsules for a variety of applications such as medicines, perfumes, nutrients, pesticides, and phase change materials. Surface hydrophobization treatments for CNCs were performed by grafting poly(lactic acid) oligomers and fatty acids (FAs) to enhance the dispersion of nanoparticles in the polymeric shell. Then, a straightforward process is demonstrated to design sustained release microcapsules by the incorporation of the modified CNCs (mCNCs) in the shell structure. The combination of the mCNC dispersion with subsequent interfacial polyurea (PU) to form composite capsules as well as their morphology, composition, mechanical properties, and release rates were examined in this study. The PU microcapsules embedded with the mCNC were characterized by Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA). The morphologies of the microcapsules were characterized by optical microscopy (OM) and scanning electron microscope (SEM). The rupture stress and failure behavior of the microcapsules were determined through single-capsule compression tests. Oil-soluble Sudan II dye solution in mineral oil was utilized as a model hydrophobic fill, representing other latent fills with low partition coefficients, and their encapsulation efficiency was measured spectroscopically. The release rates of the encapsulated dye from the microcapsules were examined spectroscopically by both ethanol and 2-ethyl-1-hexanol medium at room temperature. The concentration of released dye was determined by using UV-vis absorption spectrometry (UV-vis). The mCNC embedded poly(urea-urethane) capsules have strong and dense walls, which function as excellent barriers against leakage due to their extended diffusion path length and ensure enough mechanical strength from rupture for handling or postprocessing.

  1. Range extender module. Enabler for electric mobility; Range-Extender-Modul. Wegbereiter fuer elektrische Mobilitaet

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Robert; Fraidl, Guenter Karl; Hubmann, Christian; Kapus, Paul Ernst; Kunzemann, Ralf; Sifferlinger, Bernhard; Beste, Frank [AVL List GmbH, Graz (Austria)

    2009-10-15

    The Range Extender as an auxiliary power supply for extended driving ranges is of significant importance in achieving a high level of customer acceptance for electric vehicles. The AVL concept is optimized for electric power generation in single-point operation and allows a compactly integrated, cost-efficient and weight-efficient module design. The internal combustion engine requirements of the Pure Range Extender from AVL permit not only the use of simplified four-stroke concepts but also the application of emission-optimized and fuel consumption-optimized two-stroke and rotary piston engines. (orig.)

  2. ATP Release Channels

    Directory of Open Access Journals (Sweden)

    Akiyuki Taruno

    2018-03-01

    Full Text Available Adenosine triphosphate (ATP has been well established as an important extracellular ligand of autocrine signaling, intercellular communication, and neurotransmission with numerous physiological and pathophysiological roles. In addition to the classical exocytosis, non-vesicular mechanisms of cellular ATP release have been demonstrated in many cell types. Although large and negatively charged ATP molecules cannot diffuse across the lipid bilayer of the plasma membrane, conductive ATP release from the cytosol into the extracellular space is possible through ATP-permeable channels. Such channels must possess two minimum qualifications for ATP permeation: anion permeability and a large ion-conducting pore. Currently, five groups of channels are acknowledged as ATP-release channels: connexin hemichannels, pannexin 1, calcium homeostasis modulator 1 (CALHM1, volume-regulated anion channels (VRACs, also known as volume-sensitive outwardly rectifying (VSOR anion channels, and maxi-anion channels (MACs. Recently, major breakthroughs have been made in the field by molecular identification of CALHM1 as the action potential-dependent ATP-release channel in taste bud cells, LRRC8s as components of VRACs, and SLCO2A1 as a core subunit of MACs. Here, the function and physiological roles of these five groups of ATP-release channels are summarized, along with a discussion on the future implications of understanding these channels.

  3. Recycling research on spent fluorescent lamps on the basis of extended producer responsibility in China.

    Science.gov (United States)

    Peng, Lihong; Wang, Yejun; Chang, Chang-Tang

    2014-11-01

    Mercury is a physiological toxin released by spent fluorescent lamps (SFLs) and is considered a serious pollutant. As the world's largest producer of fluorescent lamps, China suffers from SFL pollution because of inefficient recycling and management of SFLs. Drawing upon the most successful practices worldwide, this paper suggests the recycling of SFLs on the basis of the extended producer responsibility (EPR) system in China. Manufacturers and importers are the main parties responsible for the take-back, recycling, and disposal ofSFLs in the EPR system. In view of the situation in China and to address the objectives of the EPR system, this paper recommends the implementation of a third-party take-back mode for small- and medium-scale enterprises and of a takeback mode for large enterprises to be carried out by original equipment manufacturers. This paper suggests an extended responsibility fund to finance and support the SFL recycling system and discusses in detail the different recycling network systems and fund flows of the two take-back modes. By conducting a case study, the authors determine that the subsidy rate for SFLs that a recycling company can obtain from the extended responsibility fund for recycling and disposing of lamps can be set at $1.35/kg. The authors also predict the levy level that fluorescent lamp manufacturers must submit.

  4. Release kinetics of tocopherol and quercetin from binary antioxidant controlled-release packaging films.

    Science.gov (United States)

    Chen, Xi; Lee, Dong Sun; Zhu, Xuntao; Yam, Kit L

    2012-04-04

    This paper investigated the feasibility of manipulating packaging polymers with various degrees of hydrophobicity to release two antioxidants, tocopherol and quercetin, at rates suitable for long-term inhibition of lipid oxidation in food. For example, one antioxidant can be released at a fast rate to provide short-term/intermediate protection, whereas the other antioxidant can be released at a slower rate to provide intermediate/long-term protection of lipid oxidation. Controlled-release packaging films containing tocopherol and quercetin were produced using ethylene vinyl alcohol (EVOH), ethylene vinyl acetate (EVA), low-density polyethylene (LDPE), and polypropylene (PP) polymers; the release of these antioxidants to 95% ethanol (a fatty food simulant) was measured using UV-vis spectrophotometry, and Fickian diffusion models with appropriate initial and boundary conditions were used to fit the data. For films containing only quercetin, the results show that the release of quercetin was much faster but lasted for a much shorter time for hydrophilic polymers (EVOH and EVA) than for hydrophobic polymers (LDPE and PP). For binary antioxidant films containing tocopherol and quercetin, the results show that tocopherol released more rapidly but for a shorter period of time than quercetin in LDPE and EVOH films, and the difference is more pronounced for LDPE films than EVOH films. The results also show the presence of tocopherol can accelerate the release of quercetin. Although none of the films produced is acceptable for long-term lipid oxidation inhibition, the study provides encouraging results suggesting that acceptable films may be produced in the future using polymer blend films.

  5. Effectiveness and gastrointestinal tolerability during conversion and titration with once-daily OROS® hydromorphone extended release in opioid-tolerant patients with chronic low back pain

    Science.gov (United States)

    Hale, Martin E; Nalamachu, Srinivas R; Khan, Arif; Kutch, Michael

    2013-01-01

    Purpose To describe the efficacy and safety of hydromorphone extended-release tablets (OROS hydromorphone ER) during dose conversion and titration. Patients and methods A total of 459 opioid-tolerant adults with chronic moderate to severe low back pain participated in an open-label, 2- to 4-week conversion/titration phase of a double-blind, placebo-controlled, randomized withdrawal trial, conducted at 70 centers in the United States. Patients were converted to once-daily OROS hydromorphone ER at 75% of the equianalgesic dose of their prior total daily opioid dose (5:1 conversion ratio), and titrated as frequently as every 3 days to a maximum dose of 64 mg/day. The primary outcome measure was change in pain intensity numeric rating scale; additional assessments included the Patient Global Assessment and the Roland–Morris Disability Questionnaire scores. Safety assessments were performed at each visit and consisted of recording and monitoring all adverse events (AEs) and serious AEs. Results Mean (standard deviation) final daily dose of OROS hydromorphone ER was 37.5 (17.8) mg. Mean (standard error of the mean [SEM]) numeric rating scale scores decreased from 6.6 (0.1) at screening to 4.3 (0.1) at the final titration visit (mean [SEM] change, −2.3 [0.1], representing a 34.8% reduction). Mean (SEM) change in Patient Global Assessment was −0.6 (0.1), and mean change (SEM) in the Roland–Morris Disability Questionnaire was −2.8 (0.3). Patients achieving a stable dose showed greater improvement than patients who discontinued during titration for each of these measures (P < 0.001). Almost 80% of patients achieving a stable dose (213/268) had a ≥30% reduction in pain. Commonly reported AEs were constipation (15.4%), nausea (11.9%), somnolence (8.7%), headache (7.8%), and vomiting (6.5%); 13.0% discontinued from the study due to AEs. Conclusion The majority of opioid-tolerant patients with chronic low back pain were successfully converted to effective doses of

  6. PCDD/PCDF release inventories

    Energy Technology Data Exchange (ETDEWEB)

    Fiedler, H. [UNEP Chemicals, Chatelaine (Switzerland)

    2004-09-15

    The Stockholm Convention on Persistent Organic Pollutants (POPs) entered into force on 17 May 2004 with 50 Parties. In May 2004, 59 countries had ratified or acceded the Convention. The objective of the Convention is ''to protect human health and the environment from persistent organic pollutants''. For intentionally produced POPs, e.g., pesticides and industrial chemicals such as hexachlorobenzene and polychlorinated biphenyls, this will be achieved by stop of production and use. For unintentionally generated POPs, such as polychlorinated dibenzo-pdioxins (PCDD) and polychlorinated dibenzofurans (PCDF), measures have to be taken to ''reduce the total releases derived from anthropogenic sources''; the final goal is ultimate elimination, where feasible. Under the Convention, Parties have to establish and maintain release inventories to prove the continuous release reduction. Since many countries do not have the technical and financial capacity to measure all releases from all potential PCDD/PCDF sources, UNEP Chemicals has developed the ''Standardized Toolkit for the Identification of Quantification of Dioxin and Furan Releases'' (''Toolkit'' for short), a methodology to estimate annual releases from a number of sources. With this methodology, annual releases can be estimated by multiplying process-specific default emission factors provided in the Toolkit with national activity data. At the seventh session of the Intergovernmental Negotiating Committee, the Toolkit was recommended to be used by countries when reporting national release data to the Conference of the Parties. The Toolkit is especially used by developing countries and countries with economies in transition where no measured data are available. Results from Uruguay, Thailand, Jordan, Philippines, and Brunei Darussalam have been published.

