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Sample records for sublingual combination formulation

  1. Pharmacokinetics of a Prototype Formulation of Sublingual Testosterone and a Buspirone Tablet, Versus an Advanced Combination Tablet of Testosterone and Buspirone in Healthy Premenopausal Women

    NARCIS (Netherlands)

    Van Rooij, Kim; De Leede, Leo; Frijlink, Henderik W.; Bloemers, Jos; Poels, Saskia; Koppeschaar, Hans; Olivier, Berend; Tuiten, Adriaan

    2014-01-01

    The study aimed to compare the kinetics of two novel combination drug products for Female Sexual Interest/Arousal Disorder (FSIAD). Thirteen women received testosterone via the sublingual route followed 2.5 hours later by a buspirone tablet, versus a single combination tablet swallowed at once. The

  2. Formulation and evaluation of sublingual tablets of losartan potassium

    Directory of Open Access Journals (Sweden)

    Nikunj J. Aghera

    2012-05-01

    Full Text Available Objective: Sublingual tablets of Losartan Potassium were prepared to improve its bioavailability, to avoid pre-systemic metabolism in the gastrointestinal tract and hepatic first pass elimination. Methods: The Sublingual tablets were prepared by direct compression procedure using different concentration of Starch 1500 and microcrystalline cellulose. Compatibility studies of drug and polymer were performed by FTIR spectroscopy and DSC. Preformulation property of API was evaluated. Postcompressional parameters such disintegration time, wetting time, water absorption ratio, in vitro drug release and in vivo bioavailability study of optimized formulation were determined. Results: FTIR spectroscopy and DSC study revealed that there was no possible interaction between drug and polymers. The precompression parameters were in acceptable range of pharmacopoeial specification. The disintegration time of optimized formulation (F3 was upto 48 sec. The in vitro release of Losartan Potassium was upto 15 min. The percentage relative bioavailability of Losartan Potassium from optimized sublingual tablets was found to be 144.7 %. Conclusions: Sublingual tablets of Losartan Potassium were successfully prepared with improved bioavailability.

  3. Formulation and Evaluation of New Glimepiride Sublingual Tablets

    Directory of Open Access Journals (Sweden)

    Wafa Al-Madhagi

    2017-01-01

    Full Text Available Oral mucosal delivery of drugs promotes rapid absorption and high bioavailability, with a subsequent immediate onset of pharmacological effect. However, many oral mucosal deliveries are compromised by the possibility of the patient swallowing the active substance before it has been released and absorbed locally into the systemic circulation. The aim of this research was to introduce a new glimepiride formula for sublingual administration and rapid drug absorption that can be used in an emergency. The new sublingual formulation was prepared after five trials to prepare the suitable formulation. Two accepted formulations of the new sublingual product were prepared, but one of them with disintegration time of 1.45 min and searching for preferred formulation, the binder, is changed with Flulac and starch slurry to prepare formula with disintegration time of 21 seconds that supports the aim of research to be used in an emergency. The five formulations were done, after adjusting to the binder as Flulac and aerosil with disintegration time of 21 seconds and accepted hardness as well as the weight variation. The assay of a new product (subglimepiride is 103% which is a promising result, confirming that the formula succeeded. The new product (subglimepiride is accepted in most quality control tests and it is ready for marketing.

  4. Adrenaline (epinephrine) microcrystal sublingual tablet formulation: enhanced absorption in a preclinical model.

    Science.gov (United States)

    Rawas-Qalaji, Mutasem; Rachid, Ousama; Mendez, Belacryst A; Losada, Annette; Simons, F Estelle R; Simons, Keith J

    2015-01-01

    For anaphylaxis treatment in community settings, adrenaline (epinephrine) administration using an auto-injector in the thigh is universally recommended. Despite this, many people at risk of anaphylaxis in community settings do not carry their prescribed auto-injectors consistently and hesitate to use them when anaphylaxis occurs.The objective of this research was to study the effect of a substantial reduction in adrenaline (Epi) particle size to a few micrometres (Epi microcrystals (Epi-MC)) on enhancing adrenaline dissolution and increasing the rate and extent of sublingual absorption from a previously developed rapidly disintegrating sublingual tablet (RDST) formulation in a validated preclinical model. The in-vivo absorption of Epi-MC 20 mg RDSTs and Epi 40 mg RDSTs was evaluated in rabbits. Epi 0.3 mg intramuscular (IM) injection in the thigh and placebo RDSTs were used as positive and negative controls, respectively. Epimean (standard deviation) area under the plasma concentration vs time curves up to 60 min and Cmax from Epi-MC 20 mg and Epi 40 mg RDSTs did not differ significantly (P > 0.05) from Epi 0.3 mg IM injection. After adrenaline, regardless of route of administration, pharmacokinetic parameters were significantly higher (P adrenaline levels). Epi-MC RDSTs facilitated a twofold increase in Epi absorption and a 50% reduction in the sublingual dose. This novel sublingual tablet formulation is potentially useful for the first-aid treatment of anaphylaxis in community settings. © 2014 Royal Pharmaceutical Society.

  5. In vitro and in vivo evaluation of a sublingual fentanyl wafer formulation

    Directory of Open Access Journals (Sweden)

    Lim SCB

    2013-04-01

    Full Text Available Stephen CB Lim,1,3 Michael J Paech,2 Bruce Sunderland,3 Yandi Liu3 1Pharmacy Department, Armadale Health Service, Armadale, 2School of Medicine and Pharmacology, University of Western Australia, and Department of Anaesthesia and Pain Medicine, King Edward Memorial Hospital for Women, Subiaco, 3School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia Background: The objective of this study was to prepare a novel fentanyl wafer formulation by a freeze-drying method, and to evaluate its in vitro and in vivo release characteristics, including its bioavailability via the sublingual route. Methods: The wafer formulation was prepared by freeze-drying an aqueous dispersion of fentanyl containing sodium carboxymethylcellulose and amylogum as matrix formers. Uniformity of weight, friability, and dissolution testing of the fentanyl wafer was achieved using standard methods, and the residual moisture content was measured. The fentanyl wafer was also examined using scanning electron microscopy and x-ray diffraction. The absolute bioavailability of the fentanyl wafer was evaluated in 11 opioid-naïve adult female patients using a randomized crossover design. Results: In vitro release showed that almost 90% of the fentanyl dissolved in one minute. In vivo, the first detectable plasma fentanyl concentration was observed after 3.5 minutes and the peak plasma concentration between 61.5 and 67 minutes. The median absolute bioavailability was 53.0%. Conclusion: These results indicate that this wafer has potential as an alternative sublingual fentanyl formulation. Keywords: absolute bioavailability, fentanyl wafer, in vitro dissolution, in vivo study, pharmacokinetics, sublingual

  6. In vitro and in vivo evaluation of a sublingual fentanyl wafer formulation

    Science.gov (United States)

    Lim, Stephen CB; Paech, Michael J; Sunderland, Bruce; Liu, Yandi

    2013-01-01

    Background The objective of this study was to prepare a novel fentanyl wafer formulation by a freeze-drying method, and to evaluate its in vitro and in vivo release characteristics, including its bioavailability via the sublingual route. Methods The wafer formulation was prepared by freeze-drying an aqueous dispersion of fentanyl containing sodium carboxymethylcellulose and amylogum as matrix formers. Uniformity of weight, friability, and dissolution testing of the fentanyl wafer was achieved using standard methods, and the residual moisture content was measured. The fentanyl wafer was also examined using scanning electron microscopy and x-ray diffraction. The absolute bioavailability of the fentanyl wafer was evaluated in 11 opioid-naïve adult female patients using a randomized crossover design. Results In vitro release showed that almost 90% of the fentanyl dissolved in one minute. In vivo, the first detectable plasma fentanyl concentration was observed after 3.5 minutes and the peak plasma concentration between 61.5 and 67 minutes. The median absolute bioavailability was 53.0%. Conclusion These results indicate that this wafer has potential as an alternative sublingual fentanyl formulation. PMID:23596347

  7. Bioavailability of House Dust Mite Allergens in Sublingual Allergy Tablets Is Highly Dependent on the Formulation.

    Science.gov (United States)

    Ohashi-Doi, Katsuyo; Kito, Hirokazu; Du, Weibin; Nakazawa, Hiroshi; Ipsen, Henrik; Gudmann, Pernille; Lund, Kaare

    2017-01-01

    In sublingual immunotherapy (SLIT), the immune system is addressed by solubilized allergen that interacts with immunocompetent cells of the oral mucosa, the efficiency of which is governed by 2 main factors of SLIT allergen bioavailability: the allergen concentration and the mucosal contact time. Recently, 3 house dust mite (HDM) SLIT tablets were developed that differ with regard to allergen content, nominal strength (maintenance doses: 6 SQ-HDM/10,000 Japanese Allergen Units [JAU], 12 SQ-HDM/ 20,000 JAU, and 300 IR/57,000 JAU), and formulation (freeze-dried/compressed). Here, the importance of the SLIT tablet formulation for HDM major allergen bioavailability is examined. The HDM major allergen content, tablet disintegration times, and allergen release kinetics were determined. Dissolution kinetics (allergen concentration vs. time) of Der f 1, Der p 1, and Der 2 were measured. Area under the curve (AUC) was used as a surrogate parameter for allergen bioavailability. The release of HDM major allergens from the freeze-dried tablets was complete after 30 s, while only partial release was achieved with the compressed tablets, even after prolonged dissolution. At 1 min, i.e., the recommended sublingual holding time for the freeze-dried tablets, the allergen bioavailability (AUC) of the compressed 300 IR/57,000 JAU tablet was 4.7-fold (Der f 1), 10.8-fold (Der p 1), and 23.6-fold (Der 2) lower than that of the freeze-dried 12 SQ-HDM/20,000 JAU tablet and similar to (Der f 1) and 5.3-fold (Der p 1) and 12.5-fold (Der 2) lower than that of the freeze-dried 6 SQ-HDM/10,000 JAU tablet. SLIT tablet allergen bioavailability depends highly on the tablet formulation. Only the fast-dissolving freeze-dried tablets provide maximal delivery of soluble allergens and achieve allergen concentrations that reflect the nominal tablet strengths within the recommended sublingual holding time. © 2017 S. Karger AG, Basel.

  8. Adenoid cystic carcinoma of sublingual glands. Surgery and radiotherapy combination

    International Nuclear Information System (INIS)

    Campagnale, Ramiro; Campagnale, Rodrigo; Varalli, Lucas

    2005-01-01

    The Adenoid Cystic Carcinoma (ACC) or Cilindroma is a strange entity classified by the WHO within the carcinomas of salivary glands. It represents only 1 % of all the wicked tumours of the oral and maxillofacial region although, when making reference to the salivary glands, it constitutes 5% of the parotid, submaxilar and sublingual carcinomas, and about 50% of the smallest ones. The most frequent location is in the palatine glands and its main characteristics are: slow but persistent growth, high rates of local relapse and metastasis at distance originating the death between the first 5 and 10 years in 50-70% of the cases approximately. A case of localization is presented in sublingual gland which was first treated surgically and later with radiotherapy, obtaining good results. (author) [es

  9. Formulation and evaluation of sublingual delivery of piroxicam using thermosensitive polymer with an inverted Franz diffusion cell.

    Science.gov (United States)

    Sivaraman, Arunprasad; Banga, Ajay K

    2016-01-01

    The aim of the study was to prepare a sublingual formulation for piroxicam using a thermosensitive polymer and to evaluate its permeation through porcine sublingual mucosa. Formulation technique utilized the transition property of poloxamer from solution state at room temperature to gel state at oromucosal temperature (37 °C). The permeation of the drug was evaluated using an inverted Franz diffusion cell technique that allowed the dosage form to be directly applied onto the substrate with required volume of saliva. The formulation was characterized for microscopy of the piroxicam crystals, sol-gel transition property and in-vitro diffusion study. Poloxamer-based formulation enhanced solubility and increased permeability of the piroxicam. Poloxamer formulation with 0.1% w/w piroxicam delivered a cumulative amount of 11.99 ± 7.82 and 11.23 ± 1.79 μg/cm(2), while non-poloxamer formulation delivered 3.57 ± 2.20 and 4.60 ± 6.90 μg/cm(2) with 0.1 and 0.5 ml artificial saliva, respectively, through porcine sublingual tissue in 6 h. A similar delivery profile was observed for 0.05% w/w piroxicam formulation as well. © 2015 Royal Pharmaceutical Society.

  10. Comparative Study Between Different Ready-Made Orally Disintegrating Platforms for the Formulation of Sumatriptan Succinate Sublingual Tablets.

    Science.gov (United States)

    Tayel, Saadya A; El Nabarawi, Mohamed A; Amin, Maha M; AbouGhaly, Mohamed H H

    2017-02-01

    Sumatriptan succinate (SS) is a selective serotonin receptor agonist used for the treatment of migraine attacks, suffering from extensive first-pass metabolism and low oral bioavailability (∼14%). The aim of this work is to compare the performance of different ready-made co-processed platforms (Pharmaburst®, Prosolv ODT®, Starlac®, Pearlitol Flash®, or Ludiflash®) in the formulation of SS sublingual orodispersible tablets (ODTs) using direct compression technique. The prepared SS ODT formulae were evaluated regarding hardness, friability, simulated wetting time, and in vitro disintegration and dissolution tests. Different mucoadhesive polymers-HPMC K4M, Carbopol®, chitosan, or Polyox®-were tested aiming to increase the residence time in the sublingual area. A pharmacokinetic study on healthy human volunteers was performed, using LC/MS/MS assay, to compare the optimum sublingual formula (Ph25/HPMC) with the conventional oral tablet Imitrex®. Results showed that tablets prepared using Pharmaburst® had significantly (p disintegration times of 17.17 and 23.50 s, respectively, with Q 5 min of 83.62%. HPMC showed a significant (p tablet Imitrex®. In conclusion, Pharmaburst® was chosen as the optimum ready-made co-processed platform that can be successfully used in the preparation of SS sublingual tablets for the rapid relief of migraine attacks.

  11. Formulation and Characterization of Fast-Dissolving Sublingual Film of Iloperidone Using Box-Behnken Design for Enhancement of Oral Bioavailability.

    Science.gov (United States)

    Londhe, Vaishali; Shirsat, Rucha

    2018-04-01

    Iloperidone is a second-generation antipsychotic drug which is used for the treatment of schizophrenia and has very low aqueous solubility and bioavailability. This drug also undergoes first-pass metabolism. The aim of this work is to formulate fast-dissolving sublingual films of iloperidone to improve its bioavailability. Sublingual films were prepared by solvent casting method. Hydroxypropyl methyl cellulose E5, propylene glycol 400, and transcutol HP were optimized using Box-Behnken three-level statistical design on the basis of disintegration time and folding endurance of films. Iloperidone:hydroxypropyl-β-cyclodextrin kneaded complex was used in films instead of plain drug due to its low solubility. Optimized film was further evaluated for drug content, pH, dissolution studies, ex vivo permeation studies, and pharmacokinetic studies in rats. The optimized film disintegrated within 30 s. The in vitro dissolution of the film showed 80.3 ± 3.4% drug dissolved within first 5 min. In ex vivo permeation studies using sublingual tissue, flux achieved within first 15 min by film was around 117.1 ± 0.35 (mcg/cm 2 /h) which was ten times more than that of plain drug. This formulation showed excellent uniformity. AUC and C max of film were significantly higher (p films was 148% when compared to the plain drug. Thus, this study showed optimized fast-dissolving sublingual film to improve permeation and bioavailability of iloperidone. Fast-dissolving films will be customer-friendly approach for geadiatric schizophrenic patients.

  12. The Influence of Low Salivary Flow Rates on the Absorption of a Sublingual Fentanyl Citrate Formulation for Breakthrough Cancer Pain.

    Science.gov (United States)

    Davies, Andrew; Mundin, Gill; Vriens, Joanna; Webber, Kath; Buchanan, Alison; Waghorn, Melanie

    2016-03-01

    Salivary gland hypofunction may affect the absorption of drugs through the oral mucosa, which in turn may affect their clinical efficacy (e.g., onset of action). The aim of this study was to assess the pharmacokinetics of a sublingual fentanyl orally disintegrating tablet (Abstral, Prostrakan Inc.) in a group of cancer patients with salivary gland hypofunction. Nine cancer patients with salivary gland hypofunction underwent a series of three pharmacokinetic studies with the sublingual fentanyl orally disintegrating tablet. In the first phase, the patients received no pretreatment; in the second phase, the patients were allowed to moisten the oral cavity before dosing; in the third phase, the patients were given pilocarpine hydrochloride (saliva stimulant) before dosing. Fentanyl concentrations were measured using a method of high-performance liquid chromatography with validated tandem mass spectrometric detection. The Tmax was longer, the Cmax was lower, the AUC0-30 lower, and the AUClast lower in the phase involving no pretreatment; the Tmax/Cmax/AUC0-30/AUClast were similar in the phase involving moistening of the oral cavity and the phase involving giving pilocarpine hydrochloride. The pharmacokinetics of the sublingual fentanyl orally disintegrating tablet appear to be negatively affected by the presence of salivary gland hypofunction, although the moistening of the oral cavity before dosing results in a pharmacokinetic profile similar to that seen with the giving of pilocarpine hydrochloride. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  13. Formulation and Evaluation of Fast-Disintegrating Sublingual Tablets of Atropine Sulfate: the Effect of Tablet Dimensions and Drug Load on Tablet Characteristics.

    Science.gov (United States)

    Aodah, Alhussain; Bafail, Rawan S; Rawas-Qalaji, Mutasem

    2017-07-01

    In this study, we formulated and evaluated the effects of tablet dimensions and drug load on the characteristics of atropine sulfate (AS) fast-disintegrating sublingual tablets (FDSTs). We aim to develop AS FDSTs as an alternative non-invasive and portable dosage form for the emergency treatment of organophosphate (OP) toxicity. AS autoinjector, AtroPen®, is the only self-administered dosage form available as an antidote for-out-of-hospital emergency use, but it is associated with several limitations and drawbacks. Seven FDST formulations of two tablet sizes, 150 mg (A) and 50 mg (B), and of several AS loads, 0 mg (A1, B1), 2 mg (A2, B2), 4 mg (B3), and 8 mg (B4a, B4b), were formulated and manufactured by direct compression. AS FDST characteristics were evaluated using USP and non-USP tests. Results were statistically compared at p < 0.05. All FDSTs passed the USP content uniformity and friability tests, disintegrated and released AS in ≤30 and 60 s. B1 and B2 were significantly harder than A1 and A2. Water uptake of A1 was significantly the highest. However, B1 and B2 had shorter disintegration and wetting times and higher amounts of AS dissolved than did A1 and A2 (p < 0.05). Increasing AS negatively affected FDST tensile strength (p < 0.05 for B4a) and water uptake (p < 0.05 for B3, B4a and B4b), however, without affecting AS dissolution. Formulation of AS up to 16% into smaller FDSTs was successful. Smaller FDSTs were harder and disintegrated more quickly. These AS FDSTS have the potential for further in vivo testing to evaluate their OP antidote potential.

  14. Role of Combining Peripheral with Sublingual Perfusion on Evaluating Microcirculation and Predicting Prognosis in Patients with Septic Shock.

    Science.gov (United States)

    Pan, Pan; Liu, Da-Wei; Su, Long-Xiang; He, Huai-Wu; Wang, Xiao-Ting; Yu, Chao

    2018-05-20

    Measurement of general microcirculation remains difficult in septic shock patients. The peripheral perfusion index (PI) and sublingual microcirculation monitoring are thought to be possible methods. This study was performed to determine whether assessing microcirculation by PI and a new parameter, proportion of perfusion vessel change rate (△PPV) from sublingual microcirculation monitoring, can be associated with patients' outcome. A prospective observational study was carried out, including 74 patients with septic shock in a mixed intensive care unit. Systemic hemodynamic variables were obtained at T0 and 6 h after (T6). PI and sublingual microcirculation indicators were obtained using a bedside monitor and a sidestream dark-field device, respectively. The t-test, analysis of variance, Mann-Whitney U-test, Kruskal-Wallis test, receiver operating characteristic curve analysis with the Hanley-McNeil test, survival curves using the Kaplan-Meier method, and the log-rank (Mantel-Cox) test were used to statistical analysis. Systemic hemodynamics and microcirculation data were obtained and analyzed. Patients were divided into two groups based on whether the first 6 h lactate clearance (LC) was ≥20%; PI and △PPV were lower at T6 in the LC <20% group compared with LC ≥20% (PI: 1.52 [0.89, 1.98] vs. 0.79 [0.44, 1,81], Z = -2.514, P = 0.012; △PPV: 5.9 ± 15.2 vs. 17.9 ± 20.0, t = -2.914, P = 0.005). The cutoff values of PI and △PPV were 1.41% and 12.1%, respectively. The cutoff value of the combined indicators was 1.379 according to logistic regression. Area under the curve demonstrated 0.709 (P < 0.05), and the sensitivity and specificity of using combined indicators were 0.622 and 0.757, respectively. Based on the PI and △PPV cutoff, all the participants were divided into the following groups: (1) high PI and high △PPV group, (2) high PI and low △PPV group, (3) low PI and high △PPV group, and (4) low PI and low △PPV group. The highest Sequential

  15. Buccal and sublingual vaccine delivery.

    Science.gov (United States)

    Kraan, Heleen; Vrieling, Hilde; Czerkinsky, Cecil; Jiskoot, Wim; Kersten, Gideon; Amorij, Jean-Pierre

    2014-09-28

    Because of their large surface area and immunological competence, mucosal tissues are attractive administration and target sites for vaccination. An important characteristic of mucosal vaccination is its ability to elicit local immune responses, which act against infection at the site of pathogen entry. However, mucosal surfaces are endowed with potent and sophisticated tolerance mechanisms to prevent the immune system from overreacting to the many environmental antigens. Hence, mucosal vaccination may suppress the immune system instead of induce a protective immune response. Therefore, mucosal adjuvants and/or special antigen delivery systems as well as appropriate dosage forms are required in order to develop potent mucosal vaccines. Whereas oral, nasal and pulmonary vaccine delivery strategies have been described extensively, the sublingual and buccal routes have received considerably less attention. In this review, the characteristics of and approaches for sublingual and buccal vaccine delivery are described and compared with other mucosal vaccine delivery sites. We discuss recent progress and highlight promising developments in the search for vaccine formulations, including adjuvants and suitable dosage forms, which are likely critical for designing a successful sublingual or buccal vaccine. Finally, we outline the challenges, hurdles to overcome and formulation issues relevant for sublingual or buccal vaccine delivery. Copyright © 2014. Published by Elsevier B.V.

  16. Sublingual Immunotherapy: Recent Advances

    Directory of Open Access Journals (Sweden)

    Enrico Compalati

    2013-01-01

    Full Text Available The practice of administering sublingual immunotherapy for respiratory allergy is gaining more and more diffusion worldwide as a consequence of the robust demonstration of clinical efficacy and safety provided by recent high-powered and well-designed studies, confirming for individual seasonal allergens the results of previous metanalyses in adult and pediatric populations. Preliminary evidence derives from recent rigorous trials on perennial allergens, like house dust mites, and specifically designed studies addressed the benefits on asthma. Emerging research suggests that SLIT may have a future role in other allergic conditions such as atopic dermatitis, food, latex and venom allergy. Efforts to develop a safer and more effective SLIT for inhalant allergens have led to the development of allergoids, recombinant allergens and formulations with adjuvants and substances targeting antigens to dendritic cells that possess a crucial role in initiating immune responses. The high degree of variation in the evaluation of clinical effects and immunological changes requires further studies to identify the candidate patients to SLIT and biomarkers of short and long term efficacy. Appropriate management strategies are urgently needed to overcome the barriers to SLIT compliance.

  17. Monoid sublingual immunotherapy.

    Science.gov (United States)

    Palma-Carlos, A G; Santos, A S; Branco-Ferreira, M; Pregal, A L; Palma-Carlos, M L

    2006-03-01

    Sublingual monoid immunotherapy with monomeric allergoids has been largely used in Europe in the last few years. An open trial of allergoid in tablets has been done in rhinitic patients allergic to house dust mites, grass pollens and Parietaria with clear improvement in clinics and drug consumption scores. In a second phase a double blind placebo controlled trial of grass pollens allergoids have been done in hay fever patients with significant decrease on the scores of rhinorrea, sneezing and conjunctivitis nasal steroid consumption and clinical score after serial nasal challenges. Monomeric allergoids are an efficace and safe immunotherapy in allergic rhinitis.

  18. Sublingual allergen immunotherapy

    DEFF Research Database (Denmark)

    Calderón, M A; Simons, F E R; Malling, Hans-Jørgen

    2012-01-01

    To cite this article: Calderón MA, Simons FER, Malling H-J, Lockey RF, Moingeon P, Demoly P. Sublingual allergen immunotherapy: mode of action and its relationship with the safety profile. Allergy 2012; 67: 302-311. ABSTRACT: Allergen immunotherapy reorients inappropriate immune responses......-presenting cells (mostly Langerhans and myeloid dendritic cells) exhibit a tolerogenic phenotype, despite constant exposure to danger signals from food and microbes. This reduces the induction of pro-inflammatory immune responses leading to systemic allergic reactions. Oral tissues contain relatively few mast...... cells and eosinophils (mostly located in submucosal areas) and, in comparison with subcutaneous tissue, are less likely to give rise to anaphylactic reactions. SLIT-associated immune responses include the induction of circulating, allergen-specific Th1 and regulatory CD4+ T cells, leading to clinical...

  19. Tumors of the sublingual gland

    DEFF Research Database (Denmark)

    Andreasen, Simon; Bjørndal, K; Agander, T K

    2016-01-01

    Tumors of the salivary glands are a heterogeneous group of diseases most often originating in the major salivary glands. Only a minor proportion of mainly malignant tumors arise in the sublingual gland. Due to the rarity of sublingual gland tumors (SGTs), little is known about the clinicopathologic...... are malignant, most frequently ACC with a high rate of metastatic spread. The diagnostic value of FNAC in SGTs seems inferior to what is found for other major salivary glands. DSS is determined by stage and T-stage and not by histopathological parameters. International collaboration is warranted to confirm...

  20. Sublingual piroxicam in migraine without aura.

    Science.gov (United States)

    Ravishankar, K; Tayade, Himanshu; Mandlik, Rahul

    2011-08-01

    The aim of the present study was to compare the analgesic efficacy of a single dose of sublingual piroxicam to that of a placebo during acute attacks of migraine without aura. The drug (N = 30) or a placebo (N = 30) was administered, on randomisation and double-blind basis, to 60 patients between 18 and 50 years of age suffering from migraine without aura. The patients were instructed to take a single tablet sublingually [corresponding to piroxicam 40 mg or placebo] and the severity of the painful symptomatology and associated symptoms were evaluated by this study. The patients treated with sublingual piroxicam showed a significant (P piroxicam administration. In 83.3%, the drug resulted in excellent to good response as compared to only 10% in the placebo group. No local and systemic side effects were reported with sublingual piroxicam. The present study has demonstrated that for the acute management of migraine without aura sublingual piroxicam showed significant analgesic effect with excellent tolerability.

  1. Development of a new formulation combining calcipotriol and betamethasone dipropionate in an ointment vehicle

    DEFF Research Database (Denmark)

    Simonsen, Lene; Høy, Gert; Didriksen, Erik

    2004-01-01

    was to develop a formulation which combines calcipotriol and betamethasone dipropionate in a single vehicle hereby achieving optimal delivery of both substances into the skin. As the two substances are incompatible in aqueous and alcoholic medias, different non-aqueous formulations were prepared. Skin permeation...

  2. Combined Helmholtz Integral Equation - Fourier series formulation of acoustical radiation and scattering problems

    CSIR Research Space (South Africa)

    Fedotov, I

    2006-07-01

    Full Text Available The Combined Helmholtz Integral Equation – Fourier series Formulation (CHIEFF) is based on representation of a velocity potential in terms of Fourier series and finding the Fourier coefficients of this expansion. The solution could be substantially...

  3. Development of midazolam sublingual tablets: in vitro study.

    Science.gov (United States)

    Odou, P; Barthelemy, C; Robert, H

    1998-01-01

    Midazolam is a benzodiazepine with short elimination half-life, used as induction or continuous agent for general anesthesia. At present, only injectable solution is available from French hospital pharmacies. The aim of the study is the development of 5 mg midazolam sublingual tablets to realize a short general anesthesia without intravenous or intramuscular injection. Incorporation of citric acid in the tablet formulation leads to an increase of dissolution rates of active drug, but a decrease of diffusion through lipid membranes is observed with 10 mg of citric acid when using the Dibbern's Resomat three phases apparatus. One explanation of this result is that midazolam (pKa = 6.1) in presence of 10 mg of citric acid is ionised. The ionised form, more hydrophilic, cannot cross the artificial lipid membrane and therefore the diffusion decreases. On the other hand, the decrease of diffusion's rate, when pH increases, is explained by the precipitation of midazolam at pH higher than 6. A compromise between dissolution and diffusion results leads us to choose the sublingual formulation containing 5 mg of citric acid per tablet.

  4. Biopharmaceutical evaluation of transnasal, sublingual, and buccal disk dosage forms of butorphanol.

    Science.gov (United States)

    Shyu, W C; Mayol, R F; Pfeffer, M; Pittman, K A; Gammans, R E; Barbhaiya, R H

    1993-07-01

    A series of three-way crossover randomized studies were conducted to evaluate the absolute bioavailability of butorphanol, a potent agonist-antagonist analgesic, from transnasal, sublingual, and buccal disk formulations in order to identify a practical alternative to oral administration. In each study, healthy male volunteers received 2 mg doses of butorphanol tartrate intravenously and either transnasally, sublingually or buccally. Serial blood samples were collected over 12 h and butorphanol plasma concentrations were determined by radioimmunoassay. The plasma concentration data were subjected to non-compartmental pharmacokinetic analysis. The elimination half-life of butorphanol was about 3-5 h and was independent of the route of administration. Absorption of butorphanol following transnasal administration was faster than that observed following sublingual or buccal administration. Mean absolute bioavailabilities of sublingual tablet and buccal disk formulation were only 19 per cent and 29 per cent, respectively, but for transnasal administration the value rose significantly, to 70 per cent. Based on the results of these studies, transnasal dosage form of butorphanol was selected for further clinical trials of treatment of moderate to severe pain.

  5. Development and evaluation of a sublingual film of the antiemetic granisetron hydrochloride.

    Science.gov (United States)

    Kalia, Vani; Garg, Tarun; Rath, Gautam; Goyal, Amit Kumar

    2016-05-01

    The objective of this study was to develop an oral transmucosal formulation of an antiemetic drug that can not only serve in the active form but also provide a controlled release profile. In this study, sublingual films based on the biodegradable and water-soluble polymers, that is HPMCK-4M and PVPK-30, were developed by the solvent casting method, and were loaded with the antiemetic drug granisetron hydrochloride (granisetron HCl). The entrapment efficiency of the developed formulation was found to be 86%. The in vitro profile showed an instant release of the drug from the sublingual film, in a pattern following the first order kinetics array. The in vivo studies showed that granisetron HCl was delivered in its active state and showed effective results, as compared to its activity in the marketed formulation.

  6. Intranasal and sublingual delivery of inactivated polio vaccine.

    Science.gov (United States)

    Kraan, Heleen; Soema, Peter; Amorij, Jean-Pierre; Kersten, Gideon

    2017-05-09

    Polio is on the brink of eradication. Improved inactivated polio vaccines (IPV) are needed towards complete eradication and for the use in the period thereafter. Vaccination via mucosal surfaces has important potential advantages over intramuscular injection using conventional needle and syringe, the currently used delivery method for IPV. One of them is the ability to induce both serum and mucosal immune responses: the latter may provide protection at the port of virus entry. The current study evaluated the possibilities of polio vaccination via mucosal surfaces using IPV based on attenuated Sabin strains. Mice received three immunizations with trivalent sIPV via intramuscular injection, or via the intranasal or sublingual route. The need of an adjuvant for the mucosal routes was investigated as well, by testing sIPV in combination with the mucosal adjuvant cholera toxin. Both intranasal and sublingual sIPV immunization induced systemic polio-specific serum IgG in mice that were functional as measured by poliovirus neutralization. Intranasal administration of sIPV plus adjuvant induced significant higher systemic poliovirus type 3 neutralizing antibody titers than sIPV delivered via the intramuscular route. Moreover, mucosal sIPV delivery elicited polio-specific IgA titers at different mucosal sites (IgA in saliva, fecal extracts and intestinal tissue) and IgA-producing B-cells in the spleen, where conventional intramuscular vaccination was unable to do so. However, it is likely that a mucosal adjuvant is required for sublingual vaccination. Further research on polio vaccination via sublingual mucosal route should include the search for safe and effective adjuvants, and the development of novel oral dosage forms that improve antigen uptake by oral mucosa, thereby increasing vaccine immunogenicity. This study indicates that both the intranasal and sublingual routes might be valuable approaches for use in routine vaccination or outbreak control in the period after

  7. Benefits of Combinations of Vitamin A, C and E Derivatives in the Stability of Cosmetic Formulations

    Directory of Open Access Journals (Sweden)

    Patrícia Maria Berardo Gonçalves Maia Campos

    2012-02-01

    Full Text Available Chemically stable ester derivatives of vitamins A, C and E have become a focus of interest for their role in the satisfactory results in skin aging treatments. Accordingly, the aim of this study was to evaluate the physical and chemical stability of a cosmetic formulation containing 1% retinyl palmitate, ascorbyl tetraisopalmitate and tocopheryl acetate, alone or in combination. In the studies of physical stability, a Brookfield rheometer was used to determine rheological behavior of formulations containing the vitamins. Chemical stability was determined by HPLC on a Shimadzu system with UV detection. Results showed that formulations had pseudoplastic behavior and that vitamins did not alter their apparent viscosity and thixotropy. In the chemical stability studies, first-order reaction equations were used for determinations of the shelf-life of vitamins derivatives considering a remaining concentration of 85%. Combined vitamins in a single formulation had a slightly lower degradation rate as compared to different preparations containing only one of the vitamins. Considering that many cosmetic formulations contain vitamin combinations it is suggested that the present study may contribute to the development of more stable formulations containing liposoluble vitamins.

  8. Benefits of combinations of vitamin A, C and E derivatives in the stability of cosmetic formulations.

    Science.gov (United States)

    Gianeti, Mirela Donato; Gaspar, Lorena Rigo; Camargo, Flávio Bueno de; Campos, Patrícia Maria Berardo Gonçalves Maia

    2012-02-22

    Chemically stable ester derivatives of vitamins A, C and E have become a focus of interest for their role in the satisfactory results in skin aging treatments. Accordingly, the aim of this study was to evaluate the physical and chemical stability of a cosmetic formulation containing 1% retinyl palmitate, ascorbyl tetraisopalmitate and tocopheryl acetate, alone or in combination. In the studies of physical stability, a Brookfield rheometer was used to determine rheological behavior of formulations containing the vitamins. Chemical stability was determined by HPLC on a Shimadzu system with UV detection. Results showed that formulations had pseudoplastic behavior and that vitamins did not alter their apparent viscosity and thixotropy. In the chemical stability studies, first-order reaction equations were used for determinations of the shelf-life of vitamins derivatives considering a remaining concentration of 85%. Combined vitamins in a single formulation had a slightly lower degradation rate as compared to different preparations containing only one of the vitamins. Considering that many cosmetic formulations contain vitamin combinations it is suggested that the present study may contribute to the development of more stable formulations containing liposoluble vitamins.

  9. Investigation of dielectric properties of different cake formulations during microwave and infrared-microwave combination baking.

    Science.gov (United States)

    Sakiyan, Ozge; Sumnu, Gulum; Sahin, Serpil; Meda, Venkatesh

    2007-05-01

    Dielectric properties can be used to understand the behavior of food materials during microwave processing. Dielectric properties influence the level of interaction between food and high frequency electromagnetic energy. Dielectric properties are, therefore, important in the design of foods intended for microwave preparation. In this study, it was aimed to determine the variation of dielectric properties of different cake formulations during baking in microwave and infrared-microwave combination oven. In addition, the effects of formulation and temperature on dielectric properties of cake batter were examined. Dielectric constant and loss factor of cake samples were shown to be dependent on formulation, baking time, and temperature. The increase in baking time and temperature decreased dielectric constant and loss factor of all formulations. Fat content was shown to increase dielectric constant and loss factor of cakes.

  10. Tinnitus after administration of sublingual immunotherapy

    DEFF Research Database (Denmark)

    Juel, Jacob

    2017-01-01

    , for example, itching, swelling, irritation, ulceration of the oropharynx and nausea, abdominal pain, diarrhoea, and vomiting. More severe side effects are dominated by systemic and respiratory tract manifestations. RESULTS: In this clinical case, the author reports a right-sided transient tinnitus lasting...... for 48 h after administration of sublingual immunotherapy for house dust mite in allergic rhinitis. CONCLUSIONS: This case provide important insights for clinical practice, as tinnitus has not been previously reported as a side effect of sublingual immunotherapy with house dust mite allergens....

  11. Sublingual immunotherapy in children with allergic rhinitis : quality of systematic reviews

    NARCIS (Netherlands)

    de Bot, Cindy M. A.; Moed, Heleen; Berger, Marjolein Y.; Roeder, Esther; van Wijk, Roy G.; van der Wouden, Johannes C.

    Systematic reviews have gained popularity as a way to combine the increasing amount of research information. This study assessed the quality of systematic reviews and meta-analyses of sublingual immunotherapy (SLIT) for allergic rhinitis in children, published since 2000. Eligible reviews were

  12. A New Formulation for the Combined Maritime Fleet Deployment and Inventory Management Problem

    OpenAIRE

    Dong, Bo; Bektas, Tolga; Chandra, Saurabh; Christiansen, Marielle; Fagerholt, Kjetil

    2017-01-01

    This paper addresses the fleet deployment problem and in particular the treatment of inventory in the maritime case. A new model based on time-continuous formulation for the combined maritime fleet deployment and inventory management problem in Roll-on Roll-off shipping is presented. Tests based on realistic data from the Ro-Ro business show that the model yields good solutions to the combined problem within reasonable time.

  13. Poly (amidoamine) dendrimer-mediated hybrid formulation for combination therapy of ramipril and hydrochlorothiazide.

    Science.gov (United States)

    Singh, Mayank Kumar; Pooja, Deep; Kulhari, Hitesh; Jain, Sanjay Kumar; Sistla, Ramakrishna; Chauhan, Abhay Singh

    2017-01-01

    We present a dendrimer-based hybrid formulation strategy to explore the potential of poly (amidoamine) PAMAM dendrimers to be used as drug carriers for combination therapy of an anti-hypertensive drug ramipril (RAPL) and a diuretic hydrochlorothiazide (HCTZ). The drug-dendrimer complexes were prepared by phase-equilibration method. The results showed that the solubility of RAPL and HCTZ was dependent on dendrimer concentration and pH of dendrimer solution. The solubility profile of both RAPL and HCTZ dendrimer complexes illustrated a non-linear relationship with dendrimer concentration. At 0.8% (w/v) dendrimer concentration, solubility of RAPL was increased 4.91 folds with amine-terminated while for HCTZ, solubility enhancement was highest (3.72 folds) with carboxy-terminated. The complexes were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance analysis and high performance liquid chromatography. In-vitro drug dissolution performance of pure drugs, individual drug loaded dendrimer formulations and hybrid formulations was studied in USP dissolution medium (pH7.0) and in simulated gastric fluid (pH1.2). Dendrimer mediated formulations showed faster and complete dissolution compared to pure RAPL or HCTZ. Surprisingly, similar pattern of dissolution profile was established with hybrid formulations as compared to individual drug loaded dendrimers. The dendrimer-based hybrid formulations were found to be stable at dark and refrigerated conditions up to 5weeks. Conclusively, the proposed formulation strategy establishes a novel multitasking platform using dendrimer for simultaneous loading and delivery of multiple drugs for pharmaceutical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Evaluation of alternative Plutella xylostella control by two Isaria fumosorosea conidial formulations - oil-based formulation and wettable powder - combined with Bacillus thuringiensis.

    Science.gov (United States)

    Nian, Xiao-Ge; He, Yu-Rong; Lu, Li-Hua; Zhao, Rui

    2015-12-01

    Entomopathogenic fungi are potential candidates for controlling the diamondback moth Plutella xylostella (L.) (Lepidoptera: Plutellidae). The control efficacy of two Isaria fumosorosea conidial formulations - wettable powder and oil-based formulation - combined with Bacillus thuringiensis against P. xylostella was tested. In the laboratory, the combined application of two pathogens increased larval mortality either in an additive or a synergistic way. P. xylostella larvae treated with oil-based formulation died sooner than larvae infected with wettable powder. For pot and field experiments, each formulation was applied alone or combined with B. thuringiensis 668 µg mL(-1) , and then larval mortality, pupation rate, adult emergence rate, female longevity and fecundity were recorded. In pot experiments there was no evidence of any antagonistic effects between the two pathogens. Combined application of B. thuringiensis and a high concentration of the two I. fumosorosea formulations resulted in higher mortality (84.4 and 86.2%) with minimum pupation (15.6 and 11.9%) and adult emergence rates (8.7 and 7.0%). Female longevity and fecundity were significantly reduced by the two formulations at high concentration compared with the control. Similar results were also observed in field experiments. The combined application of I. fumosorosea and B. thuringiensis is a promising alternative strategy for P. xylostella control. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  15. Prevention of postpartum haemorrhage with sublingual misoprostol or oxytocin: a double-blind randomised controlled trial.

    Science.gov (United States)

    Bellad, M B; Tara, D; Ganachari, M S; Mallapur, M D; Goudar, S S; Kodkany, B S; Sloan, N L; Derman, R

    2012-07-01

    Sublingual misoprostol produces a rapid peak concentration, and is more effective than oral administration. We compared the postpartum measured blood loss with 400 μg powdered sublingual misoprostol and after standard care using 10 iu intramuscular (IM) oxytocin. Double-blind randomised controlled trial. A teaching hospital: J N Medical College, Belgaum, India. A cohort of 652 consenting eligible pregnant women admitted to the labour room. Subjects were assigned to receive the study medications and placebos within 1 minute of clamping and cutting the cord by computer-generated randomisation. Chi-square and bootstrapped Student's t-tests were used to test categorical and continuous outcomes, respectively. Measured mean postpartum blood loss and haemorrhage (PPH, loss ≥ 500 ml), >10% pre- to post-partum decline in haemoglobin, and reported side effects. The mean blood loss with sublingual misoprostol was 192 ± 124 ml (n=321) and 366 ± 136 ml with oxytocin IM (n=331, P ≤ 0.001). The incidence of PPH was 3.1% with misoprostol and 9.1% with oxytocin (P=0.002). No woman lost ≥ 1000 ml of blood. We observed that 9.7% and 45.6% of women experienced a haemoglobin decline of >10% after receiving misoprostol and oxytocin, respectively (P ≤ 0.001). Side effects were significantly greater in the misoprostol group than in the oxytocin group. Unlike other studies, this trial found sublingual misoprostol more effective than intramuscular oxytocin in reducing PPH, with only transient side effects being greater in the misoprostol group. The sublingual mode and/or powdered formulation may increase the effectiveness of misoprostol, and render it superior to injectable oxytocin for the prevention of PPH. Further research is needed to confirm these results. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.