  7. Policy options to reduce consumer waste to zero: comparing product stewardship and extended producer responsibility for refrigerator waste.

    Science.gov (United States)

    Nicol, Scott; Thompson, Shirley

    2007-06-01

    Today, over-consumption, pollution and resource depletion threaten sustainability. Waste management policies frequently fail to reduce consumption, prevent pollution, conserve resources and foster sustainable products. However, waste policies are changing to focus on lifecycle impacts of products from the cradle to the grave by extending the responsibilities of stakeholders to post-consumer management. Product stewardship and extended producer responsibility are two policies in use, with radically different results when compared for one consumer product, refrigerators. North America has enacted product stewardship policies that fail to require producers to take physical or financial responsibility for recycling or for environmentally sound disposal, so that releases of ozone depleting substances routinely occur, which contribute to the expanding the ozone hole. Conversely, Europe's Waste Electrical and Electronic Equipment (WEEE) Directive requires extended producer responsibility, whereby producers collect and manage their own post-consumer waste products. WEEE has resulted in high recycling rates of greater than 85%, reduced emissions of ozone-depleting substances and other toxins, greener production methods, such as replacing greenhouse gas refrigerants with environmentally friendly hydrocarbons and more reuse of refrigerators in the EU in comparison with North America.

  8. Controlled-release tablet formulation of isoniazid.

    Science.gov (United States)

    Jain, N K; Kulkarni, K; Talwar, N

    1992-04-01

    Guar (GG) and Karaya gums (KG) alone and in combination with hydroxy-propylmethylcellulose (HPMC) were evaluated as release retarding materials to formulate a controlled-release tablet dosage form of isoniazid (1). In vitro release of 1 from tablets followed non-Fickian release profile with rapid initial release. Urinary excretion studies in normal subjects showed steady-state levels of 1 for 13 h. In vitro and in vivo data correlated (r = 0.9794). The studies suggested the potentiality of GG and KG as release retarding materials in formulating controlled-release tablet dosage forms of 1.

  9. Interpenetrating network hydrogel membranes of sodium alginate and poly(vinyl alcohol) for controlled release of prazosin hydrochloride through skin.

    Science.gov (United States)

    Kulkarni, Raghavendra V; Sreedhar, V; Mutalik, Srinivas; Setty, C Mallikarjun; Sa, Biswanath

    2010-11-01

    Interpenetrating network (IPN) hydrogel membranes of sodium alginate (SA) and poly(vinyl alcohol) (PVA) were prepared by solvent casting method for transdermal delivery of an anti-hypertensive drug, prazosin hydrochloride. The prepared membranes were thin, flexible and smooth. The X-ray diffraction studies indicated the amorphous dispersion of drug in the membranes. Differential scanning calorimetric analysis confirmed the IPN formation and suggests that the membrane stiffness increases with increased concentration of glutaraldehyde (GA) in the membranes. All the membranes were permeable to water vapors depending upon the extent of cross-linking. The in vitro drug release study was performed through excised rat abdominal skin; drug release depends on the concentrations of GA in membranes. The IPN membranes extended drug release up to 24 h, while SA and PVA membranes discharged the drug quickly. The primary skin irritation and skin histopathology study indicated that the prepared IPN membranes were less irritant and safe for skin application. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Viability of bull semen extended with commercial semen extender ...

    African Journals Online (AJOL)

    Andrea Raseona

    stored at 24 °C. Sperm motility parameters, morphology, and viability were analysed ... body size, slow average daily weight gain, decreased fertility, extended .... were determined by counting a total of 200 spermatozoa per each stained slide.

  11. Interfacial adsorption and surfactant release characteristics of magnetically functionalized halloysite nanotubes for responsive emulsions.

    Science.gov (United States)

    Owoseni, Olasehinde; Nyankson, Emmanuel; Zhang, Yueheng; Adams, Daniel J; He, Jibao; Spinu, Leonard; McPherson, Gary L; Bose, Arijit; Gupta, Ram B; John, Vijay T

    2016-02-01

    Magnetically responsive oil-in-water emulsions are effectively stabilized by a halloysite nanotube supported superparamagnetic iron oxide nanoparticle system. The attachment of the magnetically functionalized halloysite nanotubes at the oil-water interface imparts magnetic responsiveness to the emulsion and provides a steric barrier to droplet coalescence leading to emulsions that are stabilized for extended periods. Interfacial structure characterization by cryogenic scanning electron microscopy reveals that the nanotubes attach at the oil-water interface in a side on-orientation. The tubular structure of the nanotubes is exploited for the encapsulation and release of surfactant species that are typical of oil spill dispersants such as dioctyl sulfosuccinate sodium salt and polyoxyethylene (20) sorbitan monooleate. The magnetically responsive halloysite nanotubes anchor to the oil-water interface stabilizing the interface and releasing the surfactants resulting in reduction in the oil-water interfacial tension. The synergistic adsorption of the nanotubes and the released surfactants at the oil-water interface results in oil emulsification into very small droplets (less than 20μm). The synergy of the unique nanotubular morphology and interfacial activity of halloysite with the magnetic properties of iron oxide nanoparticles has potential applications in oil spill dispersion, magnetic mobilization and detection using magnetic fields. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Linear free energy correlations for fission product release from the Fukushima-Daiichi nuclear accident.

    Science.gov (United States)

    Abrecht, David G; Schwantes, Jon M

    2015-03-03

    This paper extends the preliminary linear free energy correlations for radionuclide release performed by Schwantes et al., following the Fukushima-Daiichi Nuclear Power Plant accident. Through evaluations of the molar fractionations of radionuclides deposited in the soil relative to modeled radionuclide inventories, we confirm the initial source of the radionuclides to the environment to be from active reactors rather than the spent fuel pool. Linear correlations of the form In χ = −α ((ΔGrxn°(TC))/(RTC)) + β were obtained between the deposited concentrations, and the reduction potentials of the fission product oxide species using multiple reduction schemes to calculate ΔG°rxn (TC). These models allowed an estimate of the upper bound for the reactor temperatures of TC between 2015 and 2060 K, providing insight into the limiting factors to vaporization and release of fission products during the reactor accident. Estimates of the release of medium-lived fission products 90Sr, 121mSn, 147Pm, 144Ce, 152Eu, 154Eu, 155Eu, and 151Sm through atmospheric venting during the first month following the accident were obtained, indicating that large quantities of 90Sr and radioactive lanthanides were likely to remain in the damaged reactor cores.

  13. A mathematical model for LH release in response to continuous and pulsatile exposure of gonadotrophs to GnRH

    Directory of Open Access Journals (Sweden)

    Reed Michael C

    2004-09-01

    Full Text Available Abstract In a previous study, a model was developed to investigate the release of luteinizing hormone (LH from pituitary cells in response to a short pulse of gonadotropin-releasing hormone (GnRH. The model included: binding of GnRH to its receptor (R, dimerization and internalization of the hormone receptor complex, interaction with a G protein, production of inositol 1,4,5-trisphosphate (IP3, release of calcium from the endoplasmic reticulum (ER, entrance of calcium into the cytosol via voltage gated membrane channels, pumping of calcium out of the cytosol via membrane and ER pumps, and release of LH. The extended model, presented in this paper, also includes the following physiologically important phenomena: desensitization of calcium channels; internalization of the dimerized receptors and recycling of some of the internalized receptors; an increase in Gq concentration near the plasma membrane in response to receptor dimerization; and basal rates of synthesis and degradation of the receptors. With suitable choices of the parameters, good agreement with a variety of experimental data of the LH release pattern in response to pulses of various durations, repetition rates, and concentrations of GnRH were obtained. The mathematical model allows us to assess the effects of internalization and desensitization on the shapes and time courses of LH response curves.

  14. COMMERCIAL SNF ACCIDENT RELEASE FRACTIONS

    Energy Technology Data Exchange (ETDEWEB)

    S.O. Bader

    1999-10-18

    The purpose of this design analysis is to specify and document the total and respirable fractions for radioactive materials that are released from an accident event at the Monitored Geologic Repository (MGR) involving commercial spent nuclear fuel (CSNF) in a dry environment. The total and respirable release fractions will be used to support the preclosure licensing basis for the MGR. The total release fraction is defined as the fraction of total CSNF assembly inventory, typically expressed as an activity inventory (e.g., curies), of a given radionuclide that is released to the environment from a waste form. The radionuclides are released from the inside of breached fuel rods (or pins) and from the detachment of radioactive material (crud) from the outside surfaces of fuel rods and other components of fuel assemblies. The total release fraction accounts for several mechanisms that tend to retain, retard, or diminish the amount of radionuclides that are available for transport to dose receptors or otherwise can be shown to reduce exposure of receptors to radiological releases. The total release fraction includes a fraction of airborne material that is respirable and could result in inhalation doses. This subset of the total release fraction is referred to as the respirable release fraction. Potential accidents may involve waste forms that are characterized as either bare (unconfined) fuel assemblies or confined fuel assemblies. The confined CSNF assemblies at the MGR are contained in shipping casks, canisters, or disposal containers (waste packages). In contrast to the bare fuel assemblies, the container that confines the fuel assemblies has the potential of providing an additional barrier for diminishing the total release fraction should the fuel rod cladding breach during an accident. However, this analysis will not take credit for this additional bamer and will establish only the total release fractions for bare unconfined CSNF assemblies, which may however be

  15. COMMERCIAL SNF ACCIDENT RELEASE FRACTIONS

    International Nuclear Information System (INIS)

    S.O. Bader

    1999-01-01

    The purpose of this design analysis is to specify and document the total and respirable fractions for radioactive materials that are released from an accident event at the Monitored Geologic Repository (MGR) involving commercial spent nuclear fuel (CSNF) in a dry environment. The total and respirable release fractions will be used to support the preclosure licensing basis for the MGR. The total release fraction is defined as the fraction of total CSNF assembly inventory, typically expressed as an activity inventory (e.g., curies), of a given radionuclide that is released to the environment from a waste form. The radionuclides are released from the inside of breached fuel rods (or pins) and from the detachment of radioactive material (crud) from the outside surfaces of fuel rods and other components of fuel assemblies. The total release fraction accounts for several mechanisms that tend to retain, retard, or diminish the amount of radionuclides that are available for transport to dose receptors or otherwise can be shown to reduce exposure of receptors to radiological releases. The total release fraction includes a fraction of airborne material that is respirable and could result in inhalation doses. This subset of the total release fraction is referred to as the respirable release fraction. Potential accidents may involve waste forms that are characterized as either bare (unconfined) fuel assemblies or confined fuel assemblies. The confined CSNF assemblies at the MGR are contained in shipping casks, canisters, or disposal containers (waste packages). In contrast to the bare fuel assemblies, the container that confines the fuel assemblies has the potential of providing an additional barrier for diminishing the total release fraction should the fuel rod cladding breach during an accident. However, this analysis will not take credit for this additional bamer and will establish only the total release fractions for bare unconfined CSNF assemblies, which may however be

  16. Cobalt release from inexpensive jewellery

    DEFF Research Database (Denmark)

    Thyssen, Jacob Pontoppidan; Jellesen, Morten Stendahl; Menné, Torkil

    2010-01-01

    . Conclusions: This study showed that only a minority of inexpensive jewellery purchased in Denmark released cobalt when analysed with the cobalt spot test. As fashion trends fluctuate and we found cobalt release from dark appearing jewellery, cobalt release from consumer items should be monitored in the future......Objectives: The aim was to study 354 consumer items using the cobalt spot test. Cobalt release was assessed to obtain a risk estimate of cobalt allergy and dermatitis in consumers who would wear the jewellery. Methods: The cobalt spot test was used to assess cobalt release from all items...

  17. A clinical trial to determine if corelease of morphine and naltrexone from crushed extended-release capsules induces withdrawal in opioid-dependent patients: a descriptive analysis of six patients.

    Science.gov (United States)

    Setnik, Beatrice; Roland, Carl L; Goli, Veeraindar; Sommerville, Kenneth; Webster, Lynn

    2013-01-01

    To evaluate whether intact or crushed doses of an extended-release formulation of morphine sulfate surrounding an inner core of sequestered naltrexone (MSN) induces signs and symptoms of withdrawal in opioid-dependent patients. Randomized, double-blind, two-way crossover study. Single center. Fourteen patients with chronic moderate-to-severe noncancer pain receiving opioids were enrolled into the study; six completed the maintenance and treatment phases prior to early study discontinuation for issues with manufacturing; eight discontinued: adverse effects (4), noncompliance (1), patient decision (1), study termination (2). Patients were titrated to a stable dose of MSN (ranging from 30/1.2 to 100/4.0 mg of morphine/naltrexone) that was used in the single-dose crossover evaluation of crushed and intact MSN. Clinical Opiate Withdrawal Scale (COWS). Clinically significant withdrawal (COWS ≥ 13) was observed with rapid onset (≤0.8 hours postdose) in three patients (50 percent) following treatment with crushed MSN at the highest doses administered of ≥60/2.4 mg. Although naltrexone exposure was negligible following exposure to intact MSN, increasing plasma levels of naltrexone and 6-β-naltrexol were associated with COWS score ≥13 in patients who received crushed MSN. COWS ≥ 13 was observed in one patient receiving intact MSN without quantifiable naltrexone concentrations. Crushing the MSN capsule may precipitate moderate-to-severe signs and symptoms of opioid withdrawal in opioid-dependent individuals. The negligible exposure to naltrexone following exposure to intact MSN supports that intact capsules may be taken safely without precipitating withdrawal in opioid-dependent individuals.

  18. Predicted radionuclide release from reactor-related unenclosed solid objects dumped in the Sea of Japan and the Pacific Ocean, east coast of Kamchatka

    International Nuclear Information System (INIS)

    Mount, M.E.; Lynn, N.M.; Warden, J.M.

    1996-06-01

    Between 1978 and 1991 reactor-related solid radioactive waste was dumped by the former Soviet Union as unenclosed objects in the Pacific Ocean, east coast of Kamchatka, and the Sea of Japan. This paper presented estimates for the current (1994) inventory of activation and corrosion products contained in the reactor-related unenclosed solid objects. In addition, simple models derived for prediction of radionuclide release from marine reactors dumped in the Kara Sea are applied to certain of the dumped objects to provide estimates of radionuclide release to the Pacific Ocean, east coast of Kamchatka, and Sea of Japan environments. For the Pacific Ocean, east coast of Kamchatka, total release rates start below 0.01 GBq yr -1 and over 1,000 years, fall to 100 Bq yr -1 . In the Sea of Japan, the total release rate starts just above 1 GBq yr - 1 , dropping off to a level less than 0.1 GBq yr -1 , extending past the year 4,000

  19. Evaluation of the Microbiological Efficacy of a Single 2-Gram Dose of Extended-Release Azithromycin by Population Pharmacokinetics and Simulation in Japanese Patients with Gonococcal Urethritis.

    Science.gov (United States)

    Soda, Midori; Ito, Shin; Matsumaru, Naoki; Nakamura, Sakiko; Nagase, Izumi; Takahashi, Hikari; Ohno, Yuta; Yasuda, Mitsuru; Yamamoto, Miho; Tsukamoto, Katsura; Itoh, Yoshinori; Deguchi, Takashi; Kitaichi, Kiyoyuki

    2018-01-01

    The objective of this study was to analyze the relationship between the pharmacokinetic (PK)/pharmacodynamic (PD) parameters of a single 2-g dose of extended-release formulation of azithromycin (AZM-SR) and its microbiological efficacy against gonococcal urethritis. Fifty male patients with gonococcal urethritis were enrolled in this study. In 36 patients, the plasma AZM concentrations were measured using liquid chromatography-tandem mass spectrometry, the AZM MIC values for the Neisseria gonorrhoeae isolates were determined, and the microbiological outcomes were assessed. AZM-SR monotherapy eradicated N. gonorrhoeae in 30 (83%) of the 36 patients. AZM MICs ranged from 0.03 to 2 mg/liter. The mean value of the area under the concentration-time curve (AUC), estimated by population PK analysis using a two-compartment model, was 20.8 mg · h/liter. Logistic regression analysis showed that the PK/PD target value required to predict an N. gonorrhoeae eradication rate of ≥95% was a calculated AUC/MIC of ≥59.5. The AUC/MIC value was significantly higher in patients who achieved microbiological cure than in patients who achieved microbiological failure. Monte Carlo simulation using this MIC distribution revealed that the probability that AZM-SR monotherapy would produce an AUC/MIC exceeding the AUC/MIC target of 59.5 was 47%. Furthermore, the MIC distribution for strains isolated in this study was mostly consistent with that for strains currently circulating in Japan. In conclusion, in Japan, AZM-SR monotherapy may not be effective against gonococcal urethritis. Therefore, use of a single 2-g dose of AZM-SR either with or without other antibiotics could be an option to treat gonococcal urethritis if patients are allergic to ceftriaxone and spectinomycin or are diagnosed to be infected with an AZM-sensitive strain. Copyright © 2017 American Society for Microbiology.