  16. Sublingual fast dissolving niosomal films for enhanced bioavailability and prolonged effect of metoprolol tartrate

    Directory of Open Access Journals (Sweden)

    Allam A

    2016-08-01

    Full Text Available Ayat Allam, Gihan Fetih Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt Abstract: The aim of the present work was to prepare and evaluate sublingual fast dissolving films containing metoprolol tartrate-loaded niosomes. Niosomes were utilized to allow for prolonged release of the drug, whereas the films were used to increase the drug’s bioavailability via the sublingual route. Niosomes were prepared using span 60 and cholesterol at different drug to surfactant ratios. The niosomes were characterized for size, zeta-potential, and entrapment efficiency. The selected niosomal formulation was incorporated into polymeric films using hydroxypropyl methyl cellulose E15 and methyl cellulose as film-forming polymers and Avicel as superdisintegrant. The physical characteristics (appearance, texture, pH, uniformity of weight and thickness, disintegration time, and palatability of the prepared films were studied, in addition to evaluating the in vitro drug release, stability, and in vivo pharmacokinetics in rabbits. The release of the drug from the medicated film was fast (99.9% of the drug was released within 30 minutes, while the drug loaded into the niosomes, either incorporated into the film or not, showed only 22.85% drug release within the same time. The selected sublingual film showed significantly higher rate of drug absorption and higher drug plasma levels compared with that of commercial oral tablet. The plasma levels remained detectable for 24 hours following sublingual administration, compared with only 12 hours after administration of the oral tablet. In addition, the absolute bioavailability of the drug (ie, relative to intravenous administration following sublingual administration was found to be significantly higher (91.06%±13.28%, as compared with that after oral tablet administration (39.37%±11.4%. These results indicate that the fast dissolving niosomal film could be a promising delivery system to

  17. Sublingual fast dissolving niosomal films for enhanced bioavailability and prolonged effect of metoprolol tartrate.

    Science.gov (United States)

    Allam, Ayat; Fetih, Gihan

    2016-01-01

    The aim of the present work was to prepare and evaluate sublingual fast dissolving films containing metoprolol tartrate-loaded niosomes. Niosomes were utilized to allow for prolonged release of the drug, whereas the films were used to increase the drug's bioavailability via the sublingual route. Niosomes were prepared using span 60 and cholesterol at different drug to surfactant ratios. The niosomes were characterized for size, zeta-potential, and entrapment efficiency. The selected niosomal formulation was incorporated into polymeric films using hydroxypropyl methyl cellulose E15 and methyl cellulose as film-forming polymers and Avicel as superdisintegrant. The physical characteristics (appearance, texture, pH, uniformity of weight and thickness, disintegration time, and palatability) of the prepared films were studied, in addition to evaluating the in vitro drug release, stability, and in vivo pharmacokinetics in rabbits. The release of the drug from the medicated film was fast (99.9% of the drug was released within 30 minutes), while the drug loaded into the niosomes, either incorporated into the film or not, showed only 22.85% drug release within the same time. The selected sublingual film showed significantly higher rate of drug absorption and higher drug plasma levels compared with that of commercial oral tablet. The plasma levels remained detectable for 24 hours following sublingual administration, compared with only 12 hours after administration of the oral tablet. In addition, the absolute bioavailability of the drug (ie, relative to intravenous administration) following sublingual administration was found to be significantly higher (91.06%±13.28%), as compared with that after oral tablet administration (39.37%±11.4%). These results indicate that the fast dissolving niosomal film could be a promising delivery system to enhance the bioavailability and prolong the therapeutic effect of metoprolol tartrate.

  18. Microemulsion Formulation of Combination of Virgin Coconut Oil and Rice Bran Oil for Hair Growth

    Directory of Open Access Journals (Sweden)

    Wira Noviana Suhery

    2018-04-01

    Full Text Available Research on micro emulsion formulation of combination of virgin coconut oil (VCO and rice bran oil (RBO as a hair growth promoter has been done. The purpose of this study was to formulate and produce the best formula that is physically stable and optimally promoting the hair growth by varying the content of VCO and RBO in the form of micro emulsions. These dosage formulations were prepared in three formulas using 45% tween 80 as surfactants and 20% glycerin as co surfactant i.e.: F,I containing a combination of VCO and RBO 1:1; FII (1:2 and FIII (2:1. Physical evaluation of the preparation was carried out for 8 weeks of storage which included organoleptic examination, pH, homogeneity, density, globule particle size, phase freeze thaw, and rabbit hair growth activity test for 18 days. Based on the results of the evaluation, it was found that the FI, FII and FIII micro emulsion formulations were physically stable for 8 weeks of storage with a pH ranging from 6.7 to 7.0, density of 1.085-1.088 g/mL, average globul particle size of FI (34.6 nm , FII (54 nm and FIII (68.8 nm. The best formulas is FIII for hair growth length of 1.26 cm for 18 days.

  19. Problem formulation for risk assessment of combined exposures to chemicals and other stressors in humans.

    Science.gov (United States)

    Solomon, Keith R; Wilks, Martin F; Bachman, Ammie; Boobis, Alan; Moretto, Angelo; Pastoor, Timothy P; Phillips, Richard; Embry, Michelle R

    2016-11-01

    When the human health risk assessment/risk management paradigm was developed, it did not explicitly include a "problem formulation" phase. The concept of problem formulation was first introduced in the context of ecological risk assessment (ERA) for the pragmatic reason to constrain and focus ERAs on the key questions. However, this need also exists for human health risk assessment, particularly for cumulative risk assessment (CRA), because of its complexity. CRA encompasses the combined threats to health from exposure via all relevant routes to multiple stressors, including biological, chemical, physical and psychosocial stressors. As part of the HESI Risk Assessment in the 21st Century (RISK21) Project, a framework for CRA was developed in which problem formulation plays a critical role. The focus of this effort is primarily on a chemical CRA (i.e., two or more chemicals) with subsequent consideration of non-chemical stressors, defined as "modulating factors" (ModFs). Problem formulation is a systematic approach that identifies all factors critical to a specific risk assessment and considers the purpose of the assessment, scope and depth of the necessary analysis, analytical approach, available resources and outcomes, and overall risk management goal. There are numerous considerations that are specific to multiple stressors, and proper problem formulation can help to focus a CRA to the key factors in order to optimize resources. As part of the problem formulation, conceptual models for exposures and responses can be developed that address these factors, such as temporal relationships between stressors and consideration of the appropriate ModFs.

  20. Fast-Acting Sublingual Zolpidem for Middle-of-the-Night Wakefulness

    Directory of Open Access Journals (Sweden)

    Joseph V. Pergolizzi

    2014-01-01

    Full Text Available Sleep disorders (somnipathies are conditions characterized by disruptions of sleep quality or of sleep pattern. They can involve difficulty falling asleep (prolonged sleep onset latency, difficulty staying asleep (disturbance of sleep maintenance, sleep of poor quality (unrefreshing, or combinations of these and can lead to poor health and quality of life problems. A subtype of sleep-maintenance insomnia is middle-of-the-night wakefulness, a relatively common occurrence. Zolpidem, a nonbenzodiazepine benzodiazepine receptor agonist, allosterically modulates an ion channel and increases the influx of Cl−, thereby dampening the effect of excitatory (sleep disrupting input. Recently, product label changes to some zolpidem containing products have been implemented by the FDA in order to reduce the risk associated with their morning after residual side effects. A new formulation of zolpidem tartrate (Intermezzo sublingual tablet, an approved product indicated exclusively for the treatment of middle-of-the-night wakefulness and difficulty returning to sleep, did not have its label changed. We present a short summary of its basic science and clinical attributes in light of the recent regulatory changes for zolpidem products.

  1. Forecasting of development of acute poisonings in agricultural workers while using combined formulations based on difenoconazole

    Directory of Open Access Journals (Sweden)

    Stavnichenko P.V.

    2017-10-01

    Full Text Available In the general structure of occupational diseases, a large proportion belongs to acute poisoning with pesticides (mainly group cases. However, today it is impossible to drop the use of pesticides in agriculture. Their application ensures high biological and economic efficiency of the latter, reduces losses of the yield. The purpose of the work was to predict the possibility of acute toxic effects in agricultural workers when working with combined formulations based on difenoconazole. Materials and methods. To assess the influence on the organism of the workers of the above-mentioned substances and formulations on their basis, the coefficient of inhalation poisoning possibility (CIPP, the coefficient of selective action of the pesticide in inhalation effect (CSAing and the selective action of the pesticide in the dermal effect (CSAderm were calculated. Results. Calculated values of CSAing (103.4-4701.2 and CSAderm (237.4-12345.7 for all investigated active substances were more than 100, this indicates to a rather high selectivity of their action. By the CSAing value formulations Celeste Top, Celeste Trio, Dinali, Cydeli Top belong to pesticides with a relatively low selectivity of action when they are inhaled by workers in the process of crops treating, the remaining formulations have a sufficient selectivity of action in inhalation intake. In addition, it should be noted that in general, for all combined preparations CSA values are significantly lower than for separate active ingredients, in addition to the above assumption, can be explained by the presence of other formulants in the preparation that may have not significant but toxic effect on the body of workers. All investigated substances in the probability of occurrence of acute poisoning with the use of combined preparations on their basis are related to the 4th grade of danger according to State Standards 8.8.1.002-98. There was proved relative safety in case of penetration into the

  2. Fixed-dose combinations of drugs versus single-drug formulations for treating pulmonary tuberculosis

    Science.gov (United States)

    Gallardo, Carmen R; Rigau Comas, David; Valderrama Rodríguez, Angélica; Roqué i Figuls, Marta; Parker, Lucy Anne; Caylà, Joan; Bonfill Cosp, Xavier

    2016-01-01

    Background People who are newly diagnosed with pulmonary tuberculosis (TB) typically receive a standard first-line treatment regimen that consists of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampicin. Fixed-dose combinations (FDCs) of these drugs are widely recommended. Objectives To compare the efficacy, safety, and acceptability of anti-tuberculosis regimens given as fixed-dose combinations compared to single-drug formulations for treating people with newly diagnosed pulmonary tuberculosis. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library, Issue 11 2015); MEDLINE (1966 to 20 November 2015); EMBASE (1980 to 20 November 2015); LILACS (1982 to 20 November 2015); the metaRegister of Controlled Trials; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), without language restrictions, up to 20 November 2015. Selection criteria Randomized controlled trials that compared the use of FDCs with single-drug formulations in adults (aged 15 years or more) newly diagnosed with pulmonary TB. Data collection and analysis Two review authors independently assessed studies for inclusion, and assessed the risk of bias and extracted data from the included trials. We used risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with 95% confidence intervals (CIs). We attempted to assess the effect of treatment for time-to-event measures with hazard ratios and their 95% CIs. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used the fixed-effect model when there was little heterogeneity and the random-effects model with moderate heterogeneity. We used an I² statistic value of 75% or greater to denote significant heterogeneity, in which case we did not perform a

  3. Immunity of foot-and-mouth disease serotype Asia 1 by sublingual vaccination.

    Directory of Open Access Journals (Sweden)

    Hao-tai Chen

    Full Text Available Foot-and-mouth disease virus (FMDV causes vesicular disease of cloven-hoofed animals, with severe agricultural and economic losses. Here we present study using a sublingual (SL route with the killed serotype Asia 1 FMDV vaccine. Guinea pigs were vaccinated using a commercially available vaccine formulation at the manufacturer's recommended full, 1/4, and 1/16 antigen doses. Animals were challenged with homologous FMDV Asia1 strain at various times following vaccination. All control guinea pigs exhibited clinical disease, including fever, viremia, and lesions, specifically vesicle formation in feet. Animals vaccinated with the 1/16 and 1/4 doses were protected after challenge at days 7, 28, and 35 post vaccination. These data suggest that effective protection against foot-and-mouth disease can be achieved with 1/16 of the recommended vaccine dose using SL vaccination, indicating that the sublingual route is an attractive alternative for the administration of the FMDV vaccine.

  4. A randomized trial of rectal indomethacin and sublingual nitrates to prevent post-ERCP pancreatitis.

    Science.gov (United States)

    Sotoudehmanesh, Rasoul; Eloubeidi, Mohamad Ali; Asgari, Ali Ali; Farsinejad, Maryam; Khatibian, Morteza

    2014-06-01

    Acute pancreatitis is the most common adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Recent data suggest that indomethacin can reduce the risk of post-ERCP pancreatitis (PEP) in high-risk individuals. However, whether the combination of indomethacin and sublingual nitrates is superior to indomethacin alone is unknown. Therefore, we aimed to evaluate the efficacy of rectally administered indomethacin plus sublingual nitrate compared with indomethacin alone to prevent PEP. During a 17-month period, all eligible patients who underwent ERCP were enrolled in this study. We excluded patients who had undergone a prior endoscopic sphincterotomy. In a double-blind controlled randomized trial, patients received a suppository containing 100 mg of indomethacin, plus 5 mg of sublingual nitrate (group A), or a suppository containing 100 mg of indomethacin, plus sublingual placebo (group B), before ERCP. Serum amylase levels and clinically pertinent evaluations were measured in all patients after ERCP. Of the 300 enrolled patients, 150 received indomethacin plus nitrate. Thirty-three patients developed pancreatitis: 10 (6.7%) in group A and 23 (15.3%) in group B (P=0.016, risk ratio=0.39, 95% confidence intervals (CI): 0.18-0.86). More than 80% of the patients were at high risk of developing pancreatitis after ERCP. Absolute risk reduction, relative risk reduction, and number needed to treat for the prevention of PEP were 8.6% (95% CI: 4.7-14.5), 56.2% (95% CI: 50.6-60.8), and 12 (95% CI: 7-22), respectively. Combination of rectal indomethacin and sublingual nitrate given before ERCP was significantly more likely to reduce the incidence of PEP than indomethacin suppository alone. Multicenter trials to confirm these promising findings are needed.

  5. Orally-dissolving film for sublingual and buccal delivery of ropinirole.

    Science.gov (United States)

    Lai, Ka Lun; Fang, Yuan; Han, Hao; Li, Qingqing; Zhang, Shuai; Li, Ho Yin; Chow, Shing Fung; Lam, Tai Ning; Lee, Wai Yip Thomas

    2018-03-01

    Ropinirole is a very important treatment option for Parkinson's disease (PD), a major threat to the aging population. However, this drug undergoes extensive first-pass metabolism, resulting in a low oral bioavailability. Moreover, the necessity of frequent administration due to the short half-life of ropinirole may jeopardize patient compliance. Indeed, taking this drug in solid oral dosage forms (e.g. Tablet) can be a challenge because of the tremor, rigidity, limited mobility, and impaired drug absorption experienced by PD patients. In light of these, there is a pressing need to devise formulations for the delivery of ropinirole that allow simple and easy administration and fast drug action, as well as avoidance of first-pass metabolism and overcoming the challenge of impaired absorption due to gastrointestinal dysfunctions, etc. Herein, we seek to overcome all these challenges via sublingual or buccal delivery of orally-dissolving films. Accordingly, we aimed to fabricate and characterize orally-dissolving films of ropinirole and assess their in vivo pharmacokinetics after sublingual and buccal administration. The ropinirole oral film was non-toxic and exhibited fast disintegration and dissolution and was physically stable for at least 28 days. Upon buccal/sublingual administration of the oral films, ropinirole reached the systemic circulation within 15 min and bioavailability was significantly improved, which may be attributable to avoidance of first-pass metabolism via absorption through the oral cavity. In conclusion, our ropinirole oral film improved bioavailability after sublingual or buccal administration. This formulation potentially overcomes biopharmaceutical challenges and provide a convenient means of administration of ropinirole or other anti-PD drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. High resolution sonography of sublingual space

    International Nuclear Information System (INIS)

    Jain, P.

    2008-01-01

    Full text: Ultrasound examination of the sublingual region is a non-invasive, safe, inexpensive and widely available procedure, unaffected by the amalgam in teeth which is a source of considerable artefact on CT and MRI images. With a little practice and good understanding of the anatomy, ultrasound can be a very helpful primary examination. If the lesion is clearly seen, no further imaging may be required.

  7. Improved efficacy of cisplatin in combination with a nano-formulation of pentacyclic triterpenediol

    Energy Technology Data Exchange (ETDEWEB)

    Alam, Noor [Formulation & Drug Delivery Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001 (India); Qayum, Arem; Kumar, Ashok [Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110001 (India); Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001 (India); Khare, Vaibhav [Formulation & Drug Delivery Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001 (India); Sharma, Parduman Raj [Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001 (India); Andotra, Samar Singh [Natural Product Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001 (India); Singh, Shashank K. [Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110001 (India); Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001 (India); Koul, Surinder, E-mail: skoul@iiim.ac.in [Natural Product Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001 (India); Gupta, Prem N., E-mail: pngupta10@gmail.com [Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110001 (India); Formulation & Drug Delivery Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001 (India)

    2016-11-01

    Cisplatin is widely used for the treatment of various cancers including cervical, ovarian, lung and head and neck, however, its clinical success is limited owing to the dose-dependent adverse effects, mainly nephrotoxicity and neurotoxicity. In order to address this limitation, the present study was undertaken to investigate growth inhibitory effect of cisplatin in combination with a triterpenediol (3a, 24-dihydroxyurs-12-ene and 3a, 24-dihydroxyolean-12-ene, TPD) on human ovarian cancer cell line. Poly(dl-lactic-co-glycolic) acid nanoparticles loaded with TPD (TPD-PLGA-NPs) were successfully developed by emulsion solvent evaporation method. The TPD-PLGA-NPs were characterized for size distribution and zeta potential which was in order of 152.56 ± 3.01 nm and − 17.36 ± 0.37 mV respectively. The morphological evaluation was carried out by transmission electron microscopy and the formulation was also characterized using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The drug loading of the optimized formulation was 51.03 ± 1.52 μg/mg and the formulation exhibited sustained drug release profile. The in vitro cellular uptake study of coumarin-6 loaded PLGA nanoparticles in OVCAR-5 cells demonstrated a time dependent increase in uptake efficiency. Further, growth inhibitory effect of cisplatin was investigated in combination with TPD-PLGA-NPs. The combination index (CI) was < 1, indicating a synergistic interaction. Further, at 75% of cell growth inhibition (ED{sub 75}) the dose of cisplatin was reduced to 3.8 folds using this combination. The results indicated the potential of cisplatin and TPD-PLGA-NPs combination in order to reduce to dose limiting toxicities of the former. - Highlights: • TPD nanoparticles showed a time dependent increase in cellular uptake efficiency. • TPD nanoparticles showed synergistic interaction between cisplatin. • The dose of cisplatin was reduced to 3.8 folds using this combination

  8. Bioequivalence Studies of a Reformulated Dutasteride and Tamsulosin Hydrochloride Combination Capsule and a Commercially Available Formulation.

    Science.gov (United States)

    Kurczewski, Renee; Bowen, Chet; Collins, David; Zhu, John; Serbest, Gulyeter; Manyak, Michael

    2017-09-01

    A dutasteride 0.5 mg and tamsulosin hydrochloride 0.4 mg combination (DTC) capsule (Duodart ® ) was reformulated to reduce the capsule size and enhance product stability. Bioequivalence of the reformulated DTC capsule with the commercial formulation was evaluated in 2 single-dose, open-label, randomized, 2-way crossover studies in healthy adult male volunteers. Subjects in a fasted or fed state received a single oral dose of either the reformulated DTC or the commercial formulation followed by a 28-day washout period between treatments. Blood samples were taken predose and up to 72 hours postdose for pharmacokinetic (PK) analysis of dutasteride and tamsulosin serum concentrations. From the serum concentration-vs-time data, a noncompartmental method was used to calculate the maximum observed serum concentration (C max ) and area under the serum concentration-time curve (AUC 0-t ) for dutasteride and tamsulosin, and AUC 0-∞ for tamsulosin. The 90% confidence intervals for the ratios of the C max and AUC 0-t (for dutasteride and tamsulosin) and for AUC 0-∞ (for tamsulosin) were all completely contained within the range of 80% to 125%; therefore, the reformulated DTC capsule is bioequivalent to the commercial formulation under both fed and fasted states. © 2017, The American College of Clinical Pharmacology.

  9. Formulation and characterization of polymeric films containing combinations of antiretrovirals (ARVs) for HIV prevention.

    Science.gov (United States)

    Akil, Ayman; Agashe, Hrushikesh; Dezzutti, Charlene S; Moncla, Bernard J; Hillier, Sharon L; Devlin, Brid; Shi, Yuan; Uranker, Kevin; Rohan, Lisa Cencia

    2015-02-01

    To develop polymeric films containing dual combinations of anti-HIV drug candidate tenofovir, maraviroc and dapivirine for vaginal application as topical microbicides. A solvent casting method was used to manufacture the films. Solid phase solubility was used to identify potential polymers for use in the film formulation. Physical and chemical properties (such as water content, puncture strength and in vitro release) and product stability were determined. The bioactivity of the film products against HIV was assessed using the TZM-bl assay and a cervical explant model. Polymers identified from the solid phase solubility study maintained tenofovir and maraviroc in an amorphous state and prevented drug crystallization. Three combination film products were developed using cellulose polymers and polyvinyl alcohol. The residual water content in all films was 50% of film drug content within 30 min. Stability testing confirmed that the combination film products were stable for 12 months at ambient temperature and 6 months under stressed conditions. Antiviral activity was confirmed in TZM-bl and cervical explant models. Polymeric films can be used as a stable dosage form for the delivery of antiretroviral combinations as microbicides.

  10. Splitting method for the combined formulation of fluid-particle problem

    International Nuclear Information System (INIS)

    Choi, Hyung Gwon; Yoo, Jung Yul; Joseph, D. D.

    2000-01-01

    A splitting method for the direct numerical simulation of solid-liquid mixtures is presented, where a symmetric pressure equation is newly proposed. Through numerical experiment, it is found that the newly proposed splitting method works well with a matrix-free formulation for some bench mark problems avoiding an erroneous pressure field which appears when using the conventional pressure equation of a splitting method. When deriving a typical pressure equation of a splitting method, the motion of a solid particle has to be approximated by the 'intermediate velocity' instead of treating it as unknowns since it is necessary as a boundary condition. Therefore, the motion of a solid particle is treated in such an explicit way that a particle moves by the known form drag(pressure drag) that is calculated from the pressure equation in the previous step. From the numerical experiment, it was shown that this method gives an erroneous pressure field even for the very small time step size as a particle velocity increases. In this paper, coupling the unknowns of particle velocities in the pressure equation is proposed, where the resulting matrix is reduced to the symmetric one by applying the projector of the combined formulation. It has been tested over some bench mark problems and gives reasonable pressure fields

  11. Photostability and efficacy studies of topical formulations containing UV-filters combination and vitamins A, C and E.

    Science.gov (United States)

    Gaspar, L R; Campos, P M B G Maia

    2007-10-01

    It is already known that the photostability of a sunscreen is important for its performance on human skin. On the other hand, there are many formulations besides sunscreens containing combinations of UV-filters and daily use active substances with other claims like hydration and anti-aging effects. Vitamins A, C and E are frequently added in these kinds of products and it is not known if the UV-filters have some influence on the hydration and anti-aging effects of these vitamins on the skin as well as on their stability mainly when photounstable UV-filters like avobenzone and octyl methoxycinnamate are present in the formulation. Thus, the aim of this study was to evaluate the influence of two different UV-filters combinations, a photostable and a photounstable one, on the photostability as well as on the efficacy of a formulation containing vitamin A, C and E derivatives. The formulations that were investigated contained or not (vehicle: formulation 1) a combination of 0.6 % (w/w) vitamin A palmitate (1,700,000 UI/g), 2 % (w/w) vitamin E acetate and 2% (w/w) ascorbyl tetraisopalmitate (formulation 2) supplemented with a photounstable UV filter combination octyl methoxycinnamate (OMC), avobenzone (AVB) and 4-methylbenzilidene camphor (MBC) (formulation 3) or with a photostable UV filter combination OMC, benzophenone-3 (BP-3) and octocrylene (OC) (formulation 4). In the photostability studies, all formulations were spread onto a glass plate and exposed to UVA/UVB irradiation. The filter components and vitamins were quantified by HPLC analysis with detection at 325 and 235 nm and by spectrophotometry. To simulate the effects of these formulations daily use, all of them (formulations 1-4) were applied on the dorsum of hairless mice, which were submitted to a controlled light-dark cycle (and were not irradiated), once a day for 5 days. Transepidermal water loss (TEWL), water content of the stratum corneum and viscoelastic properties of the skin were analyzed by using

  12. A combined single-multiphase flow formulation of the premixing phase using the level set method

    International Nuclear Information System (INIS)

    Leskovar, M.; Marn, J.

    1999-01-01

    The premixing phase of a steam explosion covers the interaction of the melt jet or droplets with the water prior to any steam explosion occurring. To get a better insight of the hydrodynamic processes during the premixing phase beside hot premixing experiments, where the water evaporation is significant, also cold isothermal premixing experiments are performed. The specialty of isothermal premixing experiments is that three phases are involved: the water, the air and the spheres phase, but only the spheres phase mixes with the other two phases whereas the water and air phases do not mix and remain separated by a free surface. Our idea therefore was to treat the isothermal premixing process with a combined single-multiphase flow model. In this combined model the water and air phase are treated as a single phase with discontinuous phase properties at the water air interface, whereas the spheres are treated as usually with a multiphase flow model, where the spheres represent the dispersed phase and the common water-air phase represents the continuous phase. The common water-air phase was described with the front capturing method based on the level set formulation. In the level set formulation, the boundary of two-fluid interfaces is modeled as the zero set of a smooth signed normal distance function defined on the entire physical domain. The boundary is then updated by solving a nonlinear equation of the Hamilton-Jacobi type on the whole domain. With this single-multiphase flow model the Queos isothermal premixing Q08 has been simulated. A numerical analysis using different treatments of the water-air interface (level set, high-resolution and upwind) has been performed for the incompressible and compressible case and the results were compared to experimental measurements.(author)

  13. Local immunological mechanisms of sublingual immunotherapy.

    Science.gov (United States)

    Allam, Jean-Pierre; Novak, Natalija

    2011-12-01

    To summarize novel insights into the immunological mechanisms of sublingual immunotherapy (SLIT). Within the recent decades, several alternative noninvasive allergen application strategies have been investigated in allergen-specific immunotherapy (AIT), of which intra-oral allergen application to sublingual mucosa has been proven to be well tolerated and effective. To date, SLIT is widely accepted by most allergists as an alternative option to conventional subcutaneous immunotherapy (SCIT). Although detailed immunological mechanisms remain to be elucidated, much scientific effort has been made to shed some light on local and systemic immunological responses to SLIT in mice as well as humans. Only a few studies focused on the detailed mechanisms following allergen application to the oral mucosa as part of the sophisticated mucosal immunological network. Within this network, the pro-tolerogenic properties of local antigen-presenting cells (APCs) such as dendritic cells - which are able to enforce tolerogenic mechanisms and to induce T-cell immune responses - play a central role. Further on, basic research focused not only on the immune response in nasal and bronchial mucosa but also on the systemic T-cell immune response. Thus, much exiting data have been published providing a better understanding of immunological features of SLIT but far more investigations are necessary to uncover further exciting details on the key mechanisms of SLIT.

  14. Biocompatible Nanoemulsions for Improved Aceclofenac Skin Delivery: Formulation Approach Using Combined Mixture-Process Experimental Design.

    Science.gov (United States)

    Isailović, Tanja; Ðorđević, Sanela; Marković, Bojan; Ranđelović, Danijela; Cekić, Nebojša; Lukić, Milica; Pantelić, Ivana; Daniels, Rolf; Savić, Snežana

    2016-01-01

    We aimed to develop lecithin-based nanoemulsions intended for effective aceclofenac (ACF) skin delivery utilizing sucrose esters [sucrose palmitate (SP) and sucrose stearate (SS)] as additional stabilizers and penetration enhancers. To find the suitable surfactant mixtures and levels of process variables (homogenization pressure and number of cycles - high pressure homogenization manufacturing method) that result in drug-loaded nanoemulsions with minimal droplet size and narrow size distribution, a combined mixture-process experimental design was employed. Based on optimization data, selected nanoemulsions were evaluated regarding morphology, surface charge, drug-excipient interactions, physical stability, and in vivo skin performances (skin penetration and irritation potential). The predicted physicochemical properties and storage stability were proved satisfying for ACF-loaded nanoemulsions containing 2% of SP in the blend with 0%-1% of SS and 1%-2% of egg lecithin (produced at 50°C/20 cycles/800 bar). Additionally, the in vivo tape stripping demonstrated superior ACF skin absorption from these nanoemulsions, particularly from those containing 2% of SP, 0.5% of SS, and 1.5% of egg lecithin, when comparing with the sample costabilized by conventional surfactant - polysorbate 80. In summary, the combined mixture-process experimental design was shown as a feasible tool for formulation development of multisurfactant-based nanosized delivery systems with potentially improved overall product performances.

  15. Sublingual injection of microparticles containing glycolipid ligands for NKT cells and subunit vaccines induces antibody responses in oral cavity.

    Science.gov (United States)

    DeLyria, Elizabeth S; Zhou, Dapeng; Lee, Jun Soo; Singh, Shailbala; Song, Wei; Li, Fenge; Sun, Qing; Lu, Hongzhou; Wu, Jinhui; Qiao, Qian; Hu, Yiqiao; Zhang, Guodong; Li, Chun; Sastry, K Jagannadha; Shen, Haifa

    2015-03-20

    Natural Killer T (NKT) cells are a unique type of innate immune cells which exert paradoxical roles in animal models through producing either Th1 or Th2 cytokines and activating dendritic cells. Alpha-galactosylceramide (αGalCer), a synthetic antigen for NKT cells, was found to be safe and immune stimulatory in cancer and hepatitis patients. We recently developed microparticle-formulated αGalCer, which is selectively presented by dendritic cells and macrophages, but not B cells, and thus can avoid the anergy of NKT cells. In this study, we have examined the immunogenicity of microparticles containing αGalCer and protein vaccine components through sublingual injection in mice. The results showed that sublingual injection of microparticles containing αGalCer and ovalbumin triggered IgG responses in serum (titer >1:100,000), which persisted for more than 3months. Microparticles containing ovalbumin alone also induced comparable level of IgG responses. However, immunoglobulin subclass analysis showed that sublingually injected microparticles containing αGalCer and ovalbumin induced 20 fold higher Th1 biased antibody (IgG2c) than microparticles containing OVA alone (1:20,000 as compared to 1:1000 titer). Sublingual injection of microparticles containing αGalCer and ovalbumin induced secretion of both IgG (titer >1:1000) and IgA (titer=1:80) in saliva secretion, while microparticles containing ovalbumin alone only induced secretion of IgG in saliva. Our results suggest that sublingual injection of microparticles and their subsequent trafficking to draining lymph nodes may induce adaptive immune responses in mucosal compartments. Ongoing studies are focused on the mechanism of antigen presentation and lymphocyte biology in the oral cavity, as well as the toxicity and efficacy of these candidate microparticles for future applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. CT features of invasion of sublingual space by malignant oropharyngeal tumors

    International Nuclear Information System (INIS)

    Wei Yi; Xiao Jiahe; Zhou Xiangping; Deng Kaihong

    2003-01-01

    Objective: To investigate the CT features of the invasion of sublingual space by malignant oropharyngeal tumors in order to provide more accurate information for clinical treatment. Methods: Fifty-eight cases of pathologically proven malignant oropharyngeal tumors were collected and retrospectively analyzed. Results: Among all the cases, invasion of sublingual space by malignant oropharyngeal tumors could be seen in 14 cases, of which, 7 cases got access to sublingual space through tongue base, 3 cases through parapharyngeal space, 2 cases through pterygomandibular raphe, 2 cases through uncertain routes. Invasion of sublingual space manifested on CT scan as obliteration of fat plane in sublingual space and involvement of the sublingual vessels in the space. Conclusion: Malignant oropharyngeal tumors can invade the adjacent sublingual space via tongue base, pterygomandibular raphe, and parapharyngeal space. The invasion of sublingual space by malignant oropharyngeal tumors manifests in CT as effacement of sublingual fat plane and envelopment of hyoid artery

  17. [Treatment of small and sublingual salivary glands cysts by laser].

    Science.gov (United States)

    Bogatov, V V; Vybornov, V V; Malinovskiĭ, I Iu

    2011-01-01

    The differents variants of treatment of retention cysts of mucous membrane of oral cavity and sublingual salivary gland cysts were presented and analysed. Results of doppler examination as a method of research blood microcirculation in postoperation time were presented.

  18. Development of nanoparticle based delivery systems for sublingual immunotherapy

    DEFF Research Database (Denmark)

    Alija, Hava; Rask, Carola; Brimnes, Jens

    The prevalence of IgE mediated allergic diseases is increasing dramatically in industrialized countries. Sublingual immunotherapy (SLIT) has been demonstrated to be a safe and efficacious treatment for IgE mediated allergic diseases, but requires protracted treatment duration. Even though SLIT...... (OVA)-induced allergic airway inflammation model for their ability to improve immune tolerance induction of ovalbumin (protein and peptide) when delivered sublingually. In the liposome study, mice were treated sublingually during two weeks with free or liposome encapsulated OVA (OVA-liposomes) followed...... by intraperitoneal injections and intranasal challenge. Mice treated sublingually with OVA-liposomes showed a significant reduction of airway eosinophilia, OVA-specific IgE antibodies and splenocyte proliferation in comparison to free OVA. In addition, reduced levels of IFN-ɣ and IL-5 were observed in spleen cell...

  19. Efficacy Evaluation of a Multifunctional Cosmetic Formulation: The Benefits of a Combination of Active Antioxidant Substances

    Directory of Open Access Journals (Sweden)

    Mirela D. Gianeti

    2014-11-01

    Full Text Available This study presents the association of active antioxidants substances in a multifunctional cosmetic formulation with established efficacy against signs of aging. A multifunctional cosmetic formulation containing an association of UV filters and antioxidant substances (liposoluble vitamins A, C and E, Ginkgo biloba and Phorphyra umbilicalis extracts was evaluated. This formulation was submitted to a clinical efficacy study using biophysics techniques and skin images analysis (digital photography imaging systems, 20 MHz ultrasound, and reflectance confocal microscopy. The volunteers applied the formulation containing the UV filters and antioxidant substances during the day and the formulation with antioxidant substances and without the UV filters at night, for 90 days. The formulation increased the hydration and protected the skin barrier function after a single application. At the long term assessment the formulation provided an improvement in skin barrier function and skin hydration to the deeper layers of the epidermis, leading to an improvement in skin appearance by reducing wrinkles and skin roughness. The multifunctional cosmetic formulation studied can be suggested to preventing signs of aging and improving skin conditions. In addition, this study presents the benefits of associating different active antioxidants substances in a single cosmetic formulation to prevent skin aging.

  20. Artificial neural network combined with principal component analysis for resolution of complex pharmaceutical formulations.

    Science.gov (United States)

    Ioele, Giuseppina; De Luca, Michele; Dinç, Erdal; Oliverio, Filomena; Ragno, Gaetano

    2011-01-01

    A chemometric approach based on the combined use of the principal component analysis (PCA) and artificial neural network (ANN) was developed for the multicomponent determination of caffeine (CAF), mepyramine (MEP), phenylpropanolamine (PPA) and pheniramine (PNA) in their pharmaceutical preparations without any chemical separation. The predictive ability of the ANN method was compared with the classical linear regression method Partial Least Squares 2 (PLS2). The UV spectral data between 220 and 300 nm of a training set of sixteen quaternary mixtures were processed by PCA to reduce the dimensions of input data and eliminate the noise coming from instrumentation. Several spectral ranges and different numbers of principal components (PCs) were tested to find the PCA-ANN and PLS2 models reaching the best determination results. A two layer ANN, using the first four PCs, was used with log-sigmoid transfer function in first hidden layer and linear transfer function in output layer. Standard error of prediction (SEP) was adopted to assess the predictive accuracy of the models when subjected to external validation. PCA-ANN showed better prediction ability in the determination of PPA and PNA in synthetic samples with added excipients and pharmaceutical formulations. Since both components are characterized by low absorptivity, the better performance of PCA-ANN was ascribed to the ability in considering all non-linear information from noise or interfering excipients.

  1. Sublingual immunotherapy: World Allergy Organization position paper 2013 update

    Science.gov (United States)

    2014-01-01

    We have prepared this document, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2013 Update”, according to the evidence-based criteria, revising and updating chapters of the originally published paper, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2009”, available at http://www.waojournal.org. Namely, these comprise: “Mechanisms of sublingual immunotherapy;” “Clinical efficacy of sublingual immunotherapy” – reporting all the data of all controlled trials published after 2009; “Safety of sublingual immunotherapy” – with the recently published Grading System for adverse reactions; “Impact of sublingual immunotherapy on the natural history of respiratory allergy” – with the relevant evidences published since 2009; “Efficacy of SLIT in children” – with detailed analysis of all the studies; “Definition of SLIT patient selection” – reporting the criteria for eligibility to sublingual immunotherapy; “The future of immunotherapy in the community care setting”; “Methodology of clinical trials according to the current scientific and regulatory standards”; and “Guideline development: from evidence-based medicine to patients' views” – including the evolution of the methods to make clinical recommendations. Additionally, we have added new chapters to cover a few emerging crucial topics: “Practical aspects of schedules and dosages and counseling for adherence” – which is crucial in clinical practice for all treatments; “Perspectives and new approaches” – including recombinant allergens, adjuvants, modified allergens, and the concept of validity of the single products. Furthermore, “Raising public awareness about sublingual immunotherapy”, as a need for our patients, and strategies to increase awareness of allergen immunotherapy (AIT) among patients, the medical community, all healthcare stakeholders, and public opinion, are also reported in detail. PMID:24679069

  2. Baryonic 3P2-dominant superfluidity under combined pion condensation with Δ isobar. 1. Formulation

    International Nuclear Information System (INIS)

    Tamagaki, Ryozo

    2006-01-01

    Baryonic superfluidity is studied in the combined pion condensation with the Δ degrees of freedom. We adopt a model previously proposed, in which both condensates of the neutral and charged pions coexist without interference in neutron star matter above the nuclear density. In setting up the most probable pairing correlation in such situation, it is crucial to extract attractive effects of the baryon-baryon spin-orbit interaction playing a decisive role in realizing the superfluid at moderate high densities. To this aim, using the quasi-baryon basis having the good angular-momentum quantum number, we define the quasi-baryon pairs with the stretched two-dimensional angular momentum with m J =±2, being the sum of a spin component m s =±1 and an orbital-angular momentum m L =±1 of the quasi-baryon pairs. Pairing interaction is given in terms of the operators of these quasi-baryon pairs. This choice enables us to include the usual 3 P 2 pair as a dominant component in the quasi-baryon pairs thus defined. Then we rewrite the quasi-baryon pair operations in terms of the operators of the quasi-particles (denoted as η) describing the single-particle eigenmode in the combined pion condensation. The Bogoliubov transformation is performed according to the scheme previously developed in the study of the neutron 3 P 2 pairing, since both cases are similar in formal structure although different in physical content. Finally we obtain a coupled gap equation among three channels corresponding to three different charge states of the quasi-baryon pairs. This paper presents such a formulation. Analysis of the matrix element of the pairing interaction and numerical results of energy gaps will be reported in a succeeding paper. (author)

  3. New approaches for the management of bipolar disorder: role of sublingual asenapine in the treatment of mania

    Directory of Open Access Journals (Sweden)

    Warren CG

    2013-05-01

    Full Text Available Calvert G Warren,1 Steven L Dubovsky1,21Department of Psychiatry, State University of New York at Buffalo, Buffalo, NY, USA; 2Departments of Psychiatry and Medicine, University of Colorado, Boulder, CO, USAAbstract: Bipolar disorder is a prevalent disorder that tends to become progressive without treatment and with inadequate treatment. Second generation (atypical antipsychotic drugs have increasingly been used as adjunctive treatment or monotherapy for mania, but they have the potential for significant adverse effects and their role in maintenance treatment remains unclear. Asenapine is a new atypical antipsychotic medication formulated in a sublingual preparation that has been studied for mania but not maintenance therapy. Evidence indicating efficacy, adverse effects, and potential benefits and drawbacks of using asenapine in the treatment of bipolar disorder based on currently available published data are summarized.Keywords: bipolar disorder, antipsychotic drug, mania, maintenance, sublingual

  4. Innovative Formulation Combining Al, Zr and Si Precursors to Obtain Anticorrosion Hybrid Sol-Gel Coating

    Directory of Open Access Journals (Sweden)

    Clément Genet

    2018-05-01

    Full Text Available The aim of our study is to improve the aluminium alloy corrosion resistance with Organic-Inorganic Hybrid (OIH sol-gel coating. Coatings are obtained from unusual formulation with precursors mixing: glycidoxypropyltrimethoxysilane (GPTMS, zirconium (IV propoxide (TPOZ and aluminium tri-sec-butoxide (ASB. This formulation was characterized and compared with sol formulations GPTMS/TPOZ and GPTMS/ASB. In each formulation, a corrosion inhibitor, cerium (III nitrate hexahydrate, is employed to improve the corrosion performance. Coatings obtained from sol based on GPTMS/TPOZ/ASB have good anti-corrosion performances with Natural Salt Spray (NSS resistance of 500 h for a thickness lower than 4 µm. Contact angle measurement showed a coating hydrophobic behaviour. To understand these performances, nuclear magnetic resonance (NMR analyses were performed, results make sol-gel coating condensation evident and are in very good agreement with previous results.

  5. Innovative Formulation Combining Al, Zr and Si Precursors to Obtain Anticorrosion Hybrid Sol-Gel Coating.

    Science.gov (United States)

    Genet, Clément; Menu, Marie-Joëlle; Gavard, Olivier; Ansart, Florence; Gressier, Marie; Montpellaz, Robin

    2018-05-10

    The aim of our study is to improve the aluminium alloy corrosion resistance with Organic-Inorganic Hybrid (OIH) sol-gel coating. Coatings are obtained from unusual formulation with precursors mixing: glycidoxypropyltrimethoxysilane (GPTMS), zirconium (IV) propoxide (TPOZ) and aluminium tri-sec-butoxide (ASB). This formulation was characterized and compared with sol formulations GPTMS/TPOZ and GPTMS/ASB. In each formulation, a corrosion inhibitor, cerium (III) nitrate hexahydrate, is employed to improve the corrosion performance. Coatings obtained from sol based on GPTMS/TPOZ/ASB have good anti-corrosion performances with Natural Salt Spray (NSS) resistance of 500 h for a thickness lower than 4 µm. Contact angle measurement showed a coating hydrophobic behaviour. To understand these performances, nuclear magnetic resonance (NMR) analyses were performed, results make sol-gel coating condensation evident and are in very good agreement with previous results.

  6. Enhanced efficacy of sublingual immunotherapy by liposome-mediated delivery of allergen

    DEFF Research Database (Denmark)

    Aliu, Have; Rask, Carola; Brimnes, Jens

    2017-01-01

    Immunotherapy by sublingual administration of allergens provides high patient compliance and has emerged as an alternative to subcutaneous immunotherapy for the - treatment of IgE-associated allergic diseases. However, sublingual immunotherapy (SLIT) can cause adverse events. Development...

  7. Formulation and in vitro/in vivo evaluation of combining DNA repair and immune enhancing nutritional supplements.

    Science.gov (United States)

    Pero, R W; Amiri, A; Sheng, Y; Welther, M; Rich, M

    2005-04-01

    Combining nutritional supplements to achieve synergistic benefit is a common practice in the nutraceutical industry. However, establishing added health benefit from a combination of natural ingredients is often assumed, untested and without regard to the principle of metabolic competition between the active components. Here, we report on the combination of a cat's claw water extract (C-Med-100, carboxy alkyl esters = active ingredients) + medicinal mushroom extracts (Cordyceps sinensis, Grifola blazei, Grifolafrondosa, Trametes versicolor and Ganoderma lucidum, polysaccharides = active ingredients) + nicotinamide + zinc into a formulation designed to optimize different modes of immunostimulatory action, and yet that would avoid metabolic antioxidant competition yielding less than expected efficacious effects. Isobole curve analyses of these two active classes of ingredients determined by growth inhibition of HL-60 human leukemic cells in vitro confirmed they were indeed synergistic when in combination, and not metabolically competitive. Furthermore, an in vivo study showed significant health benefit for 14 subjects treated for 4 weeks with the unique C-Med-100/mushroom extract formulation in that they had reduced pain, reduced fatigue, weight loss and a reduced presence of DNA damage in peripheral blood assessed by (8-OH) guanine DNA adducts and elevation in serum protein thiols. Because this broad-based panel of clinical parameters indicating clinical efficacy has never been demonstrated before for either of the active ingredients evaluated alone in humans, these data were taken as strong evidence that the combination of C-Med-100 + mushroom extracts + nicotinamide + zinc gave additive or synergistic effects to health benefit, and thus supported no efficacious limits from metabolic competition regarding this particular formulation.