  20. In Vitro-In Vivo Predictive Dissolution-Permeation-Absorption Dynamics of Highly Permeable Drug Extended-Release Tablets via Drug Dissolution/Absorption Simulating System and pH Alteration.

    Science.gov (United States)

    Li, Zi-Qiang; Tian, Shuang; Gu, Hui; Wu, Zeng-Guang; Nyagblordzro, Makafui; Feng, Guo; He, Xin

    2018-05-01

    Each of dissolution and permeation may be a rate-limiting factor in the absorption of oral drug delivery. But the current dissolution test rarely took into consideration of the permeation property. Drug dissolution/absorption simulating system (DDASS) valuably gave an insight into the combination of drug dissolution and permeation processes happening in human gastrointestinal tract. The simulated gastric/intestinal fluid of DDASS was improved in this study to realize the influence of dynamic pH change on the complete oral dosage form. To assess the effectiveness of DDASS, six high-permeability drugs were chosen as model drugs, including theophylline (pK a1  = 3.50, pK a2  = 8.60), diclofenac (pK a  = 4.15), isosorbide 5-mononitrate (pK a  = 7.00), sinomenine (pK a  = 7.98), alfuzosin (pK a  = 8.13), and metoprolol (pK a  = 9.70). A general elution and permeation relationship of their commercially available extended-release tablets was assessed as well as the relationship between the cumulative permeation and the apparent permeability. The correlations between DDASS elution and USP apparatus 2 (USP2) dissolution and also between DDASS permeation and beagle dog absorption were developed to estimate the predictability of DDASS. As a result, the common elution-dissolution relationship was established regardless of some variance in the characteristic behavior between DDASS and USP2 for drugs dependent on the pH for dissolution. Level A in vitro-in vivo correlation between DDASS permeation and dog absorption was developed for drugs with different pKa. The improved DDASS will be a promising tool to provide a screening method on the predictive dissolution-permeation-absorption dynamics of solid drug dosage forms in the early-phase formulation development.

  1. A Bayesian Analysis of the Radioactive Releases of Fukushima

    DEFF Research Database (Denmark)

    Tomioka, Ryota; Mørup, Morten

    2012-01-01

    the types of nuclides and their levels of concentration from the recorded mixture of radiations to take necessary measures. We presently formulate a Bayesian generative model for the data available on radioactive releases from the Fukushima Daiichi disaster across Japan. From the sparsely sampled...... the Fukushima Daiichi plant we establish that the model is able to account for the data. We further demonstrate how the model extends to include all the available measurements recorded throughout Japan. The model can be considered a first attempt to apply Bayesian learning unsupervised in order to give a more......The Fukushima Daiichi disaster 11 March, 2011 is considered the largest nuclear accident since the 1986 Chernobyl disaster and has been rated at level 7 on the International Nuclear Event Scale. As different radioactive materials have different effects to human body, it is important to know...

  2. Attenuation of fluorocarbons released from foam insulation in landfills

    DEFF Research Database (Denmark)

    Scheutz, Charlotte; Dote, Yukata; Fredenslund, Anders Michael

    2007-01-01

    Chlorofluorocarbons (CFCs), hydrochlorofluorocarbons (HCFCs), and hydrofluorocarbons (HFCs) have been used as blowing agents (BAs) for foam insulation in home appliances and building materials, which after the end of their useful life are disposed of in landfills. The objective of this project...... was to evaluate the potential for degradation of BAs in landfills, and to develop a landfill model, which could simulate the fate of BAs in landfills. The investigation was performed by use of anaerobic microcosm studies using different types of organic waste and anaerobic digested sludge as inoculum. The BAs...... in any of the experiments within a run time of up to 200 days. The obtained degradation rate coefficients were used as input for an extended version of an existing landfill fate model incorporating a time dependent BA release from co-disposed foam insulation waste. Predictions with the model indicate...

  3. Simulation of the thermomechanical interaction between pellet and cladding and fission gas release

    International Nuclear Information System (INIS)

    Denis, Alicia C.; Soba, Alejandro

    2000-01-01

    This paper summarizes the present status of a computer code that simulates some of the main phenomena occurring in a fuel element of a nuclear power reactor throughout its life. Temperature distribution, thermal expansion, elastic and plastic strains, creep, mechanical interaction between pellet and cladding, fission gas release, swelling and densification are modeled. Thermal expansion gives origin to elastic or plastic strains, which adequately describe the bamboo effect. The code assumes an axial symmetric rod and hence, cylindrical finite elements are employed for the discretization. The fission gas inventory is calculated by means of a diffusion model, which assumes spherical grains and uses also a finite element scheme. Once the temperature distribution in the pellet and the cladding is obtained and in order to reduce the calculation time, the rod is divided into five cylindrical rings where the temperature is averaged. In each ring the gas diffusion problem is solved in one representative grain and the results are then extended to the whole ring. The pressure, increased by the released gas, interacts with the stress field. Densification and swelling due to solid and gaseous fission products are also considered. Experiments, particularly those of the FUMEX series, are simulated with this code. A good agreement is obtained for the fuel center line temperature, the inside rod pressure and the fractional gas release. (author)

  4. Extending dry storage of spent LWR fuel for up to 100 years

    International Nuclear Information System (INIS)

    Einziger, R.E.; McKinnon, M.A.; Machiels, A.J.

    1999-01-01

    Because of delays in closing the back end of the fuel cycle in the U.S., there is a need to extend dry inert storage of spent fuel beyond its originally anticipated 20-year duration. Many of the methodologies developed to support initial licensing for 20-year storage should be able to support the longer storage periods envisioned. This paper evaluates the applicability of existing information and methodologies to support dry storage up to 100 years. The thrust of the analysis is the potential behavior of the spent fuel. In the USA, the criteria for dry storage of LWR spent fuel are delineated in 10 CFR 72. The criteria fall into four general categories: maintain subcriticality, prevent the release of radioactive material above acceptable limits, ensure that radiation rates and doses do not exceed acceptable levels, and maintain retrievability of the stored radioactive material. These criteria need to be considered for normal, off-normal, and postulated accident conditions. The initial safety analysis report submitted for licensing evaluated the fuel's ability to meet the requirements for 20 years. It is not the intent to repeat these calculations, but to look at expected behavior over the additional 80 years, during which the temperatures and radiation fields are lower. During the first 20 years, the properties of the components may change because of elevated temperatures, presence of moisture, effects of radiation, etc. During normal storage in an inert atmosphere, there is potential for the cladding mechanical properties to change due to annealing or interaction with cask materials. The emissivity of the cladding could also change due to storage conditions. If there is air leakage into the cask, additional degradation could occur through oxidation in breached rods, which could lead to additional fission gas release and enlargement of cladding breaches. Air in-leakage could also affect cover gas conductivity, cladding oxidation, emissivity changes, and excessive

  5. Extending dry storage of spent LWR fuel for up to 100 years

    International Nuclear Information System (INIS)

    Einziger, R. E.

    1998-01-01

    Because of delays in closing the back end of the fuel cycle in the U.S., there is a need to extend dry inert storage of spent fuel beyond its originally anticipated 20-year duration. Many of the methodologies developed to support initial licensing for 20-year storage should be able to support the longer storage periods envisioned. This paper evaluates the applicability of existing information and methodologies to support dry storage up to 100 years. The thrust of the analysis is the potential behavior of the spent fuel. In the USA, the criteria for dry storage of LWR spent fuel are delineated in 10 CFR 72 [1]. The criteria fall into four general categories: maintain subcriticality, prevent the release of radioactive material above acceptable limits, ensure that radiation rates and doses do not exceed acceptable levels, and maintain retrievability of the stored radioactive material. These criteria need to be considered for normal, off-normal, and postulated accident conditions. The initial safety analysis report submitted for licensing evaluated the fuel's ability to meet the requirements for 20 years. It is not the intent to repeat these calculations, but to look at expected behavior over the additional 80 years, during which the temperatures and radiation fields are lower. During the first 20 years, the properties of the components may change because of elevated temperatures, presence of moisture, effects of radiation, etc. During normal storage in an inert atmosphere, there is potential for the cladding mechanical properties to change due to annealing or interaction with cask materials. The emissivity of the cladding could also change due to storage conditions. If there is air leakage into the cask, additional degradation could occur through oxidation in breached rods, which could lead to additional fission gas release and enlargement of cladding breaches. Air in-leakage could also affect cover gas conductivity, cladding oxidation, emissivity changes, and

  6. Relative Release-to-Birth Indicators for Investigating TRISO Fuel Fission Gas Release Models

    International Nuclear Information System (INIS)

    Harp, Jason M.; Hawari, Ayman I.

    2008-01-01

    TRISO microsphere fuel is the fundamental fuel unit for Very High Temperature Reactors (VHTR). A single TRISO particle consists of an inner kernel of uranium dioxide or uranium oxycarbide surrounded by layers of pyrolytic carbon and silicon carbide. If the silicon carbide layer fails, fission products, especially the noble fission gases Kr and Xe, will begin to escape the failed particle. The release of fission gas is usually quantified by measuring the ratio of the released activity (R) to the original birth activity (B), which is designated as the R/B ratio. In this work, relative Release-to-Birth indicators (I) are proposed as a technique for interpreting the results of TRISO irradiation experiments. By implementing a relative metric, it is possible to reduce the sensitivity of the indicators to instrumental uncertainties and variations in experimental conditions. As an example, relative R/B indicators are applied to the interpretation of representative data from the Advanced Gas Reactor-1 TRISO fuel experiment that is currently taking place at the Advanced Test Reactor of Idaho National Laboratory. It is shown that the comparison of measured to predicted relative R/B indicators (I) gives insight into the physics of release and helps validate release models. Different trends displayed by the indicators are related to the mechanisms of fission gas release such as diffusion and recoil. The current analysis shows evidence for separate diffusion coefficients for Kr and Xe and supports the need to account for recoil release. (authors)

  7. Conditional release of materials from decommissioning process into the environment in the form of steel railway tracks

    International Nuclear Information System (INIS)

    Tatransky, Peter; Necas, Vladimir

    2009-01-01

    This work points to the possibilities of conditional release of materials from the process of decommissioning the nuclear unit from the operation. According to the valid legislation, materials which do not meet the condition of direct-unconditional release into the environment, should be modified and processed into the matrix designed for the final disposal in the storing place. However there exists a group of materials which activity is on the borderline of the limit of releasing into the environment and it is possible to release them conditionally. The matter of conditional release is that notable amount of materials, mainly metals, is usually contaminated only by radionuclids with relatively short time of half decay. These materials are suitable to use for a specific industrial purpose where the longtime fixation of shortly living radionuclids is expected in one place. This work deals with the conditional release of metals into the form of steel railway tracks. It describes the (working) groups of workers working with the steel railway tracks and defines in the numbers the critical group and its critical individual. For critical individual it dimensions the amounts of materials, which are possible to be released conditionally from one double-unit of the plant of the type VVER 440 V-230 which operation was ended on the regular basis. According to the calculations in the software VISIPLAN and OMEGA there is defined a number of released steel in such way that the internationally recommended rate of maximal effective dose for critical individual-10 μSv/year [IAEA, 2008. Managing low radioactivity material from the decommissioning of nuclear facility. Technical reports series no. 462] is not extended. In the final part there are compared the estimates of the costs of the decommissioning process with the application of conditional release and without it, which is directly reflected in the amount of saved costs and number of containers for surface disposal.

  8. SOL-Gel microspheres and nanospheres for controlled release applications

    International Nuclear Information System (INIS)

    Barbe, C.; Beyer, R.; Kong, L.; Blackford, M.; Trautman, R.; Bartlett, J.

    2002-01-01

    We present a novel approach to the synthesis of inorganic sol-gel microspheres for encapsulating organic and bioactive molecules, and controlling their subsequent release kinetics. The bioactive species are incorporated, at ambient temperature, into the inorganic particles using an emulsion gelation process. Independent control of the release rate (by adapting the nanostructure of the internal pore network to the physico-chemical properties of the bioactive molecules) and particle size (by tailoring the emulsion chemistry) is demonstrated. Sol-gel chemistry has been shown to be a flexible technique for producing inorganic silica matrices with tailored microstructures, which can be used for the encapsulation and controlled release of organic and bioactive molecules. The present paper extends this concept by combining sol-gel chemistry with an emulsion approach for producing inorganic particles with controlled dimensions, and demonstrates how the particle size and microstructure can be independently controlled. Sol-Gel Chemistry and Encapsulation of Model Compounds. A stock solution of 4-(2-hydroxy-l-naphthylazo) benzene sulfonic acid (Orange II) was produced by dissolving Orange II in water (0.1 wt%), and adjusting the pH to the required value. Sol-gel solutions were subsequently prepared by mixing the aqueous solution with tetramethylorthosilicate (TMOS) and methanol (MeOH), to achieve H 2 O:TMOS (W] and MeOH:TMOS mole ratios (D) of four. The resulting solution was stirred and left to age at ambient temperature for one day. A transparent emulsion was prepared by mixing selected surfactants and organic solvents. The surfactants used included sorbitan monooleate, sorbitan monolaurate and bis-2-ethylhexylsulfo-succinate (AOT), while the organic phase was typically chosen from the group consisting of kerosene, hexane, heptane, octane, decane, dodecane and cyclohexane. The sol-gel solution was added to the emulsion, and the resulting mixture was stirred at 500 rpm for

  9. Drug release from non-aqueous suspensions. II. The release of methylxanthines from paraffin suspensions

    NARCIS (Netherlands)

    Blaey, C.J. de; Fokkens, J.G.

    1984-01-01

    The release of 3 methylxanthines, i.e. caffeine, theobromine and theophylline, from suspensions in liquid paraffin to an aqueous phase was determined in an in vitro apparatus. The release rates were determined as a function of the pH of the aqueous phase. It was proved that the release process was

  10. The dialogically extended mind

    DEFF Research Database (Denmark)

    Fusaroli, Riccardo; Gangopadhyay, Nivedita; Tylén, Kristian

    2014-01-01

    A growing conceptual and empirical literature is advancing the idea that language extends our cognitive skills. One of the most influential positions holds that language – qua material symbols – facilitates individual thought processes by virtue of its material properties. Extending upon this model...... relate our approach to other ideas about collective minds and review a number of empirical studies to identify the mechanisms enabling the constitution of interpersonal cognitive systems....

  11. Quasi-extended asymptotic functions

    International Nuclear Information System (INIS)

    Todorov, T.D.

    1979-01-01

    The class F of ''quasi-extended asymptotic functions'' is introduced. It contains all extended asymptotic functions as well as some new asymptotic functions very similar to the Schwartz distributions. On the other hand, every two quasiextended asymptotic functions can be multiplied as opposed to the Schwartz distributions; in particular, the square delta 2 of an asymptotic function delta similar to Dirac's delta-function, is constructed as an example

  12. In vitro effect of Δ9-tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E2

    International Nuclear Information System (INIS)

    Rettori, V.; Aguila, M.C.; McCann, S.M.; Gimeno, M.F.; Franchi, A.M.

    1990-01-01

    Previous in vivo studies have shown that Δ 9 -tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were deigned to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or nonrepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E 2 (PGE 2 ) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE 2 suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE 2 synthesis and release. The authors speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release

  13. Streamlined approach for environmental restoration closure report for Corrective Action Unit 454: Historical underground storage tank release sites, Nevada Test Site, Nevada

    International Nuclear Information System (INIS)

    1998-04-01

    This report addresses the characterization of three historical underground storage tank (UST) petroleum hydrocarbon release sites identified as 12-B-1, 12-B-3, and 12-COMM-1. The sites are located within the Nevada Test Site in Area 12 at B Tunnel and a former Communications/Power Maintenance Shop. Release Site 12-B-1 was not able to be clean-closed as proposed in the SAFER Plan. However, hydrocarbon impacted soils were excavated down to bedrock. Release Site 12-B-3 was evaluated to verify that the identified release was not associated with the UST removed from the site. Analytical results support the assumption that wood or possibly a roof sealant used as part of the bunker construction could have been the source of hydrocarbons detected. Release Site 12-COMM-1 was not clean closed as proposed in the SAFER Plan. The vertical extent of impacted soils was determined not to extend below a depth of 2.7 m (9 ft) below ground surface (bgs). The lateral extent could not be defined due to the presence of a discontinuous lens of hydrocarbon-impacted soil

  14. Streamlined approach for environmental restoration closure report for Corrective Action Unit 454: Historical underground storage tank release sites, Nevada Test Site, Nevada

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-04-01

    This report addresses the characterization of three historical underground storage tank (UST) petroleum hydrocarbon release sites identified as 12-B-1, 12-B-3, and 12-COMM-1. The sites are located within the Nevada Test Site in Area 12 at B Tunnel and a former Communications/Power Maintenance Shop. Release Site 12-B-1 was not able to be clean-closed as proposed in the SAFER Plan. However, hydrocarbon impacted soils were excavated down to bedrock. Release Site 12-B-3 was evaluated to verify that the identified release was not associated with the UST removed from the site. Analytical results support the assumption that wood or possibly a roof sealant used as part of the bunker construction could have been the source of hydrocarbons detected. Release Site 12-COMM-1 was not clean closed as proposed in the SAFER Plan. The vertical extent of impacted soils was determined not to extend below a depth of 2.7 m (9 ft) below ground surface (bgs). The lateral extent could not be defined due to the presence of a discontinuous lens of hydrocarbon-impacted soil.