  8. [Characteristics of sublingual vein and expressions of vascular endothelial growth factor and hypoxia-inducible factor 1alpha proteins in sublingual tissues of Beagle dogs with portal hypertension].

    Science.gov (United States)

    Li, Bai-yu; Wang, Li-na; Yue, Xiao-qiang; Li, Bai

    2009-05-01

    To observe sublingual vein characteristics and the expressions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1alpha (HIF-1alpha) proteins in sublingual tissues of Beagle dogs with cirrhotic portal hypertension. Twelve Beagle dogs were randomly divided into normal control group and cirrhotic portal hypertension group. There were 6 dogs in each group. A canine model of cirrhosis portal hypertension was established by injecting dimethylnitrosamine (DMN) into portal vein once a week for 7 weeks. The characteristics of sublingual vein were observed. Portal venous pressure was measured by using bioelectric recording techniques. The expressions of VEGF and HIF-1alpha proteins in sublingual vein were detected by immunohistochemical method. The shape and color of sublingual vein in beagle dogs in the cirrhotic portal hypertension group changed obviously as compared with the normal control group. Immunohistochemical results showed that there were almost no expressions of VEGF and HIF-1alpha proteins in sublingual tissues in the normal control group; however, the expressions of VEGF and HIF-1alpha proteins in sublingual tissues in the cirrhotic portal hypertension group significantly increased. Changes of portal pressure may lead to the formation of the abnormal sublingual vein by increasing the expressions of VEGF and HIF-1alpha proteins in sublingual tissues in Beagle dogs with portal hypertension.

  9. The nature and combination of subunits used in epitope-based Schistosoma japonicum vaccine formulations affect their efficacy

    Directory of Open Access Journals (Sweden)

    Liu Feng

    2010-11-01

    Full Text Available Abstract Background Schistosomiasis remains a major public health problem in endemic countries and is caused by infections with any one of three primary schistosome species. Although there are no vaccines available to date, this strategy appears feasible since natural immunity develops in individuals suffering from repeated infection during a lifetime. Since vaccinations resulting in both Th1- and Th2-type responses have been shown to contribute to protective immunity, a vaccine formulation with the capacity for stimulating multiple arms of the immune response will likely be the most effective. Previously we developed partially protective, single Th- and B cell-epitope-based peptide-DNA dual vaccines (PDDV (T3-PDDV and B3-PDDV, respectively capable of eliciting immune responses against the Schistosoma japonicum 22.6 kDa tegument antigen (Sj22.6 and a 62 kDa fragment of myosin (Sj62, respectively. Results In this study, we developed PDDV cocktails containing multiple epitopes of S. japonicum from Sj22.6, Sj62 and Sj97 antigens by predicting cytotoxic, helper, and B-cell epitopes, and evaluated vaccine potential in vivo. Results showed that mice immunized with a single-epitope PDDV elicited either Tc, Th, or B cell responses, respectively, and mice immunized with either the T3- or B3- single-epitope PDDV formulation were partially protected against infection. However, mice immunized with a multicomponent (3 PDDV components formulation elicited variable immune responses that were less immunoprotective than single-epitope PDDV formulations. Conclusions Our data show that combining these different antigens did not result in a more effective vaccine formulation when compared to each component administered individually, and further suggest that immune interference resulting from immunizations with antigenically distinct vaccine targets may be an important consideration in the development of multicomponent vaccine preparations.

  10. Time Evolution of Sublingual Microcirculatory Changes in Recreational Marathon Runners

    Science.gov (United States)

    Arstikyte, Justina; Vaitkaitiene, Egle; Vaitkaitis, Dinas

    2017-01-01

    We aimed to evaluate changes in sublingual microcirculation induced by a marathon race. Thirteen healthy male controls and 13 male marathon runners volunteered for the study. We performed sublingual microcirculation, using a Cytocam-IDF device (Braedius Medical, Huizen, Netherlands), and systemic hemodynamic measurements four times: 24 hours prior to their participation in the Kaunas Marathon (distance: 41.2 km), directly after finishing the marathon, 24 hours after the marathon, and one week after the marathon. The marathon runners exhibited a higher functional capillary density (FCD) and total vascular density of small vessels at the first visit compared with the controls. Overall, we did not find any changes in sublingual microcirculation of the marathon runners at any of the other visits. However, in a subgroup of marathon runners with a decreased FCD compared to the subgroup with increased FCD, the subgroup with decreased FCD had shorter running time (190.37 ± 30.2 versus 221.80 ± 23.4 min, p = 0.045), ingested less fluids (907 ± 615 versus 1950 ± 488 mL, p = 0.007) during the race, and lost much more weight (−2.4 ± 1.3 versus −1.0 ± 0.8 kg, p = 0.041). Recreational marathon running is not associated with an alteration of sublingual microcirculation. However, faster running and dehydration may be crucial for further impairing microcirculation. PMID:28828386

  11. Time Evolution of Sublingual Microcirculatory Changes in Recreational Marathon Runners.

    Science.gov (United States)

    Pranskunas, Andrius; Arstikyte, Justina; Pranskuniene, Zivile; Bernatoniene, Jurga; Kiudulaite, Inga; Vaitkaitiene, Egle; Vaitkaitis, Dinas; Brazaitis, Marius

    2017-01-01

    We aimed to evaluate changes in sublingual microcirculation induced by a marathon race. Thirteen healthy male controls and 13 male marathon runners volunteered for the study. We performed sublingual microcirculation, using a Cytocam-IDF device (Braedius Medical, Huizen, Netherlands), and systemic hemodynamic measurements four times: 24 hours prior to their participation in the Kaunas Marathon (distance: 41.2 km), directly after finishing the marathon, 24 hours after the marathon, and one week after the marathon. The marathon runners exhibited a higher functional capillary density (FCD) and total vascular density of small vessels at the first visit compared with the controls. Overall, we did not find any changes in sublingual microcirculation of the marathon runners at any of the other visits. However, in a subgroup of marathon runners with a decreased FCD compared to the subgroup with increased FCD, the subgroup with decreased FCD had shorter running time (190.37 ± 30.2 versus 221.80 ± 23.4 min, p = 0.045), ingested less fluids (907 ± 615 versus 1950 ± 488 mL, p = 0.007) during the race, and lost much more weight (-2.4 ± 1.3 versus -1.0 ± 0.8 kg, p = 0.041). Recreational marathon running is not associated with an alteration of sublingual microcirculation. However, faster running and dehydration may be crucial for further impairing microcirculation.

  12. Time Evolution of Sublingual Microcirculatory Changes in Recreational Marathon Runners

    Directory of Open Access Journals (Sweden)

    Andrius Pranskunas

    2017-01-01

    Full Text Available We aimed to evaluate changes in sublingual microcirculation induced by a marathon race. Thirteen healthy male controls and 13 male marathon runners volunteered for the study. We performed sublingual microcirculation, using a Cytocam-IDF device (Braedius Medical, Huizen, Netherlands, and systemic hemodynamic measurements four times: 24 hours prior to their participation in the Kaunas Marathon (distance: 41.2 km, directly after finishing the marathon, 24 hours after the marathon, and one week after the marathon. The marathon runners exhibited a higher functional capillary density (FCD and total vascular density of small vessels at the first visit compared with the controls. Overall, we did not find any changes in sublingual microcirculation of the marathon runners at any of the other visits. However, in a subgroup of marathon runners with a decreased FCD compared to the subgroup with increased FCD, the subgroup with decreased FCD had shorter running time (190.37±30.2 versus 221.80±23.4 min, p=0.045, ingested less fluids (907±615 versus 1950±488 mL, p=0.007 during the race, and lost much more weight (-2.4±1.3 versus -1.0±0.8 kg, p=0.041. Recreational marathon running is not associated with an alteration of sublingual microcirculation. However, faster running and dehydration may be crucial for further impairing microcirculation.

  13. Efficacy of Combined Formulations of Fungicides with Different Modes of Action in Controlling Botrytis Gray Mold Disease in Chickpea

    Science.gov (United States)

    Rashid, M. H.; Hossain, M. Ashraf; Kashem, M. A.; Kumar, Shiv; Rafii, M. Y.; Latif, M. A.

    2014-01-01

    Botrytis gray mold (BGM) caused by Botrytis cinerea Pers. Ex. Fr. is an extremely devastating disease of chickpea (Cicer arietinum L.) and has a regional as well as an international perspective. Unfortunately, nonchemical methods for its control are weak and ineffective. In order to identify an effective control measure, six fungicides with different modes of action were evaluated on a BGM susceptible chickpea variety BARIchhola-1 at a high BGM incidence location (Madaripur) in Bangladesh for three years (2008, 2009, and 2010). Among the six fungicides tested, one was protectant [Vondozeb 42SC, a.i. mancozeb (0.2%)], two systemic [Bavistin 50 WP, a.i. carbendazim (0.2%), and Protaf 250EC, propiconazole (0.05%)], and three combination formulations [Acrobat MZ690, dimethomorph 9% + mancozeb 60%, (0.2%); Secure 600 WG, phenomadone + mancozeb (0.2%); and Companion, mancozeb 63% + carbendazim 12% (0.2%)]. The results showed superiority of combination formulations involving both protectant and systemic fungicides over the sole application of either fungicide separately. Among the combination fungicides, Companion was most effective, resulting in the lowest disease severity (3.33 score on 1–9 scale) and the highest increase (38%) of grain yield in chickpea. Therefore, this product could be preferred over the sole application of either solo protectant or systemic fungicides to reduce yield losses and avoid fungicide resistance. PMID:24723819

  14. Efficacy of Combined Formulations of Fungicides with Different Modes of Action in Controlling Botrytis Gray Mold Disease in Chickpea

    Directory of Open Access Journals (Sweden)

    M. H. Rashid

    2014-01-01

    Full Text Available Botrytis gray mold (BGM caused by Botrytis cinerea Pers. Ex. Fr. is an extremely devastating disease of chickpea (Cicer arietinum L. and has a regional as well as an international perspective. Unfortunately, nonchemical methods for its control are weak and ineffective. In order to identify an effective control measure, six fungicides with different modes of action were evaluated on a BGM susceptible chickpea variety BARIchhola-1 at a high BGM incidence location (Madaripur in Bangladesh for three years (2008, 2009, and 2010. Among the six fungicides tested, one was protectant [Vondozeb 42SC, a.i. mancozeb (0.2%], two systemic [Bavistin 50 WP, a.i. carbendazim (0.2%, and Protaf 250EC, propiconazole (0.05%], and three combination formulations [Acrobat MZ690, dimethomorph 9% + mancozeb 60%, (0.2%; Secure 600 WG, phenomadone + mancozeb (0.2%; and Companion, mancozeb 63% + carbendazim 12% (0.2%]. The results showed superiority of combination formulations involving both protectant and systemic fungicides over the sole application of either fungicide separately. Among the combination fungicides, Companion was most effective, resulting in the lowest disease severity (3.33 score on 1–9 scale and the highest increase (38% of grain yield in chickpea. Therefore, this product could be preferred over the sole application of either solo protectant or systemic fungicides to reduce yield losses and avoid fungicide resistance.

  15. Characterization and formulation of a new eco-friendly hydraulic binder based on combination of inorganic and organic admixtures

    Directory of Open Access Journals (Sweden)

    Khudhair M.H.R.

    2018-01-01

    Full Text Available This work aims to valorize a mineral and natural resources such as the Limestone Fillers (F-Lime and the Natural Pozzolan (PN by incorporating them into the formulation matrix of cement or concrete. In order to minimize the CO2 emissions into the atmosphere, to reduce the energy and raw materials consumption and as well as, to improve the physical and mechanical properties in fresh cement paste and of mortar or concrete in the hardened state. In this present manuscript, we substituted the clinker by the combination between the F-Lime and NP at 40% by weight of cement with steps of 5% with the admixture of superplasticizers. The influences of the incorporation of these additions on physical and mechanical properties of mortar or concrete in the fresh cement paste and hardened state were evaluated. The obtained results by different formulations elaborated to show that the replacement a part of clinker by the mixing of F-Lime and PN has produced a new hydraulic binder eco-friendly and durable with improved physicochemical, physical and mechanical properties. These results show that we have succeeded to manufacture, characteristic and formulated of new ecofriendly hydraulic binder and sustainable with improved physical, chemical, and mechanical properties while minimizing greenhouse gas emissions on one hand and the reducing the energy raw materials consumption on the other hand.

  16. Fast Disintegrating Combination Tablet of Taste Masked Levocetrizine Dihydrochloride and Montelukast Sodium: Formulation Design, Development, and Characterization

    Directory of Open Access Journals (Sweden)

    M. M. Gupta

    2014-01-01

    Full Text Available The aim of this study was to prepare fast disintegrating combination tablet of taste masked Levocetrizine dihydrochloride and Montelukast sodium by using direct compression method. To prevent bitter taste and unacceptable odour of the Levocetrizine dihydrochloride drug, the drug was taste masked with ion exchange resins like Kyron-T-104 and Tulsion-412. Among the two resins, Kyron-T-104 was selected for further studies because of high drug loading capacity, low cost, and better drug release profile. An ion exchange resin complex was prepared by the batch technique and various parameters; namely, resin activation, drug: resin ratio, pH, temperature, and stirring time, and swelling time were optimized to successfully formulate the tasteless drug resin complex (DRC. The tablets were prepared using microcrystalline cellulose (MCC PH 102 as diluent along with crospovidone (CP, croscarmellose sodium (CCM, and sodium starch glycolate (SSG as a superdisintegrants. The tablets were evaluated for weight variation, hardness, friability, wetting time, water absorption ratio, disintegration time (DT, and dissolution study and it was concluded that the tablet formulation prepared with 2% SSG + CCS showed better disintegration time in comparison with other formulation and good drug release. The stability studies were carried out for the optimized batch for three months and it showed acceptable results.

  17. Combination of Microfluidics with SAXS for the investigation of pharmaceutical formulations

    DEFF Research Database (Denmark)

    Ghazal, Aghiad

    Due to the latest advancements in microfluidics and synchrotron facilities, researchers started exploring the possibility of harnessing the benefits of combining both fields of science to address questions that were deemed unanswerable. Moreover, this combination made experiments that were believed......-ray inspired us to explore interesting nanoparticles that have been gaining interest in the recent years for drug delivery applications and bio-imaging. These drug nanocarriers are superior in terms of their efficiency in solubilizing various drugs and may help in controlling their release. They are lipid...... of efficient tools to investigate them thoroughly. Therefore, we became enthusiastic about performing mixing experiments on these nanoparticles using microfluidics while performing in situ characterization using synchrotron small angle X-ray scattering (SAXS). We were able to locate the time range at which...

  18. Development and evaluation of fixed dose bi therapy sublingual tablets for treatment stress hypertension and anxiety

    Directory of Open Access Journals (Sweden)

    Mohamed A El-Nabarawi

    2013-01-01

    Full Text Available Objective: A stress induced rise in the blood pressure. Some believe that patients with hypertension are characterized by a generalized state of increased anxiety. Aim: The purpose of this study is to prepare a fixed dose bi therapy using bisoprolol hemifumarate (BH as antihypertensive drug and buspirone hydrochloride (BuHCl as anxiolytic drug, which can be used to treat both diseases concomitantly. Using sublingual tablets is hopeful to improve the BuHCl poor oral bioavailability and to facilitate administration to patients experiencing problems with swallowing. Materials and Methods: A total of 5mg BH and 10mg BuHCl were selected based on compatibility study. A 3×22 full factorial design was adopted for the optimization of the tablets prepared by direct compression method. The effects of the filler type, the binder molecular weight, and the binder type were studied. The prepared formulae were evaluated according to their physical characters as hardness, friability, disintegration time (new modified method and in vivo disintegration time and wetting properties. In vitro drugs dissolute, permeation through the buccal mucosa and the effect of storage were analyzed by a new valid high pressure liquid chromatography (HPLC method. Bioavailability study of the selected formula study was carried out and followed by the clinical. Results: The optimized tablet formulation showed accepted average weight, hardness, wetting time, friability, content uniformity, disintegration time (less than 3 min. Maximum drug release could be achieved with in 10 min. In addition enhancing drug permeation through the buccal mucosa and, the maximum concentration of the drug that reached the blood was in the first 10 min which means a rapid onset of action and improved the extent of both drug′s absorption. Conclusion: The results revealed that sublingual (F6 tablets containing both drugs would maintain rapid onset of action, and increase bioavailability. BuHCl with BH

  19. Time evolution of sublingual microcirculatory changes in recreational marathon runners

    OpenAIRE

    Pranskūnas, Andrius; Kiudulaitė, Inga; Šimkienė, Jūratė; Damanskytė, Diana; Pranskūnienė, Živilė; Arštikytė, Justina; Vaitkaitis, Dinas; Pilvinis, Vidas; Brazaitis, Marius

    2017-01-01

    Introduction: Marathon race transiently elevates the probability of sudden death. Also during long-distance run may occur various gastrointestinal symptoms with range from mild nausea to hemorrhagic stool. However microcirculatory nature of this disturbances is not clear. Microcirculation of sublingual mucosa is part of interest, because it is easy and noninvasively accessible, changes have relation with mortality and it is part of the upper digestive tract. Here, we evaluate changes in subli...

  20. Stability evaluation of house dust mite vaccines for sublingual immunotherapy

    Directory of Open Access Journals (Sweden)

    MARIJA GAVROVIĆ-JANKULOVIĆ

    2010-01-01

    Full Text Available Allergen-specific immunotherapy with house dust mite (HDM allergen extracts can effectively alleviate the symptoms of allergic rhinitis and asthma. The efficacy of the immunotherapeutic treatment is highly dependent on the quality of house dust mite vaccines. This study was performed to assess the stability of house dust mite allergen vaccines prepared for sublingual immunotherapy. Lyophilized Dermatophagoides pteronyssinus (Dpt mite bodies were the starting material for the production of sublingual vaccines in four therapeutic concentrations. The stability of the extract for vaccine production, which was stored below 4 °C for one month, showed consistence in the protein profile in SDS PAGE. ELISA-inhibition showed that the potencies of Dpt vaccines during a 12 month period were to 65–80 % preserved at all analyzed therapeutic concentrations. This study showed that glycerinated Dpt vaccines stored at 4 °C preserved their IgE-binding potential during a 12 month period, implying their suitability for sublingual immunotherapeutic treatment of HDM allergy.

  1. Sublingual epidermoid cyst presenting with distinctive magnetic resonance imaging findings.

    Science.gov (United States)

    Yoshida, Naohiro; Kodama, Kozue; Iino, Yukiko

    2014-06-18

    A case of sublingual epidermoid cyst presenting distinctive magnetic resonance imaging (MRI) findings is described. A 39-year-old man presented to our hospital with a three months progressive left submandibular swelling, difficulty moving his tongue, and snoring. Preoperative evaluation with MRI and fine needle aspiration cytology (FNAC) revealed that the heterogeneous cystic lesion contained the squamous cells, which is compatible with ectodermal tissue. The mass was located above the mylohyoid muscle and spread to the pharyngeal space. By considering the size, infection history, patient age, and location, the cyst was completely resected under general anesthesia via cervical approach without any complication. Histopathologically, the cyst wall was lined by stratified squamous epithelium with no skin appendage, suggesting an epidermoid cyst. Ultrasound (US), MRI and FNAC were very useful of the preoperative diagnosis for oral and sublingual lesion. The postoperative course was uneventful and without recurrence after 24 months. This case showed that epidermoid cysts formed the rarely heterogeneous cystic tumor and it underlined usefulness of preoperative diagnosis, such as US, MRI and FNAC for oral and sublingual tumor.

  2. Bioavailability of isoniazid, rifampicin and pyrazinamide (in free combination or fixed-triple formulation) in intermittent antituberculous chemotherapy.

    Science.gov (United States)

    Acocella, G; Luisetti, M; Grassi, G G; Peona, V; Pozzi, E; Grassi, C

    1993-01-01

    A study was carried out in six human volunteers, to assess the blood kinetics of isoniazid, rifampicin and pyrazinamide, administered in a fixed-triple combination intended for use in intermittent chemotherapy of tuberculosis. The formulation employed contained 125 mg of isoniazid (H), 100 mg of rifampicin (R) and 375 mg of pyrazinamide (Z) per tablet; six tablets were administered to every subject, giving a total dosage of 750 mg of isoniazid, 600 mg of rifampicin and 2,250 mg of pyrazinamide. In each subject, the same dose of each drug was administered individually in separate sessions and the results compared. The results indicated that, at the level of dose of the intermittent tablet, no negative interactions between the drugs were observed.

  3. Optimization of formulation of soy-cakes baked in infrared-microwave combination oven by response surface methodology.

    Science.gov (United States)

    Şakıyan, Özge

    2015-05-01

    The aim of present work is to optimize the formulation of a functional cake (soy-cake) to be baked in infrared-microwave combination oven. For this optimization process response surface methodology was utilized. It was also aimed to optimize the processing conditions of the combination baking. The independent variables were the baking time (8, 9, 10 min), the soy flour concentration (30, 40, 50 %) and the DATEM (diacetyltartaric acid esters of monoglycerides) concentration (0.4, 0.6 and 0.8 %). The quality parameters that were examined in the study were specific volume, weight loss, total color change and firmness of the cake samples. The results were analyzed by multiple regression; and the significant linear, quadratic, and interaction terms were used in the second order mathematical model. The optimum baking time, soy-flour concentration and DATEM concentration were found as 9.5 min, 30 and 0.72 %, respectively. The corresponding responses of the optimum points were almost comparable with those of conventionally baked soy-cakes. So it may be declared that it is possible to produce high quality soy cakes in a very short time by using infrared-microwave combination oven.

  4. Quantitative Studies of Sublingual PCO2 as a Resuscitation End-Point in the Diagnosis and Treatment of Hemorrhagic Shock

    National Research Council Canada - National Science Library

    Ivatury, Pao

    2005-01-01

    This clinical study is examining the relationship between sublingual PCO2 (PslCO2) to real-time changes in microcirculatory blood flow of the sublingual mucosa in victims of traumatic and hemorrhagic shock...

  5. Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific immunotherapy

    DEFF Research Database (Denmark)

    Khinchi, M S; Poulsen, Lars K.; Carat, F

    2004-01-01

    Both sublingual allergen-specific immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) have a documented clinical efficacy, but only few comparative studies have been performed.......Both sublingual allergen-specific immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) have a documented clinical efficacy, but only few comparative studies have been performed....

  6. Development and Characterization of an Amorphous Solid Dispersion of Furosemide in the Form of a Sublingual Bioadhesive Film to Enhance Bioavailability.

    Science.gov (United States)

    De Caro, Viviana; Ajovalasit, Alessia; Sutera, Flavia Maria; Murgia, Denise; Sabatino, Maria Antonietta; Dispenza, Clelia

    2017-06-24

    Administered by an oral route, Furosemide (FUR), a diuretic used in several edematous states and hypertension, presents bioavailability problems, reported as a consequence of an erratic gastrointestinal absorption due to various existing polymorphic forms and low and pH-dependent solubility. A mucoadhesive sublingual fast-dissolving FUR based film has been developed and evaluated in order to optimize the bioavailability of FUR by increasing solubility and guaranteeing a good dissolution reproducibility. The Differential Scanning Calorimetry (DSC) analyses confirmed that the film prepared using the solvent casting method entrapped FUR in the amorphous state. As a solid dispersion, FUR increases its solubility up to 28.36 mg/mL. Drug content, thickness, and weight uniformity of film were also evaluated. The measured Young's Modulus, yield strength, and relative elongation of break percentage (EB%) allowed for the classification of the drug-loaded film as an elastomer. Mucoadhesive strength tests showed that the force to detach film from mucosa grew exponentially with increasing contact time up to 7667 N/m². FUR was quickly discharged from the film following a trend well fitted with the Weibull kinetic model. When applied on sublingual mucosa, the new formulation produced a massive drug flux in the systemic compartment. Overall, the proposed sublingual film enhances drug solubility and absorption, allowing for the prediction of a rapid onset of action and reproducible bioavailability in its clinical application.

  7. Formulation and evaluation of a topical niosomal gel containing a combination of benzoyl peroxide and tretinoin for antiacne activity

    Directory of Open Access Journals (Sweden)

    Gupta A

    2014-12-01

    Full Text Available Ankush Gupta,1,* Sima Singh,1,* Niranjan G Kotla,1 Thomas J Webster2,3 1Department of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India; 2Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 3Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia *These authors contributed equally to this work Abstract: A skin disease, like acne, is very common and normally happens to everyone at least once in their lifetime. The structure of the stratum corneum is often compared with a brick wall, with corneocytes surrounded by the mortar of the intercellular lipid lamellae. One of the best options for successful drug delivery to the affected area of skin is the use of elastic vesicles (niosomes which can be transported through the skin through channel-like structures. In this study, a combination of tretinoin (keratolytic agent and benzoyl peroxide (BPO (a potent antibacterial was given by using niosomes as promising carriers for the effective treatment of acne by acting on a pathogenic site. In this section, niosomal gel formulation encapsulated drugs have been evaluated for in vitro, ex vivo, and in vivo, for their predetermined characteristics; and finally the stability of the niosome gel was tested at different temperature conditions for understanding of the storage conditions required for maintaining the quality of formulation attributes. The prepared niosome was found to be in the range of 531 nm with a zeta potential of -43 mV; the entrapment efficiencies of tretinoin (TRA and BPO niosomes were found to be 96.25%±0.56% and 98.75%±1.25%, respectively. The permeated amount of TRA and BPO from the niosomal gel after 24 hours was calculated as 6.25±0.14 µg/cm2 and 5.04±0.014 µg/cm2, respectively. A comparative drug retention study in Wistar rat skin using cream, an alcoholic solution, and a niosomal gel showed 11.54 µg, 2.68 µg, and 15.54 µg

  8. Pharmacokinetics and pharmacodynamics of detomidine following sublingual administration to horses.

    Science.gov (United States)

    Dimaio Knych, Heather K; Stanley, Scott D

    2011-10-01

    To characterize pharmacokinetics and pharmacodynamics of detomidine gel administered sublingually in accordance with label instructions to establish appropriate withdrawal guidelines for horses before competition. 12 adult racehorses. Horses received a single sublingual administration of 0.04 mg of detomidine/kg. Blood samples were collected before and up to 72 hours after drug administration. Urine samples were collected for 5 days after detomidine administration. Plasma and urine samples were analyzed via liquid chromatography-mass spectrometry, and resulting data were analyzed by use of noncompartmental analysis. Chin-to-ground distance, heart rate and rhythm, glucose concentration, PCV, and plasma protein concentration were also assessed following detomidine administration. Mean ± SD terminal elimination half-life of detomidine was 1.5 ± 1 hours. Metabolite concentrations were below the limit of detection (0.02, 0.1, and 0.5 ng/mL for detomidine, carboxydetomidine, and hydroxydetomidine, respectively) in plasma by 24 hours. Concentrations of detomidine and its metabolites were below the limit of detection (0.05 ng/mL for detomidine and 0.10 ng/mL for carboxydetomidine and hydroxydetomidine) in urine by 3 days. All horses had various degrees of sedation after detomidine administration. Time of onset was ≤ 40 minutes, and duration of sedation was approximately 2 hours. Significant decreases, relative to values at time 0, were detected for chin-to-ground distance and heart rate. There was an increased incidence and exacerbation of preexisting atrioventricular blocks after detomidine administration. A 48-hour and 3-day withdrawal period for detection in plasma and urine samples, respectively, should be adopted for sublingual administration of detomidine gel.

  9. Immunological mechanisms of sublingual allergen-specific immunotherapy.

    Science.gov (United States)

    Novak, Natalija; Bieber, T; Allam, J-P

    2011-06-01

    Within the last 100 years of allergen-specific immunotherapy, many clinical and scientific efforts have been made to establish alternative noninvasive allergen application strategies. Thus, intra-oral allergen delivery to the sublingual mucosa has been proven to be safe and effective. As a consequence, to date, sublingual immunotherapy (SLIT) is widely accepted by most allergists as an alternative to conventional subcutaneous immunotherapy. Although immunological mechanisms remain to be elucidated in detail, several studies in mice and humans within recent years provided deeper insights into local as well as systemic immunological features in response to SLIT. First of all, it was shown that the target organ, the oral mucosa, harbours a sophisticated immunological network as an important prerequisite for SLIT, which contains among other cells, local antigen-presenting cells (APC), such as dendritic cells (DCs), with a constitutive disposition to enforce tolerogenic mechanisms. Further on, basic research on local DCs within the oral mucosa gave rise to possible alternative strategies to deliver the allergens to other mucosal regions than sublingual tissue, such as the vestibulum oris. Moreover, characterization of oral DCs led to the identification of target structures for both allergens as well as adjuvants, which could be applied during SLIT. Altogether, SLIT came a long way since its very beginning in the last century and some, but not all questions about SLIT could be answered so far. However, recent research efforts as well as clinical approaches paved the way for another exciting 100 years of SLIT. © 2011 John Wiley & Sons A/S.

  10. The employment of FTIR spectroscopy in combination with chemometrics for analysis of rat meat in meatball formulation.

    Science.gov (United States)

    Rahmania, Halida; Sudjadi; Rohman, Abdul

    2015-02-01

    For Indonesian community, meatball is one of the favorite meat food products. In order to gain economical benefits, the substitution of beef meat with rat meat can happen due to the different prices between rat meat and beef. In this present research, the feasibility of FTIR spectroscopy in combination with multivariate calibration of partial least square (PLS) was used for the quantitative analysis of rat meat in the binary mixture of beef in meatball formulation. Meanwhile, the chemometrics of principal component analysis (PCA) was used for the classification between rat meat and beef meatballs. Some frequency regions in mid infrared region were optimized, and finally, the frequency region of 750-1000 cm(-1) was selected during PLS and PCA modeling.For quantitative analysis, the relationship between actual values (x-axis) and FTIR predicted values (y-axis) of rat meat is described by the equation of y= 0.9417x+ 2.8410 with coefficient of determination (R2) of 0.993, and root mean square error of calibration (RMSEC) of 1.79%. Furthermore, PCA was successfully used for the classification of rat meat meatball and beef meatball.

  11. Optimization of operation for combined heat and power plants - CHP plants - with heat accumulators using a MILP formulation

    Energy Technology Data Exchange (ETDEWEB)

    Grue, Jeppe; Bach, Inger [Aalborg Univ. (Denmark). Inst. of Energy Technology]. E-mails: jeg@iet.auc.dk; ib@iet.auc.dk

    2000-07-01

    The power generation system in Denmark is extensively based on small combined heat and power plants (CHP plants), producing both electricity and district heating. This project deals with smaller plants spread throughout the country. Often a heat accumulator is used to enable electricity production, even when the heat demand is low. This system forms a very complex problem, both for sizing, designing and operation of CHP plants. The objective of the work is the development of a tool for optimisation of the operation of CHP plants, and to even considering the design of the plant. The problem is formulated as a MILP-problem. An actual case is being tested, involving CHP producing units to cover the demand. The results from this project show that it is of major importance to consider the operation of the plant in detail already in the design phase. It is of major importance to consider the optimisation of the plant operation, even at the design stage, as it may cause the contribution margin to rise significantly, if the plant is designed on the basis of a de-tailed knowledge of the expected operation. (author)

  12. Schwannoma of the sublingual gland: report of a case

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Sook; Choi, Soon Chul; Park, Tae Won; You, Dong Soo [Dept. of Oral and Maxillofacial Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1994-08-15

    Schwannoma, also referred to as neurilemmoma, is a solitary, benign and slow growing tumor of nerve sheath origin. This rare lesion originates from Schwann cell of peripheral, autonomic and cranial nerve. Extracranial neurogenic tumor of the head and neck is uncommon. Schwannoma of the salivary gland is a particularly rare form of an extracranial neurogenic tumor, with most presenting in the parotid gland originating from a peripheral branch of the facial nerve. In this report, an unusual case of schwannoma in the sublingual region is presented and the literature concerning this subject is reviewed.

  13. Efficacies of Gel Formulations Containing Foscarnet, Alone or Combined with Sodium Lauryl Sulfate, against Establishment and Reactivation of Latent Herpes Simplex Virus Type 1

    Science.gov (United States)

    Piret, Jocelyne; Lamontagne, Julie; Désormeaux, André; Bergeron, Michel G.

    2001-01-01

    The influence of sodium lauryl sulfate (SLS) on the efficacies of gel formulations of foscarnet against herpes simplex virus type 1 (HSV-1) cutaneous lesions and on the establishment and reactivation of latent virus has been evaluated in a murine model of orofacial infection. Topical treatments were given twice daily for 3 days and were initiated at 6, 24, and 48 h after virus inoculation. The gel formulation that contained both 3% foscarnet and 5% SLS and that was administered within 48 h postinfection reduced the rate of development of herpetic skin lesions. This formulation also significantly decreased the viral content in skin tissues and in ipsilateral trigeminal ganglia when it was given within 24 and 6 h postinfection, respectively. A lower level of efficacy was observed for the gel formulation containing 3% foscarnet alone. Of prime interest, the gel formulation containing 5% SLS reduced significantly the mortality rate among mice in a zosteriform model of infection. Both formulations of foscarnet had no effect on the mean titers of reactivated virus in explant cultures of ipsilateral and contralateral trigeminal ganglia from latently infected mice. The use of a gel formulation containing combinations of foscarnet and SLS could represent an attractive approach for the treatment of herpetic mucocutaneous infections. PMID:11257012

  14. Formulation and evaluation of a topical niosomal gel containing a combination of benzoyl peroxide and tretinoin for antiacne activity

    Science.gov (United States)

    Gupta, Ankush; Singh, Sima; Kotla, Niranjan G; Webster, Thomas J

    2015-01-01

    A skin disease, like acne, is very common and normally happens to everyone at least once in their lifetime. The structure of the stratum corneum is often compared with a brick wall, with corneocytes surrounded by the mortar of the intercellular lipid lamellae. One of the best options for successful drug delivery to the affected area of skin is the use of elastic vesicles (niosomes) which can be transported through the skin through channel-like structures. In this study, a combination of tretinoin (keratolytic agent) and benzoyl peroxide (BPO) (a potent antibacterial) was given by using niosomes as promising carriers for the effective treatment of acne by acting on a pathogenic site. In this section, niosomal gel formulation encapsulated drugs have been evaluated for in vitro, ex vivo, and in vivo, for their predetermined characteristics; and finally the stability of the niosome gel was tested at different temperature conditions for understanding of the storage conditions required for maintaining the quality of formulation attributes. The prepared niosome was found to be in the range of 531 nm with a zeta potential of −43 mV; the entrapment efficiencies of tretinoin (TRA) and BPO niosomes were found to be 96.25%±0.56% and 98.75%±1.25%, respectively. The permeated amount of TRA and BPO from the niosomal gel after 24 hours was calculated as 6.25±0.14 μg/cm2 and 5.04±0.014 μg/cm2, respectively. A comparative drug retention study in Wistar rat skin using cream, an alcoholic solution, and a niosomal gel showed 11.54 μg, 2.68 μg, and 15.54 μg amounts of TRA and 68.85 μg, 59.98 μg, and 143.78 μg amounts of BPO were retained in the layers of skin, respectively. In vivo studies of the niosomal gel and antiacne cream of TRA and BPO showed that the niosomal gel was more efficacious than the antiacne cream because niosomal gels with a 4.16-fold lower dose of BPO provided the same therapeutic index at targeted sites in comparison to the antiacne cream. PMID

  15. Formulation and evaluation of a topical niosomal gel containing a combination of benzoyl peroxide and tretinoin for antiacne activity.

    Science.gov (United States)

    Gupta, Ankush; Singh, Sima; Kotla, Niranjan G; Webster, Thomas J

    2015-01-01

    A skin disease, like acne, is very common and normally happens to everyone at least once in their lifetime. The structure of the stratum corneum is often compared with a brick wall, with corneocytes surrounded by the mortar of the intercellular lipid lamellae. One of the best options for successful drug delivery to the affected area of skin is the use of elastic vesicles (niosomes) which can be transported through the skin through channel-like structures. In this study, a combination of tretinoin (keratolytic agent) and benzoyl peroxide (BPO) (a potent antibacterial) was given by using niosomes as promising carriers for the effective treatment of acne by acting on a pathogenic site. In this section, niosomal gel formulation encapsulated drugs have been evaluated for in vitro, ex vivo, and in vivo, for their predetermined characteristics; and finally the stability of the niosome gel was tested at different temperature conditions for understanding of the storage conditions required for maintaining the quality of formulation attributes. The prepared niosome was found to be in the range of 531 nm with a zeta potential of -43 mV; the entrapment efficiencies of tretinoin (TRA) and BPO niosomes were found to be 96.25%±0.56% and 98.75%±1.25%, respectively. The permeated amount of TRA and BPO from the niosomal gel after 24 hours was calculated as 6.25±0.14 μg/cm(2) and 5.04±0.014 μg/cm(2), respectively. A comparative drug retention study in Wistar rat skin using cream, an alcoholic solution, and a niosomal gel showed 11.54 μg, 2.68 μg, and 15.54 μg amounts of TRA and 68.85 μg, 59.98 μg, and 143.78 μg amounts of BPO were retained in the layers of skin, respectively. In vivo studies of the niosomal gel and antiacne cream of TRA and BPO showed that the niosomal gel was more efficacious than the antiacne cream because niosomal gels with a 4.16-fold lower dose of BPO provided the same therapeutic index at targeted sites in comparison to the antiacne cream.

  16. Evaluation of sublingual microcirculation in children with dengue shock

    Directory of Open Access Journals (Sweden)

    Daniella Mancino da Luz Caixeta

    2013-07-01

    Full Text Available OBJECTIVE: To report the sublingual microcirculation observed using Sidestream Dark Field imaging in two children with dengue shock. METHOD: Two children, aged 9 and 10 years, were admitted to the pediatric intensive care unit with dengue shock and multiple organ dysfunction. Sublingual microcirculation was assessed in each patient on the first and second days of shock and was assessed a final time when the patients were no longer in shock (on the day prior to extubation using Sidestream Dark Field technology. The De Backer score and microvascular flow index were used for the analyses. RESULTS: Both patients had reduced perfused small vessel density in the first two days and showed predominantly intermittent or no microcirculation flow, as demonstrated by a low microvascular flow index. The blood flow in the large vessels was not affected. Prior to the extubation, the microvascular flow index had increased, although the perfused small vessel density remained diminished, suggesting persistent endothelial dysfunction. CONCLUSIONS: Severe microcirculation changes may be involved in the pathophysiological mechanisms that lead to the final stages of dengue shock, which is frequently irreversible and associated with high mortality rates. Microcirculatory monitoring may help elucidate the physiopathology of dengue shock and prove useful as a prognostic tool or therapeutic target.

  17. Debut of Gastroesophageal Reflux Concomitant with Administration of Sublingual Immunotherapy

    Directory of Open Access Journals (Sweden)

    Jacob Juel

    2017-01-01

    Full Text Available Gastroesophageal reflux disease (GORD is an often debilitating condition characterised by retrograde flow of content from stomach into the oesophagus, where the low pH of the stomach acid irritates the mucosa of the oesophagus. The most dominant symptoms in GORD are pyrosis, regurgitation, and dysphagia. Sublingual immunotherapy (SLIT was first described in 1986. Following this description, the use has greatly increased in the treatment of allergic rhinitis, as an alternative to subcutaneously administered immunotherapy. Side effects are commonly of oropharyngeal and gastrointestinal nature, for example, swelling, itching, irritation, ulceration of the oropharynx and nausea, abdominal pain, vomiting, and diarrhoea. More serious side effects are dominated by respiratory tract and systemic manifestations. A 30-year-old male experienced refractory, relentless, and debilitation GORD subsequent to administration of sublingual immunotherapy for house dust mite in allergic rhinitis. The patient had to stop the SLIT after two weeks of administration due to GORD. The cessation resulted in rapid resolution of symptoms.

  18. Duration of immunity induced by an equine influenza and tetanus combination vaccine formulation adjuvanted with ISCOM-Matrix.

    Science.gov (United States)

    Heldens, J G M; Pouwels, H G W; Derks, C G G; Van de Zande, S M A; Hoeijmakers, M J H

    2010-10-08

    Equine influenza is a contagious disease caused by equine influenza virus which belongs to the orthomyxovirus family. Outbreaks of equine influenza cause severe economic loses to the horse industry and consequently horses in competition are required to be regularly vaccinated against equine influenza. Unlike the existing inactivated vaccines, Equilis Prequenza Te is the only one able to induce protection against clinical disease and virus excretion after a primary vaccination course consisting of two vaccine applications 4-6 weeks apart until the recommended time of the third vaccination. In this paper we describe the duration of immunity profile, tested in an experimental setting according to European legislation, of this inactivated equine influenza and tetanus combination vaccine. In addition to influenza antigen, the formulation contains a second generation ISCOM (the so called ISCOMatrix) as an adjuvant. The vaccine aims at the induction of protection from the primary vaccination course until the time of annual revaccination 12 months later, against challenge with a virulent equine influenza strain. The protection against A/equine/Kentucky/95 (H3N8) at the time of annual revaccination was evidenced by a significant reduction of clinical signs of influenza, a significant reduction of virus excretion and a significant reduction of fever. The effect of the annual revaccination on the duration of immunity against influenza and tetanus was also studied by serology. For tetanus, as a consequence of the 24 months duration of immunity, an alternating annual vaccination schedule consisting of Prequenza and Prequenza Te is proposed after the first three doses of Prequenza Te. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Use of formulated Trichoderma sp. Tri-1 in combination with reduced rates of chemical pesticide for control of Sclerotinia sclerotiorium on oilseed rape

    Science.gov (United States)

    Sustainable strategies for control of Sclerotinia sclerotiorum on oilseed rape are needed. Here we tested combinations of Trichoderma sp. Tri-1, formulated with oilseed rape seedcake and straw, with reduced application rates of the chemical pesticide Carbendazim for control of this pathogen on oils...

  20. Combined use of MSWI bottom ash and fly ash as aggregate in concrete formulation: environmental and mechanical considerations.

    Science.gov (United States)

    Ginés, O; Chimenos, J M; Vizcarro, A; Formosa, J; Rosell, J R

    2009-09-30

    This paper reports the experimental results obtained after casting concrete formulated with different mix proportions of municipal solid waste incineration (MSWI) by-products, bottom ash (BA) and air pollution control fly ash (APCFA), as aggregates. Several tests were performed to determine the properties of the mixed proportions. Mechanical properties of the formulations, such as compressive strength, were also determined, and two different leaching tests were performed to study their environmental effects. Some suitable concrete formulations were obtained for the 95/5 and 90/10 BA/APCFA mix proportions. These formulations showed the highest compressive strength test results, above 15 MPa, and the lowest amount of released trace metals in reference to the leaching test. The leaching mechanisms involved in the release of trace metals for the best formulations were also studied, revealing that the washing-off process may play an important role. Given the experimental data it can be concluded that these concrete mix proportions are suitable for use as non-structural concrete.