  15. EAES: Extended Advanced Encryption Standard with Extended Security

    Directory of Open Access Journals (Sweden)

    Abul Kalam Azad

    2018-05-01

    Full Text Available Though AES is the highest secure symmetric cipher at present, many attacks are now effective against AES too which is seen from the review of recent attacks of AES. This paper describes an extended AES algorithm with key sizes of 256, 384 and 512 bits with round numbers of 10, 12 and 14 respectively. Data block length is 128 bits, same as AES. But unlike AES each round of encryption and decryption of this proposed algorithm consists of five stages except the last one which consists of four stages. Unlike AES, this algorithm uses two different key expansion algorithms with two different round constants that ensure higher security than AES. Basically, this algorithm takes one cipher key and divides the selected key of two separate sub-keys: FirstKey and SecondKey. Then expand them through two different key expansion schedules. Performance analysis shows that the proposed extended AES algorithm takes almost same amount of time to encrypt and decrypt the same amount of data as AES but with higher security than AES.

  16. Sustained release vancomycin-coated titanium alloy using a novel electrostatic dry powder coating technique may be a potential strategy to reduce implant-related infection.

    Science.gov (United States)

    Han, Jing; Yang, Yi; Lu, Junren; Wang, Chenzhong; Xie, Youtao; Zheng, Xuebin; Yao, Zhenjun; Zhang, Chi

    2017-07-24

    In order to tackle the implant-related infection, a novel way was developed in this study to coat vancomycin particles mixed with controlled release coating materials onto the surface of titanium alloy by using an electrostatic dry powder coating technique. To characterize this sustained release antibacterial coating, surface morphology, in vitro and in vivo drug release were sequentially evaluated. In vitro cytotoxicity was tested by Cell Counting Kit-8 (CCK-8) assay and cytological changes were observed by inverted microscope. The antibacterial properties against MRSA, including a bacterial growth inhibition assay and a colony-counting test by spread plate method were performed. Results indicated that the vancomycin-coated sample was biocompatible for Human osteoblast cell line MG-63 and displayed effective antibacterial ability against MRSA. The coating film was revealed uniform by scanning electron microscopy. Both the in vitro and in vivo drug release kinetics showed an initially high release rate, followed by an extended period of sustained drug release over 7 days. These results suggest that with good biocompatibility and antibacterial ability, the sustained release antibacterial coating of titanium alloy using our novel electrostatic dry powder coating process may provide a promising candidate for the treatment of orthopedic implant-related infection.

  17. Commercial SNF Accident Release Fractions

    Energy Technology Data Exchange (ETDEWEB)

    J. Schulz

    2004-11-05

    The purpose of this analysis is to specify and document the total and respirable fractions for radioactive materials that could be potentially released from an accident at the repository involving commercial spent nuclear fuel (SNF) in a dry environment. The total and respirable release fractions are used to support the preclosure licensing basis for the repository. The total release fraction is defined as the fraction of total commercial SNF assembly inventory, typically expressed as an activity inventory (e.g., curies), of a given radionuclide that is released to the environment from a waste form. Radionuclides are released from the inside of breached fuel rods (or pins) and from the detachment of radioactive material (crud) from the outside surfaces of fuel rods and other components of fuel assemblies. The total release fraction accounts for several mechanisms that tend to retain, retard, or diminish the amount of radionuclides that are available for transport to dose receptors or otherwise can be shown to reduce exposure of receptors to radiological releases. The total release fraction includes a fraction of airborne material that is respirable and could result in inhalation doses; this subset of the total release fraction is referred to as the respirable release fraction. Accidents may involve waste forms characterized as: (1) bare unconfined intact fuel assemblies, (2) confined intact fuel assemblies, or (3) canistered failed commercial SNF. Confined intact commercial SNF assemblies at the repository are contained in shipping casks, canisters, or waste packages. Four categories of failed commercial SNF are identified: (1) mechanically and cladding-penetration damaged commercial SNF, (2) consolidated/reconstituted assemblies, (3) fuel rods, pieces, and debris, and (4) nonfuel components. It is assumed that failed commercial SNF is placed into waste packages with a mesh screen at each end (CRWMS M&O 1999). In contrast to bare unconfined fuel assemblies, the

  18. Commercial SNF Accident Release Fractions

    International Nuclear Information System (INIS)

    Schulz, J.

    2004-01-01

    The purpose of this analysis is to specify and document the total and respirable fractions for radioactive materials that could be potentially released from an accident at the repository involving commercial spent nuclear fuel (SNF) in a dry environment. The total and respirable release fractions are used to support the preclosure licensing basis for the repository. The total release fraction is defined as the fraction of total commercial SNF assembly inventory, typically expressed as an activity inventory (e.g., curies), of a given radionuclide that is released to the environment from a waste form. Radionuclides are released from the inside of breached fuel rods (or pins) and from the detachment of radioactive material (crud) from the outside surfaces of fuel rods and other components of fuel assemblies. The total release fraction accounts for several mechanisms that tend to retain, retard, or diminish the amount of radionuclides that are available for transport to dose receptors or otherwise can be shown to reduce exposure of receptors to radiological releases. The total release fraction includes a fraction of airborne material that is respirable and could result in inhalation doses; this subset of the total release fraction is referred to as the respirable release fraction. Accidents may involve waste forms characterized as: (1) bare unconfined intact fuel assemblies, (2) confined intact fuel assemblies, or (3) canistered failed commercial SNF. Confined intact commercial SNF assemblies at the repository are contained in shipping casks, canisters, or waste packages. Four categories of failed commercial SNF are identified: (1) mechanically and cladding-penetration damaged commercial SNF, (2) consolidated/reconstituted assemblies, (3) fuel rods, pieces, and debris, and (4) nonfuel components. It is assumed that failed commercial SNF is placed into waste packages with a mesh screen at each end (CRWMS M andO 1999). In contrast to bare unconfined fuel assemblies, the

  19. Extending cosmology: the metric approach

    OpenAIRE

    Mendoza, S.

    2012-01-01

    Comment: 2012, Extending Cosmology: The Metric Approach, Open Questions in Cosmology; Review article for an Intech "Open questions in cosmology" book chapter (19 pages, 3 figures). Available from: http://www.intechopen.com/books/open-questions-in-cosmology/extending-cosmology-the-metric-approach

  20. Extended cognition and epistemic luck

    NARCIS (Netherlands)

    Carter, J.A.

    2013-01-01

    When extended cognition is extended into mainstream epistemology, an awkward tension arises when considering cases of environmental epistemic luck. Surprisingly, it is not at all clear how the mainstream verdict that agents lack knowledge in cases of environmental luck can be reconciled with

  1. Novel Nitric Oxide (NO)-Releasing Polymers and Their Biomedical Applications

    Science.gov (United States)

    Brisbois, Elizabeth J.

    -capped PLGA additive extended the NO release for up to 14 d. The pH changes corresponding to the NO release profiles from these films was visualized by doping films with pH indicator dyes. Poly(vinyl chloride)- and Elast-eon E2As were used as the base polymers for combined DBHD/N 2 O 2 and PLGA coatings on the inner walls of ECC circuits. After 4 h of blood flow in a rabbit model, the E2As-based NOrel circuits preserved platelets at a higher level than PVC-based NOrel circuits (97% and 80% of baseline, respectively). This demonstrates that the inherent hemocompatibility properties of the base polymer can also influence the efficiency of the NO release coatings. A DBHD/N2 O 2-doped SG-80A polymer material was also studied and used to fabricate patches that were applied to scald burn wounds infected with Acinetobacter baumannii. The NO released from these patches applied to the wounds is shown to significantly reduce the A. baumannii infection after 24 h (˜4 log reduction). The results for both of types of NO-releasing polymers studied here demonstrated greatly enhanced biocompatibility properties, in terms of reducing thrombus and infection. These materials have the potential for improving the hemocompatibility of a wide variety of blood-contacting medical devices.

  2. Extended-Release Guaifenesin/Pseudoephedrine Hydrochloride for Symptom Relief in Support of a Wait-and-See Approach for the Treatment of Acute Upper Respiratory Tract Infections: A Randomized, Double-Blind, Placebo-Controlled Study.

    Science.gov (United States)

    Septimus, Edward J; Albrecht, Helmut H; Solomon, Gail; Shea, Tim; Guenin, Eric P

    2017-01-01

    Despite the well-known fact that antibiotics (AB) are not effective against viruses, many patients ask for - and all too often doctors provide - AB for treating URTIs. Over-prescribing of AB is one of the key causes for the development of bacterial resistance, which the U.S. Centers for Disease Control and Prevention (CDC) calls "one of the world's most pressing public health problems". In addition to the CDC initiated "Get Smart About Antibiotics" campaign, focused on educating doctors the public about the importance of appropriate AB use, other programs tackling this problem include the development of new treatment paradigms. Data published at the Oregon Health & Science University demonstrated that a 'wait-and-see' approach, without an AB prescription for the treatment of acute childhood ear infections, was as quick, safe, and effective in resolving the infections as an AB prescription (Spiro DM, Tay KY, Arnold DH, Dziura JD, Baker MD, Shapiro ED. Wait-and-See Prescription for the Treatment of Acute Otitis Media. JAMA 2006; 296:1235-1241). To try and reduce inappropriate prescribing practices, a wait and see or delayed approach requires patients to return for a prescription if their symptoms persist or worsen. The aim of this study was to determine whether treatment with Mucinex D (Reckitt Benckiser LLC, Parsippany, New Jersey) lowers the use of antibiotics in the treatment of URTIs when compared with placebo. Patients aged 18 to 75 years with symptoms of acute URTIs were randomized to 1200 mg guaifenesin/120 mg pseudoephedrine hydrochloride extended-release, bilayer tablets or matching placebo for 7 consecutive days. Eligible patients met physician's criteria for antibiotic therapy but were considered suitable for a wait and see approach (withholding antibiotics for ≥48 hours). Patients recorded symptom ratings via an interactive voice response system. One thousand one hundred eighty-nine patients enrolled; data are presented for the modified intent

  3. Toxics Release Inventory (TRI)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxics Release Inventory (TRI) is a dataset compiled by the U.S. Environmental Protection Agency (EPA). It contains information on the release and waste...

  4. Extending Mondrian Memory Protection

    Science.gov (United States)

    2010-11-01

    a kernel semaphore is locked or unlocked. In addition, we extended the system call interface to receive notifications about user-land locking...operations (such as calls to the mutex and semaphore code provided by the C library). By patching the dynamically loadable GLibC5, we are able to test... semaphores , and spinlocks. RTO-MP-IST-091 10- 9 Extending Mondrian Memory Protection to loading extension plugins. This prevents any untrusted code

  5. Preparation and characterization of novel functionalized prochloraz microcapsules using silica-alginate-elements as controlled release carrier materials.

    Science.gov (United States)

    Zhang, Wenbing; He, Shun; Liu, Yao; Geng, Qianqian; Ding, Guanglong; Guo, Mingcheng; Deng, Yufang; Zhu, Juanli; Li, Jianqiang; Cao, Yongsong

    2014-07-23

    Controlled release formulation of pesticides is an effective approach to achieve the desirable purpose of increasing the utilization of pesticides and reducing the environmental residuals. In this work, a novel functionalized microcapsule using silica cross-linked with alginate, and some beneficial elements to crops, was prepared. The microcapsules were structurally characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, and X-ray photoelectron spectroscopy. The results showed that the microcapsules had a high loading efficiency of prochloraz (about 30% w/w) and could effectively protect prochloraz against degradation under UV irradiation and alkaline conditions, showed sustainable release for at least 60 days, and also likely increased disease resistance due to the element on the surface. Given the advantages of the microcapsules, this delivery system may be extended to other photosensitive or pH-sensitive pesticides in the future.

  6. Extended Cognitive System and Epistemic Subject

    Directory of Open Access Journals (Sweden)

    Trybulec Barbara

    2015-03-01

    Full Text Available The concept of an extended cognitive system is central to contemporary studies of cognition. In the paper I analyze the place of the epistemic subject within the extended cognitive system. Is it extended as well? In answering this question I focus on the differences between the first and the second wave of arguments for the extended mind thesis. I argue that the position of Cognitive Integration represented by Richard Menary is much more intuitive and fruitful in analyses of cognition and knowledge than the early argument formulated by Andy Clark and David Chalmers. Cognitive Integration is compatible with virtue epistemology of John Greco’s agent reliabilism. The epistemic subject is constituted by its cognitive character composed of an integrated set of cognitive abilities and processes. Some of these processes are extended, they are a manipulation of external informational structures and, as such, they constitute epistemic practices. Epistemic practices are normative; to conduct them correctly the epistemic subject needs to obey epistemic norms embedded in the cultural context. The epistemic subject is not extended because of the casual coupling with external informational artifacts which extend his mind from inside the head and into the world. Rather, cognitive practices constitute the subject’s mind, they transform his cognitive abilities, and this is what makes the mind and epistemic subject “extended”.

  7. Sustained release of radioprotective agents

    International Nuclear Information System (INIS)

    Shani, J.

    1980-11-01

    New pharmaceutical formulations for the sustained release into the G.I. tract of radioprotective agents have been developed by the authors. The experimental method initially consisted in the production of methylcellulose microcapsules. This method failed apparently because of the premature ''explosion'' of the microcapsules and the consequent premature release of massive amounts of the drug. A new method has been developed which consists in drying and pulverising cysteamine and cysteine preparations, mixing them in various proportions with stearic acid and ethylcellulose as carriers. The mixture is then compressed into cylindrical tablets at several pressure values and the leaching rate of the radioprotective agents is then measured by spectrophotometry. The relation between the concentration of the active drug and its rate of release, and the effect on the release rate of the pressure applied to the tablet during its formation were also investigated. Results indicating that the release rate was linearly related to the square root of ''t'' seem to be in agreement with what is predictable, according to Higuchi's equation, save for the very initial and terminal phases. A clear correlation was also established between the stearic acid/ethylcellulose ratios and the release of 20% cysteine, namely a marked decrease in the rate of cysteine release was observed with increasing concentrations of stearic acid. Finally, it was observed that a higher formation pressure results in quicker release of the drug

  8. Extended asymptotic functions - some examples

    International Nuclear Information System (INIS)

    Todorov, T.D.

    1981-01-01

    Several examples of extended asymptotic functions of two variables are given. This type of asymptotic functions has been introduced as an extension of continuous ordinary functions. The presented examples are realizations of some Schwartz distributions delta(x), THETA(x), P(1/xsup(n)) and can be multiplied in the class of the asymptotic functions as opposed to the theory of Schwartz distributions. The examples illustrate the method of construction of extended asymptotic functions similar to the distributions. The set formed by the extended asymptotic functions is also considered. It is shown, that this set is not closed with respect to addition and multiplication

  9. On the Cλ-extended w∞-symmetry

    International Nuclear Information System (INIS)

    Douari, J.; El Kinani, E.H.

    2003-08-01

    Starting from the C λ -extended oscillator algebras, we obtain a new deformed w ∞ -algebra. More precisely, we show that the C λ -extended w ∞ -algebra generators may be expressed via the annihilation and creation operators of the C λ -extended oscillator algebras a and a † as an infinite-dimensional extension of the realization of sp(2) algebra. (author)

  10. Extended recency effect extended: blocking, presentation mode, and retention interval.

    Science.gov (United States)

    Glidden, L M; Pawelski, C; Mar, H; Zigman, W

    1979-07-01

    The effect of blocking of stimulus items on the free recall of EMR adolescents was examined. In Experiment 1 a multitrial free-recall list of 15 pictures was presented either simultaneously in groups of 3, or sequentially, one at a time. Consistent ordering was used in both conditions, so that on each trial, each item in each set of 3 pictures was presented contiguously with the other 2 items from that set. In addition, recall came immediately or after a filled or unfilled delay of 24.5 seconds. Results showed that simultaneous presentation led to higher recall, subjective organization, and clustering than did sequential presentation, but analysis of serial-position curves showed a much reduced extended recency effect in comparison with previous studies. Experiment 2 was designed to determine whether the cause of the reduced extended recency was the use of pictures rather than words as stimuli. Stimuli were presented either as pictures, as pictures with auditory labels, or as words with auditory labels, with both simultaneous and consistent ordering for all conditions. Results indicated a strong extended recency effect for all groups, eliminating presentation mode as a causal factor in the data of Experiment 1. We concluded that blocking leads to increased organization and recall over a variety of presentation modes, rates, and block sizes.

  11. Bacteriospermia in extended porcine semen.

    Science.gov (United States)

    Althouse, Gary C; Lu, Kristina G

    2005-01-15

    Bacteriospermia is a frequent finding in freshly extended porcine semen and can result in detrimental effects on semen quality and longevity if left uncontrolled. The primary source of bacterial contamination is the boar. Other sources that have been identified include environment, personnel, and the water used for extender preparation. A 1-year retrospective study was performed on submissions of extended porcine semen for routine quality control bacteriological screening at the University of Pennsylvania. Out of 250 sample submissions, 78 (31.2%) tested positive for bacterial contamination. The most popular contaminants included Enterococcus spp. (20.5%), Stenotrophomonas maltophilia (15.4%), Alcaligenes xylosoxidans (10.3%), Serratia marcescens (10.3%), Acinetobacter lwoffi (7.7%), Escherichia coli (6.4%), Pseudomonas spp. (6.4%), and others (23.0%). Prudent individual hygiene, good overall sanitation, and regular monitoring can contribute greatly in controlling bacterial load. Strategies that incorporate temperature-dependent bacterial growth and hyperthermic augmentation of antimicrobial activity are valuable for effective control of susceptible bacterial loads. Aminoglycosides remain the most popular antimicrobial class used in porcine semen extenders, with beta-lactam and lincosamide use increasing. With the advent of more novel antimicrobial selection and semen extender compositions in swine, prudent application and understanding of in vitro pharmacodynamics are becoming paramount to industry success in the use of this breeding modality.

  12. Fission-product release during accidents

    International Nuclear Information System (INIS)

    Hunt, C.E.L.; Cox, D.S.