  1. Relationship between sublingual and intestinal microcirculatory perfusion in patients with abdominal sepsis

    NARCIS (Netherlands)

    Boerma, E. Christiaan; van der Voort, Peter H. J.; Spronk, Peter E.; Ince, Can

    2007-01-01

    Objective: To evaluate the relation between sublingual and intestinal microcirculatory alterations in patients with abdominal sepsis. Design. Prospective observational study. Setting. A 23-bed mixed intensive care unit of a tertiary teaching hospital. Patients: Twenty-three patients with abdominal

  2. Sublingual Nitroglycerin Administration in Coronary Computed Tomography Angiography : a Systematic Review

    NARCIS (Netherlands)

    Takx, Richard A. P.; Suchá, D.; Park, Jakob; Leiner, Tim; Hoffmann, Udo

    2015-01-01

    To systematically investigate the literature for the influence of sublingual nitroglycerin administration on coronary diameter, the number of evaluable segments, image quality, heart rate and blood pressure, and diagnostic accuracy of coronary computed tomography (CT) angiography. A systematic

  3. Critical appraisal of the clinical utility of sublingual immunotherapy in allergy

    Directory of Open Access Journals (Sweden)

    S. Aissa

    2016-12-01

    We performed a literature review in order to remind the mechanisms of action and to demonstrate efficacy and tolerability of the sublingual immunotherapy in the treatment of allergic rhinoconjunctivitis and asthma and its impact on the quality of life.

  4. Adenoid cystic carcinoma of the sublingual gland: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ji Young [Dept. of Oral and Maxillofacial Surgery, School of Medicine, Jeju National University, Jeju (Korea, Republic of)

    2016-12-15

    Adenoid cystic carcinoma (ACC) of the sublingual gland is an extremely rare neoplasm. The clinicopathological characteristics of ACC are slow-growing swelling with or without ulceration, perineural spread, local recurrence, and distant metastasis. This report describes a 58-year-old male who had a slowly growing swelling without ulceration on the right side of the mouth floor that had been present for 1 month. In a radiological examination, the mass showed multilocular cystic features and no bony or tongue muscle invasion. No enlarged cervical lymph nodes were detected. Excisional biopsy and histological analysis showed that the lesion was ACC. In addition to reporting a rare case of ACC, this report also discusses the differential diagnosis and treatment of ACC with a review of the relevant literature.

  5. Sublingual immunotherapy for allergic rhinitis: where are we now?

    Science.gov (United States)

    Incorvaia, Cristoforo; Mauro, Marina; Ridolo, Erminia

    2015-01-01

    Sublingual immunotherapy (SLIT) was introduced in the 1980s as a safer option to subcutaneous immunotherapy and in the latest decade achieved significant advances. Its efficacy in allergic rhinitis is supported by a number of meta-analyses. The development of SLIT preparations in tablets to fulfill the requirements of regulatory agencies for quality of allergen extracts made available optimal products for grass-pollen-induced allergic rhinitis. Preparations of other allergens based on the same production methods are currently in progress. A notable outcome of SLIT, that is shared with subcutaneous immunotherapy, is the evident cost-effectiveness, showing significant cost savings as early as 3 months from starting the treatment, that become as high as 80% compared with drug treatment in the ensuing years.

  6. Sublingual fast dissolving niosomal films for enhanced bioavailability and prolonged effect of metoprolol tartrate

    OpenAIRE

    Allam, Ayat; Fetih, Gihan

    2016-01-01

    Ayat Allam, Gihan Fetih Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt Abstract: The aim of the present work was to prepare and evaluate sublingual fast dissolving films containing metoprolol tartrate-loaded niosomes. Niosomes were utilized to allow for prolonged release of the drug, whereas the films were used to increase the drug’s bioavailability via the sublingual route. Niosomes were prepared using span 60 and cholesterol at different drug to...

  7. Histoanatomical study of the Sublingual Salivary Gland in the Camel

    Directory of Open Access Journals (Sweden)

    M.a Ebrahimi

    2008-02-01

    Full Text Available The heads of ten adult camels were used in this study. Following skin removal, the length, width and thickness of the gland was measured by ruler and caliper. Dye injection was used to distinguish the sublingual duct papilla and 1cm sections from the gland were removed and fixed to prepare histologic sections stained with H & E for microscopic studies. The long, ribbon like and lobulated monostomatic part of the gland is situated underneath the tongue alongside the hypoglossus muscle. This part of the gland begins from the mandibular symphysis and is continued caudally to near the root of the tongue. The average length, width and thickness of this part were 15.2±0.02, 2.2±0.03 and 0.5±0.05 cm respectively. The polystomatic part was observed as scattered and lobulated near the submucosa and in front of the monostomatic part with decreasing concentration caudally. The average size of these fragments was approximately 0.5±0.02 cm. The overall appearance of the gland was lobulated with a pink colour. The monostomatic part has a single duct entering the sublingual caruncle. The minute polystomatic ducts open into the depressions alongside the tongue inside the oral cavity. These ducts are numerous. Histologically, the gland is surrounded by a capsule of dense connective tissue. Trabcules from the capsule penetrate the gland and divide it into lobules. Loose connective tissue makes up the framework of the gland and there are tubulo-acinus glands in the spaces of this framework. Approximately 95% of the secretory cells of this gland consist of mucous secreting cells. Myoepithelial cells are seen on the external surface of the secretory cells and also alongside the connecting ducts.

  8. Monitoring Microcirculatory Blood Flow with a New Sublingual Tonometer in a Porcine Model of Hemorrhagic Shock

    Directory of Open Access Journals (Sweden)

    Péter Palágyi

    2015-01-01

    Full Text Available Tissue capnometry may be suitable for the indirect evaluation of regional hypoperfusion. We tested the performance of a new sublingual capillary tonometer in experimental hemorrhage. Thirty-six anesthetized, ventilated mini pigs were divided into sham-operated (n=9 and shock groups (n=27. Hemorrhagic shock was induced by reducing mean arterial pressure (MAP to 40 mmHg for 60 min, after which fluid resuscitation started aiming to increase MAP to 75% of the baseline value (60–180 min. Sublingual carbon-dioxide partial pressure was measured by tonometry, using a specially coiled silicone rubber tube. Mucosal red blood cell velocity (RBCV and capillary perfusion rate (CPR were assessed by orthogonal polarization spectral (OPS imaging. In the 60 min shock phase a significant drop in cardiac index was accompanied by reduction in sublingual RBCV and CPR and significant increase in the sublingual mucosal-to-arterial PCO2 gap (PSLCO2 gap, which significantly improved during the 120 min resuscitation phase. There was significant correlation between PSLCO2 gap and sublingual RBCV (r=-0.65, p<0.0001, CPR (r=-0.64, p<0.0001, central venous oxygen saturation (r=-0.50, p<0.0001, and central venous-to-arterial PCO2 difference (r=0.62, p<0.0001. This new sublingual tonometer may be an appropriate tool for the indirect evaluation of circulatory changes in shock.

  9. Clinical benefits of treatment with SQ house dust mite sublingual tablet in house dust mite allergic rhinitis.

    Science.gov (United States)

    Demoly, P; Kleine-Tebbe, J; Rehm, D

    2017-10-01

    Treatment with SQ (standardised quality) house dust mite sublingual tablet for 1 year resulted in a decreased probability of having an allergic rhinitis (AR) exacerbation day (from 11% [placebo] to 5% [SQ house dust mite sublingual tablet]) and an increased probability of having a mild AR day (from 16% [placebo] to 34% [SQ house dust mite sublingual tablet]). © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  10. Buccal or sublingual misoprostol for cervical ripening and induction of labour.

    Science.gov (United States)

    Muzonzini, G; Hofmeyr, G J

    2004-10-18

    This is one of a series of reviews of cervical ripening and labour induction using standardised methodology. Misoprostol administered by the oral and sublingual routes have the advantage of rapid onset of action, while the sublingual and vaginal routes have the advantage of prolonged activity and greatest bioavailability. To determine the effectiveness and safety of misoprostol administered buccally or sublingually for third trimester cervical ripening and induction of labour. We searched the Cochrane Pregnancy and Childbirth Group trials register (8 December 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), and bibliographies of relevant papers. Randomised controlled trials comparing buccal or sublingual misoprostol used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods. A generic strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. Data were extracted onto standardized forms, checked for accuracy, and analysed using RevMan software. Three studies (502 participants) compared buccal/sublingual misoprostol respectively with a vaginal regimen (200 microg versus 50 microg) and with oral administration (50 versus 50 microg and 50 versus 100microg).The buccal route was associated with a trend to fewer caesarean sections than with the vaginal route (18/73 versus 28/79; relative risk (RR) 0.70; 95% confidence interval (CI) 0.42 to 1.15). There were no significant differences in any other outcomes. When the same dosage was used sublingually versus orally, the sublingual route was associated with less failures to achieve vaginal delivery within 24 hours (12/50 versus 19/50; RR 0.63, 95% CI 0.34 to 1.16), reduced oxytocin augmentation (17/50 versus 23/50; RR 0.74, 95% CI 0.45 to 1.21) and reduced caesarean section (8/50 versus 15/50; RR 0.53, 95% CI 0.25 to

  11. Generalization of the Hofmann-Zotter combined-function formulation for application to 50x50 GeV e+e- storage rings

    International Nuclear Information System (INIS)

    Sakazaki, L.E.; Talman, R.M.

    1983-01-01

    Though all existing strong-focusing electron storage rings have separated-function lattices, the combined-function lattice would reduce energy loss to synchrotron radiation. Robinson and Hofmann and Zotter have shown how to overcome the anti-damping that was once thought to rule out this possibility. Their formulation is generalized to achieve a more realistic machine design having FODO cells to incorporate the inevitable straight sections between magnets and to allow for any subsequent insertion of nonlinear elements. An analysis is performed to estimate the energy savings for a 50x50 GeV e+e- facility using combined-function magnets

  12. Sublingual immunization with the phosphate-binding-protein (PstS) reduces oral colonization by Streptococcus mutans.

    Science.gov (United States)

    Ferreira, E L; Batista, M T; Cavalcante, R C M; Pegos, V R; Passos, H M; Silva, D A; Balan, A; Ferreira, L C S; Ferreira, R C C

    2016-10-01

    Bacterial ATP-binding cassette (ABC) transporters play a crucial role in the physiology and pathogenicity of different bacterial species. Components of ABC transporters have also been tested as target antigens for the development of vaccines against different bacterial species, such as those belonging to the Streptococcus genus. Streptococcus mutans is the etiological agent of dental caries, and previous studies have demonstrated that deletion of the gene encoding PstS, the substrate-binding component of the phosphate uptake system (Pst), reduced the adherence of the bacteria to abiotic surfaces. In the current study, we generated a recombinant form of the S. mutans PstS protein (rPstS) with preserved structural features, and we evaluated the induction of antibody responses in mice after sublingual mucosal immunization with a formulation containing the recombinant protein and an adjuvant derived from the heat-labile toxin from enterotoxigenic Escherichia coli strains. Mice immunized with rPstS exhibited systemic and secreted antibody responses, measured by the number of immunoglobulin A-secreting cells in draining lymph nodes. Serum antibodies raised in mice immunized with rPstS interfered with the adhesion of bacteria to the oral cavity of naive mice challenged with S. mutans. Similarly, mice actively immunized with rPstS were partially protected from oral colonization after challenge with the S. mutans NG8 strain. Therefore, our results indicate that S. mutans PstS is a potential target antigen capable of inducing specific and protective antibody responses after sublingual administration. Overall, these observations raise interesting perspectives for the development of vaccines to prevent dental caries. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Synergistic Combinations of a Pyrethroid Insecticide and an Emulsifiable Oil Formulation of Beauveria bassiana to Overcome Insecticide Resistance in Listronotus maculicollis (Coleoptera: Curculionidae).

    Science.gov (United States)

    Wu, Shaohui; Kostromytska, Olga S; Koppenhöfer, Albrecht M

    2017-08-01

    The annual bluegrass weevil, Listronotus maculicollis (Kirby), is a major pest of golf course turf in eastern North America and has become particularly problematic owing to widespread development of insecticide resistance. As an alternative option to manage resistant adult L. maculicollis, we explored combinations of the pyrethroid insecticide bifenthrin with an emulsifiable oil formulation of the entomopathogenic fungus Beauveria bassiana strain GHA (Bb ES). Combinations synergistically enhanced mortality in both insecticide-susceptible and insecticide-resistant L. maculicollis adults in the laboratory when bifenthrin was used at LC50s for each population. To determine the component behind the synergism, technical spores of B. bassiana GHA and the emulsifiable oil carrier in the fungal formulation were tested separately or in combination with bifenthrin. In both separate and combined applications, the emulsifiable oil carrier was responsible for high mortality within 3 d after treatment and interacted synergistically with bifenthrin, whereas fungus-induced mortality started later. Strong synergism was also observed in three field experiments with a relatively resistant L. maculicollis population. Combinations of Bb ES and bifenthrin hold promise as an effective L. maculicollis management tool, particularly of pyrethroid-resistant populations. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Bioequivalence assessment of rifampicin, isoniazid and pyrazinamide in a fixed dose combination of rifampicin, isoniazid, pyrazinamide and ethambutol vs. separate formulations.

    Science.gov (United States)

    Agrawal, S; Singh, I; Kaur, K J; Bhade, S R; Kaul, C L; Panchagnula, R

    2002-10-01

    Depending on the patient category, tuberculosis requires treatment with 3 to 5 drugs which means that patient's compliance to therapy may not be optimal. To increase patient's adherence to treatment schedules, these drugs can be given as single drug preparations or fixed dose combinations (FDCs) of 2 or more drugs in a single formulation. However, an important issue associated with a rifampicin-containing FDC is its quality. Hence, to avoid spurious formulations entering the market, the World Health Organization and the International Union Against Tuberculosis and Lung Disease have recommended FDCs only of proven bioavailability. In this study, the relative bioavailability of rifampicin, isoniazid and pyrazinamide was assessed in a group of 14 healthy male subjects using the FDC tablet containing 4 drugs versus separate formulations at the same dose levels. The study was designed as an open, crossover trial. A total of 9 blood samples were collected over a period of 24 h. The concentration of rifampicin, its main metabolite desacetyl rifampicin, isoniazid and pyrazinamide in plasma were assessed using HPLC analysis. The pharmacokinetic parameters AUC(0-24) and Cmax were subjected to parametric and non-parametric statistical tests at 90% confidence interval. In addition, time to reach peak concentration (tmax), elimination rate constant (Kel) and terminal elimination half-life (t1/2) for each drug were also calculated. It was concluded that the FDC tablet containing 4 drugs is bioequivalent to separate rifampicin, isoniazid and pyrazinamide formulations at the same dose levels.

  15. Current issues on sublingual allergen-specific immunotherapy in children with asthma and allergic rhinitis

    Directory of Open Access Journals (Sweden)

    Živković Zorica

    2016-01-01

    Full Text Available In 1993 the European Academy of Allergy and Clinical Immunology was the first official organization to recognize that sublingual administration could be “promising route” for allergic desensitization. A few years later, the World Health Organization recommended this therapy as “a viable alternative to the injection route in adults.” The first meta-analysis showed sublingual allergen specific immunotherapy (SLIT effectiveness for allergic rhinitis and another study showed SLIT can actually help prevent the development of asthma both in adults and in children. The main goal of this review article is to present insight into the most up-to-date understanding of the clinical efficacy and safety of immunotherapy in the treatment of pediatric patients with allergic rhinitis and asthma. A literature review was performed on PubMed from 1990 to 2015 using the terms “asthma,” “allergic rhinitis,” “children,” “allergen specific immune therapy.” Evaluating data from double-blind placebo-controlled randomized clinical trials (DB-PC-RCTs, the clinical efficacy (assessed as the reduction of symptom score and the need of rescue medicament of SLIT for allergic rhinitis and allergic asthma, has been confirmed in various meta-analysis Outcomes such as rhinoconjunctivitis score and medication scores, combined scores, quality of life, days with severe symptoms, immunological endpoints, and safety parameters were all improved in the SLIT-tablet compared with placebo group. SLIT safety has been already proven in many DB-PC-RCTs and real-life settings. In accordance with all of the above mentioned, the goals for future trials and studies are the development of comprehensive guidelines for clinical practice on immunotherapy, embracing all the different potential participants. The importance of allergen immunotherapy is of special relevance in the pediatric age, when the plasticity and modulability of the immune system are maximal, and when

  16. Immunotherapy (oral and sublingual) for food allergy to fruits.

    Science.gov (United States)

    Yepes-Nuñez, Juan Jose; Zhang, Yuan; Roqué i Figuls, Marta; Bartra Tomas, Joan; Reyes, Juan Manuel; Pineda de la Losa, Fernando; Enrique, Ernesto

    2015-11-09

    Food allergy is an abnormal immunological response following exposure (usually ingestion) to a food. Elimination of the allergen is the principle treatment for food allergy, including allergy to fruit. Accidental ingestion of allergenic foods can result in severe anaphylactic reactions. Allergen-specific immunotherapy (SIT) is a specific treatment, when the avoidance of allergenic foods is problematic. Recently, studies have been conducted on different types of immunotherapy for the treatment of food allergy, including oral (OIT) and sublingual immunotherapy (SLIT). To determine the efficacy and safety of oral and sublingual immunotherapy in children and adults with food allergy to fruits, when compared with placebo or an elimination strategy. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and AMED were searched for published results along with trial registries and the Journal of Negative Results in BioMedicine for grey literature. The date of the most recent search was July 2015. Randomised controlled trials (RCTs) comparing OIT or SLIT with placebo or an elimination diet were included. Participants were children or adults diagnosed with food allergy who presented immediate fruit reactions. We used standard methodological procedures expected by the Cochrane Collaboration. We assessed treatment effect through risk ratios (RRs) for dichotomous outcomes. We identified two RCTs (N=89) eligible for inclusion. These RCTs addressed oral or sublingual immunotherapy, both in adults, with an allergy to apple or peach respectively. Both studies enrolled a small number of participants and used different methods to provide these differing types of immunotherapy. Both studies were judged to be at high risk of bias in at least one domain. Overall, the quality of evidence was judged to be very low due to the small number of studies and participants and possible bias. The studies were clinically heterogeneous and hence we did not pool the

  17. Prehospital high-dose sublingual nitroglycerin rarely causes hypotension.

    Science.gov (United States)

    Clemency, Brian M; Thompson, Jeffrey J; Tundo, Gina N; Lindstrom, Heather A

    2013-10-01

    High-dose intravenous nitroglycerin is a common in-hospital treatment for respiratory distress due to congestive heart failure (CHF) with hypertension. Intravenous (IV) nitroglycerin administration is impractical in the prehospital setting. In 2011, a new regional Emergency Medical Services (EMS) protocol was introduced allowing advanced providers to treat CHF with high-dose oral nitroglycerin. The protocol calls for patients to be treated with two sublingual tabs (0.8 mg) when systolic blood pressure (SBP) was >160 mm Hg, or three sublingual tabs (1.2 mg) when SBP was >200 mm Hg, every five minutes as needed. Hypothesis/Problem To assess the protocol's safety, the incidence of hypotension following prehospital administration of multiple simultaneous nitroglycerin (MSN) tabs by EMS providers was studied. This study was a retrospective cohort study of patients from a single commercial EMS agency over a 6-month period. Records from patients with at least one administration of MSN were reviewed. For each administration, the first documented vital signs pre- and post-administration were compared. Administrations were excluded if pre- or post-administration vital signs were missing. One hundred case-patients had at least one MSN administration by an advanced provider during the study period. Twenty-five case-patients were excluded due to incomplete vital signs. Seventy-five case-patients with 95 individual MSN administrations were included for analysis. There were 65 administrations of two tabs, 29 administrations of three tabs, and one administration of four tabs. The mean change in SBP following MSN was -14.7 mm Hg (SD = 30.7; range, +59 to -132). Three administrations had documented systolic hypotension in the post-administration vital signs (97/71, 78/50 and 66/47). All three patients were over 65 years old, were administered two tabs, had documented improved respiratory status, and had repeat SBP of at least 100. The incidence of hypotension following MSN

  18. Misoprostol sublingual versus vaginal para indução do parto a termo Sublingual versus vaginal misoprostol for labor induction of term pregnancies

    Directory of Open Access Journals (Sweden)

    Olímpio Barbosa de Moraes Filho

    2005-01-01

    Full Text Available OBJETIVO: comparar efetividade e segurança de uso de comprimido sublingual de 25 µg de misoprostol com o comprimido vaginal de 25 µg do misoprostol na indução do parto com idade gestacional e > 37 semanas e colo uterino desfavorável. MÉTODOS: realizou-se ensaio clínico controlado e aleatorizado, não cego, na Maternidade Monteiro de Morais (CISAM-UPE, em Recife, no período de outubro de 2003 a fevereiro de 2004. Participaram do estudo 123 gestantes com idade gestacional e > 37 semanas, índice de Bishop PURPOSE: to compare the effectiveness and safety of sublingual misoprostol (25 µg versus vaginal misoprostol (25 µg (Prostokos® for labor induction with gestational age > 37 weeks and unripe cervices. METHODS: a randomized controlled clinical trial was performed at the Maternidade Monteiro de Morais (CISAM-UPE, in Recife - PE, Brazil, from October 2003 to February 2004. One hundred and twenty-three women with gestational age > 37 weeks, Bishop score <8, not in labor and with medical indication for interruption of pregnancy were included in this study. The women received randomly 25 µg sublingual misoprostol or 25 µg vaginal misoprostol every 6 h, not exceeding eight doses. In order to evaluate the differences between the groups, means, standard deviations, Student's t-test, c² trend and Mann-Whitney test were used. The statistical significance was considered to be 5%. RESULTS: there were no significant differences between the number of women with vaginal delivery in the sublingual group as compared with the vaginal group (65.5 vs 75.8%, p<0.22, or in the interval of time between the induction onset and delivery (24 h and 42 min vs 20 h and 37 min respectively, p=0.11. The two groups, sublingual and vaginal, also did not differ as to the hyperstimulation syndrome (1.7 vs 3.2%, p=0.95, meconium incidence (5.2 vs 4.8%, p=0.74, Apgar score <7 at 5 min (3.4 vs 4.8%, p=0.98 and other adverse effects. CONCLUSION: twenty-five micrograms of

  19. Comparative bioavailability of rifampicin, isoniazid and pyrazinamide from a four drug fixed dose combination with separate formulations at the same dose levels.

    Science.gov (United States)

    Agrawal, Shrutidevi; Singh, Inderjit; Kaur, Kanwal Jit; Bhade, Shantaram R; Kaul, Chaman Lal; Panchagnula, Ramesh

    2004-05-19

    Fixed dose combination (FDC) formulations became popular in the treatment of tuberculosis (TB) because of the better patient compliance, reduced risk of monotherapy and emergence of drug resistance in contrast to treatment with separate formulations of two to four first-line drugs. However, its successful implementation in national programs is limited by probable bioinequivalency of rifampicin if present in FDC form. In this regard, World Health Organization (WHO) and International Union Against Tuberculosis and Lung Disease (IUATLD) recommend FDCs only of proven bioavailability. Hence, bioequivalence study of four drug FDC tablet was conducted using 22 healthy male volunteers according to WHO recommended protocol to determine bioavailability of rifampicin, isoniazid and pyrazinamide compared to standard separate combination at the same dose level. The study was designed as two period, two treatment crossover experiment with a washout period of 1 week. Bioequivalence of rifampicin was estimated by plasma and urinary method for both rifampicin and its active metabolite, des-acetyl rifampicin whereas isoniazid and pyrazinamide were estimated from plasma. Mean concentration time profiles and all the pharmacokinetic parameters of rifampicin, isoniazid and pyrazinamide from FDC tablet were comparable to individual formulations and passed the bioequivalence test with power of the test above 95%. Further, bioequivalence of both rifampicin and isoniazid shows that in vitro interaction of rifampicin and isoniazid is clinically insignificant. Thus, it was concluded that FDC formulation is bioequivalent for rifampicin, isoniazid and pyrazinamide and ensures the successful treatment of TB without compromising therapeutic efficacy of any of these components of anti-TB therapy.

  20. Morphology and morphometry of the human sublingual glands in mouth floor enlargements of edentulous patients

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    Josiane Costa Rodrigues de SA

    2013-12-01

    Full Text Available Asymptomatic mouth floor enlargements may be observed in edentulous patients. These masses, which protrude from the mouth floor, may complicate the fitting of dentures and require surgery. Whether this "entity" may be considered an anatomical variation of the mouth floor or represent specific alterations in the sublingual gland is not known. Objective: The aim of this work is to investigate the morphological and morphometric aspects of the sublingual glands of edentulous patients with mouth floor enlargements and compare the glands of these patients with the sublingual glands of human cadavers. Material and Methods: Microscopic evaluation was performed on human sublingual glands from edentulous patients with mouth floor enlargements (n=20 and edentulous cadavers (n=20. The patients and cadavers were of similar ages. The data were compared using Mann-Whitney U, Fisher's exact and Student's t tests (p0.05. Only the variables "autolysis" and "congested blood vessels" presented statistical difference between groups (p=0.014; p=0.043. The morphometric study revealed that the volume densities of acini, ducts, stroma and adipose tissue were similar between the groups (p>0.05. CONCLUSION: The microscopic characteristics of the sublingual glands in mouth floor enlargements in edentulous patients correspond to characteristics associated with the normal aging process. The glands are not pathological and represent an age-related alteration that occurs with or without the presence of the mouth floor enlargements.

  1. Selection of patients for sublingual versus subcutaneous immunotherapy.

    Science.gov (United States)

    Larenas Linnemann, Désirée E S; Blaiss, Michael S

    2014-01-01

    Allergen immunotherapy is the sole treatment for IgE-mediated allergic diseases directed at the underlying mechanism. The two widely accepted administration routes are sublingual (SLIT) and subcutaneous (SCIT). We reviewed how patients should best be selected for immunotherapy and how the optimal administration route can be defined. Before deciding SCIT or SLIT, appropriate selection of patients for allergen immunotherapy (AIT) is mandatory. To be eligible for AIT, subjects must have a clear medical history of allergic disease, with exacerbation of symptoms on exposure to one or more allergens and a corresponding positive skin or in vitro test. Then the route of administration should be based on: published evidence of clinical and immunologic efficacy (which varies per allergic disease and per allergen); mono- or multi-allergen immunotherapy, for SLIT multi-allergen immunotherapy was not effective; safety: adverse events with SLIT are more frequent, but less severe; and, costs and patient preferences, closely related to adherence issues. All these are discussed in the article.

  2. Local Side Effects of Sublingual and Oral Immunotherapy.

    Science.gov (United States)

    Passalacqua, Giovanni; Nowak-Węgrzyn, Anna; Canonica, Giorgio Walter

    Sublingual immunotherapy (SLIT) is increasingly used worldwide, and several products have been recently registered as drugs for respiratory allergy by the European Medicine Agency and the Food and Drug Administration. Concerning inhalant allergens, the safety of SLIT is overall superior to that of subcutaneous immunotherapy in terms of systemic adverse events. No fatality has been ever reported, and episodes of anaphylaxis were described only exceptionally. Looking at the historical and recent trials, most (>90%) adverse events are "local" and confined to the site of administration. For this reason, a specific grading system has been developed by the World Allergy Organization to classify and describe local adverse events. There is an increasing amount of literature concerning oral desensitization for food allergens, referred to as oral immunotherapy. Also, in this case, local side effects are predominant, although systemic adverse events are more frequent than with inhalant allergens. We review herein the description of local side effects due to SLIT, with a special focus on large trials having a declared sample size calculation. The use of the Medical Dictionary for Regulatory Activities nomenclature for adverse events is mentioned in this context, as recommended by regulatory agencies. It is expected that a uniform classification/grading of local adverse events will improve and harmonize the surveillance and reporting on the safety of SLIT. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  3. Two-stage in vitro digestibility assay, a tool for formulating non-starch polysaccharide degrading enzyme combinations for commonly used feed ingredients of poultry rations

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    Y. Ramana Reddy

    2013-05-01

    Full Text Available Aim: An attempt was made to assess the effect of pure enzyme combinations with the objective of formulating customized enzyme mixtures based on sugar release when subjected to two-stage in vitro digestion assay. Materials and Methods: A two-stage in vitro digestibility assay was carried out for commonly used feed ingredients for poultry viz., maize, soy bean meal, sunflower cake, and de-oiled rice bran supplemented with three concentrations of xylanase (5000; 7500 and 10000 IU/kg, cellulase (50; 100 and 400 IU/kg and â-D-glucanase (100; 200 and 400 IU/kg were used to formulate various NSP enzymes combinations. In total 27 NSP enzyme combinations (3x3x3 were formulated and the sugar released due to NSP digestion was quantified by phenol sulphuric acid method. Results: The total sugar release was significantly (P<0.05 higher with supplementation of various enzymes combinations for maize, sunflower cake and de-oiled rice bran where as no significant (P<0.05 interaction of various NSP enzymes combinations was observed for soy bean meal. The NSP digestibility was highest in combination (xylanase-5000, cellulase-50 and â-D-glucanase-400 IU/kg, (xylanase-10000, cellulase-50 and â-D-glucanase-200 IU/kg and (xylanase-7500, cellulase- 100 and â-D-glucanase-100 IU/kg for maize, sunflower cake and de-oiled rice bran respectively. In case of sunflower cake, significant (P<0.01 three way interaction was observed among the xylanase, cellulose, and â-D-glucanase enzymes and the two-way interactions between the enzymes were also significant (P<0.01. Conclusion: It is concluded that 'n' number of non-starch Polysaccharide enzymes combinations can be screened for their efficiency to digest non-starch Polysaccharides present in various feed ingredients commonly used in poultry rations by employing two-stage in vitro digestibility assay as a tool. [Vet World 2013; 6(8.000: 525-529

  4. Efficacy and safety of sublingual tablets of house dust mite allergen extracts in adults with allergic rhinitis

    NARCIS (Netherlands)

    Bergmann, Karl-Christian; Demoly, Pascal; Worm, Margitta; Fokkens, Wytske J.; Carrillo, Teresa; Tabar, Ana I.; Nguyen, Hélène; Montagut, Armelle; Zeldin, Robert K.

    2014-01-01

    Preliminary studies have suggested the efficacy of sublingual tablets of house dust mite (HDM) extracts in adults with allergic rhinitis. We sought to assess the efficacy and safety of 2 doses of HDM sublingual tablets over 1 treatment year and the subsequent immunotherapy-free year. Adults with

  5. Assessment of bioequivalence of rifampicin, isoniazid and pyrazinamide in a four drug fixed dose combination with separate formulations at the same dose levels.

    Science.gov (United States)

    Agrawal, Shrutidevi; Kaur, Kanwal Jit; Singh, Inderjit; Bhade, Shantaram R; Kaul, Chaman Lal; Panchagnula, Ramesh

    2002-02-21

    Tuberculosis (TB) needs treatment with three to five different drugs simultaneously, depending on the patient category. These drugs can be given as single drug preparations or fixed dose combinations (FDCs) of two more drugs in a single formulation. World Health Organization and International Union against Tuberculosis and Lung Disease (IUATLD) recommend FDCs only of proven bioavailability. The relative bioavailability of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PYZ) was assessed on a group of 13 healthy male subjects from a four drug FDC versus separate formulations at the same dose levels. The study was designed to be an open, crossover experiment. A total of nine blood samples each of 3 ml volume were collected over a period of 24-h. The concentrations of RIF, its main metabolite desacetyl RIF (DRIF), INH and PYZ in plasma were assessed by HPLC analysis. Pharmacokinetic parameters namely AUC(0-24), AUC(0-inf), C(max), T(max), were calculated and subjected to different statistical tests (Hauschke analysis, two way ANOVA, normal and log transformed confidence interval) at 90% confidence interval. In addition, elimination rate constant (K(el)) and absorption efficiencies for each drug were also calculated. It was concluded that four drugs FDC tablet is bioequivalent for RIF, INH and PYZ to separate formulation at the same dose levels.

  6. Sharp tooth induced sublingual hematoma in a patient with elevated international normalized ratio

    Directory of Open Access Journals (Sweden)

    John Baliah

    2015-01-01

    Full Text Available Sublingual hematoma secondary to anticoagulation is a rare fatal condition. Hemorrhagic complications of warfarin are well-known. This particular case is unique because the patient was on warfarin for the past 2 years but did not develop the sublingual hematoma. However, a trauma by an attrited sharp cusp triggered the episode of the sublingual hematoma in this patient. Being a medical emergency, patient was promptly hospitalized in cardiac care unit and managed by medical team. The patient was transfused with 2 units of fresh frozen plasma and warfarin was temporarily stopped for 4 days. Alternate day regimen of warfarin was started after 4 days, and international normalized ratio dropped to 3. In dental management, enameloplasty of the mandibular first molar tooth was done to prevent trauma and ulcer development in the floor of the mouth. The hematoma resolved, and no new hematoma formation was observed for a period of 6 months.

  7. Clinical utility and development of the fluticasone/formoterol combination formulation (Flutiform® for the treatment of asthma

    Directory of Open Access Journals (Sweden)

    Tan RA

    2014-09-01

    Full Text Available Ricardo Antonio Tan,1 Jonathan Corren2 1California Allergy and Asthma Medical Group, 2David Geffen School of Medicine at UCLA, Los Angeles, CA, USAAbstract: Pharmacologic treatment of asthma should be done with a stepwise approach recommended in treatment guidelines. If inhaled corticosteroids (ICSs alone are not adequate, ICSs in combination with long-acting β-agonists (LABAs are now established and widely used as the next step in effective controller therapy. Fixed-dose ICS/LABA combinations in a single device are the preferred form of delivery and improve compliance by enabling patients to get symptom relief from the LABA while receiving the anti-inflammatory benefits of ICSs. Fluticasone propionate/formoterol fumarate is one of the newest fixed-dose combinations. It has been in use in Europe in 2012, but is still under regulatory review in the US. Fluticasone is a synthetic ICS with potent anti-inflammatory effects, while formoterol is a selective β2-adrenergic receptor agonist with a rapid onset of bronchodilation within 5–10 minutes and a 12-hour duration of action. Fluticasone/formoterol has shown superior efficacy when compared to fluticasone or formoterol alone in multiple well-designed studies. The combination has shown comparable or “noninferior” benefits in lung function, clinical symptoms, and asthma control when compared with fluticasone and formoterol administered concurrently in separate inhalers. Fluticasone/formoterol provides similar efficacy with fluticasone/salmeterol, but with more rapid symptom relief. It has been compared directly with budesonide/formoterol with comparable results. Fluticasone/formoterol is well tolerated, with no unusual or increased safety concerns versus each individual component or other available ICS/LABA combinations. Fluticasone/formoterol is the latest entry into a relatively crowded market of branded fixed-dose preparations. Upcoming generic fixed-dose combinations and once-daily agents

  8. Analysis of Piroxicam in Pharmaceutical Formulation and Human Urine by Dispersive Liquid–Liquid Microextraction Combined with Spectrophotometry

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    Nakisa Seyyedeh Tutunchi

    2013-02-01

    Full Text Available Purpose: Piroxicam, is non–steroidal anti–inflammatory and analgesic agent, which is widely used in the treatment of patients with rheumatologic disorders. A new analytical approach based on the dispersive liquid–liquid microextraction (DLLME has been developed for the extraction and determination of PX in pharmaceutical preparation and human urine. Methods: From the PX standard solution or solutions prepared from real samples, aliquot volumes were pipetted into centrifuge tubes and mixed with acetate buffer at pH 3.0 and NaCl solution. The contents were subjected to the DLLME, so 700 μL of methanol containing 70 μL of chloroform was injected rapidly into a sample solution. A cloudy solution was rapidly produced and the PX extracted into dispersed fine droplets. The mixture was centrifuged, thus these fine droplets of chloroform were settled. The supernatant aqueous phase was readily decanted, then the remained organic phase was diluted with ethanol and the absorbance measured at 355 ± 3 nm against a reagent blank. Results: The main factors affecting the extraction efficiency such as pH, extraction and disperser solvent types and etc. were studied and optimized systematically. Under optimized conditions, the calibration graphs were linear over the range of 0.2 to 4.8 μg/mL. The limit of detection and relative standard deviation were found to be 0.058 μg/mL and 2.83%, respectively. Relative recoveries in the spiked samples ranged from 97 to 110%. Conclusion: Using the developed method PX can be analyzed in pharmaceutical formulation and human urine sample in a simpler, cheaper and more rapid manner.

  9. Low-fat frankfurters formulated with a healthier lipid combination as functional ingredient: microstructure, lipid oxidation, nitrite content, microbiological changes and biogenic amine formation.

    Science.gov (United States)

    Delgado-Pando, Gonzalo; Cofrades, Susana; Ruiz-Capillas, Claudia; Solas, Maria Teresa; Triki, Mehdi; Jiménez-Colmenero, Francisco

    2011-09-01

    Oil (healthier lipid combination of olive, linseed and fish oils)-in-water emulsions stabilized with different protein systems (prepared with sodium caseinate (SC), soy protein isolate (SPI), and microbial transglutaminase (MTG)) were used as pork backfat replacers in low-fat frankfurters. Microstructure, lipid oxidation, nitrite content, microbiological changes and biogenic amine formation of frankfurters were analyzed and found to be affected by the type of oil-in-water emulsion and by chilling storage (2° C, 41 days). Although the lipid oxidation levels attained were low, replacement of animal fat by healthier oil combinations in frankfurter formulation did promote a slight increase in lipid oxidation. Residual nitrite was affected (P nitrite was detectable in the product after processing and 17-46% at the end of storage. The microbial population was low in all formulations during chilling storage. Spermine was the most abundant amine (19-20 mg/kg), but similar in level to all samples. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Postmortem acinar autolysis in rat sublingual gland: a morphometric study.

    Science.gov (United States)

    Nery, Leticia Rodrigues; Moreira, Carla Ruffeil; Cestari, Tania Mary; Taga, Rumio; Damante, José Humberto

    2010-01-01

    To analyze and to quantify morphological acinar postmortem changes in rat sublingual glands (SLG). MATERIAL AND METHODSs: Fifty rats were divided into two groups of 25 animals each. Group I was used for morphological and morphometric evaluations and group II for the determination of gland density and processed gland volume. Acinar autolytic changes were studied at 0 (control group), 3, 6, 12 and 24 h postmortem periods. The morphometric analysis of the volume density (Vv) and total volume (Vt) of intact (ia) and autolyzed (aa) acini was performed under light microscopy using a Zeiss II integration grid with 100 symmetrically distributed points. Morphologically, temporal progressive nuclear alterations and gradual loss of the structural architecture of acinar cells were found. Regarding quantitative results, both the Vvaa and the Vvia showed statistically significant differences among all postmortem periods (p0.05), respectively. Vtaa increased from 0.18 mm³ at 0 h to 38.17 mm³ at 12 h, while Vtia showed a decrease from 33.47 mm³ to 0 mm³ between 3-24 h postmortem. Data concerning Vtaa were adjusted by two-variable linear regression, obtaining the equation: y=-3.54+3.38x (r²=0.90). The Vtaa growth rate calculated by this equation was 3.38 mm³/h between 0-12 h. Acinar autolysis on rat SLG demonstrated the most significant signs during the first 6 h postmortem and was widely spread through the gland at 12 h.

  11. Efficacy and safety of two ramipril and hydrochlorothiazide fixed-dose combination formulations in adults with stage 1 or stage 2 arterial hypertension evaluated by using ABPM.

    Science.gov (United States)

    Oigman, Wille; Gomes, Marco Antônio Mota; Pereira-Barretto, Antônio Carlos; Póvoa, Rui; Kohlmann, Osvaldo; Rocha, João Carlos; Nobre, Fernando

    2013-05-01

    Fixed-dose combinations of antihypertensive agents demonstrate advantages in terms of efficacy, tolerability, and treatment adherence. This study was designed to compare the efficacy and safety of 2 ramipril and hydrochlorothiazide (HCTZ) fixed-dose combinations in patients with hypertension stage 1 or 2. Patients' blood pressure (BP) profiles were evaluated by using 24-hour ambulatory BP monitoring (ABPM). This was a multicenter, prospective, randomized, open-label, parallel-group, noninferiority trial of adult patients (age ≥18 years) with hypertension stage 1 or 2 and systolic blood pressure (SBP) within 140 to 179 mm Hg or diastolic blood pressure (DBP) 90 to 109 mm Hg. After a 2-week washout period, eligible patients were randomized to receive 1 of 2 ramipril/HCTZ fixed-dose combination formulations (5/25 mg/d) for 8 weeks. The primary end point was the difference in 24-hour ABPM SBP/DBP mean reductions between groups after 8 weeks of treatment. The secondary end points were the changes in daytime and nighttime ABPM and in office BP. Safety profile and tolerability assessments included monitoring of adverse events. A total of 102 patients with hypertension (54 in group A [test formulation] and 48 in group B [reference formulation]), aged 27 to 85 years, completed the 8-week treatment period. The decreases in SBP and DBP according to 24-hour ABPM from baseline to week 8 were significant and similar in both groups. SBP decreased from 149.1 to 133.0 mm Hg (-16.1 mm Hg) in group A and from 146.2 to 130.6 mm Hg in group B (-15.6 mm Hg) (P = 0.8537); DBP was reduced by 8.8 mm Hg in group A and by 8.5 mm Hg in group B (P = 0.8748). Because the lower 95% CI limit for the difference between groups A and B of 3.96 mm Hg in SBP and 3.54 mm Hg in DBP was lower than that preestablished by the trial protocol (4 mm Hg), noninferiority of the test formulation was demonstrated compared with the reference formulation. For the secondary end points, there was no significant

  12. Using Light Microscopy and Liquid Chromatography Tandem Mass Spectrometry for Qualitative and Quantitative Control of a Combined Three-Herb Formulation in Different Preparations

    Directory of Open Access Journals (Sweden)

    Tun-Pin Hsueh

    2016-12-01

    Full Text Available Artemisia capillaries Thunb, Gardenia jasminoides Ellis, and Rheum officinale Baill have been combined to treat jaundice for thousands of years. Studies have revealed that these herbs induce anti-hepatic fibrosis and anti-hepatic apoptosis and alleviate hepatic oxidative stress. This study aims to determine the quality and quantity of an herbal formulation (Chinese name: Yin-Chen-Hao-Tang using physical and chemical examinations. Physical examination of Yin-Chen-Hao-Tang in pharmaceutical herbal products, raw fiber powders, and decoction preparations was performed using Congo red and iodine-potassium staining. A sensitive and validated method employing ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS was developed to simultaneously quantify the bioactive compounds scoparone, geniposide, and rhein in the Yin-Chen-Hao-Tang formulation in different preparations. Physical examination indicated that cellulose fibers with irregular round shapes were present in the pharmaceutical herbal products. The developed UHPLC-MS/MS method showed good linearity and was well validated. The quantification results revealed that the decoction preparations had the highest amounts of geniposide and rhein. Scoparone appeared in pharmaceutical herbal products from two manufacturers. This experiment provides a qualitative and quantitative method using physical and chemical examinations to test different preparations of herbal products. The results provide a reference for clinical herbal product preparations and further pharmacokinetic research.

  13. A functional and chemical study of radiation effects on rat parotid and submandibular/sublingual glands

    International Nuclear Information System (INIS)

    Vissink, A.; S-Gravenmade, E.J.; Ligeon, E.E.; Konings, W.T.

    1990-01-01

    The aim of this study was to monitor composition and rate of secretion of rat parotid and submandibular/sublingual saliva following local single doses of X-rays ranging from 5 to 20 Gy. Pilocarpine-stimulated samples of parotid and submandibular/sublingual saliva were simultaneously collected with miniaturized Lashley cups before and 1-30 days after irradiation. The lag phase (period between injection of pilocarpine and start of the secretion) and flow rate were recorded and the concentrations of sodium, potassium, calcium, phosphate, and amylase were measured. With increasing dose and time, the salivary flow rate as well as sodium concentration decreased, while potassium concentrations increased throughout the follow-up period. The lag phase and the concentration of amylase reached their maximum at 3 and 10 days after irradiation, respectively. The changes in lag phase and flow rate were most obvious after doses of 15 or 20 Gy and showed a great similarity for parotid and submandibular/sublingual saliva. No dose-response relationship was observed for the changes in concentrations of calcium and phosphate. It is concluded that for radiation doses of 10 Gy and above, irreversible changes (lag phase, flow rate, potassium, sodium) were observed. A saturation of the irradiation effects (lag phase, flow rate) seems to exist at doses larger than 15 Gy. No significant differences were observed between the radiation-induced functional changes in parotid and submandibular/sublingual salivary gland tissue

  14. 78 FR 34108 - Determination That SUBOXONE (Buprenorphine Hydrochloride and Naloxone Hydrochloride) Sublingual...

    Science.gov (United States)

    2013-06-06

    ... naloxone HCl) sublingual tablets, 2 mg/0.5 mg and 8 mg/2 mg, are the subject of NDA 20-733, held by Reckitt Benckiser Pharmaceuticals, Inc. (Reckitt), and initially approved on October 8, 2002. SUBOXONE is indicated...,'' http://www.rb.com/site/rkbr/templates/mediainvestorsgeneral2.aspx?pageid=1332&cc=GB , Reckitt Benckiser...

  15. Sublingual nitroglycerin administration in coronary computed tomography angiography: a systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Takx, Richard A.P. [Harvard Medical School, Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital, Boston, MA (United States); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Sucha, Dominika; Leiner, Tim [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Park, Jakob [Harvard Medical School, Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital, Boston, MA (United States); University of Heidelberg, Department of Cardiology, Heidelberg (Germany); Hoffmann, Udo [Harvard Medical School, Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital, Boston, MA (United States)

    2015-12-15

    To systematically investigate the literature for the influence of sublingual nitroglycerin administration on coronary diameter, the number of evaluable segments, image quality, heart rate and blood pressure, and diagnostic accuracy of coronary computed tomography (CT) angiography. A systematic search was performed in PubMed, EMBASE and Web of Science. The studies were evaluated for the effect of sublingual nitroglycerin on coronary artery diameter, evaluable segments, objective and subjective image quality, systemic physiological effects and diagnostic accuracy. Due to the heterogeneous reporting of outcome measures, a narrative synthesis was applied. Of the 217 studies identified, nine met the inclusion criteria: seven reported on the effect of nitroglycerin on coronary artery diameter, six on evaluable segments, four on image quality, five on systemic physiological effects and two on diagnostic accuracy. Sublingual nitroglycerin administration resulted in an improved evaluation of more coronary segments, in particular, in smaller coronary branches, better image quality and improved diagnostic accuracy. Side effects were mild and were alleviated without medical intervention. Sublingual nitroglycerin improves the coronary diameter, the number of assessable segments, image quality and diagnostic accuracy of coronary CT angiography without major side effects or systemic physiological changes. (orig.)

  16. Efficacy and safety of 5-grass-pollen sublingual immunotherapy tablets in pediatric allergic rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Wahn, Ulrich; Tabar, Ana; Kuna, Piotr

    2009-01-01

    BACKGROUND: The efficacy and safety of the 300-index of reactivity (IR) dose of 5-grass-pollen sublingual immunotherapy (SLIT) tablets (Stallergènes, Antony, France) have been demonstrated for the treatment of hay fever in adults. OBJECTIVE: We sought to assess the efficacy and safety of this tab...

  17. Intestinal and sublingual microcirculation are more severely compromised in hemodilution than in hemorrhage

    NARCIS (Netherlands)

    Ferrara, Gonzalo; Kanoore Edul, Vanina Siham; Martins, Enrique; Canales, Héctor Saúl; Canullán, Carlos; Murias, Gastón; Pozo, Mario Omar; Estenssoro, Elisa; Ince, Can; Dubin, Arnaldo

    2016-01-01

    The alterations in O2 extraction in hemodilution have been linked to fast red blood cell (RBC) velocity, which might affect the complete release of O2 from Hb. Fast RBC velocity might also explain the normal mucosal-arterial Pco2 (ΔPco2). Yet sublingual and intestinal microcirculation have not been

  18. Efficacy of Sublingual Misoprostol versus Intramuscular Methylergometrine in Prevention of Primary Postpartum Hemorrhage

    International Nuclear Information System (INIS)

    Anwar, R.; Ambreen, A.; Khuram, A.; Mushtaq, M.

    2013-01-01

    Post partum hemorrhage still remains a major cause of maternal morbidity and mortality in developing countries. Most of oxytocics like methylergometrine require parenteral administration, which requires special storage. Misoprostol is thermo stable, has a long shelf life and is widely recommended for prevention of postpartum hemorrhage. This can be a choice of oxytocic in developing countries like ours, where storage facilities and resources are limited. Objectives: To compare efficacy of sublingual Misoprostol versus intramuscular Methylergometrine in prevention of primary postpartum hemorrhage after delivery. Study Design: Quasi experimental study Place and Duration of Study: Department of Gynae/Obs, Military Hospital and Combined Military Hospital Rawalpindi cantt. December 2007 to July 2008. Material and Methods: One hundred and thirty six pregnant ladies were selected. On arrival each patient was examined thoroughly along with baseline investigations. Therapeutic option was allocated to the patients simply by using a table of random numbers and dividing them in two equal groups. Informed written consent was taken. Each patient was observed for blood loss estimation and hematocrit drop. All the data was analyzed using SPSS version 10.0. Mean +- SD for age, pre-delivery and post-delivery hematocrit, percentage of drop in hematocrit and blood loss during labour was calculated. Results: Mean drop of hematocrit and blood loss were compared among two groups. At the end, it was revealed that there was no significant difference among two groups in blood loss (p=0.49) and hematocrit drop (p=0.14). Conclusion: There is no significant better effect in preventing post partum hemorrhage among the two drugs. (author)

  19. A polymeric nanoparticle formulation of curcumin in combination with sorafenib synergistically inhibits tumor growth and metastasis in an orthotopic model of human hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hu, Bo; Sun, Ding; Sun, Chao; Sun, Yun-Fan; Sun, Hai-Xiang; Zhu, Qing-Feng; Yang, Xin-Rong; Gao, Ya-Bo; Tang, Wei-Guo; Fan, Jia; Maitra, Anirban

    2015-01-01

    Curcumin, a yellow polyphenol extracted from the rhizome of turmeric root (Curcuma longa) has potent anti-cancer properties in many types of tumors with ability to reverse multidrug resistance of cancer cells. However, widespread clinical application of this agent in cancer and other diseases has been limited due to its poor aqueous solubility. The recent findings of polymeric nanoparticle formulation of curcumin (NFC) have shown the potential for circumventing the problem of poor solubility, however evidences for NFC's anti-cancer and reverse multidrug resistance properties are lacking. Here we provide models of human hepatocellular carcinoma (HCC), the most common form of primary liver cancer, in vitro and in vivo to evaluate the efficacy of NFC alone and in combination with sorafenib, a kinase inhibitor approved for treatment of HCC. Results showed that NFC not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. Moreover, in combination with sorafenib, NFC induced HCC cell apoptosis and cell cycle arrest. Mechanistically, NFC and sorafenib synergistically down-regulated the expression of MMP9 via NF-κB/p65 signaling pathway. Furthermore, the combination therapy significantly decreased the population of CD133-positive HCC cells, which have been reported as cancer initiating cells in HCC. Taken together, NanoCurcumin provides an opportunity to expand the clinical repertoire of this agent. Additional studies utilizing a combination of NanoCurcumin and sorafenib in HCC are needed for further clinical development. - Highlights: • Polymeric nanoparticle formulation of curcumin not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. • In combination with sorafenib, NanoCurcumin induced HCC cell apoptosis and cell cycle arrest. • NanoCurcumin and

  20. A polymeric nanoparticle formulation of curcumin in combination with sorafenib synergistically inhibits tumor growth and metastasis in an orthotopic model of human hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Bo [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Sun, Ding [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Department of Hepatobiliary Surgery, First Affiliated Hospital of Soochow University, Suzhou, 215004 (China); Sun, Chao; Sun, Yun-Fan; Sun, Hai-Xiang [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Zhu, Qing-Feng [The Johns Hopkins University School of Medicine, Division of Gastrointestinal and Liver Pathology, Baltimore, MD, 21205 (United States); Institute of Biomedical Sciences, Fudan University, Shanghai, 200032 (China); Yang, Xin-Rong [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Gao, Ya-Bo [Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032 (China); Tang, Wei-Guo [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Fan, Jia [Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032 (China); Institute of Biomedical Sciences, Fudan University, Shanghai, 200032 (China); Maitra, Anirban [The Sol Goldman Pancreatic Cancer Research Center, Departments of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205 (United States); and others

    2015-12-25

    Curcumin, a yellow polyphenol extracted from the rhizome of turmeric root (Curcuma longa) has potent anti-cancer properties in many types of tumors with ability to reverse multidrug resistance of cancer cells. However, widespread clinical application of this agent in cancer and other diseases has been limited due to its poor aqueous solubility. The recent findings of polymeric nanoparticle formulation of curcumin (NFC) have shown the potential for circumventing the problem of poor solubility, however evidences for NFC's anti-cancer and reverse multidrug resistance properties are lacking. Here we provide models of human hepatocellular carcinoma (HCC), the most common form of primary liver cancer, in vitro and in vivo to evaluate the efficacy of NFC alone and in combination with sorafenib, a kinase inhibitor approved for treatment of HCC. Results showed that NFC not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. Moreover, in combination with sorafenib, NFC induced HCC cell apoptosis and cell cycle arrest. Mechanistically, NFC and sorafenib synergistically down-regulated the expression of MMP9 via NF-κB/p65 signaling pathway. Furthermore, the combination therapy significantly decreased the population of CD133-positive HCC cells, which have been reported as cancer initiating cells in HCC. Taken together, NanoCurcumin provides an opportunity to expand the clinical repertoire of this agent. Additional studies utilizing a combination of NanoCurcumin and sorafenib in HCC are needed for further clinical development. - Highlights: • Polymeric nanoparticle formulation of curcumin not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. • In combination with sorafenib, NanoCurcumin induced HCC cell apoptosis and cell cycle arrest. • NanoCurcumin and

  1. Cost-Utility of a Single-Injection Combined Corticosteroid-Hyaluronic Acid Formulation vs a 2-Injection Regimen of Sequential Corticosteroid and Hyaluronic Acid Injections.

    Science.gov (United States)

    Belzile, Etienne L; Deakon, Robert T; Vannabouathong, Christopher; Bhandari, Mohit; Lamontagne, Martin; McCormack, Robert

    2017-01-01

    Research has shown early and sustained relief with a combination therapy of a corticosteroid (CS) and hyaluronic acid (HA) in knee osteoarthritis (OA) patients. This can be administered via a single injection containing both products or as separate injections. The former may be more expensive when considering only product cost, but the latter incurs the additional costs and time of a second procedure. The purpose of this study was to compare the cost-utility of the single injection with the 2-injection regimen. The results of this analysis revealed that the single-injection formulation of a CS and HA may be cost-effective, assuming a willingness-to-pay of $50 000 per quality-adjusted life year gained, for symptomatic relief of OA symptoms. This treatment may also be more desirable to patients who find injections to be inconvenient or unpleasant.

  2. A combined finite element-boundary integral formulation for solution of two-dimensional scattering problems via CGFFT. [Conjugate Gradient Fast Fourier Transformation

    Science.gov (United States)

    Collins, Jeffery D.; Volakis, John L.; Jin, Jian-Ming

    1990-01-01

    A new technique is presented for computing the scattering by 2-D structures of arbitrary composition. The proposed solution approach combines the usual finite element method with the boundary-integral equation to formulate a discrete system. This is subsequently solved via the conjugate gradient (CG) algorithm. A particular characteristic of the method is the use of rectangular boundaries to enclose the scatterer. Several of the resulting boundary integrals are therefore convolutions and may be evaluated via the fast Fourier transform (FFT) in the implementation of the CG algorithm. The solution approach offers the principal advantage of having O(N) memory demand and employs a 1-D FFT versus a 2-D FFT as required with a traditional implementation of the CGFFT algorithm. The speed of the proposed solution method is compared with that of the traditional CGFFT algorithm, and results for rectangular bodies are given and shown to be in excellent agreement with the moment method.

  3. Heterologous prime-boost strategy in non-human primates combining the infective dengue virus and a recombinant protein in a formulation suitable for human use.

    Science.gov (United States)

    Valdés, Iris; Hermida, Lisset; Gil, Lázaro; Lazo, Laura; Castro, Jorge; Martín, Jorge; Bernardo, Lídice; López, Carlos; Niebla, Olivia; Menéndez, Tamara; Romero, Yaremis; Sánchez, Jorge; Guzmán, María G; Guillén, Gerardo

    2010-05-01

    The aim of the present work was to test the concept of the heterologous prime-boost strategy combining an infective dengue virus with a recombinant chimeric protein carrying domain III of the envelope protein. Two studies in monkeys, combining recombinant protein PD5 (domain III of the envelope protein from dengue-2 virus, fused to the protein carrier P64k) and the infective dengue virus in the same immunization schedules were carried out. Humoral and cell-mediated immunity were evaluated. In the first study, monkeys received four doses of the protein PD5 and were subsequently infected with one dose of dengue virus. Antibody response measured after virus inoculation was significantly higher compared to that in non-primed monkeys and comparable to that elicited after two doses of infective virus. In a second study, monkeys were infected with one dose of the virus and subsequently boosted with one dose of the recombinant protein, reaching high levels of neutralizing antibodies, which were still detectable 14 months after the last immunization. In addition, the cellular immune response was also recalled. The results obtained in the present work support the approach of heterologous prime-boosting, in either order prime or boost, combining the chimeric protein PD5 (formulated in alum-CPS-A) and an infective dengue virus. The latter could potentially be replaced by an attenuated vaccine candidate. Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  4. A vaccine formulation combining rhoptry proteins NcROP40 and NcROP2 improves pup survival in a pregnant mouse model of neosporosis.

    Science.gov (United States)

    Pastor-Fernández, Iván; Arranz-Solís, David; Regidor-Cerrillo, Javier; Álvarez-García, Gema; Hemphill, Andrew; García-Culebras, Alicia; Cuevas-Martín, Carmen; Ortega-Mora, Luis M

    2015-01-30

    Currently there are no effective vaccines for the control of bovine neosporosis. During the last years several subunit vaccines based on immunodominant antigens and other proteins involved in adhesion, invasion and intracellular proliferation of Neospora caninum have been evaluated as targets for vaccine development in experimental mouse infection models. Among them, the rhoptry antigen NcROP2 and the immunodominant NcGRA7 protein have been assessed with varying results. Recent studies have shown that another rhoptry component, NcROP40, and NcNTPase, a putative dense granule antigen, exhibit higher expression levels in tachyzoites of virulent N. caninum isolates, suggesting that these could be potential vaccine candidates to limit the effects of infection. In the present work, the safety and efficacy of these recombinant antigens formulated in Quil-A adjuvant as monovalent vaccines or pair-wise combinations (rNcROP40+rNcROP2 and rNcGRA7+rNcNTPase) were evaluated in a pregnant mouse model of neosporosis. All the vaccine formulations elicited a specific immune response against their respective native proteins after immunization. Mice vaccinated with rNcROP40 and rNcROP2 alone or in combination produced the highest levels of IFN-γ and exhibited low parasite burdens and low IgG antibody levels after the challenge. In addition, most of the vaccine formulations were able to increase the median survival time in the offspring. However, pup survival only ensued in the groups vaccinated with rNcROP40+rNcROP2 (16.2%) and rNcROP2 (6.3%). Interestingly, vertical transmission was not observed in those survivor pups immunized with rNcROP40+rNcROP2, as shown by PCR analyses. These results show a partial protection against N. caninum infection after vaccination with rNcROP40+rNcROP2, suggesting a synergistic effect of the two recombinant rhoptry antigens. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Premedication with benzodiazepines for upper gastrointestinal endoscopy: Comparison between oral midazolam and sublingual alprazolam

    Directory of Open Access Journals (Sweden)

    Vahid Sebghatollahi

    2017-01-01

    Full Text Available Background: Premedication with orally administered benzodiazepines is effective in reducing anxiety and discomfort related to endoscopic procedures. We evaluated the efficacy and safety of oral midazolam in comparison to sublingual alprazolam as premedication for esophagogastroduodenoscopy (EGD. Materials and Methods: Adult candidates for diagnostic EGD received either oral midazolam (7.5 mg in 15 cc apple juice or sublingual alprazolam (0.5 mg 30 min before EGD. Procedural anxiety and pain/discomfort were assessed using 11-point numerical rating scales. Patients' overall tolerance (using a four-point Likert scale and willingness to repeat the EGD, if necessary, were also assessed. Blood pressure, heart rate, and arterial oxygen saturation were monitored from medication to 30 min after the procedure. Results: Patients experienced a similar reduction in procedural anxiety after medication with oral midazolam and sublingual alprazolam; mean (standard deviation [SD] of 1.86 [1.63] and 2.02 [1.99] points, respectively, P = 0.91. Compared to oral midazolam, pain/discomfort scores were lower with sublingual alprazolam; mean (SD of 4.80 (3.01 versus 3.68 (3.28, P = 0.024. There was no significant difference between the two groups in patients' tolerance, willingness to repeat the procedure, or hemodynamic events. Conclusion: Oral midazolam and sublingual alprazolam are equally effective in reducing EGD-related anxiety; however, EGD-related pain/discomfort is lower with alprazolam. Both benzodiazepines are equally safe and can be used as premedication for patients undergoing diagnostic EGD.

  6. Sublingual flagellin protects against acute pneumococcal pneumonia in a TLR5-dependent and NLRC4-independent fashion.

    Science.gov (United States)

    Muñoz-Wolf, Natalia; Rial, Analía; Fougeron, Delphine; Tabareau, Julien; Sirard, Jean-Claude; Chabalgoity, José A

    2016-09-01

    To evaluate efficacy of sublingual flagellin to treat acute pneumonia. Mice were treated sublingually with flagellin and challenged intranasally with a lethal dose of pneumococcus. Flagellins lacking TLR5 or NLRC4 activation domains were used to assess their contribution to protection. Sublingual flagellin protected mice in a TLR5-dependent, NLRC4-independent fashion. Neutrophils were required for protection. Flagellin-stimulated lung epithelial cells recapitulated the lung's transcriptional profile suggesting they could be targeted by flagellin in vivo. Ligation of TLR5, a pathogen recognition receptor not naturally engaged by pneumococcus, protects mice from invasive pneumonia when administered via sublingual route. This can be a highly cost-effective alternative therapy against pneumonia.

  7. Evaluation of alternative rice planthopper control by the combined action of oil-formulated Metarhizium anisopliae and low-rate buprofezin.

    Science.gov (United States)

    Jin, Shao-Feng; Feng, Ming-Guang; Ying, Sheng-Hua; Mu, Wen-Jing; Chen, Jue-Qi

    2011-01-01

    High resistance of brown planthopper (BPH) Nilaparvata lugens Stål to common insecticides is a challenge for control of the pest. An alternative control strategy based on the combined application of fungal and chemical agents has been evaluated. Three gradient spore concentrations of oil-formulated Metarhizium anisopliae (Metschnikoff) Sorokin (Ma456) were sprayed onto third-instar nymphs in five bioassays comprising the low buprofezin rates of 0, 10, 20, 30 and 40 µg mL(-1) respectively. Fungal LC(50) after 1 week at 25 °C and 14:10 h light:dark photoperiod decreased from 386 conidia mm(-2) in the buprofezin-free bioassay to 40 at the highest chemical rate. Buprofezin (LC(50): 1647, 486 and 233 µg mL(-1) on days 2 to 4) had no significant effect on the fungal outgrowths of mycosis-killed cadavers at the low application rates. The fungal infection was found to cause 81% reduction in reproductive potential of BPH adults. In two 40 day field trials, significant planthopper (mainly BPH) control (54-60%) was achieved by biweekly sprays of two fungal candidates (Ma456 and Ma576) at 1.5 × 10(13) conidia ha(-1) and elevated to 80-83% by incorporating 30.8 g buprofezin ha(-1) into the fungal sprays. The combined application of the fungal and chemical agents is a promising alternative strategy for BPH control. Copyright © 2010 Society of Chemical Industry.

  8. Impact of extrafine formulations of inhaled corticosteroids/long-acting beta-2 agonist combinations on patient-related outcomes in asthma and COPD

    Directory of Open Access Journals (Sweden)

    Scichilone N

    2014-11-01

    Full Text Available Nicola Scichilone,1 Alida Benfante,1 Luca Morandi,2 Federico Bellini,2 Alberto Papi21Biomedical Department of Internal and Specialist Medicine, Section of Pulmonology, University of Palermo, Italy; 2Respiratory Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, ItalyAbstract: Asthma and chronic obstructive pulmonary disease (COPD are among the most common chronic diseases worldwide, characterized by a condition of variable degree of airway obstruction and chronic airway inflammation. A large body of evidence has demonstrated the importance of small airways as a pharmacological target in these clinical conditions. Despite a deeper understanding of the pathophysiological mechanisms, the epidemiological observations show that a significant proportion of asthmatic and COPD patients have a suboptimal (or lack of control of their diseases. Different factors could influence the effectiveness of inhaled treatment in chronic respiratory diseases: patient-related (eg, aging; disease-related (eg, comorbid conditions; and drug-related/formulation-related factors. The presence of multiple illnesses is common in the elderly patient as a result of two processes: the association between age and incidence of degenerative diseases; and the development over time of complications of the existing diseases. In addition, specific comorbidities may contribute to impair the ability to use inhalers, such as devices for efficient drug delivery in the respiratory system. The inability to reach and treat the peripheral airways may contribute to the lack of efficacy of inhaled treatments. The recent development of inhaled extrafine formulations allows a more uniform distribution of the inhaled treatment throughout the respiratory tree to include the peripheral airways. The beclomethasone/formoterol extrafine formulation is available for the treatment of asthma and COPD. Different biomarkers of peripheral airways are improved by beclomethasone

  9. 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

  10. FORMULATION OF NANOEMULSION MOUTHWASH COMBINATION OF LEMONGRASS OIL (Cymbopogon citratus AND KAFFIR LIME OIL (Citrus hystrix FOR ANTICANDIDIASIS AGAINST Candida albicans ATCC 10231

    Directory of Open Access Journals (Sweden)

    Meta Juniatik

    2017-04-01

    Full Text Available Candidiasis is a fungal infection disease that still become health problem in Indonesia, especially oral candidiasis that largerly caused by Candida albicans abnormal growth on oral cavity. Lemongrass oil and kaffir lime oil have been proven to have antifungal activity against Candida albicans. The composition of limonen, α-terpineol, sitronelil acetate, terpineol, β-pinene, on kaffir lime oil and citronelal on lemongrass oil make the combination of both oils have the potential as an alternative theraphy for oral candidiasis. It formulates in the form of nanoemulsion mouthwash. Nanoemulsion is chosen because it has some advantages like clear, stable, and increasing the antifungal activity of lemongrass oil and kaffir lime oil. The study begins with plants determination, essential oils charecterization tests (solubility, refractative index, and specific gravity, and essential oil content analysis by GC-MS. Nanoemulision formulates by water titration method. Optimization of oil mix and VCO do to get a clear and stable nanoemulsion. The best formula is characterized (transmittance, particle size, viscosity, zeta potential, and stability test, then analyze the essential oil chemical compounds in the optimum formula and test the inhibitory effect of the formula by microdilution method. Inhibiton data analysis use One Way ANOVA. Based on the results of the study, 0.4 % oil mix, 3.6 % VCO, 17.3 % tween 80, 8.7 % PEG 400 dan 70 % water is the best formula that can form a nanoemulsion system with an average particle size 21,4 nm, low viscosity, low zeta potential and stable during freez-thaw storage. Nanoemulsion significantly has inhibitory effect more effective than positive control.

  11. Warfarin-induced sublingual hematoma mimicking Ludwig angina: Conservative management of a potentially life-threatening condition.

    LENUS (Irish Health Repository)

    Cashman, Emma

    2012-02-01

    Sublingual hematoma secondary to excessive anticoagulation is a rare, life-threatening condition. Reports in the literature have emphasized the importance of a prompt reversal of the causative coagulopathy by intravenous administration of vitamin K and fresh frozen plasma. In the event of an unstable airway, surgical intervention via tracheostomy or cricothyroidectomy is advocated. We report a case of sublingual hematoma that was treated conservatively, and we discuss the presentation and management of this entity.

  12. Warfarin-induced sublingual hematoma mimicking Ludwig angina: Conservative management of a potentially life-threatening condition.

    LENUS (Irish Health Repository)

    Cashman, Emma

    2011-02-01

    Sublingual hematoma secondary to excessive anticoagulation is a rare, life-threatening condition. Reports in the literature have emphasized the importance of a prompt reversal of the causative coagulopathy by intravenous administration of vitamin K and fresh frozen plasma. In the event of an unstable airway, surgical intervention via tracheostomy or cricothyroidectomy is advocated. We report a case of sublingual hematoma that was treated conservatively, and we discuss the presentation and management of this entity.

  13. MR imaging of squamous cell carcinoma of the floor of the mouth. Appearance of the sublingual and submandibular glands

    International Nuclear Information System (INIS)

    Murakami, R.; Baba, Y.; Nishimura, R.; Baba, T.; Nakaura, T.; Takahashi, M.; Ishikawa, T.

    1999-01-01

    Purpose: To determine the diagnostic value of MR imaging for tumors of the floor of the mouth and the effects of the tumors on the sublingual and submandibular glands. Material and methods: Thirty-seven patients with proven squamous cell carcinoma of the floor of the mouth underwent MR imaging, including unenhanced T1-weighted, T2-weighted, dynamic, and contrast-enhanced T1-weighted images. The appearance of the tumor and the sublingual and submandibular glands was assessed qualitatively and quantitatively. Results: All tumors demonstrated replacement of the normal signal intensity in the adjacent sublingual gland. Twenty-one patients (57%) had abnormal signal intensity of the submandibular gland without tumor invasion, presumably secondary to submandibular duct obstruction by the tumor. Unenhanced T1-weighted images provided high contrast between tumor and sublingual gland. Tumors limited within the gland were well detected on unenhanced T1-weighted images. Large tumors extending beyond the gland were well delineated on dynamic images, but no better than on T2-weighted images. Conclusion: At MR imaging for tumor of the floor of the mouth, one must carefully evaluate the appearance of the sublingual and submandibular glands. Contrast-enhanced studies are unnecessary when the tumor is limited within the sublingual gland on precontrast MR images. (orig.)

  14. Efficacy and safety of 4 months of sublingual immunotherapy with recombinant Mal d 1 and Bet v 1 in patients with birch pollen-related apple allergy.

    Science.gov (United States)

    Kinaciyan, Tamar; Nagl, Birgit; Faustmann, Sandra; Frommlet, Florian; Kopp, Stephan; Wolkersdorfer, Martin; Wöhrl, Stefan; Bastl, Katharina; Huber, Hans; Berger, Uwe; Bohle, Barbara

    2018-03-01

    Birch pollen-related apple allergy is among the most prevalent food allergies in adolescent/adult subjects and mainly results from sensitization to the major birch pollen allergen Bet v 1 and subsequent cross-reaction with the apple protein Mal d 1. However, specific immunotherapy with birch pollen has inconsistent effects on apple allergy. We sought to compare the safety and efficacy of sublingual immunotherapy (SLIT) with 2 formulations containing either rMal d 1 or rBet v 1 on birch pollen-related apple allergy. Sixty participants with birch pollen-related apple allergy were randomized to daily sublingual application of placebo (n = 20) or 25 μg of rMal d 1 (n = 20) or rBet v 1 (n = 20) for 16 weeks. Adverse events were regularly recorded. Sublingual challenges with standardized doses of rMal d 1, skin prick tests with recombinant allergens, and measurements of allergen-specific IgE and IgG 4 antibodies were performed before and after treatment. Both formulations caused comparable, mainly local adverse events. No systemic reactions occurred. Compared with the placebo and rBet v 1-treated groups, SLIT with rMal d 1 reduced rMal d 1-induced oral symptoms (P = .001 and P = .038) accompanied by longitudinally reduced rMal d 1-specific cutaneous reactions (P = .022) and enhanced IgG 4 /IgE ratios (P = .012). SLIT with rBet v 1 neither improved the clinical reactivity to rMal d 1 nor enhanced rMal d 1-specific IgG 4 /IgE ratios. Participants receiving placebo showed no allergen-specific changes. Sublingual treatment with a recombinant food allergen was safe and clinically effective, as determined by using standardized challenges. We present a promising approach for the effective treatment of birch pollen-related apple allergy. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  15. CHANGES OF IMMUNE INDEXES DURING SUBLINGUAL ALLERGEN-SPECIFIC IMMUNOTHERAPY IN CHILDREN WITH HAY FEVER

    Directory of Open Access Journals (Sweden)

    I. M. Gaiduk

    2013-01-01

    Full Text Available Aims of study: evaluation of immunological parameters in course of sublingual allergen-specific immunotherapy with tree pollen mixture in children with hay fever.Materials and methods: the study included one-hundred patients 5 to 18 years of age with hay fever (pollen rhinitis, rhinoconjunctivitis and/or asthma. Allergen-specific immunotherapy was administered pre-seasonally for three consecutive years. Cytokinechanges were studied in blood serum and in lavages from nasal cavity. Samples assessed before treatment and after 2nd and 3rd courses SLIT completion.Results: increased serum concentrations of IL-10, IFNγ, and decreased IL-4 contents were revealed in the course of treatment. No significant changes in cytokineconcentrations were detectable in nasal lavages.Conclusions: the changes revealed correspond to a shift of T cell response profile towards Th1 pathway, thus confirming pathogenetic effects of sublingual allergen-specific

  16. An accelerometric measure of the gait pattern in horses after the administration of sublingual detomidine.

    Science.gov (United States)

    López-Sanromán, F J; de la Riva Andrés, S; Holmbak-Petersen, R; Pérez-Nogués, M; Forés Jackson, P; Santos González, M

    2014-10-01

    The locomotor pattern alterations produced after the administration of a sublingual detomidine gel was measured by an accelerometric method in horses. Using a randomized two-way crossover design, all animals (n = 6) randomly received either detomidine gel or a placebo administered sublingually. A triaxial accelerometric device was used for gait assessment 15 minutes before (baseline) and every 10 minutes after each treatment for a period of 180 minutes. Eight different parameters were calculated, including speed, stride frequency, stride length, regularity, dorsoventral, propulsion, mediolateral, and total power. Force of acceleration and the three components of power were also calculated. Significant statistical differences were observed between groups in all the parameters but stride length. The majority of significant changes started between 30 and 70 minutes after drug administration and lasted for 160 minutes. This route of administration is definitely useful in horses in which a prolonged sedation is required, with stability being a major concern. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Sublingual administration of detomidine to calves prior to disbudding: a comparison with the intravenous route.

    OpenAIRE

    Hokkanen, Ann-Helena; Raekallio, Marja R.; Salla, Kati; Hänninen, Laura; Viitasaari, Elina Anna Maria; Norring, Marianna; Raussi, Satu; Rinne, Valtteri; Scheinin, Mika; Vainio, Outi M.

    2014-01-01

    Objective To study the effects of oromucosal detomidine gel administered sublingually to calves prior to disbudding, and to compare its efficacy with intravenously (IV) administered detomidine. Study design Randomised, prospective clinical study. Animals Twenty dairy calves aged 12.4 ± 4.4days (mean ± SD), weight 50.5 ± 9.0 kg. Methods Detomidine at 80 μg kg−1 was administered to ten calves sublingually (GEL) and at 30 μg kg−1 to ten control calves IV (V. jugularis). Meloxicam (0.5 mg kg−1) a...

  18. Stress degradation studies and development of stability-indicating TLC-densitometry method for determination of prednisolone acetate and chloramphenicol in their individual and combined pharmaceutical formulations

    Directory of Open Access Journals (Sweden)

    Musharraf Syed

    2012-01-01

    Full Text Available Abstract A rapid and reproducible stability indicating TLC method was developed for the determination of prednisolone acetate and chloramphenicol in presence of their degraded products. Uniform degradation conditions were maintained by refluxing sixteen reaction mixtures for two hours at 80°C using parallel synthesizer including acidic, alkaline and neutral hydrolysis, oxidation and wet heating degradation. Oxidation at room temperature, photochemical and dry heating degradation studies were also carried out. Separation was done on TLC glass plates, pre-coated with silica gel 60F-254 using chloroform: methanol (14:1 v/v. Spots at Rf 0.21 ± 0.02 and Rf 0.41 ± 0.03 were recognized as chloramphenicol and prednisolone acetate, respectively. Quantitative analysis was done through densitometric measurements at multiwavelength (243 nm, λmax of prednisolone acetate and 278 nm, λmax of chloramphenicol, simultaneously. The developed method was optimized and validated as per ICH guidelines. Method was found linear over the concentration range of 200-6000 ng/spot with the correlation coefficient (r2 ± S.D. of 0.9976 ± 3.5 and 0.9920 ± 2.5 for prednisolone acetate and chloramphenicol, respectively. The developed TLC method can be applied for routine analysis of prednisolone acetate and chloramphenicol in presence of their degraded products in their individual and combined pharmaceutical formulations.

  19. An explanation for the physical instability of a marketed fixed dose combination (FDC) formulation containing isoniazid and ethambutol and proposed solutions.

    Science.gov (United States)

    Bhutani, Hemant; Mariappan, T T; Singh, Saranjit

    2004-07-01

    An investigation was carried out to explore the possible reason for the physical instability of a marketed strip packaged anti-TB fixed dose combination (FDC) tablet containing 300 mg of isoniazid (H) and 800 mg of ethambutol hydrochloride (E). The instability was in the form of distribution of white powder inside the strip pockets. High-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS-MS) studies confirmed that both H and E were present in the powder. The same was also confirmed through Fourier-transform infrared (FTIR) spectroscopy, which also indicated absence of interaction between the two drugs. No sublimation of the drugs was observed up to 110 degrees C, indicating that the observed instability was not due to this reason. Subsequently, attention was paid to the possibility of moisture gain by the tablets through defective packaging (which was established) due to hygroscopicity of E. To understand the phenomenon further, pure drugs and their mixtures were stored under accelerated conditions of temperature and humidity [40 degrees C/75% relative humidity (RH)] and both increase in weight and physical changes were recorded periodically. The mixtures gained moisture at a higher rate than pure E and those with higher content of E became liquid, which on withdrawal from the chambers, became crystallized. The drug mixture containing H:E at a ratio of 30:70 w/w, which was similar to the ratio of the drugs in the tablets (27:73 w/w), crystallized fastest, indicating formation of a rapid crystallizing saturated system at this ratio of the drugs. It is postulated that the problem of instability arises because of the formation of a saturated layer of drugs upon moisture gain through the defective packaging material and drying of this layer with time. The study suggests that barrier packaging free from defects and alternatively (or in combination) film coating of the tablets with water-resistant polymers are essential for this

  20. Sublingual sugar for hypoglycaemia in children with severe malaria: A pilot clinical study

    Science.gov (United States)

    Graz, Bertrand; Dicko, Moussa; Willcox, Merlin L; Lambert, Bernard; Falquet, Jacques; Forster, Mathieu; Giani, Sergio; Diakite, Chiaka; Dembele, Eugène M; Diallo, Drissa; Barennes, Hubert

    2008-01-01

    Background Hypoglycaemia is a poor prognostic indicator in severe malaria. Intravenous infusions are rarely feasible in rural areas. The efficacy of sublingual sugar (SLS) was assessed in a pilot randomized controlled trial among hypoglycaemic children with severe malaria in Mali. Methods Of 151 patients with presumed severe malaria, 23 children with blood glucose concentrations = 3.3 mmol/l (60 mg/dl) within 40 minutes after admission. Secondary outcome measures were early treatment response at 20 minutes, relapse (early and late), maximal BGC gain (CGmax), and treatment delay. Results There was no significant difference between the groups in the primary outcome measure. Treatment response occurred in 71% and 67% for SLS and IVG, respectively. Among the responders, relapses occurred in 30% on SLS at 40 minutes and in 17% on IVG at 20 minutes. There was one fatality in each group. Treatment failures in the SLS group were related to children with clenched teeth or swallowing the sugar, whereas in the IVG group, they were due to unavoidable delays in beginning an infusion (median time 17.5 min (range 3–40). Among SLS, the BGC increase was rapid among the nine patients who really kept the sugar sublingually. All but one increased their BGC by 10 minutes with a mean gain of 44 mg/dl (95%CI: 20.5–63.4). Conclusion Sublingual sugar appears to be a child-friendly, well-tolerated and effective promising method of raising blood glucose in severely ill children. More frequent repeated doses are needed to prevent relapse. Children should be monitored for early swallowing which leads to delayed absorption, and in this case another dose of sugar should be given. Sublingual sugar could be proposed as an immediate "first aid" measure while awaiting intravenous glucose. In many cases it may avert the need for intravenous glucose. PMID:19025610

  1. Sublingual sugar for hypoglycaemia in children with severe malaria: A pilot clinical study

    Directory of Open Access Journals (Sweden)

    Giani Sergio

    2008-11-01

    Full Text Available Abstract Background Hypoglycaemia is a poor prognostic indicator in severe malaria. Intravenous infusions are rarely feasible in rural areas. The efficacy of sublingual sugar (SLS was assessed in a pilot randomized controlled trial among hypoglycaemic children with severe malaria in Mali. Methods Of 151 patients with presumed severe malaria, 23 children with blood glucose concentrations = 3.3 mmol/l (60 mg/dl within 40 minutes after admission. Secondary outcome measures were early treatment response at 20 minutes, relapse (early and late, maximal BGC gain (CGmax, and treatment delay. Results There was no significant difference between the groups in the primary outcome measure. Treatment response occurred in 71% and 67% for SLS and IVG, respectively. Among the responders, relapses occurred in 30% on SLS at 40 minutes and in 17% on IVG at 20 minutes. There was one fatality in each group. Treatment failures in the SLS group were related to children with clenched teeth or swallowing the sugar, whereas in the IVG group, they were due to unavoidable delays in beginning an infusion (median time 17.5 min (range 3–40. Among SLS, the BGC increase was rapid among the nine patients who really kept the sugar sublingually. All but one increased their BGC by 10 minutes with a mean gain of 44 mg/dl (95%CI: 20.5–63.4. Conclusion Sublingual sugar appears to be a child-friendly, well-tolerated and effective promising method of raising blood glucose in severely ill children. More frequent repeated doses are needed to prevent relapse. Children should be monitored for early swallowing which leads to delayed absorption, and in this case another dose of sugar should be given. Sublingual sugar could be proposed as an immediate "first aid" measure while awaiting intravenous glucose. In many cases it may avert the need for intravenous glucose.

  2. A randomised controlled trial of sublingual misoprostol and intramuscular oxytocin for prevention of postpartum haemorrhage.

    Science.gov (United States)

    Al-Sawaf, A; El-Mazny, A; Shohayeb, A

    2013-04-01

    This study aims to evaluate the efficacy and side-effects of 200 μg sublingual misoprostol vs 5 IU i.m. oxytocin, administered immediately following cord clamping in normal non-augmented vaginal delivery, in prevention of postpartum haemorrhage (PPH). A total of 104 women were randomised into three groups: misoprostol group (28 patients); oxytocin group (37 patients) and control group (39 patients). Misoprostol and oxytocin significantly minimised the blood loss during the third stage of labour and reduced the need for additional treatments for PPH as compared with the control group. Oxytocin was more effective than misoprostol in minimising blood loss and the need for additional uterotonic treatments. However, a significant decrease in systolic and diastolic blood pressure, associated with tachycardia was observed in the oxytocin group. In conclusion, sublingual misoprostol appears to be less effective than i.m. oxytocin in the prevention of PPH; however, it has the potential advantages of being easily used, cost-effective and stable at room temperature. Therefore, sublingual misoprostol is still a feasible drug for routine management of third stage, especially in areas with limited medical facilities.

  3. [Efficacy of the dust mites drops sublingual immunotherapy in pediatric allergic rhinitis].

    Science.gov (United States)

    Xie, Lisheng; Jiang, Yinzhu; Li, Qi

    2016-03-01

    To observe the role of the dust mites drops sublingual immunotherapy(SLIT) in pediatric allergic rhiriitis caused by dust mites and compare its efficacy between monosensitized and polysensitized children. A total of 77 pediatric allergic rhinitis patients received Dermatophagoides farina extracts sublingual immunotherapy for 2 years were enrolled as desensitization group and were allocated into monosensitized group (41 cases) and polysensitized group (36 cases) according to the number of coexisting allergens. Meanwhile another 33 allergic rhinitis children treated by pharmacotherapy during the period were collected as control group. The total symptom scores (TNSS), total medication scores (TMS) and visual analogue scale(VAS) were assessed at the beginning, six months, 1 year and 2 years of the treatment. SPSS 13. 0 software was used to analyze the data. the score of TNSS and VAS in desensitization was slightly higher than the control after six months treatment, but without difference at l year and 2 years; the score of TMS had significantly improved in desensitization compared with the corresponding points in control. All the parameters in monosensitized group were equivalent with polysensitizend group, except the score of TMS was slightly lower than the polysensitizend group at six months. Dust mite drops sublingual immunotherapy is effective for the allergic rhinitis children caused by mites. And it has similar immunotherapy efficacy between monosensitized and polysensitized children.

  4. Bioavailability of detomidine administered sublingually to horses as an oromucosal gel.

    Science.gov (United States)

    Kaukinen, H; Aspegrén, J; Hyyppä, S; Tamm, L; Salonen, J S

    2011-02-01

    The objective of the study was to determine the absorption, bioavailability and sedative effect of detomidine administered to horses as an oromucosal gel compared to intravenous and intramuscular administration of detomidine injectable solution. The study was open and randomized, with three sequences crossover design. Nine healthy horses were given 40 μg/kg detomidine intravenously, intramuscularly or administered under the tongue with a 7-day wash-out period between treatments. Blood samples were collected before and after drug administration for the measurement of detomidine concentrations in serum. The effects of the route of administration on heart rate and rhythm were evaluated and the depth of sedation assessed. Mean (±SD) bioavailability of detomidine was 22% (±5.3%) after sublingual administration and 38.2% (±7.9%) after intramuscular administration. The sedative effects correlated with detomidine concentrations regardless of the route of administration. We conclude that less detomidine is absorbed when given sublingually than when given intramuscularly, because part of it does not reach the circulation. Sublingual administration of detomidine oromucosal gel at 40 μg/kg produces safe sedation in horses. Slow absorption leads to fewer and less pronounced adverse effects than the more rapid absorption after intramuscular injection. © 2010 Blackwell Publishing Ltd.

  5. The clinical impact of vehicle technology using a patented formulation of benzoyl peroxide 5%/clindamycin 1% gel: comparative assessments of skin tolerability and evaluation of combination use with a topical retinoid.

    Science.gov (United States)

    Del Rosso, James Q; Tanghetti, Emil

    2006-02-01

    A major challenge encountered in clinical practice in patients with acne vulgaris is irritation related to topical medications used for treatment. Advances in vehicle technology have improved formulations containing active ingredients known to produce irritation in some patients, such as benzoyl peroxide (BP) and topical retinoids. Clinical studies, including combination therapy studies have demonstrated that certain additives, such as silicates and specific humectants, reduce irritation by maintaining barrier integrity. A patented gel formulation of BP 5%/clindamycin phosphate 1% (clindamycin) containing dimethicone and glycerin has been studied both as a monotherapy and in combination with topical retinoid use. This article evaluates specific vehicle additives included in this gel formulation and explains their role in reducing irritation. Data from clinical trials utilizing this technology in acne management are also reviewed.

  6. Effects of a topical anaesthetic formulation and systemic carprofen, given singly or in combination, on the cortisol and behavioural responses of Merino lambs to castration.