    1991-09-01

    One of the aims when managing a reactor accident is to minimize the release of radioactive fission products. Release is dependent not only on the temperature, but also on the partial pressure of oxygen. Strongly oxidizing atmospheres, such as those that occurred during the Chernobyl accident, released semi-volatile elements like ruthenium, which has volatile oxides. At low temperatures, UO 2 oxidization to U 3 O 8 can result in extensive breakup of the fuel, resulting in the release of non-volatile fission products as aerosols. Under less oxidizing conditions, when hydrogen accumulates from the zirconium-water reaction, the resulting low oxygen partial pressure can significantly reduce these reactions. At TMI-2, only the noble gases and volatile fission products were released in significant quantities. A knowledge of the effect of atmosphere as well as temperature on the release of fission products from damaged reactor cores is therefore a useful, if not necessary, component of information required for accident management

  13. RAVEN Beta Release

    International Nuclear Information System (INIS)

    Rabiti, Cristian; Alfonsi, Andrea; Cogliati, Joshua Joseph; Mandelli, Diego; Kinoshita, Robert Arthur; Wang, Congjian; Maljovec, Daniel Patrick; Talbot, Paul William

    2016-01-01

    This documents the release of the Risk Analysis Virtual Environment (RAVEN) code. A description of the RAVEN code is provided, and discussion of the release process for the M2LW-16IN0704045 milestone. The RAVEN code is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. RAVEN is capable of investigating the system response as well as the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. RAVEN has now increased in maturity enough for the Beta 1.0 release.

  14. RAVEN Beta Release

    Energy Technology Data Exchange (ETDEWEB)

    Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Alfonsi, Andrea [Idaho National Lab. (INL), Idaho Falls, ID (United States); Cogliati, Joshua Joseph [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mandelli, Diego [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kinoshita, Robert Arthur [Idaho National Lab. (INL), Idaho Falls, ID (United States); Wang, Congjian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Maljovec, Daniel Patrick [Idaho National Lab. (INL), Idaho Falls, ID (United States); Talbot, Paul William [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-02-01

    This documents the release of the Risk Analysis Virtual Environment (RAVEN) code. A description of the RAVEN code is provided, and discussion of the release process for the M2LW-16IN0704045 milestone. The RAVEN code is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. RAVEN is capable of investigating the system response as well as the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. RAVEN has now increased in maturity enough for the Beta 1.0 release.

  15. Extended quantum mechanics

    International Nuclear Information System (INIS)

    Pavel Bona

    2000-01-01

    The work can be considered as an essay on mathematical and conceptual structure of nonrelativistic quantum mechanics which is related here to some other (more general, but also to more special and 'approximative') theories. Quantum mechanics is here primarily reformulated in an equivalent form of a Poisson system on the phase space consisting of density matrices, where the 'observables', as well as 'symmetry generators' are represented by a specific type of real valued (densely defined) functions, namely the usual quantum expectations of corresponding selfjoint operators. It is shown in this paper that inclusion of additional ('nonlinear') symmetry generators (i. e. 'Hamiltonians') into this reformulation of (linear) quantum mechanics leads to a considerable extension of the theory: two kinds of quantum 'mixed states' should be distinguished, and operator - valued functions of density matrices should be used in the role of 'nonlinear observables'. A general framework for physical theories is obtained in this way: By different choices of the sets of 'nonlinear observables' we obtain, as special cases, e.g. classical mechanics on homogeneous spaces of kinematical symmetry groups, standard (linear) quantum mechanics, or nonlinear extensions of quantum mechanics; also various 'quasiclassical approximations' to quantum mechanics are all sub theories of the presented extension of quantum mechanics - a version of the extended quantum mechanics. A general interpretation scheme of extended quantum mechanics extending the usual statistical interpretation of quantum mechanics is also proposed. Eventually, extended quantum mechanics is shown to be (included into) a C * -algebraic (hence linear) quantum theory. Mathematical formulation of these theories is presented. The presentation includes an analysis of problems connected with differentiation on infinite-dimensional manifolds, as well as a solution of some problems connected with the work with only densely defined unbounded

  16. Extended Life Coolant Testing

    Science.gov (United States)

    2016-06-06

    number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) 06-06-2016 2. REPORT TYPE Interim Report 3. DATES COVERED ... Corrosion Testing of Traditional and Extended Life Coolants 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Hansen, Gregory A. T...providing vehicle specific coolants. Several laboratory corrosion tests were performed according to ASTM D1384 and D2570, but with a 2.5x extended time

  17. Evaluation of new polysaccharides networks for extended-release purposes: mesquite seed gum (MSG, xanthan gum and chitosan Estudo da utilização de polissacarídeos no desenvolvimento de formulações de liberação prolongada: goma de semente de algaroba, goma xantana e quitosano

    Directory of Open Access Journals (Sweden)

    Carlos César dos Santos Nogueira

    2003-09-01

    Full Text Available The aim of this work was to design new hydrophilic matrix (HM systems by cross-linking Mesquite Seed Gum (MSG, a galactomannan that occurs in the endosperm layer of the seeds of a Brazilian tree,Prosopis juliflora DC, with two well-known polysaccharides with the ability of retarding drug release, chitosan and xanthan gum. This had in mind the idea of using these new compounds in the preparation of extended-release dosage oral forms. The first part of this study was dedicated to the evaluation of MSG in terms of its functionality as a hydrophilic matrix (HM system for extended-release purposes. Next, we started the study of water uptake profile of all polymers of interest (MSG, Xanthan Gum and Chitosan, in the following media: water, SGF and SIF. Following, we searched for the best cross-linking agent between Glutharaldehyde (GA and Hexamethylenediisocyanate (HMDI, which turned out to be the GA. Next step we begun to prepare new hydrophilic matrices of MSG_Chitosan and MSG_Xanthan Gum, with different ratios, 1:1, 1:2 and 2:1. Finally, after deciding which new HM system presented best results, by using statistics tools, we investigated the mechanism controlling the rate release of the model drug, from tablets made with this new matrix. As a final result we concluded that the best combination of polysaccharides was achieved with MSG and Xanthan Gum, with mass ratio of 1:2, using glutharaldehyde aqueous solution as cross-linking agent. It presented a prevalent zero order kinetics, which is a very important feature when thinking about an extended-release oral dosage.O objetivo deste trabalho foi o desenvolvimento de novos sistemas de matrizes hidrofílicas através da formação de ligações cruzadas (cross-linking entre a Goma da Semente da Algaroba (GSA, uma galactomanana que ocorre no endosperma das sementes de uma árvore nativa do Brasil, a Prosopis juliflora DC, e dois polissacarídeos bem conhecidos pela sua habilidade de retardar a libera

  18. Sustained Release of Lidocaine from Solvent-Free Biodegradable Poly[(d,l)-Lactide-co-Glycolide] (PLGA): In Vitro and In Vivo Study.

    Science.gov (United States)

    Kau, Yi-Chuan; Liao, Chia-Chih; Chen, Ying-Chi; Liu, Shih-Jung

    2014-09-16

    Local anesthetics are commonly used for pain relief by regional nerve blocking. In this study, we fabricated solvent-free biodegradable pellets to extend the duration of lidocaine release without any significant local or systemic toxicity levels. To manufacture the pellets, poly[(d,l)-lactide-co-glycolide] (PLGA) was first pre-mixed with lidocaine powder into different ratios. The powder mixture was then compressed with a mold (diameter of 1, 5, 8 or 10 mm) and sintered at 65 °C to form pellets. The in vitro release study showed that the lidocaine/PLGA pellets exhibited a tri-phase release behavior (a burst, a diffusion-controlled release and a degradation-dominated release) and reached completion around day 28. Scanning electron microscope (SEM) photos show that small channels could be found on the surfaces of the pellets on day 2. Furthermore, the polymer matrix swelled and fell apart on day 7, while the pellets became viscous after 10 days of in vitro elution. Perineural administration of the lidocaine/PLGA pellets produced anti-hypersensitivity effects lasting for at least 24 h in rats, significant when compared to the control group (a pure PLGA was pellet administered). In addition, no inflammation was detected within the nerve and in the neighboring muscle by histopathology.

  19. Sustained Release of Lidocaine from Solvent-Free Biodegradable Poly[(d,l-Lactide-co-Glycolide] (PLGA: In Vitro and In Vivo Study

    Directory of Open Access Journals (Sweden)

    Yi-Chuan Kau

    2014-09-01

    Full Text Available Local anesthetics are commonly used for pain relief by regional nerve blocking. In this study, we fabricated solvent-free biodegradable pellets to extend the duration of lidocaine release without any significant local or systemic toxicity levels. To manufacture the pellets, poly[(d,l-lactide-co-glycolide] (PLGA was first pre-mixed with lidocaine powder into different ratios. The powder mixture was then compressed with a mold (diameter of 1, 5, 8 or 10 mm and sintered at 65 °C to form pellets. The in vitro release study showed that the lidocaine/PLGA pellets exhibited a tri-phase release behavior (a burst, a diffusion-controlled release and a degradation-dominated release and reached completion around day 28. Scanning electron microscope (SEM photos show that small channels could be found on the surfaces of the pellets on day 2. Furthermore, the polymer matrix swelled and fell apart on day 7, while the pellets became viscous after 10 days of in vitro elution. Perineural administration of the lidocaine/PLGA pellets produced anti-hypersensitivity effects lasting for at least 24 h in rats, significant when compared to the control group (a pure PLGA was pellet administered. In addition, no inflammation was detected within the nerve and in the neighboring muscle by histopathology.