    Science.gov (United States)

    Paull, D R; Lee, C; Colditz, I G; Fisher, A D

    2009-06-01

    To determine the effectiveness of a topical anaesthetic formulation (Tri-Solfen) with or without the administration of a non-steroidal anti-inflammatory drug (carprofen) on the pain and distress response associated with ring or surgical castration of ram lambs. Merino ram lambs (n = 78) were allocated to 10 treatment groups: 4 groups of knife-castrated lambs and 4 groups of ring-castrated lambs received carprofen (4 mg/kg SC) and Tri-Solfen; 2 control groups (sham) received carprofen at 0 or 4 mg/kg SC. Measurements included plasma cortisol and haptoglobin concentrations, haematology, and behaviour, including posture. Knife-castrated lambs had higher peak cortisol and integrated cortisol responses for the first 6 h after treatment and greater concentration s of circulating acute phase proteins than ring-castrated lambs, both of which were significantly different from the sham controls. Tri-Solfen applied to the knife castration wound significantly reduced both the peak plasma cortisol concentration and the integrated cortisol response for the first 6 h and improved lying behaviour in the first 12 h. Carprofen reduced the cortisol response to knife castration at 30 min, but elevated the cortisol responses at 24 and 48 h. Carprofen nearly halved the number of acute pain behaviours associated with ring castration. There were no significant additive or synergistic effects from combining the analgesic treatments. Tri-Solfen applied to the tail wound provided no detectible benefits during ring castration + tail docking. The physiological and behavioural responses suggest that ring castration has less impact on the lamb than knife castration. The specific analgesic treatments can provide modest amelioration of the pain and discomfort associated with castration. Alternative doses or application methods may enhance their efficacy.

  7. Chemometrics-Assisted UV Spectrophotometric and RP-HPLC Methods for the Simultaneous Determination of Tolperisone Hydrochloride and Diclofenac Sodium in their Combined Pharmaceutical Formulation.

    Science.gov (United States)

    Gohel, Nikunj Rameshbhai; Patel, Bhavin Kiritbhai; Parmar, Vijaykumar Kunvarji

    2013-01-01

    Chemometrics-assisted UV spectrophotometric and RP-HPLC methods are presented for the simultaneous determination of tolperisone hydrochloride (TOL) and diclofenac sodium (DIC) from their combined pharmaceutical dosage form. Chemometric methods are based on principal component regression and partial least-square regression models. Two sets of standard mixtures, calibration sets, and validation sets were prepared. Both models were optimized to quantify each drug in the mixture using the information included in the UV absorption spectra of the appropriate solution in the range 241-290 nm with the intervals λ = 1 nm at 50 wavelengths. The optimized models were successfully applied to the simultaneous determination of these drugs in synthetic mixture and pharmaceutical formulation. In addition, an HPLC method was developed using a reversed-phase C18 column at ambient temperature with a mobile phase consisting of methanol:acetonitrile:water (60:30:10 v/v/v), pH-adjusted to 3.0, with UV detection at 275 nm. The methods were validated in terms of linearity, accuracy, precision, sensitivity, specificity, and robustness in the range of 3-30 μg/mL for TOL and 1-10 μg/mL for DIC. The robustness of the HPLC method was tested using an experimental design approach. The developed HPLC method, and the PCR and PLS models were used to determine the amount of TOL and DIC in tablets. The data obtained from the PCR and PLS models were not significantly different from those obtained from the HPLC method at 95% confidence limit.

  8. Effect of the herbal formulation Jianpijiedu on the TCRVβCDR3 repertoire in rats with hepatocellular carcinoma and subjected to food restriction combined with laxative.

    Science.gov (United States)

    Sun, Baoguo; Meng, Jun; Xiang, Ting; Zhang, Lei; Deng, Liuxiang; Chen, Yan; Luo, Haoxuan; Yang, Zhangbin; Chen, Zexiong; Zhang, Shijun

    2016-03-01

    The aim of this study was to investigate the effects of the Chinese herbal formulation Jianpijiedu (JPJD) in a rat model of orthotopic hepatocellular carcinoma (OHC). The tumor-bearing rats underwent food restriction combined with laxative (FRL) treatment in order to model the nutritional and digestive symptoms of patients with hepatocellular carcinoma. In addition, the study aimed to elucidate the effect of JPJD on the T cell receptor Vβ-chain complementarity-determining region 3 (TCRVβCDR3) repertoire and the underlying mechanism. The FRL rat model was established by alternate-day food restriction and the oral administration of Glauber's salt (sodium sulfate), based on which the OHC model was then established. Subsequently, the FRL-OHC induced animals received JPJD or thymopentin-5 (TP5) for 17 days. Differences in the TCRVβCDR3 repertoire in the rat thymus, liver and hepatocellular carcinoma tissues were analyzed by polymerase chain reaction. Compared with the FRL-OHC model animals without any treatment, those treated with JPJD exhibited significantly inhibited hepatocellular carcinoma growth (PSimpsons diversity index (Ds) values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in the thymus, liver and hepatocellular carcinoma tissues. However, no anti-hepatoma effects were evident in the rats treated with TP5. In addition, TP5 increased the Ds values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in hepatocellular carcinoma tissues compared with those in the JPJD-treated group. The anti-hepatoma effects of JPJD in FRL-OHC-induced animals may be due to the promotion of the Ds values of the TCRVβCDR3 repertoire.

  9. A Three-Year Course of House Dust Mite Sublingual Immunotherapy Appears Effective in Controlling the Symptoms of Allergic Rhinitis.

    Science.gov (United States)

    Novakova, Silviya M; Novakova, Plamena I; Yakovliev, Plamen H; Staevska, Maria T; Mateva, Nonka G; Dimcheva, Teodora D; Peichev, Jivko L

    2018-05-01

    Background Allergic rhinitis is the most common allergic disorder. Although the management of the disease is successful in many patients, based on guidelines, some of them remain with symptoms uncontrolled with pharmacotherapy. Presently, there is no substantiated information on the control of allergic rhinitis in patients who underwent sublingual immunotherapy. Objective The purpose of this prospective follow-up study was to assess the control of allergic rhinitis in adults after a three-year course of house dust mite sublingual immunotherapy. Methods This prospective real-life study was designed to include adults with moderate to severe allergic rhinitis sensitized to house dust mite who underwent a three-year course of sublingual immunotherapy. Control of symptoms was assessed by Rhinitis Control Assessment Test (RCAT) after three years of house dust mite sublingual immunotherapy. Additionally, patients assessed their symptoms by utilizing a visual analog scale. Results A total number of 86 consecutively enrolled patients (46 (53.49%) men; mean age 26.10 years (SD = 5.85)) with moderate to severe allergic rhinitis and clinically relevant sensitization to house dust mite were evaluated. When assessed by RCAT on the third year, 74 (86.05%) had well-controlled symptoms and 20 (27.03%) of them were completely controlled. A significant reduction in visual analog scale scores-from 7.52 cm at baseline to 2.31 cm-was established ( P house dust mite sublingual immunotherapy appears effective in controlling the symptoms of allergic rhinitis.

  10. SQ house dust mite sublingually administered immunotherapy tablet (ALK) improves allergic rhinitis in patients with house dust mite allergic asthma and rhinitis symptoms

    DEFF Research Database (Denmark)

    Mosbech, Holger; Canonica, G Walter; Backer, Vibeke

    2015-01-01

    BACKGROUND: House dust mite (HDM) allergy is associated with persistent allergic rhinitis (AR) and allergic asthma. OBJECTIVE: To investigate the efficacy and safety of a SQ HDM sublingually administered immunotherapy tablet (ALK, Hørsholm, Denmark) in adults and adolescents with HDM respiratory...... allergic disease and report the AR results. METHODS: Six hundred four subjects at least 14 years old with HDM AR and mild to moderate HDM allergic asthma were randomized 1:1:1:1 to double-blinded daily treatment with 1, 3, 6 SQ-HDM or placebo. End-of-treatment rhinoconjunctivitis symptoms and medication...... score were predefined extrapulmonary end points. A subgroup analysis was conducted post hoc in subjects with a total combined rhinitis score (TCRS) > 0 (ie, with AR symptoms and/or AR medication use during the 4-week baseline period). The subgroup was comprised of 498 subjects (82%). RESULTS...

  11. Efficacy of a combined oral formulation of derquantel-abamectin against the adult and larval stages of nematodes in sheep, including anthelmintic-resistant strains.

    Science.gov (United States)

    Little, Peter R; Hodge, Andrew; Maeder, Steven J; Wirtherle, Nicole C; Nicholas, David R; Cox, George G; Conder, George A

    2011-09-27

    Derquantel (DQL), a semi-synthetic member of a novel anthelmintic class, the spiroindoles, in combination with abamectin (ABA) [as the combination product STARTECT(®)] is a new entry for the treatment and control of parasites in sheep. The 19 studies reported herein were conducted in Australia, New Zealand, South Africa and the United Kingdom to demonstrate the efficacy of derquantel-abamectin (DQL-ABA) against a broad spectrum of gastrointestinal and respiratory nematodes of sheep, and to support registration of the combination product. Eleven studies were conducted using natural or experimental parasite infections with unknown or unconfirmed resistance, while eight studies utilised isolates/strains with confirmed or well characterised resistance to one or more currently available anthelmintics, including macrocyclic lactones. All studies included DQL-ABA and negative control groups, and in selected studies one or more reference anthelmintic groups were included. In all studies the commercial formulation of DQL-ABA was administered orally at 2mg/kg DQL and 0.2mg/kg ABA; placebo was administered in the same volume as DQL-ABA; and reference anthelmintics were administered as per label recommendations, except in one instance where levamisole was administered at twice the label dose. Infection, necropsy, worm collection and worm counting procedures were performed using standard techniques. Efficacy was calculated based on the percentage reduction in geometric mean worm count relative to negative control for each nematode species and lifecycle stage targeted. Twenty-two isolates/strains used in the eight studies targeting resistant worms had proven resistance: three to one anthelmintic class, eleven to two classes and eight to three or more classes; of these resistant strains, 16 demonstrated resistance to a macrocyclic lactone anthelmintic. Regardless of resistance status in the 19 studies, DQL-ABA controlled a broad range of economically important gastrointestinal

  12. Pharmacokinetic and bioequivalence study of a telmisartan/S-amlodipine fixed-dose combination (CKD-828) formulation and coadministered telmisartan and S-amlodipine in healthy subjects.

    Science.gov (United States)

    Kang, Woo Youl; Seong, Sook Jin; Ohk, Boram; Gwon, Mi-Ri; Kim, Bo Kyung; La, Sookie; Kim, Hyun-Ju; Cho, Seungil; Yoon, Young-Ran; Yang, Dong Heon; Lee, Hae Won

    2018-01-01

    A new fixed-dose combination (FDC) formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828) has been developed to increase convenience (as only one tablet is required per day) and improve treatment compliance. The pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study. To analyze the telmisartan and S-amlodipine plasma concentrations using a validated liquid chromatography-tandem mass spectrometry method, serial blood samples were collected up to 48 hours post-dose for telmisartan and 144 hours post-dose for S-amlodipine, in each period. Forty-eight healthy subjects were enrolled, and 43 completed the study. The mean peak plasma concentration (C max ) and the area under the plasma concentration-time curve from time 0 to the last measurement (AUC 0-t ) values of telmisartan were 522.29 ng/mL and 2,475.16 ng·h/mL for the FDC, and 540.45 ng/mL and 2,559.57 ng·h/mL for the individual agents concomitantly administered, respectively. The mean C max and AUC 0-t values of S-amlodipine were 2.71 ng/mL and 130.69 ng·h/mL for the FDC, and 2.74 ng/mL and 129.81 ng·h/mL for the individual agents concomitantly administered, respectively. The geometric mean ratio (GMR) and 90% confidence interval (CI) for the telmisartan C max and AUC 0-t (FDC of telmisartan and S-amlodipine/concomitant administration) were 0.8509 (0.7353-0.9846) and 0.9431 (0.8698-1.0226), respectively. The GMR and 90% CI for the S-amlodipine C max and AUC 0-t (FDC/concomitant administration) were 0.9829 (0.9143-1.0567) and 0.9632 (0.8798-1.0546), respectively. As the intrasubject variability of the C max for telmisartan administered individually was 42.94%, all 90% CIs of the GMRs fell within the predetermined acceptance range. Both treatments were well tolerated in this study. CKD-828 FDC tablets were shown to

  13. Immunogenicity and safety of primary and booster vaccination with 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens in a hexavalent DTPa-HBV-IPV/Hib combination vaccine in comparison with the licensed Infanrix hexa

    Science.gov (United States)

    Vesikari, Timo; Rivera, Luis; Korhonen, Tiina; Ahonen, Anitta; Cheuvart, Brigitte; Hezareh, Marjan; Janssens, Winnie; Mesaros, Narcisa

    2017-01-01

    ABSTRACT Safety and immunogenicity of 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens of the combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Hib vaccine (DTPa-HBV-IPV/Hib) were evaluated in a Primary (NCT01248884) and a Booster vaccination (NCT01453998) study. In the Primary study, 721 healthy infants (randomized 1:1:1) received 3 doses of DTPa-HBV-IPV/Hib formulation A (DATAPa-HBV-IPV/Hib), or B (DBTBPa-HBV-IPV/Hib) or the licensed DTPa-HBV-IPV/Hib vaccine (Infanrix hexa, GSK; control group) at 2, 3, 4 months of age. Infants were planned to receive a booster dose at 12–15 months of age with the same formulation received in the Primary study; however, following high incidence of fever associated with the investigational formulations in the Primary study, the Booster study protocol was amended and all infants yet to receive a booster dose (N = 385) received the licensed vaccine. In the Primary study, non-inferiority of 3-dose vaccination with investigational formulations compared with the licensed vaccine was not demonstrated due to anti-pertactin failing to meet the non-inferiority criterion. Post-primary vaccination, most infants had seroprotective levels of anti-diphtheria (100% of infants), anti-tetanus antigens (100%), against hepatitis B (≥ 97.5% across groups), polyribosyl-ribitol-phosphate (≥ 88.0%) and poliovirus types 1–3 (≥ 90.5%). Seropositivity rates for each pertussis antigen were 100% in all groups. Higher incidence of fever (> 38°C) was reported in infants receiving the investigational formulations (Primary study: 75.0% [A] and 72.1% [B] vs 58.8% [control]; Booster study, before amendment: 49.4% and 46.6% vs 37.4%, respectively). The development of the investigational formulations was not further pursued. PMID:28340322

  14. 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...

  15. Pharmacokinetic and bioequivalence study of a telmisartan/S-amlodipine fixed-dose combination (CKD-828 formulation and coadministered telmisartan and S-amlodipine in healthy subjects

    Directory of Open Access Journals (Sweden)

    Kang WY

    2018-03-01

    Full Text Available Woo Youl Kang,1,2,* Sook Jin Seong,1,* Boram Ohk,1,2 Mi-Ri Gwon,1,3 Bo Kyung Kim,1,2 Sookie La,4 Hyun-Ju Kim,3 Seungil Cho,1 Young-Ran Yoon,1,2 Dong Heon Yang,5 Hae Won Lee1 1Clinical Trial Center, Kyungpook National University Hospital, Daegu, Republic of Korea; 2Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program for Creative Talent, Kyungpook National University Graduate School, Daegu, Republic of Korea; 3Department of Molecular Medicine, Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea; 4Analytical Research Division, Biocore Co Ltd, Seoul, Republic of Korea; 5Division of Cardiology, Department of Internal Medicine, Kyungpook National University School of Medicine & Hospital, Daegu, Republic of Korea *These authors contributed equally to this work Purpose: A new fixed-dose combination (FDC formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828 has been developed to increase convenience (as only one tablet is required per day and improve treatment compliance.Methods: The pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study. To analyze the telmisartan and S-amlodipine plasma concentrations using a validated liquid chromatography–tandem mass spectrometry method, serial blood samples were collected up to 48 hours post-dose for telmisartan and 144 hours post-dose for S-amlodipine, in each period.Results: Forty-eight healthy subjects were enrolled, and 43 completed the study. The mean peak plasma concentration (Cmax and the area under the plasma concentration–time curve from time 0 to the last measurement (AUC0–t values of telmisartan were 522.29 ng/mL and 2,475.16 ng⋅h/mL for the FDC, and 540.45 ng/mL and 2,559.57 ng⋅h/mL for the individual agents

  16. Airway function indicators and blood indicators in children with dust mite allergic rhinitis after sublingual immunotherapy

    Directory of Open Access Journals (Sweden)

    Hua Xiang

    2016-07-01

    Full Text Available Objective: To evaluate the airway function indicators and blood indicators in children with dust mite allergic rhinitis after sublingual immunotherapy. Methods: A total of 68 children with dust mite allergic rhinitis treated in our hospital from November, 2012 to October, 2015 were selected as the research subjects and randomly divided into observation group 34 cases and control group 34 cases. The control group received clinical routine therapy for allergic rhinitis, the observation group received sublingual immunotherapy, and then differences in basic lung function indicator values, small airway function indicator values and levels of serum inflammatory factors as well as serum ECP, TARC, Eotaxin-2 and VCAM were compared between two groups after treatment. Results: The FVC, FEV1, PEF and FEV1/FVC values of the observation group after treatment were higher than those of the control group (P<0.05; the MMEF, MEF50% and MEF25% values of the observation group were higher than those of the control group, and the proportion of AHR was lower than that of the control group (P<0.05; the serum IL-4, IL-9, IL-12, IL-13 and IL-16 levels of the observation group after treatment were lower than those of the control group, and the IL-10 and IL-12 levels are higher than those of the control group (P<0.05; the serum ECP, TARC, Eotaxin-2 and VCAM levels of the observation group children after treatment were lower than those of the control group (P<0.05. Conclusions: Sublingual immunotherapy for children with dust mite allergic rhinitis can optimize the airway function, reduce the systemic inflammatory response and eventually improve the children’s overall state, and it’s has positive clinical significance.

  17. ROLE OF 400 MCG INTRAOPERATIVE SUBLINGUAL MISOPROSTOL FOR REDUCTION OF CAESAREAN BLOOD LOSS

    Directory of Open Access Journals (Sweden)

    Lalmohan Nayak

    2017-02-01

    Full Text Available BACKGROUND Lower segment caesarean section is a common surgical procedure. Postpartum haemorrhage incidence after LSCS is 4%. Misoprostol is a prostaglandin E1 analogue with good uterotonic properties, easy availability, low cost, thermostability, long shelf life, easy administration and few adverse effects at therapeutic dose. It is readily absorbed by oral, sublingual, buccal, vaginal or rectal route. Sublingual route attains quickest concentration. Dose of 400 mcg was chosen in this study to minimise adverse effects with optimal therapeutic benefit. The aim of the study is to determine the efficacy of sublingual misoprostol in reducing caesarean blood loss. MATERIALS AND METHODS It is a prospective experimental study done in VSSIMSAR, Burla. Women undergoing LSCS were randomly assigned to study and control groups of equal strength of 100 each. In all cases, preoperative Hb%, haematocrit, pulse, BP was noted. Study group were given 400 mcg misoprostol at the time of cord clamping. In control group, nothing was given. In all patients, active management of third stage of labour was done by using oxytocin 10 IU (IV along with uterine massage. Blood loss soaked by tetra was calculated using formula, blood loss = wet weight-dry weight/1.05 (1.05 is constant. Amount of blood loss, postoperative Hb%, haematocrit, pulse rate, BP was noted in both groups and compared. BP and pulse were noted after 1 hour and Hb%, haematocrit were noted after 24 hours. RESULTS Study group showed significant decrease in total blood loss (around 117.9 mL as compared to control group. There was significant decrease in the postoperative fall in Hb in the study group as compared to control, the mean difference being 0.631 gm%. Study group also showed decrease in postoperative fall in haematocrit as compared to control, the mean difference being 0.055. CONCLUSION Misoprostol significantly reduced caesarean blood loss and doesn’t affect foetal outcome without significant

  18. Ultrastructural changes in the sublingual salivary gland of prenatal buffalo (Bubalus bubalis

    Directory of Open Access Journals (Sweden)

    A. D. Singh

    2016-03-01

    Full Text Available Aim: The present study was aimed to elucidate ultrastructural changes in the development of sublingual salivary gland of buffalo during prenatal life. Materials and Methods: The study was carried out on sublingual salivary gland of 36 buffalo fetuses ranging from 13.2 cm curved crown-rump length (CVRL (88th day to full term. The fetuses were categorized into three groups based on their CVRL. Results: The cells lining the terminal tubules were undifferentiated with poorly developed cytoplasmic organelles but lacked secretory granules (SGs at 13.2 cm CVRL (88th day. The SGs appeared first in the form of membrane-bound secretory vesicles with homogeneous electron-dense as well as electron-lucent contents at 21.2 cm CVRL (122nd day; however, mucous acinar cells contained electron-lucent granules, while serous secretory cells as well as serous demilunes showed electron-dense granules at 34 cm CVRL (150th day of prenatal life. At 53.5 cm CVRL (194th day, both mucous and serous acini were differentiated by the density of SGs. Conclusion: The cytoplasm of acinar cells was filled with mitochondria, rough endoplasmic reticulum, and Golgi profiles in mid and late fetal age groups. The SGs were increased in number during the late fetal age group. The myoepithelial cells (MECs were located at the base of the acinar cells as well as intercalated and striated ducts and were stellate in shape. The ultrastructure of MEC revealed a parallel stream of myofilaments in the cytoplasm and its processes. The mucous cells were predominantly present in the sublingual salivary gland and were pyramidal in shape.

  19. Sedation and mechanical hypoalgesia after sublingual administration of detomidine hydrochloride gel to donkeys.

    Science.gov (United States)

    Lizarraga, Ignacio; Castillo-Alcala, Fernanda; Varner, Kelley M; Robinson, Lauren S

    2016-07-01

    OBJECTIVE To compare sedative and mechanical hypoalgesic effects of sublingual administration of 2 doses of detomidine gel to donkeys. DESIGN Randomized blinded controlled trial. ANIMALS 6 healthy castrated male donkeys. PROCEDURES In a crossover study design, donkeys received each of the following sublingual treatments 1 week apart in a randomly assigned order: 1 mL of molasses (D0) or detomidine hydrochloride gel at 20 μg/kg (9 μg/lb; D20) or 40 μg/kg (18 μg/lb; D40). Sedation score (SS), head height above the ground (HHAG), and mechanical nociceptive threshold (MNT) were assessed before and for 180 minutes after treatment. Areas under the effect change-versus-time curves (AUCs) from 0 to 30, 30 to 60, 60 to 120, and 120 to 180 minutes after administration were computed for SS, HHAG, and MNT and compared among treatments. RESULTS D20 and D40 resulted in greater SS AUCs from 60 to 120 minutes and smaller HHAG AUCs from 30 through 180 minutes than did D0. The D40 resulted in smaller HHAG AUCs from 60 to 120 minutes than did D20. Compared with D0 values, MNT AUCs from 60 to 120 minutes were higher for D20, whereas MNT AUCs from 30 through 180 minutes were higher for D40. CONCLUSIONS AND CLINICAL RELEVANCE D20 and D40 induced sedation and mechanical hypoalgesia in donkeys by > 30 minutes after administration, but only sedation was dose dependent. Sublingual administration of detomidine gel at 40 μg/kg may be useful for sedation of standing donkeys prior to potentially painful minor procedures.

  20. Disintegration of sublingual tablets: proposal for a validated test method and acceptance criterion.

    Science.gov (United States)

    Weda, M; van Riet-Nales, D A; van Aalst, P; de Kaste, D; Lekkerkerker, J F F

    2006-12-01

    In the Netherlands the market share of isosorbide dinitrate 5 mg sublingual tablets is dominated by 2 products (A and B). In the last few years complaints have been received from health care professionals on product B. During patient use the disintegration of the tablet was reported to be slow and/or incomplete, and ineffectiveness was experienced. In the European Pharmacopoeia (Ph. Eur.) no requirement is present for the disintegration time of sublingual tablets. The purpose of this study was to compare the in vitro disintegration time of products A and B, and to establish a suitable test method and acceptance criterion. A and B were tested with the Ph. Eur. method described in the monograph on disintegration of tablets and capsules as well as with 3 modified tests using the same Ph. Eur. apparatus, but without movement of the basket-rack assembly. In modified test 1 and modified test 2 water was used as medium (900 ml and 50 ml respectively), whereas in modified test 3 artificial saliva was used (50 ml). In addition, disintegration was tested in Nessler tubes with 0.5 and 2 ml of water. Finally, the Ph. Eur. method was also applied to other sublingual tablets with other drug substances on the Dutch market. With modified test 3 no disintegration could be achieved within 20 min. With the Ph. Eur. method and modified tests 1 and 2 product A and B differed significantly (p disintegration times. These 3 methods were capable of discriminating between products and between batches. The time measured with the Ph. Eur. method was significantly lower compared to modified tests 1 and 2 (p tablets the disintegration time should be tested. The Ph. Eur. method is considered suitable for this test. In view of the products currently on the market and taking into consideration requirements in the United States Pharmacopeia and Japanese Pharmacopoeia, an acceptance criterion of not more than 2 min is proposed.

  1. Reduced sublingual endothelial glycocalyx in type 1 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Winther, Signe Abitz; Frimodt-Møller, Marie; Zobel, Emilie Hein

    thickness was assessed by 5 measurements with the GlucoCheck device (GlucoCheck BV, The Netherlands), a non-invasive hand-held microscope generating video recordings of the sublingual capillaries. Endothelial glycocalyx thickness was estimated from the PBR in capillaries with a diameter range of 5-25 μm......- and macroalbuminuric patients (p=0.020) and micro- and macroalbuminuric patients (p=0.042) were significant, but the difference between normo- and microalbuminuric patients was not (p=0.74). After adjustment for age, sex, HbA1c, diabetes duration and systolic blood pressure, differences between normo...

  2. Multislice CT coronary angiography: effect of sublingual nitroglycerine on the diameter of coronary arteries

    International Nuclear Information System (INIS)

    Dewey, M.; Hamm, B.; Hoffmann, H.

    2006-01-01

    Purpose: to investigate the influence of sublingual glycerol trinitrate (1.2 mg, Nitrate [nitroglycerine], Nitrolingual N spray) on the coronary artery diameter on multislice computed tomography (MSCT) coronary angiography. Materials and methods: out of our database of patients who underwent MSCT (slice thickness of 0.5 mm, Aquilion, Toshiba) coronary angiography between July 2003 and November 2005 (950 patients) we retrospectively identified patients with follow-up examinations who received Nitrate for one examination while another examination was performed without Nitrate (10 patients). Another 10 patients who underwent two MSCT examinations with sublingual Nitrate administration were randomly selected from this database to serve as control group. For the resulting 40 MSCT examinations, blinded MSCT datasets were prepared, which were randomly evaluated by a reader blinded to the patient information and whether or not Nitrate had been given. The proximal coronary artery diameters were measured for the left main coronary artery (LMA), the left anterior descending coronary artery (LAD), the left circumflex coronary artery (LCX), and the right coronary artery (RCA) in all 40 datasets, resulting in altogether 160 measurements. Results: the proximal diameters of all four coronary arteries were significantly larger on the MSCT coronary angiograms obtained after sublingual administration of Nitrate compared with the examinations in the same 10 patients without Nitrate (p < 0.001). The average diameters without and with Nitrate for the LMA, LAD, LCX, and RCA were 4.3 ± 1.1 vs. 4.8 ± 0.9 mm (12% increase, p < 0.005), 3.0 ± 0.6 vs. 3.5 ± 0.5 mm (17% increase, p < 0.001), 2.7 ± 0.6 vs. 3.2 ± 0.7 mm (19% increase, p < 0.005), and 2.9 ± 0.9 vs. 3.5 ± 0.7 mm (21% increase, p < 0.005), respectively. In the control group of 10 patients who underwent two MSCT coronary angiographies after sublingual Nitrate, no significant difference in the proximal diameter of all four

  3. Distinct modulation of allergic T cell responses by subcutaneous versus sublingual allergen-specific immunotherapy

    DEFF Research Database (Denmark)

    Schulten, Véronique; Tripple, Victoria; Andersen, Kristian Aasbjerg

    2016-01-01

    mechanisms involved have not been fully explored. OBJECTIVE: To compare changes in the allergen-specific T cell response induced by subcutaneous versus sublingual administration of allergen-specific immunotherapy (AIT). METHODS: Grass pollen allergic patients were randomized into groups receiving either SCIT...... injections, or SLIT tablets or neither. PBMC were tested for Timothy grass (TG)-specific cytokine production by ELISPOT after in vitro expansion with TG peptide pools. Phenotypic characterization of cytokine producing cells was performed by FACS. RESULTS: In the SCIT group, decreased IL-5 production...

  4. Quality by Design (QbD) approach to optimize the formulation of a bilayer combination tablet (Telmiduo®) manufactured via high shear wet granulation.

    Science.gov (United States)

    Lee, Ah Ram; Kwon, Seok Young; Choi, Du Hyung; Park, Eun Seok

    2017-12-20

    A bilayer tablet, which consisted of telmisartan and amlodipine besylate, was formulated based on a Quality by Design (QbD) approach. The control and response factors were determined based on primary knowledge and the target values of the control tablet (Twynsta ® ). A D-optimal mixture design was used to obtain the optimal formulations in terms of D-mannitol, crospovidone, and MCC for the telmisartan layer, and CCM-Na, PVP K25, and Prosolv for the amlodipine layer. The quantitative effects of the different formulation factors on the response factors were accurately predicted using the equations of best fit and a strong linearity was observed between the predicted and actual values of the response factors. The optimized bilayer tablet was obtained using a numeric optimization technique and was characterized compared with a control (Twynsta ® ) by using various physical evaluations and in vivo pharmacokinetic parameters. The physical stability of Telmiduo ® was greater than that of Twynsta ® owing to the improvement of formulation factors. The in vivo pharmacokinetic parameters suggested that Telmiduo ® might have pharmaceutical equivalence and bioequivalence with Twynsta ® . Therefore, the bilayer tablet that consisted of telmisartan and amlodipine besylate could be produced using a more economical and simpler method than that used to produce Twynsta ® . Moreover, the suitability of QbD for effective product development in the pharmaceutical industry was shown. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Acinar autolysis and mucous extravasation in human sublingual glands: a microscopic postmortem study.

    Science.gov (United States)

    Azevedo-Alanis, Luciana Reis; Tolentino, Elen de Souza; de Assis, Gerson Francisco; Cestari, Tânia Mary; Lara, Vanessa Soares; Damante, José Humberto

    2015-10-01

    Although some morphological investigations on aged human sublingual glands (HSG) found eventual phenomena identified as autolysis and mucous extravasation, the exact meaning of these findings has not been elucidated. The aim of this work is to investigate whether acinar autolysis and mucous extravasation are related to the aging process in human sublingual glands. We also speculate if autolytic changes may assist forensic pathologists in determining time of death. 186 cadavers' glands were allocated to age groups: I (0-30 years); II (31-60), and III (61-90). Time and mode of death were also recorded. Acinar autolysis and mucous extravasation were classified as present or absent. Ultrastructural analysis was performed using transmission electron microscopy (TEM). Data were compared using Mann-Whitney U, Spearman's correlation coefficient, Kruskal-Wallis, and Dunn tests (pautolysis (r=0.38; p=0.0001). However, there was no correlation between autolysis and time of death. No differences were observed between genders. TEM showed mucous and serous cells presenting nuclear and membrane alterations and mucous cells were more susceptible to autolysis. Acinar autolysis occurred in all age groups and increased with age while mucous extravasation was rarely found. Both findings are independent. Autolysis degrees in HSG could not be used to determine time of death.

  6. Spontaneous sublingual and intramural small-bowel hematoma in a patient on oral anticoagulation

    Directory of Open Access Journals (Sweden)

    Mohamed Moftah

    2012-08-01

    Full Text Available Spontaneous sublingual hematoma and intramural small bowel hematoma are rare and serious complications of anticoagulant therapy. Though previously reported individually, there has been no previous report of the same two complications occurring in a single patient. A 71-year-old Caucasian man, who was on warfarin for atrial fibrillation, presented with difficulty in swallowing due to a sublingual hematoma. He was observed in our intensive care unit, his warfarin was held and he recovered with conservative management. He represented two months later with a two day history of abdominal pain and distension. An abdominopelvic computed tomography (CT scan now showed small bowel obstruction due to intramural small bowel hematoma and haemorrhagic ascites. Again, this was treated expectantly with a good outcome. In conclusion, life threatening haemorrhagic complications of oral anticoagulant therapy can recur. Conservative treatment is successful in most cases, but an accurate diagnosis is mandatory to avoid unnecessary surgery. CT scan is the investigation of choice for the diagnosis of suspected haemorrhagic complications of over coagulation.

  7. Sublingual administration of detomidine in horses: sedative effect, analgesia and detection time.

    Science.gov (United States)

    L'Ami, Jiske J; Vermunt, Lian E; van Loon, Johannes P A M; Sloet van Oldruitenborgh-Oosterbaan, Marianne M

    2013-05-01

    A single dose of 40 μg/kg bodyweight (BW) of oromucosal detomidine gel was administered sublingually to 10 healthy Dutch Warmblood mares aged 7 ± 4 years (mean ± SD) and BW 580 ± 69 kg. Blood and urine samples were collected before and for 8 days following administration and evaluated qualitatively in an FEI Reference Laboratory and quantitatively in a research laboratory. Clinical effects were evaluated at baseline and for 24 h after administration. Sedation was determined using head height and scores of reaction to auditory and mixed auditory/sensory stimuli. Mechanical nociceptive thresholds (MNTs) were assessed using pressure algometry to evaluate analgesia. Heart rate (HR) was measured and ataxia scored. All horses were considered negative for detomidine in blood samples by 48 h post-administration and in urine by 60 h. These results indicated that a safe withdrawal time for detomidine oromucosal gel may be 72 h following a single sublingual administration of 40 μg/kgBW. Decreases in HR and head height were maximal at 40 and 60 min post-administration, respectively. The maximal decrease in response to stimuli was observed at 100 min. Ataxia was maximal at 60 min. At 40 and 80 min MNTs were significantly increased compared to baseline. All parameters, except the MNTs of two locations, which were decreased, returned to baseline values within 24 h post-administration. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Acinar autolysis and mucous extravasation in human sublingual glands: a microscopic postmortem study

    Directory of Open Access Journals (Sweden)

    Luciana Reis AZEVEDO-ALANIS

    2015-10-01

    Full Text Available Although some morphological investigations on aged human sublingual glands (HSG found eventual phenomena identified as autolysis and mucous extravasation, the exact meaning of these findings has not been elucidated.Objective The aim of this work is to investigate whether acinar autolysis and mucous extravasation are related to the aging process in human sublingual glands. We also speculate if autolytic changes may assist forensic pathologists in determining time of death.Material and Methods 186 cadavers’ glands were allocated to age groups: I (0–30 years; II (31–60, and III (61–90. Time and mode of death were also recorded. Acinar autolysis and mucous extravasation were classified as present or absent. Ultrastructural analysis was performed using transmission electron microscopy (TEM. Data were compared using Mann-Whitney U, Spearman’s correlation coefficient, Kruskal-Wallis, and Dunn tests (p<0.05.Results There was correlation between age and acinar autolysis (r=0.38; p=0.0001. However, there was no correlation between autolysis and time of death. No differences were observed between genders. TEM showed mucous and serous cells presenting nuclear and membrane alterations and mucous cells were more susceptible to autolysis.Conclusion Acinar autolysis occurred in all age groups and increased with age while mucous extravasation was rarely found. Both findings are independent. Autolysis degrees in HSG could not be used to determine time of death.

  9. Congenital hypothyroidism due to ectopic sublingual thyroid gland in Prader-Willi Syndrome: a case report.

    Science.gov (United States)

    Bocchini, Sarah; Fintini, Danilo; Grugni, Graziano; Boiani, Arianna; Convertino, Alessio; Crinò, Antonino

    2017-09-22

    Thyroid gland disorders are variably associated with Prader-Willi syndrome (PWS). Many of the clinical features in newborns with PWS are similar to those found in congenital hypothyroidism (CH). We report a case of a girl with CH and PWS. At the age of 9 months CH caused by an ectopic sublingual thyroid was diagnosed, and hormone replacement therapy was started. In spite of this treatment a decrease in growth velocity, weight excess and delayed development were observed. At the age of 9 years PWS was suspected on the basis of phenotype and genetic tests confirmed a maternal uniparental disomy of chromosome 15. This is the second reported case of hypothyroidism due to an ectopic sublingual thyroid gland in PWS suggesting that, although rare, an association between CH and PWS may exist. In our case diagnosis of PWS was delayed because mental retardation, hypotonia, obesity and short stature were initially attributed to hypothyroidism. In this context PWS should be considered in obese children with CH who do not improve adequately with l-thyroxine therapy. Also, thyroid function in all PWS children should be assessed regularly in order to avoid delayed diagnosis of hypothyroidism.

  10. Direct action of the X-ray on the submandibular and sublingual glands. Histologic and histochemical study in rats

    International Nuclear Information System (INIS)

    Santos-Pinto, M.C. dos; Martinelli, C.; Santos-Pinto, R. dos

    1991-01-01

    The submandibular and sublingual glands of rats are surgically exposed and irradiated by X-ray. A simulated group with surgical exposition of the glands is performed. In the irradiated submandibular glands occurred atrophy, architectural disorder and degenerative processes. RNA reduction in the nucleus, nucleolus and cytoplasm of the acini cells and a decrease of protein synthesis are described. (M.A.C.)

  11. Vaccine Adjuvants in Fish Vaccines Make a Difference: Comparing Three Adjuvants (Montanide ISA763A Oil, CpG/Poly I:C Combo and VHSV Glycoprotein Alone or in Combination Formulated with an Inactivated Whole Salmonid Alphavirus Antigen

    Directory of Open Access Journals (Sweden)

    Hanna L. Thim

    2014-03-01

    Full Text Available Most commercial vaccines offered to the aquaculture industry include inactivated antigens (Ag formulated in oil adjuvants. Safety concerns are related to the use of oil adjuvants in multivalent vaccines for fish, since adverse side effects (e.g., adhesions can appear. Therefore, there is a request for vaccine formulations for which protection will be maintained or improved, while the risk of side effects is reduced. Here, by using an inactivated salmonid alphavirus (SAV as the test Ag, the combined use of two Toll-like receptor (TLR ligand adjuvants, CpG oligonucleotides (ODNs and poly I:C, as well as a genetic adjuvant consisting of a DNA plasmid vector expressing the viral haemorrhagic septicaemia virus (VHSV glycoprotein (G was explored. VHSV-G DNA vaccine was intramuscularly injected in combination with intraperitoneal injection of either SAV Ag alone or combined with the oil adjuvant, Montanide ISA763, or the CpG/polyI:C combo. Adjuvant formulations were evaluated for their ability to boost immune responses and induce protection against SAV in Atlantic salmon, following cohabitation challenge. It was observed that CpG/polyI:C-based formulations generated the highest neutralizing antibody titres (nAbs before challenge, which endured post challenge. nAb responses for VHSV G-DNA- and oil-adjuvanted formulations were marginal compared to the CpG/poly I:C treatment. Interestingly, heat-inactivated sera showed reduced nAb titres compared to their non-heated counterparts, which suggests a role of complement-mediated neutralization against SAV. Consistently elevated levels of innate antiviral immune genes in the CpG/polyI:C injected groups suggested a role of IFN-mediated responses. Co-delivery of the VHSV-G DNA construct with either CpG/polyI:C or oil-adjuvanted SAV vaccine generated higher CD4 responses in head kidney at 48 h compared to injection of this vector or SAV Ag alone. The results demonstrate that a combination of pattern recognizing

  12. Combination of argan oil and phospholipids for the development of an effective liposome-like formulation able to improve skin hydration and allantoin dermal delivery.

    Science.gov (United States)

    Manca, Maria Letizia; Matricardi, Pietro; Cencetti, Claudia; Peris, Josè Esteban; Melis, Virginia; Carbone, Claudia; Escribano, Elvira; Zaru, Marco; Fadda, Anna Maria; Manconi, Maria

    2016-05-30

    Allantoin is traditionally employed in the treatment of skin ulcers and hypertrophic scars. In the present work, to improve its local deposition in the skin and deeper tissues, allantoin was incorporated in conventional liposomes and in new argan oil enriched liposomes. In both cases, obtained vesicles were unilamellar, as confirmed by cryo-TEM observation, but the addition of argan oil allowed a slight increase of the mean diameter (∼130nm versus ∼85nm). The formulations, especially those containing argan oil, favoured the allantoin accumulation in the skin, in particular in the dermis (∼8.7μg/cm(2)), and its permeation through the skin (∼33μg/cm(2)). The performances of vesicles as skin delivery systems were compared with those obtained by water dispersion of allantoin and the commercial gel, Sameplast(®). Moreover, in this work, for the first time, the elastic and viscous moduli of the skin were measured, underlining the different hydrating/moisturizing effects of the formulations. The application of ARG liposomes seems to provide a softening and relaxing effect on the skin, thus facilitating the drug accumulation and passage into and trough it. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Fentanyl sublingual spray for breakthrough cancer pain in patients receiving transdermal fentanyl.

    Science.gov (United States)

    Alberts, David S; Smith, Christina Cognata; Parikh, Neha; Rauck, Richard L

    2016-10-01

    To investigate the relationship between effective fentanyl sublingual spray (FSS) doses for breakthrough cancer pain (BTCP) and around-the-clock (ATC) transdermal fentanyl patch (TFP). Adults tolerating ATC opioids received open-label FSS for 26 days, followed by a 26-day double-blind phase for patients achieving an effective dose (100-1600 µg). Out of 50 patients on ATC TFP at baseline, 32 (64%) achieved an effective dose. FSS effective dose moderately correlated with mean TFP dose (r = 0.4; p = 0.03). Patient satisfaction increased during the study. Common adverse event included nausea (9%) and peripheral edema (9%). FSS can be safely titrated to an effective dose for BTCP in patients receiving ATC TFP as chronic cancer pain medication. ClinicalTrials.gov identifier: NCT00538850.

  14. SQ grass sublingual allergy immunotherapy tablet for disease-modifying treatment of grass pollen allergic rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Dahl, Ronald; Roberts, Graham; de Blic, Jacques

    2016-01-01

    BACKGROUND: Allergy immunotherapy is a treatment option for allergic rhinoconjunctivitis (ARC). It is unique compared with pharmacotherapy in that it modifies the immunologic pathways that elicit an allergic response. The SQ Timothy grass sublingual immunotherapy (SLIT) tablet is approved in North...... America and throughout Europe for the treatment of adults and children (≥5 years old) with grass pollen-induced ARC. OBJECTIVE: The clinical evidence for the use of SQ grass SLIT-tablet as a disease-modifying treatment for grass pollen ARC is discussed in this review. METHODS: The review included...... the suitability of SQ grass SLIT-tablet for patients with clinically relevant symptoms to multiple Pooideae grass species, single-season efficacy, safety, adherence, coseasonal initiation, and cost-effectiveness. The data from the long-term SQ grass SLIT-tablet clinical trial that evaluated a clinical effect 2...

  15. Post-treatment efficacy of discontinuous treatment with 300IR 5-grass pollen sublingual tablet in adults with grass pollen-induced allergic rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Didier, A; Malling, H-J; Worm, Marcel

    2013-01-01

    Sustained efficacy over three pollen seasons of pre- and co-seasonal treatment with 300IR 5-grass pollen sublingual tablet has been demonstrated in adults with moderate-severe grass pollen-associated allergic rhinoconjunctivitis.......Sustained efficacy over three pollen seasons of pre- and co-seasonal treatment with 300IR 5-grass pollen sublingual tablet has been demonstrated in adults with moderate-severe grass pollen-associated allergic rhinoconjunctivitis....

  16. Histological study of human sublingual gland with special emphasis on intercalated and striated ducts

    International Nuclear Information System (INIS)

    Rana, R.; Minhas, L.A.; Mubarik, A.

    2012-01-01

    Objective: To study the histomorphological characteristics of human sublingual gland, specially of intercalated and striated ducts. Study design: Descriptive study Place and duration of study: Army Medical College from Jan 2002 to Dec 2002 Materials and methods: Fifteen sublingual glands (right and left) from postmortem cases were obtained from District Headquarter Hospital Rawalpindi, within twelve hours of death. Five micrometer thick sections were made and stained with Haematoxylin and Eosin (H and E). Morphology of intercalated and striated ducts was studied and their number was counted. Results: The mean number of intercalated ducts in the right gland 'a'and 'b' parts, and in the left gland 'a' and 'b' parts was 1.45+-0.14, 1.39+-.009, 1.31+-0.11 and 1.18+-0.10 respectively. The mean diameter of intercalated ducts in the same parts was 19.76+-0.44 micro m, 20.6+-0.53 micro m, 20.34+-0.49 micro m and 19.84+-0.98 micro m respectively. The mean number of striated ducts in the right gland ''a'' and ''b'' parts, and in the left gland ''a'' and ''b'' parts was 0.55+-.008, 0.57+-.008, 0.80+-0.14 and 0.80+-0.14 while mean diameter of striated ducts in the right gland ''a'' and ''b'' parts, and in the left gland ''a'' and ''b'' parts was 49.90+-4.70 micro m, 53.23+-2.50 micro m, 61.68+-3.93 micro m and 57.73+-2.85 micro m respectively. Conclusion: The difference between the mean number and diameter of the ducts of right and left glands was statistically insignificant. (author)

  17. Sublingual piroxicam in the management of postoperative pain after surgical removal of impacted mandibular third molar.

    Science.gov (United States)

    Mohammad, Shadab; Singh, Vibha; Wadhwani, Puneet; Tayade, Himanshu P; Rathod, Onkar K

    2012-01-01

    Surgical removal of impacted mandibular third molar is one of the most commonly performed procedures in oral and maxillofacial surgical practice. The role of preoperative and postoperative medications for management of postoperative complications has been extensively evaluated. To assess the therapeutic effect of a single dose of 40 mg sublingual piroxicam (study group) vs 150 mg oral diclofenac (50 mg thrice a day) (control group) in patients undergoing surgical removal of impacted mandibular third molar. A total of 100 patients with asymptomatic impacted mandibular third molars were randomized into two groups. One group received two 20-mg tablets of piroxicam once daily on the first and second postoperative days, followed by one 20-mg tablet on the third post-operative day. The other group received one tablet of diclofenac 50 mg orally thrice daily on the first, second, and third post-operative days. Repeated extraoral examinations were done for continuous assessment of swelling, trismus, and reduction in pain. Overall impression of the treating physician and the patient regarding efficacy of study drugs were recorded at the end of the study. In the piroxicam group there was >50% reduction in pain on all three days postoperatively. The incidence of swelling and trismus was found to be higher in the control group as compared to the study group. Adverse events, such as gastrointestinal (GI) disturbances, were significantly higher in the diclofenac group (11%) as compared to the piroxicam group (0%). Two sublingual piroxicam 20 mg tablets once daily has better efficacy and tolerability profile than diclofenac 50 mg one tablet thrice daily in the management of pain after surgical removal of impacted mandibular third molar.

  18. Uso y abuso del nifedipino por vía sublingual en nuestros sistemas de urgencia

    Directory of Open Access Journals (Sweden)

    Nancy Guinart Zayas

    1998-04-01

    Full Text Available Se observa que el incremento de la prevalencia de pacientes hipertensos en nuestras comunidades, y la implantación del Programa Nacional para el control de la hipertensión arterial, no han podido disminuir la cantidad de pacientes que acuden con cifras altas de su presión arterial a nuestros servicios de urgencia con decisiones terapéuticas indiscriminadas y agresivas. Se ha generalizado el uso del nifedipino sublingual, incluso en pacientes de la tercera edad, lo que produce bajadas bruscas de la presión arterial por disminución en la sensibilidad de los barorreceptores y con ellas una alteración de los mecanismos de autorregulación del flujo hístico. Se señala que las complicaciones producidas no son alarmantes, pero con un uso racional y si se cumplen algunas normas, podrían disminuirse aún másIt is observed that the prevalence increase of hypertensive patients in our communities and the implementation of the National Program for the Hypertension Control have not so far been able to reduce the number of hypertensive patients going to our emergency medical services by applying indiscriminate and aggressive therapeutical methods. The use of sublingual administered nifedipine is extensive even in elderly patients, which may cause a sharp blood pressure drop and also a change in the hystic flow self-regulating mechanisms. It is stressed that complications are not serious but if this drug is more rationally used and some directions are fulfilled, then these complications will be further reduced

  19. Sublingual administration of detomidine to calves prior to disbudding: a comparison with the intravenous route.

    Science.gov (United States)

    Hokkanen, Ann-Helena; Raekallio, Marja R; Salla, Kati; Hänninen, Laura; Viitasaari, Elina; Norring, Marianna; Raussi, Satu; Rinne, Valtteri M; Scheinin, Mika; Vainio, Outi M

    2014-07-01

    To study the effects of oromucosal detomidine gel administered sublingually to calves prior to disbudding, and to compare its efficacy with intravenously (IV) administered detomidine. Randomised, prospective clinical study. Twenty dairy calves aged 12.4 ± 4.4days (mean ± SD), weight 50.5 ± 9.0 kg. Detomidine at 80 μg kg(-1) was administered to ten calves sublingually (GEL) and at 30 μg kg(-1) to ten control calves IV (V. jugularis). Meloxicam (0.5 mg kg(-1) ) and local anaesthetic (lidocaine 3 mg kg(-1) ) were administered before heat cauterization of horn buds. Heart rate (HR), body temperature and clinical sedation were monitored over 240 minutes. Blood was collected from the V. cephalica during the same period for drug concentration analysis. Pharmacokinetic variables were calculated from the plasma detomidine concentration-time data using non-compartmental methods. Statistical analyses compared routes of administration by Student's t-test and linear mixed models as relevant. The maximum plasma detomidine concentration after GEL was 2.1 ± 1.2 ng mL(-1) (mean ±SD) and the time of maximum concentration was 66.0 ± 36.9 minutes. The bioavailability of detomidine was approximately 34% with GEL. Similar sedation scores were reached in both groups after administration of detomidine, but maximal sedation was reached earlier in the IV group (10 minutes) than in the GEL group (40 minutes). HR was lower after IV than GEL from 5 to 10 minutes after administration. All animals were adequately sedated, and we were able to administer local anaesthetic without resistance to all of the calves before disbudding. Oromucosally administered detomidine is an effective sedative agent for calves prior to disbudding. © 2014 The Authors Veterinary Anaesthesia and Analgesia published by John Wiley & Sons Ltd on behalf of Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  20. Buprenorphine Implants for Treatment of Opioid Dependence: Randomized Comparison to Placebo and Sublingual Buprenorphine/Naloxone

    Science.gov (United States)

    Rosenthal, Richard N.; Ling, Walter; Casadonte, Paul; Vocci, Frank; Bailey, Genie L.; Kampman, Kyle; Patkar, Ashwin; Chavoustie, Steven; Blasey, Christine; Sigmon, Stacey; Beebe, Katherine L.

    2015-01-01

    Aims To evaluate safety and efficacy of buprenorphine implants (BI) versus placebo implants (PI) for the treatment of opioid dependence. A secondary aim compared BI to open-label sublingual buprenorphine/naloxone tablets (BNX). Design Randomized, double-blind, placebo-controlled trial. Subjects received either 4 buprenorphine implants (80 mg/implant) (n=114), 4 placebo implants (n=54), or open-label BNX (12–16 mg/d) (n=119). Setting 20 addiction treatment centers. Participants Adult outpatients (ages 18 to 65) with DSM-IV-TR opioid dependence. Measurements The primary efficacy endpoint was the percent of urine samples negative for opioids collected from weeks 1 to 24, examined as a cumulative distribution function (CDF). Findings The BI CDF was significantly different from placebo (P<.0001). Mean (95% CI) proportions of urines negative for opioids were: BI: 31.2% (25.3, 37.1) and PI: 13.4% (8.3, 18.6). BI subjects had a higher study completion rate relative to placebo (64% vs. 26%, P<.0001), lower clinician-rated (P<.0001) and patient-rated (P<.0001) withdrawal, lower patient-ratings of craving (P<.0001), and better subjects’ (P=.031) and clinicians’ (P=.022) global ratings of improvement. BI also resulted in significantly lower cocaine use (P=.0016). Minor implant-site reactions were comparable in the buprenorphine (27.2% [31/114]) and placebo groups (25.9% [14/54]). BI were non-inferior to BNX on percent urines negative for opioids [mean (95% CI): 33.5 (27.3, 39.6); CI for the difference of proportions, (−10.7, 6.2)]. Conclusions Compared with placebo, buprenorphine implants result in significantly less frequent opioid use, and are non-inferior to sublingual buprenorphine/naloxone tablets. PMID:23919595

  1. About solution of multipoint boundary problem of static analysis of deep beam with the use of combined application of finite element method and discrete-continual finite element method. part 1: formulation of the problem and general principles of approximation

    Directory of Open Access Journals (Sweden)

    Lyakhovich Leonid

    2017-01-01

    Full Text Available This paper is devoted to formulation and general principles of approximation of multipoint boundary problem of static analysis of deep beam with the use of combined application of finite element method (FEM discrete-continual finite element method (DCFEM. The field of application of DCFEM comprises structures with regular physical and geometrical parameters in some dimension (“basic” dimension. DCFEM presupposes finite element approximation for non-basic dimension while in the basic dimension problem remains continual. DCFEM is based on analytical solutions of resulting multipoint boundary problems for systems of ordinary differential equations with piecewise-constant coefficients.

  2. Combining MOSCED with molecular simulation free energy calculations or electronic structure calculations to develop an efficient tool for solvent formulation and selection

    Science.gov (United States)

    Cox, Courtney E.; Phifer, Jeremy R.; Ferreira da Silva, Larissa; Gonçalves Nogueira, Gabriel; Ley, Ryan T.; O'Loughlin, Elizabeth J.; Pereira Barbosa, Ana Karolyne; Rygelski, Brett T.; Paluch, Andrew S.

    2017-02-01

    Solubility parameter based methods have long been a valuable tool for solvent formulation and selection. Of these methods, the MOdified Separation of Cohesive Energy Density (MOSCED) has recently been shown to correlate well the equilibrium solubility of multifunctional non-electrolyte solids. However, before it can be applied to a novel solute, a limited amount of reference solubility data is required to regress the necessary MOSCED parameters. Here we demonstrate for the solutes methylparaben, ethylparaben, propylparaben, butylparaben, lidocaine and ephedrine how conventional molecular simulation free energy calculations or electronic structure calculations in a continuum solvent, here the SMD or SM8 solvation model, can instead be used to generate the necessary reference data, resulting in a predictive flavor of MOSCED. Adopting the melting point temperature and enthalpy of fusion of these compounds from experiment, we are able to predict equilibrium solubilities. We find the method is able to well correlate the (mole fraction) equilibrium solubility in non-aqueous solvents over four orders of magnitude with good quantitative agreement.

  3. Using Food Grade Lye “omushelekha” in the Formulation of Health Products from Commonly Consumed African Indigenous Vegetables and Vegetable Combinations

    Directory of Open Access Journals (Sweden)

    Florence O Habwe

    2011-05-01

    Full Text Available Background: Lye, sodium hydroxide and potassium hydroxide has been used over the years in food preparation including the preparation of vegetables and dried meat products, washing or chemical peeling of fruits and vegetables, cocoa processing, caramel production, poultry scalding and cooking among others. Lye is believed to improve the organoleptic properties and also enhances the nutritional value to the products.Objective: To assess the effect of food grade lye on the levels of copper and iron in the raw, boiled and boiled-fried single vegetables and vegetable combinations treated with and without food grade lye.Methods: Single vegetables, Crotalaria occroleuca, Solanum scabrum, Vigna unguiculata and Amaranthus blitum and their combinations were cooled and kept in the fridge at 4oCs. Elemental analysis was done for the raw, boiled and boiled-fried samples using Atomic Absorption Spectrophotometry (AAS under standard conditions using wavelengths of 248.3nm for iron and 324.2nm for copper. Paired t-test was used to compare the iron and copper levels of the boiled and boiled-fried vegetables while the independent t-test was done to assess the levels of iron and copper in the raw, boiled and boiled fried samples.Results: Boiled-fried samples recorded higher content of iron and copper than the boiled ones. A combination of Amaranthus blitum-Crotolaria occloreuca boiled without lye boiled-fried with lye, and boiled-fried without lye had the highest copper contents of 1.66mg/100gram, 4.56mg/100gram, and 4.56mg/100gram respectively, compared to Amaranthus blitum aloneFunctional Foods in Heals and Disease 2011; 5:189-197(3.48mg/100gram and Crotolaria occloreuca (0.42mg/100gram. A combination of Amaranthus blitum-Crotolaria occloreuca boiled in non-lye water, and those boiled-fried with and without lye had the highest extractable iron of 557mg/100g, 859.2mg/100g, and 859.2mg/100g respectively. Iron content was high in the Solanum scabrum (281.1mg/100g

  4. Impact of mean arterial pressure on sublingual microcirculation during cardiopulmonary bypass - secondary outcome from a randomised clinical trial

    DEFF Research Database (Denmark)

    Holmgaard, Frederik; Vedel, Anne G; Ravn, Hanne Berg

    2018-01-01

    . METHODS: Thirty-six cardiac surgery patients undergoing coronary artery bypass grafting were included and randomised to either low (40-50 mmHg) or high (70-80 mmHg) mean arterial pressure during cardiopulmonary bypass. Sidestream Dark Field video images were recorded from the sublingual mucosa. Recordings...... were analysed in a blinded fashion to quantify microcirculatory variables. RESULTS: Mean arterial pressure during cardiopulmonary bypass in the low target group was 45.0 mmHg (SD 5.3) vs. 67.2 mmHg (SD 8.9) in the high target group. We found no significant difference between the two groups......OBJECTIVE: In this substudy of a randomised, clinical trial, we explored the sublingual microcirculation during cardiac surgery at two different levels of blood pressure. We hypothesised that a higher mean arterial pressure during cardiopulmonary bypass would cause higher Microvascular Flow Index...

  5. Results from the 5-year SQ grass sublingual immunotherapy tablet asthma prevention (GAP) trial in children with grass pollen allergy

    DEFF Research Database (Denmark)

    Valovirta, Erkka; Petersen, Thomas H; Piotrowska, Teresa

    2018-01-01

    BACKGROUND: Allergy immunotherapy targets the immunological cause of allergic rhinoconjunctivitis and allergic asthma and has the potential to alter the natural course of allergic disease. OBJECTIVE: The primary objective was to investigate the effect of the SQ grass sublingual immunotherapy tablet...... compared with placebo on the risk of developing asthma. METHODS: A total of 812 children (5-12 years), with a clinically relevant history of grass pollen allergic rhinoconjunctivitis and no medical history or signs of asthma, were included in the randomized, double-blind, placebo-controlled trial......, comprising 3 years of treatment and 2 years of follow-up. RESULTS: There was no difference in time to onset of asthma, defined by prespecified asthma criteria relying on documented reversible impairment of lung function (primary endpoint). Treatment with the SQ grass sublingual immunotherapy tablet...

  6. Efficacy and safety of 5-grass pollen sublingual immunotherapy tablets in patients with different clinical profiles of allergic rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Malling, Hans-Jørgen; Montagut, A; Melac, M

    2009-01-01

    pollen sublingual tablets of 100 IR (index of reactivity), 300 IR or 500 IR, or placebo starting 4 months before the pollen season. OBJECTIVE: The aim of this complementary analysis was to determine whether 300 IR 5-grass pollen SLIT-tablets is effective in different subtypes of patients who are allergic......BACKGROUND: The optimal dose of grass pollen tablets for sublingual immunotherapy (SLIT) in allergic rhinoconjunctivitis patients was previously established in a multinational, randomized, double-blind, placebo-controlled study in 628 adults. Patients were randomized to receive once-daily 5-grass...... to grass pollen. METHODS: Different subgroups could be identified regarding comorbidities (with or without asthma during the grass-pollen season), sensitization (mono/polysensitization) and symptom severity. An additional exploratory analysis was performed within four subgroups based on pre...

  7. Effect of preload alternations on a new Doppler echocardiographic index of combined systolic and diastolic performance

    DEFF Research Database (Denmark)

    Møller, J E; Poulsen, S H; Egstrup, K

    1999-01-01

    The objective of the study was to assess the effect of preload alternations on a nongeometric Doppler index of combined systolic and diastolic myocardial performance (MPI). Doppler echocardiography was performed during Valsalva maneuver, passive leg lifting, and after sublingual administration of...

  8. An evaluation of total disintegration time for three different doses of sublingual fentanyl tablets in patients with breakthrough pain.

    Science.gov (United States)

    Nalamachu, Srinivas

    2013-12-01

    Breakthrough pain is common among patients with cancer and presents challenges to effective pain management. Breakthrough pain is characterized by rapid onset, severe intensity, and duration typically lasting disintegration time of three different doses of sublingual fentanyl tablets in opioid-tolerant patients. This was a single-center, non-randomized, open-label study. Opioid-tolerant adult patients (N = 30) with chronic pain were assigned to one of three dose groups and self-administered a single 100, 200, or 300 μg sublingual fentanyl tablet (Abstral(®), Galena Biopharma, Portland, OR, USA). Time to complete disintegration was measured by each patient with a stopwatch and independently verified by study personnel. Disintegration time (mean ± SD) for sublingual fentanyl tablets (all doses) was 88.2 ± 55.1 s. Mean disintegration times tended to be slightly longer for the 200 μg (96.7 ± 57.9 s) and 300 μg doses (98.6 ± 64.8 s) compared to the 100 μg dose (69.5 ± 40.5 s). Differences were not statistically significant. Disintegration time was not significantly different between men and women and was not affected by age. Sublingual fentanyl tablets dissolved rapidly (average time <2 min) in all patients, with the higher doses taking slightly more time to dissolve.

  9. Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg responses upon sublingual delivery in mice.

    Science.gov (United States)

    Soria, I; López-Relaño, J; Viñuela, M; Tudela, J-I; Angelina, A; Benito-Villalvilla, C; Díez-Rivero, C M; Cases, B; Manzano, A I; Fernández-Caldas, E; Casanovas, M; Palomares, O; Subiza, J L

    2018-04-01

    Polymerized allergoids coupled to nonoxidized mannan (PM-allergoids) may represent novel vaccines targeting dendritic cells (DCs). PM-allergoids are better captured by DCs than native allergens and favor Th1/Treg cell responses upon subcutaneous injection. Herein we have studied in mice the in vivo immunogenicity of PM-allergoids administered sublingually in comparison with native allergens. Three immunization protocols (4-8 weeks long) were used in Balb/c mice. Serum antibody levels were tested by ELISA. Cell responses (proliferation, cytokines, and Tregs) were assayed by flow cytometry in spleen and lymph nodes (LNs). Allergen uptake was measured by flow cytometry in myeloid sublingual cells. A quick antibody response and higher IgG2a/IgE ratio were observed with PM-allergoids. Moreover, stronger specific proliferative responses were seen in both submandibular LNs and spleen cells assayed in vitro. This was accompanied by a higher IFNγ/IL-4 ratio with a quick IL-10 production by submandibular LN cells. An increase in CD4 + CD25 high FOXP3 + Treg cells was detected in LNs and spleen of mice treated with PM-allergoids. These allergoids were better captured than native allergens by antigen-presenting (CD45 + MHC-II + ) cells obtained from the sublingual mucosa, including DCs (CD11b + ) and macrophages (CD64 + ). Importantly, all the differential effects induced by PM-allergoids were abolished when using oxidized instead of nonoxidized PM-allergoids. Our results demonstrate for the first time that PM-allergoids administered through the sublingual route promote the generation of Th1 and FOXP3 + Treg cells in a greater extent than native allergens by mechanisms that might well involve their better uptake by oral antigen-presenting cells. © 2018 The Authors. Allergy Published by John Wiley & Sons Ltd.

  10. Comparison of Intravenous Morphine with Sublingual Buprenorphine in Management of Postoperative Pain after Closed Reduction Orthopedic Surgery.

    Science.gov (United States)

    Soltani, Ghasem; Khorsand, Mahmood; Shamloo, Alireza Sepehri; Jarahi, Lida; Zirak, Nahid

    2015-10-01

    Postoperative pain is a common side effect following surgery that can significantly reduce surgical quality and patient's satisfaction. Treatment options are morphine and buprenorphine. We aimed to compare the efficacy of a single dose of intravenous morphine with sublingual buprenorphine in postoperative pain control following closed reduction surgery. This triple blind clinical trial was conducted on 90 patients referred for closed reduction orthopedic surgery. They were older than 18 years and in classes I and II of the American Society of Anesthesiologists (ASA) with an operation time of 30-90 minutes. Patients were divided into two groups of buprenorphine (4.5µg/kg sublingually) and morphine (0.2mg/kg intravenously). Baseline characteristics, vital signs, pain score, level of sedation and pharmacological side effects were recorded in the recovery room (at 0 and 30 minutes), and in the ward (at 3, 6 and 12 hours). SPSS version 19 software was used for data analysis and the significance level was set at P<0.05. Ninety patients were studied, 60 males and 30 females with a mean age of 37.7±16.2 years. There was no significant difference between the two groups in terms of baseline characteristics. Pain score in the morphine group was significantly higher than the buprenorphine group with an average score of 2.5 (P<0.001). Postoperative mean heart rate in the buprenorphine group was four beats lower than the morphine group (P<0.001). Also, in the buprenorphine 48.6% and in the morphine group 86.7% of cases were conscious in recovery (P=0.001) with a higher rate of pruritus in the latter group (P=0.001). Sublingual buprenorphine administration before anesthesia induction in closed reduction surgery can lead to better postoperative pain control in comparison to intravenous morphine. Due to simple usage and longer postoperative sedation, sublingual buprenorphine is recommended as a suitable drug in closed reduction surgery.

  11. Comparison of Intravenous Morphine with Sublingual Buprenorphine in Management of Postoperative Pain after Closed Reduction Orthopedic Surgery

    OpenAIRE

    Ghasem Soltani; Mahmood Khorsand; ALireza Sepehri Shamloo; Lida Jarahi; Nahid Zirak

    2015-01-01

    Background: Postoperative pain is a common side effect following surgery that can significantly reduce surgical quality and patient’s satisfaction. Treatment options are morphine and buprenorphine. We aimed to compare the efficacy of a single dose of intravenous morphine with sublingual buprenorphine in postoperative pain control following closed reduction surgery. Methods: This triple blind clinical trial was conducted on 90 patients referred for closed reduction orthopedic surgery. They wer...

  12. Food-specific sublingual immunotherapy is well tolerated and safe in healthy dogs : a blind, randomized, placebo-controlled study

    OpenAIRE

    Maina, Elisa; Pelst, Michael; Hesta, Myriam; Cox, Eric

    2017-01-01

    Background: Food allergies are increasing in prevalence but no treatment strategies are currently available to cure dogs with food allergy. Over the past decade, experimental food allergen-specific sublingual immunotherapy (FA-SLIT) has emerged as a potential treatment for food allergies in human medicine. However, FA-SLIT has not been investigated in dogs. Therefore, the objective of this study was to prospectively evaluate the safety, tolerability and dispenser sterility of FA-SLIT in healt...

  13. Recombinant Mal d 1 facilitates sublingual challenge tests of birch pollen-allergic patients with apple allergy.

    Science.gov (United States)

    Kinaciyan, T; Nagl, B; Faustmann, S; Kopp, S; Wolkersdorfer, M; Bohle, B

    2016-02-01

    It is still unclear whether allergen-specific immunotherapy (AIT) with birch pollen improves birch pollen-related food allergy. One reason for this may be the lack of standardized tests to assess clinical reactions to birch pollen-related foods, for example apple. We tested the applicability of recombinant (r) Mal d 1, the Bet v 1-homolog in apple, for oral challenge tests. Increasing concentrations of rMal d 1 in 0.9% NaCl were sublingually administered to 72 birch pollen-allergic patients with apple allergy. The dose of 1.6 μg induced oral allergy syndromes in 26.4%, 3.2 μg in 15.3%, 6.3 μg in 27.8%, 12.5 μg in 8.3%, 25 μg in 11.1%, and 50 μg in 4.2% of the patients. No severe reactions occurred. None of the patients reacted to 0.9% NaCl alone. Sublingual administration of 50 μg of rMal d 1 induced no reactions in three nonallergic individuals. Our approach allows straight forward, dose-defined sublingual challenge tests in a high number of birch pollen-allergic patients that inter alia can be applied to evaluate the therapeutic efficacy of birch pollen AIT on birch pollen-related food allergy. © 2015 The Authors. Allergy Published by John Wiley & Sons Ltd.

  14. Crystallization Formulation Lab

    Data.gov (United States)

    Federal Laboratory Consortium — The Crystallization Formulation Lab fills a critical need in the process development and optimization of current and new explosives and energetic formulations. The...

  15. Chemical interactions study of antiretroviral drugs efavirenz and lamivudine concerning the development of stable fixed-dose combination formulations for AIDS treatment

    International Nuclear Information System (INIS)

    Gomes, Elionai C. de L.; Mussel, Wagner N.; Resende, Jarbas M.; Yoshida, Maria I.

    2013-01-01

    Lamivudine and efavirenz are among the most worldwide used drugs for acquired immune deficiency syndrome (AIDS) treatment. Solid state nuclear magnetic resonance (ssNMR), Fourier-transformed infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermo-optical analysis (TOA) were used to study possible interactions between these drugs, aiming the development of a fixed-dose drug combination. DSC and TOA have evidenced significant shifts on the melting points of both drugs in the mixture, which may be due to interaction between them. Although DSC and TOA results indicated incompatibility between the drugs, FTIR spectra were mostly unmodified due to overlapping peaks. The ssNMR analyses showed significant changes in chemical shifts values of the mixture when compared with spectra of pure drugs, especially in the signals relating to the deficient electron carbon atoms of both drugs. These results confirm the interactions suggested by DSC and TOA, which is probably due to acid-base interactions between electronegative and deficient electron atoms of both lamivudine and efavirenz. (author)

  16. Chemical interactions study of antiretroviral drugs efavirenz and lamivudine concerning the development of stable fixed-dose combination formulations for AIDS treatment

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, Elionai C. de L.; Mussel, Wagner N.; Resende, Jarbas M.; Yoshida, Maria I., E-mail: mirene@ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Instituto de Ciencias Exatas. Departamento de Quimica; Fialho, Silvia L.; Barbosa, Jamile; Fialho, Silvia L. [Fundacao Ezequiel Dias, Belo Horizonte, MG (Brazil)

    2013-04-15

    Lamivudine and efavirenz are among the most worldwide used drugs for acquired immune deficiency syndrome (AIDS) treatment. Solid state nuclear magnetic resonance (ssNMR), Fourier-transformed infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermo-optical analysis (TOA) were used to study possible interactions between these drugs, aiming the development of a fixed-dose drug combination. DSC and TOA have evidenced significant shifts on the melting points of both drugs in the mixture, which may be due to interaction between them. Although DSC and TOA results indicated incompatibility between the drugs, FTIR spectra were mostly unmodified due to overlapping peaks. The ssNMR analyses showed significant changes in chemical shifts values of the mixture when compared with spectra of pure drugs, especially in the signals relating to the deficient electron carbon atoms of both drugs. These results confirm the interactions suggested by DSC and TOA, which is probably due to acid-base interactions between electronegative and deficient electron atoms of both lamivudine and efavirenz. (author)

  17. Efficacy and safety of sublingual ramelteon as an adjunctive therapy in the maintenance treatment of bipolar I disorder in adults: A phase 3, randomized controlled trial.

    Science.gov (United States)

    Mahableshwarkar, Atul R; Calabrese, Joseph R; Macek, Thomas A; Budur, Kumar; Adefuye, Adedeji; Dong, Xinxin; Hanson, Elizabeth; Sachs, Gary S

    2017-10-15

    The optimal long-term management strategy for bipolar I disorder patients is not yet established. Evidence supports the rationale for circadian rhythm regulation to prevent mood episode relapse in bipolar patients. This study evaluated the efficacy and safety of a new sublingual formulation of the melatonin receptor agonist ramelteon (ramelteon SL) as adjunctive therapy in the maintenance treatment of bipolar I patients. In a double-blinded trial in the United States and Latin America, adult bipolar I disorder patients stable for ≥ 8 weeks before baseline and with a mood episode 8 weeks to 9 months before screening, were randomized to once-daily ramelteon SL 0.1mg (n = 164), 0.4mg (n = 160), or 0.8mg (n = 154), or placebo (n = 164), in addition to their existing treatment. The primary endpoint was time from randomization to relapse of symptoms. The prespecified futility criterion in a planned, unblinded, independent interim analysis was the failure of all ramelteon SL doses to achieve a conditional power ≥ 30% compared with placebo. No significant differences between any dose of ramelteon SL and placebo were observed. The study was terminated after meeting the futility criteria. Ramelteon SL was well tolerated, with a safety profile consistent with that for oral ramelteon. A low rate of relapse events precluded detection of any statistically significant difference between groups. The study failed to demonstrate the efficacy of ramelteon SL as adjunctive maintenance therapy for bipolar disorder. Interim analyses for futility in clinical studies are valuable in preventing unnecessary exposure of subjects to interventions. Copyright © 2017. Published by Elsevier B.V.

  18. The effect of a topical anaesthetic formulation, systemic flunixin and carprofen, singly or in combination, on cortisol and behavioural responses of Merino lambs to mulesing.

    Science.gov (United States)

    Paull, D R; Lee, C; Colditz, I G; Atkinson, S J; Fisher, A D

    2007-03-01

    lambs of mulesing could be improved by use of a combination of local anaesthetic and long acting non-steroidal anti-inflammatory drug.

  19. Sublingual immunotherapy in patients with house dust mite allergic rhinitis: prospective study of clinical outcomes over a two-year period.

    Science.gov (United States)

    Soh, J Y; Thalayasingam, M; Ong, S; Loo, E X L; Shek, L P; Chao, S S

    2016-03-01

    Sublingual immunotherapy in patients with allergic rhinitis sensitised to house dust mites is safe, but its efficacy is controversial and sublingual immunotherapy with Blomia tropicalis has not yet been studied. This study sought to evaluate the efficacy of sublingual immunotherapy with house dust mite extract in children and adults with house dust mite allergic rhinitis over a period of two years. A prospective observational study was conducted of children and adults diagnosed with house dust mite allergic rhinitis who were treated with sublingual immunotherapy from 2008 to 2012. Total Nasal Symptom Scores, Mini Rhinoconjunctivitis Quality of Life scores and medication usage scores were assessed prospectively. Thirty-nine patients, comprising 24 children and 15 adults, were studied. Total Nasal Symptom Scores and Mini Rhinoconjunctivitis Quality of Life scores dropped significantly at three months into therapy, and continued to improve. Medication usage scores improved at one year into immunotherapy. Sublingual immunotherapy with house dust mite extracts, including B tropicalis, is efficacious as a treatment for patients with house dust mite allergic rhinitis.

  20. [Breakthrough pain treatment with sublingual fentanyl in patients with chronic cutaneous ulcers].

    Science.gov (United States)

    Domingo-Triadó, V; López Alarcón, M D; Villegas Estévez, F; Alba Moratillas, C; Massa Domínguez, B; Palomares Payá, F; Mínguez Martí, A; Debón Vicent, L

    2014-10-01

    The aim of the study was to assess the efficacy and safety of opioids in the management of pain in those patients with chronic cutaneous ulcers and breakthrough/incidental pain. An open-label, multicentre, prospective, uncontrolled study was conducted in the pain and ulcer units of 5 hospitals across the Comunidad Valenciana. Eligibility criteria were baseline pain 4 in the visual analogue scale or breakthrough procedural pain 4. Exclusion criteria were cognitive impairment, opioid intolerance, or patient refusal to provide informed consent. The protocol scheduled 5 controls: baseline (enrolment), 15 days, one month, 2 months, and 3 months. The main outcome measure of the study was the visual analogue scale score during rest, movement and procedures. Opioids were administered for release of the baseline pain, and sublingual fentanyl for breakthrough pain. A total of 32 patients (86.5%) completed the study. Baseline pain achieved a mean improvement of 3.6 visual analogue scale points (SD 2.3), movement pain improved by 3.9 points (SD 2.5) and procedural pain improved by 4.5 points (SD 2.8), and the mean pain intensity improvement was statistically significant from the first control and at all controls thereafter (PDolor. Published by Elsevier España. All rights reserved.

  1. Early cytokine modulation after the rapid induction phase of sublingual immunotherapy with mite monomeric allergoids.

    Science.gov (United States)

    Di Gioacchino, M; Perrone, A; Petrarca, C; Di Claudio, F; Mistrello, G; Falagiani, P; Dadorante, V; Verna, N; Braga, M; Ballone, E; Cavallucci, E

    2008-01-01

    The influence of different treatment schedules of sublingual immunotherapy (SLIT) in activating IL-10-producing T-cells, crucial in inducing allergen-specific tolerance, is not completely understood. The present work was designed to evaluate allergen driven interleukin release by mononuclear cells in the early phase of SLIT, after application of different induction schemes. Twenty mite-allergic patients were enrolled, 10 (group A) treated with a traditional 98 day induction scheme and 10 (group B) with a 16 day scheme with monomeric allergoid vaccine. At the end of the induction phase, the cumulative doses taken by group A and group B patients were equivalent to 50.5 and 50.3 microg of mite group 1 allergens, respectively. The release of Th1-, Th2- and Treg-related interleukins was assessed in culture supernatants of 5 microg/ml Der-p1-stimulated mononuclear cells, isolated before and after the induction phases. No relevant treatment-related side effects were observed. Interleukin release was similar in the two groups at the enrolment. Non-stimulated and Der p 1 stimulated release of studied cytokines was similar in the two groups at enrolment. Der p 1 stimulation significantly increased IL-10 release (pallergoids are utilized.

  2. Specific IgE response to different grass pollen allergen components in children undergoing sublingual immunotherapy

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    Marcucci Francesco

    2012-06-01

    Full Text Available Abstract Background Grass pollen is a major cause of respiratory allergy worldwide and contain a number of allergens, some of theme (Phl p 1, Phl p 2, Phl p 5, and Phl 6 from Phleum pratense, and their homologous in other grasses are known as major allergens. The administration of grass pollen extracts by immunotherapy generally induces an initial rise in specific immunoglobulin E (sIgE production followed by a progressive decline during the treatment. Some studies reported that immunotherapy is able to induce a de novo sensitisation to allergen component previously unrecognized. Methods We investigated in 30 children (19 males and 11 females, mean age 11.3 years, 19 treated with sublingual immunotherapy (SLIT by a 5-grass extract and 11 untreated, the sIgE and sIgG4 response to the different allergen components. Results Significant increases (p  Conclusions These findings confirm that the initial phase of SLIT with a grass pollen extract enhances the sIgE synthesis and show that the sIgE response concerns the same allergen components which induce IgE reactivity during natural exposure.

  3. Suppression of TIM-1 predicates clinical efficacy of sublingual immunotherapy for allergic rhinitis in children.

    Science.gov (United States)

    Lin, Zhibin; Zhou, Lifeng; Luo, Xi; Xia, Wentong; Chen, Dehua; Xu, Rui; Wang, Jie; Luo, Renzhong; Xu, Geng; Li, Huabin

    2013-08-01

    To evaluate the clinical efficacy of sublingual immunotherapy (SLIT) with house-dust mite (HDM) extract and to examine the change of biomarkers (TIM-1, IL-5 and IL-10) after 6-month SLIT in children with allergic rhinitis (AR). One hundred and sixteen HDM-sensitized children with persistent AR were enrolled to assess the clinical efficacy of SLIT by determining the individual nasal symptom score (INSS) and total nasal symptom scores (TNSS) after 6-month SLIT. Moreover, the mRNA expression of TIM-1, IL-5 and IL-10 in peripheral blood mononuclear cells (PBMCs) was examined in 16 well-controlled and 12 uncontrolled AR patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR). After 6-month SLIT, both TNSS and INSS scores were significantly decreased compared with the baseline value (p < 0.01). The rates for well-controlled, partly controlled and uncontrolled children were 43.1%, 32.8% and 24.1%, respectively. Accordingly, the mRNA levels of TIM-1 and IL-5 decreased significantly and IL-10 mRNA level increased significantly compared with the baseline value in well-controlled children (p < 0.05). Our findings suggest SLIT with HDM extract is effective and safe for AR children and TIM-1 may be considered as an indicator for evaluating the clinical efficacy of SLIT. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Asthma control in patients receiving inhaled corticosteroid and long-acting beta2-agonist fixed combinations. A real-life study comparing dry powder inhalers and a pressurized metered dose inhaler extrafine formulation

    Directory of Open Access Journals (Sweden)

    Nicolini Gabriele

    2011-07-01

    Full Text Available Abstract Background Although patients have more problems using metered dose inhalers, clinical comparisons suggest they provide similar control to dry powder inhalers. Using real-life situations this study was designed to evaluate asthma control in outpatients with moderate to severe persistent asthma and to compare efficacy of fixed combinations of inhaled corticosteroids (ICS and long acting beta-agonists (LABA. Methods This real-life study had a cross-sectional design. Patients using fixed combinations of ICS and LABA had their asthma control and spirometry assessed during regular visits. Results 111 patients were analyzed: 53 (47.7% received maintenance therapy of extrafine beclomethasone-formoterol (BDP/F pressurized metered dose inhaler (pMDI, 25 (22.5% fluticasone-salmeterol (FP/S dry powder inhaler (DPI, and 33 (29.7% budesonide-formoterol (BUD/F DPI. Severity of asthma at time of diagnosis, assessed by the treating physician, was comparable among groups. Asthma control was achieved by 45.9% of patients; 38.7% were partially controlled and 15.3% were uncontrolled. In the extrafine BDF/F group, asthma control total score, daytime symptom score and rescue medication use score were significantly better than those using fixed DPI combinations (5.8 ± 6.2 vs. 8.5 ± 6.8; 1.4 ± 1.8 vs. 2.3 ± 2.1; 1.8 ± 2.2 vs. 2.6 ± 2.2; p = 0.0160; p = 0.012 and p = 0.025, respectively and the mean daily ICS dose were significantly lower. Conclusions pMDI extrafine BDP/F combination demonstrated better asthma control compared to DPIs formulated with larger particles. This could be due to the improved lung deposition of the dose or less reliance on the optimal inhalation technique or both.

  5. FORMULASI MIKROEMULSI MINYAK DALAM AIR (O/W YANG STABIL MENGGUNAKAN KOMBINASI TIGA SURFAKTAN NON IONIK DENGAN NILAI HLB RENDAH, TINGGI DAN SEDANG Stable O/W Microemulsion Formulation Using Combination of Three Nonionic Surfactants with Low, High and Med

    Directory of Open Access Journals (Sweden)

    Sih Yuwanti

    2012-05-01

    Full Text Available The aim of this research was to determine the proportion of oil, surfactant and water which could produce a stable O/W microemulsion using combination of three nonionic surfactants with low, high and medium HLB values; and to determine the role of surfactant with a medium HLB value in O/W microemulsion formulation. The first group of microemulsions were prepared using combination of Tween 80, Span 80 and Span 40 (80 %:10 %:10 % with dif- ferent proportions of VCO:surfactant (1:3, 1:3.5 dan 1:4.  The second goups of microemulsion were prepared using combination of Tween 80, Span 80 and Span 40 (90 %:5 %:5 % with different proportions of VCO:surfactant 1:4,1:4.5 dan 1:5.  The stability of microemulsion was determined during storage at room temperature and after being ovened at 105 0C 5 hours and centrifuged at 2300 g 15 minutes. Microemulsion stability was determined by measur- ing absorbance of the microemulsion at 502 nm and then converted to turbidity (%.  In order to determine the role of surfactant with a medium HLB value in the formulation of O/W microemulsion, one set microemulsions were made without surfactant with a medium HLB value, and another set of microemulsions were prepared with different ratios of low and medium HLB surfactant (1:1, 2:1 and 1:2. The most stable microemulsion was achieved when the proportion of VCO:surfactant:water was 4:20:76 and combination of Tween 80:Span 80:Span 40 with the ratio of 90:3.33:6.67. A more stable O/W microemulsion could be obtained when surfactant with a medium HLB value was added to O/W microemulsion formulation. Surfactant with a medium HLB value would link the oil phase and water phase with sur- factant layer, interaction of surfactant-oil and surfactant-water increased. It provided a smooth transition between oil phase and water phase, and the microemulsion became more stable. ABSTRAK Tujuan dari penelitian ini adalah untuk menentukan proporsi minyak, surfaktan dan air yang dapat

  6. Results from the 5-year SQ grass sublingual immunotherapy tablet asthma prevention (GAP) trial in children with grass pollen allergy.

    Science.gov (United States)

    Valovirta, Erkka; Petersen, Thomas H; Piotrowska, Teresa; Laursen, Mette K; Andersen, Jens S; Sørensen, Helle F; Klink, Rabih

    2018-02-01

    Allergy immunotherapy targets the immunological cause of allergic rhinoconjunctivitis and allergic asthma and has the potential to alter the natural course of allergic disease. The primary objective was to investigate the effect of the SQ grass sublingual immunotherapy tablet compared with placebo on the risk of developing asthma. A total of 812 children (5-12 years), with a clinically relevant history of grass pollen allergic rhinoconjunctivitis and no medical history or signs of asthma, were included in the randomized, double-blind, placebo-controlled trial, comprising 3 years of treatment and 2 years of follow-up. There was no difference in time to onset of asthma, defined by prespecified asthma criteria relying on documented reversible impairment of lung function (primary endpoint). Treatment with the SQ grass sublingual immunotherapy tablet significantly reduced the risk of experiencing asthma symptoms or using asthma medication at the end of trial (odds ratio = 0.66, P year posttreatment follow-up, and during the entire 5-year trial period. Also, grass allergic rhinoconjunctivitis symptoms were 22% to 30% reduced (P years). At the end of the trial, the use of allergic rhinoconjunctivitis pharmacotherapy was significantly less (27% relative difference to placebo, P < .001). Total IgE, grass pollen-specific IgE, and skin prick test reactivity to grass pollen were all reduced compared to placebo. Treatment with the SQ grass sublingual immunotherapy tablet reduced the risk of experiencing asthma symptoms and using asthma medication, and had a positive, long-term clinical effect on rhinoconjunctivitis symptoms and medication use but did not show an effect on the time to onset of asthma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Efficacy of sublingual administration of detomidine gel for sedation of horses undergoing veterinary and husbandry procedures under field conditions.

    Science.gov (United States)

    Gardner, Rachel B; White, Gary W; Ramsey, Deborah S; Boucher, Joseph F; Kilgore, W Randal; Huhtinen, Mirja K

    2010-12-15

    To determine whether sublingual detomidine gel administration to horses would be effective in providing an appropriate degree of sedation and restraint to facilitate completion of veterinary and husbandry procedures under field conditions. Multicenter, prospective, randomized, blinded, placebo-controlled clinical study. 270 client-owned horses known to require sedation or strong restraint to enable veterinary and husbandry procedures to be performed. Horses randomly received a single dose of detomidine gel (0.04 mg/kg [0.018 mg/lb]) or placebo gel administered sublingually. Horses were sedated to facilitate cleaning the prepuce, cutting of hair with electric clippers, hoof trimming or application of shoes, manual dental floating (ie, rasping or filing of the teeth to remove irregularities), nasogastric passage of a stomach tube or endoscope, and radiography. The primary determinant of efficacy was an assessment by a veterinarian on the ability or inability to successfully conduct the procedure. 171 horses met all the study protocol criteria. One hundred twenty-nine horses were treated with detomidine. The procedure was completed successfully for 76% (98/129) of the detomidine-treated horses, while the procedure was completed successfully for only 7% (3/42) of the placebo-treated horses. The percentage of horses in which the procedure was successfully completed was significantly different between detomidine-treated horses and placebo-treated horses. No serious adverse effects were reported. Detomidine gel administered to horses sublingually at a dose of 0.04 mg/kg provided an appropriate degree of sedation and restraint to facilitate completion of veterinary and husbandry procedures in horses known to require sedation for such procedures.

  8. Effectiveness of sublingual nitroglycerin before puncture compared with conventional intra-arterial nitroglycerin in transradial procedures: a randomized trial

    Energy Technology Data Exchange (ETDEWEB)

    Turan, Burak, E-mail: drburakturan@gmail.com; Daşlı, Tolga; Erkol, Ayhan; Erden, İsmail

    2015-10-15

    Aim: Sublingual (SL) nitroglycerin administered before radial artery puncture can improve cannulation success and decrease the incidence of radial artery spasm (RAS) compared with intra-arterial (IA) nitroglycerin in transradial procedures. Methods: Patients undergoing diagnostic transradial angiography were randomized to IA (200 mcg) or SL (400 mcg) nitroglycerin. Primary endpoints were puncture time and puncture attempts. Secondary endpoint was the incidence of RAS. Results: Total of 101 participants (mean age 60 ± 11 years, 53% male) were randomized (51 in IA and 50 in SL groups). Puncture time (50 [36–75] vs 50 [35–90] sec), puncture attempts (1.18 ± 0.48 vs 1.20 ± 0.49), multiple punctures (13.7 vs 16.0%) and RAS (19.6 vs 24.0%) were not statistically different between IA vs SL groups respectively. A composite endpoint of all adverse events related to transradial angiography (multiple punctures, RAS, access site crossover, hypotension/bradycardia associated with nitroglycerin and radial artery occlusion) was very similar in IA vs SL groups (39 vs 40%, respectively). However puncture time was significantly longer with SL nitroglycerin in patients < 1.65 m height (47 [36–66] vs 63 [41–110] sec, p = 0.042). Multiple punctures seemed higher with SL nitroglycerin in patients with diabetes (0 vs 30%, p = 0.028) or in patients < 1.65 m height (7.4 vs 25%, p = 0.085). Likewise, RAS with SL nitroglycerin seemed more frequent in smokers compared to IA nitroglycerin (0 vs 27%, p = 0.089). Conclusions: SL nitroglycerin was not different from IA nitroglycerin in terms of efficiency and safety in overall study population. However it may be inferior to IA nitroglycerin in certain subgroups (shorter individuals, diabetics and smokers). - Highlights: • Improvement in radial artery puncture time and success with subcutaneous nitrate was reported. • Giving nitrate sublingually may have vasodilation along entire length of radial artery and may prevent RAS

  9. Sublingual buprenorphine is effective in the treatment of chronic pain syndrome.

    Science.gov (United States)

    Malinoff, Herbert L; Barkin, Robert L; Wilson, Geoffrey

    2005-01-01

    Many patients with chronic pain have less than optimal therapeutic outcomes after prolonged treatment with opiate analgesics. Worsening of pain perception, functional capacity, and mood often result. Medical detoxification is often undertaken in this situation. Ninety-five consecutive patients (49 men and 46 women; age range, 26-84) with chronic noncancer pain (maldynia) were referred by local pain clinics for detoxification from long-term opiate analgesic (LTOA) therapy. All patients had failed treatment as manifest by increasing pain levels, worsening functional capacity, and, in 8%, the emergence of opiate addiction. Length of prior LTOA therapy ranged from 1.5 to 27 years (mean, 8.8 years). After a minimum of 12 hours of abstinence from all opiate analgesics, patients were given low doses of sublingual (SL) buprenorphine or buprenorphine/naloxone (Reckitt Benckiser). Maintenance dosing was individualized to treat chronic pain. Daily SL dose of buprenorphine ranged from 4 to 16 mg (mean, 8 mg) in divided doses. Mean duration of treatment is 8.8 months (range, 2.4-16.6 months). At clinic appointments, patients were assessed for pain reports, functional capacity, and mood inventory. Eighty-six percent of patients experienced moderate to substantial relief of pain accompanied by both improved mood and functioning. Patient and family satisfaction was robust. Only 6 patients discontinued therapy secondary to side effects and/or exacerbation of pain. In this open-label study, SL buprenorphine and buprenorphine/naloxone were well tolerated and safe and appeared to be effective in the treatment of chronic pain patients refractory to LTOA.

  10. [Onset time and efficacy of sublingual immunotherapy with Dermatophagoides farinae drops in children with allergic rhinitis].

    Science.gov (United States)

    Chen, Zhiling; Qian, Yasheng; Liu, Suqin; Huang, Liqin; Xu, Shiying; Yin, Wenhua; Chen, Yanchun; Wu, Huawei; Wang, Gan

    2015-08-01

    To investigate the onset time and efficacy of sublingual immunotherapy (SLIT) with Dermatophagoides farinae drops in children with house dust mites (HDM)-induced allergic rhinitis (AR). One hundred and forty three children with perennial moderate to severe HDM-induced AR were treated by SLIT with standardized Dermatophagoides farinae extract. One hundred children who finally completed two years treatment were divided into two groups according to the age: younger children group (aged 4-8 years, n = 52) and older children group (aged 9-14 years, n = 48). Respectively, Each children was assessed before and after 1st, 2nd, 3rd, 6th, 12th, 24th months of the treatment. Total nasal symptom score (TNSS), total medication score (TMS) and visual analogue scale (VAS) were evaluated at each visit. All clinical data were analyzed retrospectively with the SPSS 19.0 software. TNSS, TMS and VAS of two groups decreased significantly after three months of the treatment compared with before (younger children group: Z value was -3.843, -3.534, -3.940, older children group: Z value was -3.938, -3.405, -3.953, all P < 0.05). TNSS and VAS of younger children group decreased significantly after two months of the treatment compared with before (6.4 ± 1.6, 5.3 ± 1.4 vs 8.6 ± 1.2, 7.9 ± 1.6, Z value was -3.843, -3.940, both P < 0.05). Five children (5%) experienced local adverse events and 2 children (2%) experienced mild systemic adverse events. No severe adverse events happened during the treatment. SLIT with Dermatophagoides farinae drops is an efficient and safe treatment for children with HDM-induced AR. Its onset of action can be observed as early as 3 months after treatment.

  11. Influence of food on pharmacokinetics of zolpidem from fast dissolving sublingual zolpidem tartrate tablets.

    Science.gov (United States)

    Greenblatt, David J; Harmatz, Jerold S; Singh, Nikhilesh N; Roth, Thomas; Harris, Stephen C; Kapil, Ram P

    2013-11-01

    Ingesting food can impact the pharmacokinetics of sedative-hypnotic drugs. A buffered zolpidem sublingual tablet (ZST) recently became available for the treatment of middle-of-the-night awakening. In this randomized, open-label, single-site study, the pharmacokinetic profile of ZST was evaluated when administered while fasting and following a standard high-fat meal (fed state). Healthy adults aged 18-64 years received a single morning dose of 3.5 mg ZST in the fed or fasting state. From 20 min to 3 h post-dose, zolpidem plasma levels were lower in the fed state compared to the fasting state. After 4 h post-dose (corresponding to "morning wake time"), higher zolpidem plasma levels were evident in the fed state. Area under the concentration-time curve (AUC) values for the 0-8 h interval were 160 ng/mL h in the fed state and 203 ng/mL h in the fasting state (P fasting states, Cmax was 32.0 ng/mL versus 57.3 ng/mL (P < .001), respectively, and Tmax was 3.0 h versus 0.92 h (P < .001), respectively. Together these data suggest that administration of ZST in the fed state is not optimal for maximizing the likelihood of therapeutic benefit and minimizing the probability of residual sedation. © 2013, The American College of Clinical Pharmacology.

  12. Clinical and immunological responses of dust mite sensitive, atopic dogs to treatment with sublingual immunotherapy (SLIT).

    Science.gov (United States)

    DeBoer, Douglas J; Verbrugge, Maria; Morris, Mary

    2016-04-01

    Sublingual immunotherapy (SLIT) has been reported to be beneficial in people with atopic dermatitis (AD) and dust mite sensitivity. Evaluation of this therapy has not been reported in spontaneous canine AD. The objective of this study was to preliminarily evaluate the effectiveness of an established SLIT protocol, as used in human patients, in dogs with AD. Ten dust mite sensitive dogs with spontaneous AD. Dogs underwent a 6 month open trial of SLIT concurrently with decreasing dose oral methylprednisolone. Clinical evaluations and quantitative serum anti-mite IgE and IgG levels were performed every 2 months. Mean methylprednisolone use from the first 2 months of the study to the final 2 months declined from 10.2 to 4.3 mg/kg/2 months (P test); at 6 months, four dogs required no oral corticosteroid administration. Over the course of the study, median Canine Atopic Dermatitis Extent and Severity Index (CADESI)-03 scores declined from 76.5 to 59; median pruritus scores declined from 65 to 37 (P Wilcoxon signed-rank test). Pre- and post-SLIT intradermal test scores for mite allergen were not significantly different over time. Median Dermatophagoides farinae (DF)-specific IgE levels declined significantly from 150.2 × 10(3) AU/mL to 3.6 × 10(3) AU/mL (P Wilcoxon signed-rank tests). SLIT treatment produced clinical improvement in dogs with dust mite-associated AD and was associated with serological changes supporting this improvement. Further studies in larger numbers of dogs and those with polysensitization are warranted. © 2016 ESVD and ACVD.

  13. Effects of three antagonists on selected pharmacodynamic effects of sublingually administered detomidine in the horse.

    Science.gov (United States)

    Knych, Heather K; Stanley, Scott D

    2014-01-01

    To describe the effects of alpha2 -adrenergic receptor antagonists on the pharmacodynamics of sublingual (SL) detomidine in the horse. Randomized crossover design. Nine healthy adult horses with an average age of 7.6 ± 6.5 years. Four treatment groups were studied: 1) 0.04 mg kg(-1) detomidine SL; 2) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 0.075 mg kg(-1) yohimbine intravenously (IV); 3) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 4 mg kg(-1) tolazoline IV; and 4) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 0.12 mg kg(-1) atipamezole IV. Each horse received all treatments with a minimum of 1 week between treatments. Blood samples were obtained and plasma analyzed for yohimbine, atipamezole and tolazoline concentrations by liquid chromatography-mass spectrometry. Behavioral effects, heart rate and rhythm, glucose, packed cell volume (PCV) and plasma proteins were monitored. Chin-to-ground distance increased following administration of the antagonists, however, this effect was transient, with a return to pre-reversal values as early as 1 hour. Detomidine induced bradycardia and increased incidence of atrioventricular blocks were either transiently or incompletely antagonized by all antagonists. PCV and glucose concentrations increased with tolazoline administration, and atipamezole subjectively increased urination frequency but not volume. At the doses administered in this study, the alpha2 -adrenergic antagonistic effects of tolazoline, yohimbine and atipamezole on cardiac and behavioral effects elicited by SL administration of detomidine are transient and incomplete. © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  14. Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy.

    Science.gov (United States)

    Kiel, Menno A; Röder, Esther; Gerth van Wijk, Roy; Al, Maiwenn J; Hop, Wim C J; Rutten-van Mölken, Maureen P M H

    2013-08-01

    Subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT) are safe and effective treatments of allergic rhinitis, but high levels of compliance and persistence are crucial to achieving the desired clinical effects. Our objective was to assess levels and predictors of compliance and persistence among grass pollen, tree pollen, and house dust mite immunotherapy users in real life and to estimate the costs of premature discontinuation. We performed a retrospective analysis of a community pharmacy database from The Netherlands containing data from 6486 patients starting immunotherapy for 1 or more of the allergens of interest between 1994 and 2009. Two thousand seven hundred ninety-six patients received SCIT, and 3690 received SLIT. Time to treatment discontinuation was analyzed and included Cox proportional hazard models with time-dependent covariates, where appropriate. Overall, only 18% of users reached the minimally required duration of treatment of 3 years (SCIT, 23%; SLIT, 7%). Median durations for SCIT and SLIT users were 1.7 and 0.6 years, respectively (P < .001). Other independent predictors of premature discontinuation were prescriber, with patients of general practitioners demonstrating longer persistence than those of allergologists and other medical specialists; single-allergen immunotherapy, lower socioeconomic status; and younger age. Of the persistent patients, 56% were never late in picking up their medication from the pharmacy. Direct medication costs per nonpersistent patient discontinuing in the third year of treatment were €3800, an amount that was largely misspent. Real-life persistence is better in SCIT users than in SLIT users, although it is low overall. There is an urgent need for further identification of potential barriers and measures that will enhance persistence and compliance. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  15. Sublingual immunotherapy for peanut allergy: clinical and immunologic evidence of desensitization.

    Science.gov (United States)

    Kim, Edwin H; Bird, J Andrew; Kulis, Michael; Laubach, Susan; Pons, Laurent; Shreffler, Wayne; Steele, Pamela; Kamilaris, Janet; Vickery, Brian; Burks, A Wesley

    2011-03-01

    There are no treatments currently available for peanut allergy. Sublingual immunotherapy (SLIT) is a novel approach to the treatment of peanut allergy. We sought to investigate the safety, clinical effectiveness, and immunologic changes with SLIT in children with peanut allergy. In this double-blind, placebo-controlled study subjects underwent 6 months of dose escalation and 6 months of maintenance dosing followed by a double-blind, placebo-controlled food challenge. Eighteen children aged 1 to 11 years completed 12 months of dosing and the food challenge. Dosing side effects were primarily oropharyngeal and uncommonly required treatment. During the double-blind, placebo-controlled food challenge, the treatment group safely ingested 20 times more peanut protein than the placebo group (median, 1,710 vs 85 mg; P = .011). Mechanistic studies demonstrated a decrease in skin prick test wheal size (P = .020) and decreased basophil responsiveness after stimulation with 10(-2) μg/mL (P = .009) and 10(-3) μg/mL (P = .009) of peanut. Peanut-specific IgE levels increased over the initial 4 months (P = .002) and then steadily decreased over the remaining 8 months (P = .003), whereas peanut-specific IgG4 levels increased during the 12 months (P = .014). Lastly, IL-5 levels decreased after 12 months (P = .015). No statistically significant changes were found in IL-13 levels, the percentage of regulatory T cells, or IL-10 and IFN-γ production. Peanut SLIT is able to safely induce clinical desensitization in children with peanut allergy, with evidence of immunologic changes suggesting a significant change in the allergic response. Further study is required to determine whether continued peanut SLIT is able to induce long-term immune tolerance. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  16. Efficacy and safety of two fast-absorbing formulations of paracetamol in combination with caffeine for episodic tension-type headache: results from two randomized placebo- and active-controlled trials

    Directory of Open Access Journals (Sweden)

    Yue Y

    2017-06-01

    Full Text Available Yong Yue,1 Kenneth D Reed,1 Lucy Shneyer,2 Dongzhou J Liu3 1GlaxoSmithKline Consumer Healthcare, Parsippany, NJ, 2Shneyer Statistics LLC, Denville, NJ, 3GlaxoSmithKline, Collegeville, PA, USA Objectives: Two randomized placebo-controlled trials evaluated whether combining rapid-acting paracetamol formulations with caffeine resulted in faster/greater relief of episodic tension-type headache (ETTH compared with placebo and over-the-counter (OTC analgesics. Both studies were prematurely terminated. Materials and methods: In the single-blind crossover study 1, adults with ETTH (n=66 received three of the following in random sequence: paracetamol 1,000 mg with sodium bicarbonate 650 mg and caffeine 130 mg; paracetamol 1,000 mg; ibuprofen 400 mg; and placebo. In the double-blind parallel-group study 2, adults with ETTH (n=157 were randomly assigned 2:2:1 to treat up to three headaches with paracetamol with Optizorb technology 1,000 mg plus caffeine 130 mg; ibuprofen 400 mg; and placebo. Results: In study 1, the primary outcome – mean time to perceptible pain relief – was 36.7, 38, 48.9, and 42.7 minutes in the paracetamol–sodium bicarbonate–caffeine, ibuprofen, paracetamol, and placebo groups, respectively; differences were not statistically significant. In study 2, the weighted sum of pain intensity (scale of 0 [no pain] to 4 [severe pain] difference from the time of treatment to hour 4, the primary outcome, showed numerically favorable differences for paracetamol with Optizorb–caffeine compared with ibuprofen (difference in least square means −0.3, 95% confidence interval −1.05 to 0.45 and placebo (−0.47, 95% confidence interval −1.36 to 0.42. In both studies, secondary outcomes suggested faster and greater relief with rapid paracetamol–caffeine compared with placebo and paracetamol; a few of these outcomes achieved statistical significance at ~45–90 minutes in study 1. Adverse events were mostly mild and consistent with known

  17. Effects of a nutraceutical formulation based on the combination of antioxidants and ω-3 essential fatty acids in the expression of inflammation and immune response mediators in tears from patients with dry eye disorders.

    Science.gov (United States)

    Pinazo-Durán, Maria D; Galbis-Estrada, Carmen; Pons-Vázquez, Sheila; Cantú-Dibildox, Jorge; Marco-Ramírez, Carla; Benítez-del-Castillo, Javier

    2013-01-01

    Women, and those older than 65 years of age, are particularly susceptible to dry eye disorders (DEDs). Inflammation is clearly involved in the pathogenesis of DEDs, and there is mounting evidence on the antioxidant and antiinflammatory properties of essential polyunsaturated fatty acids (EPUFAs). To analyze whether a combined formulation of antioxidants and long-chain EPUFAs may improve the evolution of DEDs. We used a prospective study to address the relationship between risk factors, clinical outcomes, and expression levels of inflammation and immune response (IIR) mediators in human reflex tear samples. Participants included: (1) patients diagnosed with nonsevere DEDs (DED group [DEDG]); and (2) healthy controls (control group [CG]). Participants were randomly assigned to homogeneous subgroups according to daily oral intake (+S) or not (-NS) of antioxidants and long-chain EPUFAs for 3 months. After an interview and a systematized ophthalmic examination, reflex tears were collected simultaneously from both eyes; samples were later subjected to a multiplexed particle-based flow cytometry assay. A specific set of IIR mediators was analyzed. All data were statistically processed through the SPSS 15.0 software program. Significantly higher expressions of interleukin (IL)-1β, IL6, and IL10 and significantly lower vascular endothelial growth factor expressions were found in the DEDG as compared to the CG. In the DEDG, significant negative correlations were detected between the Schirmer test and IL-1β, IL6, IL8, and vascular endothelial growth factor levels, and between the fluorescein breakup time with IL6 and IL8 levels. However, levels of IL-1β, IL6, and IL10 in tears were significantly lower in the DEDG+S versus the DEDG-NS and in the CG+S versus the CG-NS. Subjective symptoms of dry eye significantly improved in the DEDG+S versus the DEDG-NS. IIR mediators showed different expression patterns in DED patients, and these patterns changed in response to a combined

  18. Evaluation of Anti-Trichinella spiralis Obtained by Sublingual and Conventional Immunizations with the 45kDa Protein

    Directory of Open Access Journals (Sweden)

    Francisca Chávez Ruvalcaba

    2017-05-01

    Full Text Available Trichinellosis is a cosmopolitan zoonotic disease produced mainly by the consumption of poorly cooked swine meat. Several studies have probed the efficiency of immunotherapy as a method for the treatment of trichinellosis. In this work, a 45 kDa immunodominant antigen was characterized, and the presence of IgA, IgM and IgG anti-Trichinella spiralis antibodies was evaluated during the course of the infection. In addition, the differences between sublingual and parenteral administration of the 45 kDa T. spiralis antigen were determined. Long Evans rats were used both to purify the 45 kDa antigen and to evaluate the immune response produced in six different groups: healthy and infected controls; two groups of immunized murines (sublingually and parenterally with 4 doses of the 45 kDa T. spiralis immunogen administered at days 0, 7, 14 and 21 and challenged with 500 T. spiralis infective larvae (IL 7 days after the last immunization; and finally, two groups of murines infected with 500 IL of T. spiralis, immunized at week 4 post infection by the same two routes. The humoral response was evaluated by indirect immunofluorescence by confocal microscopyin order to determine the presence of IgA, IgM and IgG antibodies.

  19. A 12-week DBPC dose-finding study with sublingual monomeric allergoid tablets in house dust mite-allergic patients.

    Science.gov (United States)

    Hüser, C; Dieterich, P; Singh, J; Shah-Hosseini, K; Allekotte, S; Lehmacher, W; Compalati, E; Mösges, R

    2017-01-01

    In sublingual immunotherapy, optimal doses are a key factor for therapeutic outcomes. The aim of this study with tablets containing carbamylated monomeric house dust mite allergoids was to determine the most effective and safe dose. In this double-blind, placebo-controlled dose-finding study, 131 patients with house dust mite-induced allergic rhinoconjunctivitis were randomized to 12-week treatments with 300 UA/day, 1000 UA/day, 2000 UA/day, 3000 UA/day or placebo. Conjunctival provocation tests (CPT) were performed before, during and after treatment. The change in mean allergic severity (primary endpoint), calculated from the severity of the CPT reaction, and the proportion of patients with an improved CPT threshold (secondary endpoint) determined the treatment effect. The mean allergic severity decreased in all groups, including the placebo group. It was lower in all active treatment groups (300 UA/day: 0.14, 1000 UA/day: 0.15, 2000 UA/day: 0.10, 3000 UA/day: 0.15) than in the placebo group (0.30). However, this difference was not statistically significant (P allergoid sublingual tablets is well tolerated and reduces the CPT reaction in house dust mite-allergic patients. © 2016 The Authors. Allergy Published by John Wiley & Sons Ltd.

  20. Sublingual immunotherapy (SLIT – indications, mechanism, and efficacy Position paper prepared by the Section of Immunotherapy, Polish Society of Allergy

    Directory of Open Access Journals (Sweden)

    Marek Jutel

    2015-12-01

    Full Text Available SLIT ( sublingual immunotherapy induces allergen-specific immune tolerance by sublingual administration of a gradually increasing dose of an allergen. The mechanism of SLIT is comparable to those during SCIT (subcutaneous immunotherapy, with the exception of local oral dendritic cells, pre-programmed to elicit tolerance. In the SLIT dose, to achieve the same efficacy as in SCIT, it should be 50–100 times higher with better safety profile. The highest quality evidence supporting the efficacy of SLIT lasting 1 – 3 years has been provided by the large scale double-blind, placebo-controlled (DBPC trials for grass pollen extracts, both in children and adults with allergic rhinitis. Current indications for SLIT are allergic rhinitis (and conjunctivitis in both children and adults sensitized to pollen allergens (trees, grass, Parietaria , house dust mites ( Dermatophagoides pteronyssinus, Dermatophagoides farinae , cat fur, as well as mild to moderate controlled atopic asthma in children sensitized to house dust mites. There are positive findings for both asthma and new sensitization prevention. Severe adverse events, including anaphylaxis, are very rare, and no fatalities have been reported. Local adverse reactions develop in up to 70 – 80% of patients. Risk factors for SLIT adverse events have not been clearly identified. Risk factors of non-adherence to treatment might be dependent on the patient, disease treatment, physician-patient relationship, and variables in the health care system organization.

  1. Comparison of Intravenous Morphine with Sublingual Buprenorphine in Management of Postoperative Pain after Closed Reduction Orthopedic Surgery

    Directory of Open Access Journals (Sweden)

    Ghasem Soltani

    2015-09-01

    Full Text Available Background: Postoperative pain is a common side effect following surgery that can significantly reduce surgical quality and patient’s satisfaction. Treatment options are morphine and buprenorphine. We aimed to compare the efficacy of a single dose of intravenous morphine with sublingual buprenorphine in postoperative pain control following closed reduction surgery. Methods: This triple blind clinical trial was conducted on 90 patients referred for closed reduction orthopedic surgery. They were older than 18 years and in classes I and II of the American Society of Anesthesiologists (ASA with an operation time of 30-90 minutes. Patients were divided into two groups of buprenorphine (4.5μg/kg sublingually and morphine (0.2mg/kg intravenously. Baseline characteristics, vital signs, pain score, level of sedation and pharmacological side effects were recorded in the recovery room (at 0 and 30 minutes, and in the ward (at 3, 6 and 12 hours. SPSS version 19 software was used for data analysis and the significance level was set at P Results: Ninety patients were studied, 60 males and 30 females with a mean age of 37.7±16.2 years. There was no significant difference between the two groups in terms of baseline characteristics.Pain score in the morphine group was significantly higher than the buprenorphine group with an average score of 2.5 (P

  2. Comparison of Intravenous Morphine with Sublingual Buprenorphine in Management of Postoperative Pain after Closed Reduction Orthopedic Surgery

    Directory of Open Access Journals (Sweden)

    Ghasem Soltani

    2015-10-01

    Full Text Available Background: Postoperative pain is a common side effect following surgery that can significantly reduce surgical quality and patient’s satisfaction. Treatment options are morphine and buprenorphine. We aimed to compare the efficacy of a single dose of intravenous morphine with sublingual buprenorphine in postoperative pain control following closed reduction surgery. Methods: This triple blind clinical trial was conducted on 90 patients referred for closed reduction orthopedic surgery. They were older than 18 years and in classes I and II of the American Society of Anesthesiologists (ASA with an operation time of 30-90 minutes. Patients were divided into two groups of buprenorphine (4.5μg/kg sublingually and morphine (0.2mg/kg intravenously. Baseline characteristics, vital signs, pain score, level of sedation and pharmacological side effects were recorded in the recovery room (at 0 and 30 minutes, and in the ward (at 3, 6 and 12 hours. SPSS version 19 software was used for data analysis and the significance level was set at P Results: Ninety patients were studied, 60 males and 30 females with a mean age of 37.7±16.2 years. There was no significant difference between the two groups in terms of baseline characteristics.Pain score in the morphine group was significantly higher than the buprenorphine group with an average score of 2.5 (P

  3. Deposition of a model substance, Tc E-HIDA, in the oral cavity after administration of lozenges, chewing gum and sublingual tablets

    DEFF Research Database (Denmark)

    Christrup, Lona Louring; Davis, S.S.; Melia, C.D.

    1990-01-01

    The deposition and clearance of a model substance, Tc E-HIDA, in the oral cavity/upper oesophagus and in the stomach after administration of lozenges, chewing gum and sublingual tablets has been followed by gamma scintigraphy in a group of healthy male volunteers. Following administration...

  4. Pharmacokinetics and safety of fentanyl sublingual spray and fentanyl citrate intravenous: a single ascending dose study in opioid-naïve healthy volunteers.

    Science.gov (United States)

    Rauck, Richard; Oh, D Alexander; Parikh, Neha; Koch, Christian; Singla, Neil; Yu, Jin; Nalamachu, Srinivas; Vetticaden, Santosh

    2017-11-01

    Fentanyl sublingual spray offers rapid pain relief in opioid-tolerant cancer patients, and may be useful in acute or post-operative pain. Both opioid-naïve and non-tolerant patients are likely to receive opioids in these settings. Understanding the relationship between systemic exposure of fentanyl sublingual spray and effects on respiratory function in opioid-naïve or non-tolerant populations is important to ensure patient safety. This study evaluated single-dose fentanyl sublingual spray in opioid-naïve participants. Participants were randomized to receive single-dose fentanyl sublingual spray (100, 200, 400, 600, 800 mcg) or fentanyl citrate IV in one of five cohorts. Dosing occurred following a 10-h fast, with fasting continuing for 4 h post-dose. Dose proportionality was assessed using analysis of variance and linear regression techniques. PK assessments and safety monitoring were performed through 24 h post-dose. Safety assessments, including adverse event (AE) monitoring, occurred from dosing through Day 7. Fifty participants (19-53 years) received fentanyl sublingual spray or fentanyl citrate IV. Mean maximum plasma concentrations were reached between 0.27-0.60 h post-dose for fentanyl sublingual spray. Peak (C max ) and total (AUC 0- t , AUC 0-∞ ) fentanyl exposures increased in a linear, but more than dose-proportional manner, with higher doses. The most common AEs were somnolence, nausea, and vomiting. All AEs were mild or moderate in severity. Doses at 400, 600, and 800 mcg were associated with nausea and vomiting, requiring pharmacologic intervention. Hypoxia episodes requiring nasal cannula oxygenation were observed with 600mcg and 800mcg doses. Overall, single-dose fentanyl sublingual spray (100-800 mcg) was generally well tolerated, with greater incidences of AEs (e.g. nausea, vomiting, hypoxia) at higher doses. Doses up to 200 mcg may be safely administered to healthy opioid-naïve individuals with routine monitoring; doses

  5. Sublingual versus subcutaneous immunotherapy: patient adherence at a large German allergy center

    Directory of Open Access Journals (Sweden)

    Lemberg M

    2017-01-01

    Full Text Available Marie-Luise Lemberg,1 Till Berk,2 Kija Shah-Hosseini,1 Elena-Manja Kasche,1,3 Ralph Mösges1 1Faculty of Medicine, Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany; 2Department of Trauma Surgery, University Hospital Zurich, Zurich, Switzerland; 3Center for Dermatology, Specific Allergology and Environmental Medicine, Hamburg, Germany Background: Many placebo-controlled studies have demonstrated that allergen immunotherapy (AIT is an effective therapy for treating allergies. Both commonly used routes, subcutaneous (SCIT and sublingual immunotherapy (SLIT, require high patient adherence to be successful. In the literature, numbers describing adherence vary widely; this investigation compares these two routes of therapy directly.Methods: All data were retrieved from the patient data management system of a center for dermatology, specific allergology, and environmental medicine in Germany. All 330 patients (aged 13–89 years included in this study had commenced AIT between 2003 and 2011, thus allowing a full 3-year AIT cycle to be considered for each investigated patient.Results: In this specific center, SCIT was prescribed to 62.7% and SLIT to 37.3% of all included patients. The total dropout rate of the whole patient cohort was 34.8%. Overall, SLIT patients showed a higher dropout rate (39.0% than did SCIT patients (32.4%; however, the difference between these groups was not significant. Also, no significant difference between the overall dropout rates for men and for women was observed. A Kaplan–Meier curve of the patient collective showed a remarkably high dropout rate for the first year of therapy.Conclusion: The analysis presented in this single-center study shows that most patients who discontinue AIT do so during the first year of therapy. Patients seem likely to finish the 3-year therapy cycle if they manage to adhere to treatment throughout the first year. Strategies for preventing

  6. Baixa dose de misoprostol sublingual (12,5 µg para indução do parto Low dose of sublingual misoprostol (12.5 µg for labor induction

    Directory of Open Access Journals (Sweden)

    Daniele Sofia de Moraes Barros Gattás

    2012-04-01

    Full Text Available OBJETIVO: Descrever os resultados maternos e perinatais utilizando 12,5 µg de misoprostol sublingual para indução do parto em gestantes com feto vivo a termo. MÉTODOS: Realizou-se um estudo multicêntrico, tipo ensaio clínico, aberto e não randomizado, no período de julho a dezembro de 2009. Foram incluídas 30 gestantes com indicação de indução do parto, a termo, feto vivo, escore de Bishop menor ou igual a seis, apresentação cefálica, peso fetal estimado menor que 4.000 g e índice de líquido amniótico maior que cinco. Foram excluídas mulheres com cicatriz uterina, alteração da vitalidade fetal, anomalias congênitas, gestação múltipla, restrição de crescimento intrauterino, hemorragia genital e contraindicações ao parto vaginal. O comprimido de misoprostol sublingual 12,5 µg foi administrado a cada seis horas, até o início do trabalho de parto, máximo de oito doses. RESULTADOS: O trabalho de parto foi induzido satisfatoriamente em 90% das gestantes. As médias dos intervalos entre a primeira dose e o início das contrações uterinas e o parto foram de 14,3±11,7 horas e 25,4±13 horas, respectivamente. A frequência de parto vaginal foi de 60%. A taquissistolia ocorreu em duas gestantes, sendo revertida em ambos os casos sem necessitar de cesariana. A eliminação de mecônio foi observada em quatro pacientes e o escore de Apgar foi menor que sete no quinto minuto em um recém-nascido. CONCLUSÃO: Os desfechos maternos e perinatais foram favoráveis depois da indução do parto com misoprostol sublingual na dose de 12,5 µg a cada seis horas. No entanto, são necessários ensaios clínicos controlados comparando esse esquema posológico com outras doses e vias de administraçãoPURPOSE: To describe the maternal and perinatal outcomes after the use of 12.5 µg of sublingual misoprostol for labor induction in women with term pregnancy and a live fetus. METHODS: We conducted a multicenter, open and non

  7. Safety of sublingual immunotherapy Timothy grass tablet in subjects with allergic rhinitis with or without conjunctivitis and history of asthma

    DEFF Research Database (Denmark)

    Maloney, J; Durham, S; Skoner, D

    2015-01-01

    BACKGROUND: Patients with asthma may be more susceptible to adverse events (AEs) with sublingual immunotherapy tablet (SLIT-tablet) treatment, such as severe systemic reactions and asthma-related events. Using data from eight trials of grass SLIT-tablet in subjects with allergic rhinitis with....../without conjunctivitis (AR/C), AE frequencies were determined in adults and children with and without reported asthma. METHODS: Data from randomized, double-blind, placebo-controlled trials of Timothy grass SLIT-tablet MK-7243 (2800 BAU/75 000 SQ-T, Merck/ALK-Abelló) were pooled for post hoc analyses. Subjects...... with asthma treated with grass SLIT-tablet versus subjects without asthma in or outside of pollen season. There were 6/120 asthma-related TRAEs assessed as severe with grass SLIT-tablet and 2/60 with placebo, without a consistent trend among subjects with and without asthma (5 and 3 events, respectively...

  8. Phenotype and cell proliferation activity of duct-like structures in human sublingual glands: a histological and immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Elen de Souza TOLENTINO

    2015-06-01

    Full Text Available There are several age-related microscopic changes in the salivary glands, including the increase in the number of duct-like structures (DLS. However, the true origin and the phenotype of the DLS are not known. Objective To evaluate the phenotype and the cell proliferation index of the DLS of human sublingual glands. Material and Methods Sixty sublingual glands obtained from human cadavers were divided into two groups - 0-30 and 61-90 years old. The phenotype was estimated by immunostaining for cytokeratin 19 (CK 19 and the S-100 protein as well as by the presence of mucin and glycogen. The cell proliferation index was determined by the Ki-67 antibody. The histochemical techniques used periodic acid-Schiff (PAS and Alcian Blue. In each captured microscopic field, the DLS were counted to establish a percentage for the staining profile. The statistical analysis was accomplished using Student's t-test, the Mann-Whitney test and Pearson's correlation coefficient (p<0.05. Results Comparing both groups, only CK 19 showed a statistically significant difference (p=0.033, with the strongest expression in the elderly group. There was no significant difference between PAS and Alcian Blue (p=0.270. In both groups, the immunostaining for CK 19 was stronger than that for S-100 (p=0.004;p<0.001, but there was no correlation between the two immunomarkers (ρ=-0.163; p=0.315. There was no immunostaining for Ki-67. Conclusions DLS demonstrate a ductal phenotypic profile and do not present cell proliferation activity. DLS may represent a regressive process arising from acini or represent the result of metaplasia.

  9. Sublingual misoprostol versus standard surgical care for treatment of incomplete abortion in five sub-Saharan African countries

    Directory of Open Access Journals (Sweden)

    Shochet Tara

    2012-11-01

    Full Text Available Abstract Background In low-resource settings, where abortion is highly restricted and self-induced abortions are common, access to post-abortion care (PAC services, especially treatment of incomplete terminations, is a priority. Standard post-abortion care has involved surgical intervention but can be hard to access in these areas. Misoprostol provides an alternative to surgical intervention that could increase access to abortion care. We sought to gather additional evidence regarding the efficacy of 400 mcg of sublingual misoprostol vs. standard surgical care for treatment of incomplete abortion in the environments where need for economical non-surgical treatments may be most useful. Methods A total of 860 women received either sublingual misoprostol or standard surgical care for treatment of incomplete abortion in a multi-site randomized trial. Women with confirmed incomplete abortion, defined as past or present history of vaginal bleeding during pregnancy and an open cervical os, were eligible to participate. Participants returned for follow-up one week later to confirm clinical status. If abortion was incomplete at that time, women were offered an additional follow-up visit or immediate surgical evacuation. Results Both misoprostol and surgical evacuation are highly effective treatments for incomplete abortion (misoprostol: 94.4%, surgical: 100.0%. Misoprostol treatment resulted in a somewhat lower chance of success than standard surgical practice (RR = 0.90; 95% CI: 0.89-0.92. Both tolerability of side effects and women’s satisfaction were similar in the two study arms. Conclusion Misoprostol, much easier to provide than surgery in low-resource environments, can be used safely, successfully, and satisfactorily for treatment of incomplete abortion. Focus should shift to program implementation, including task-shifting the provision of post-abortion care to mid- and low- level providers, training and assurance of drug availability. Trial

  10. Audits of radiopharmaceutical formulations

    International Nuclear Information System (INIS)

    Castronovo, F.P. Jr.

    1992-01-01

    A procedure for auditing radiopharmaceutical formulations is described. To meet FDA guidelines regarding the quality of radiopharmaceuticals, institutional radioactive drug research committees perform audits when such drugs are formulated away from an institutional pharmacy. All principal investigators who formulate drugs outside institutional pharmacies must pass these audits before they can obtain a radiopharmaceutical investigation permit. The audit team meets with the individual who performs the formulation at the site of drug preparation to verify that drug formulations meet identity, strength, quality, and purity standards; are uniform and reproducible; and are sterile and pyrogen free. This team must contain an expert knowledgeable in the preparation of radioactive drugs; a radiopharmacist is the most qualified person for this role. Problems that have been identified by audits include lack of sterility and apyrogenicity testing, formulations that are open to the laboratory environment, failure to use pharmaceutical-grade chemicals, inadequate quality control methods or records, inadequate training of the person preparing the drug, and improper unit dose preparation. Investigational radiopharmaceutical formulations, including nonradiolabeled drugs, must be audited before they are administered to humans. A properly trained pharmacist should be a member of the audit team

  11. Pharmacokinetics and safety of fentanyl sublingual spray and fentanyl citrate intravenous: a multiple ascending dose study in opioid-naïve healthy volunteers.

    Science.gov (United States)

    Rauck, Richard L; Oh, D Alexander; Singla, Neil; Koch, Christian; Parikh, Neha; Nalamachu, Srinivas; Wilson, Daniel; Yu, Jin; Vetticaden, Santosh

    2017-11-01

    Fentanyl sublingual spray, with its rapid onset for pain relief, may be efficacious in the management of acute or post-operative pain. Because patients in these settings may be opioid-naïve, the study was conducted to determine the safety, tolerability, and pharmacokinetics of multiple dose administration of fentanyl sublingual spray in an opioid-naïve population. Fentanyl sublingual spray (100 mcg, 200 mcg, and 400 mcg) and fentanyl citrate intravenous (IV; 50 mcg) were administered every 0.5, 1.0, 2.0, and 4.0 h for up to three doses per cohort in opioid-naïve subjects (ClinicalTrials.gov identifier: NCT02641340). Eight subjects in each cohort were randomly assigned (six subjects received fentanyl sublingual spray; two subjects received fentanyl citrate IV). Pharmacokinetic and safety-related pharmacodynamic assessments were performed through 24 h post-first dose. Safety assessments were collected through Day 7. Ninety-six opioid-naïve subjects, aged 20-55 years, with a body mass index of 18.7-31.5 kg/m 2 , participated in the study. Multiple doses of fentanyl sublingual spray (100, 200, and 400 mcg) were generally well tolerated. Hypoxia, observed in the 200-mcg and 400-mcg dose groups, increased with increasing doses and higher dosing frequency, but was readily managed by nasal cannula oxygenation. Overall, nausea increased with increasing doses, and ∼52.6% (10 out of 19) cases of nausea that occurred at the highest dose of 400 mcg were treated with concomitant medication. Overall, the reported adverse events were consistent with the known safety profile of fentanyl. Fentanyl sublingual spray (100 mcg, 200 mg, and 400 mcg) administered every 0.5, 1, 2, and 4 h was generally well tolerated in an opioid-naïve population. The results suggest that doses of 200 mcg or lower may be safe for use in an opioid-naïve population.

  12. Reactive decontamination formulation

    Science.gov (United States)

    Giletto, Anthony [College Station, TX; White, William [College Station, TX; Cisar, Alan J [Cypress, TX; Hitchens, G Duncan [Bryan, TX; Fyffe, James [Bryan, TX

    2003-05-27

    The present invention provides a universal decontamination formulation and method for detoxifying chemical warfare agents (CWA's) and biological warfare agents (BWA's) without producing any toxic by-products, as well as, decontaminating surfaces that have come into contact with these agents. The formulation includes a sorbent material or gel, a peroxide source, a peroxide activator, and a compound containing a mixture of KHSO.sub.5, KHSO.sub.4 and K.sub.2 SO.sub.4. The formulation is self-decontaminating and once dried can easily be wiped from the surface being decontaminated. A method for decontaminating a surface exposed to chemical or biological agents is also disclosed.

  13. Efficacy of a preservative-free formulation of fixed-combination bimatoprost and timolol (Ganfort PF in treatment-naïve patients vs previously treated patients

    Directory of Open Access Journals (Sweden)

    Cordeiro MF

    2015-08-01

    Full Text Available M Francesca Cordeiro,1 Ivan Goldberg,2 Rhett Schiffman,3 Paula Bernstein,3 Marina Bejanian31Western Eye Hospital, Imperial College Healthcare NHS Trust, London, UK; 2Discipline of Ophthalmology, University of Sydney, Sydney, NSW, Australia; 3Allergan, Inc., Irvine, CA, USAPurpose: To evaluate, using subgroup analysis, the effect of treatment status on the intraocular pressure (IOP-lowering efficacy of a preservative-free formulation of fixed-combination bimatoprost 0.03%/timolol 0.5% (FCBT PF.Methods: A primary, multicenter, randomized, double-masked, 12-week study compared the efficacy and safety of FCBT PF with preserved FCBT (Ganfort® in 561 patients diagnosed with glaucoma or ocular hypertension. For this analysis, eligible patients were treatment-naïve or had inadequate IOP lowering and underwent a washout of previous treatment. IOP (8 am, 10 am, and 4 pm was measured at baseline and weeks 2, 6, and 12. Subgroup analysis of the FCBT PF arm assessed changes in average eye IOP from baseline in treatment-naïve vs previously treated patients. To evaluate the effect of treatment status at baseline (treatment-naïve vs previously treated on IOP reduction in the FCBT PF treatment group, an analysis of covariance model was used with treatment status and investigator as fixed effects, and baseline average eye IOP, age, glaucoma diagnosis, and baseline average eye corneal thickness as covariates. P-values and the 95% confidence intervals were determined using the model.Results: In the FCBT PF arm, IOP mean changes from baseline ranged from -8.7 mmHg to -9.8 mmHg in treatment-naïve patients (N=50, compared with -7.3 mmHg to -8.5 mmHg in previously treated patients (N=228. Baseline IOP, age, glaucoma diagnosis, and corneal thickness significantly affected IOP reduction in the FCBT PF group. Adjusting for these covariates, FCBT PF had a greater IOP-lowering effect (0.8–1.7 mmHg in treatment-naïve patients than previously treated patients

  14. An exact approach for aggregated formulations

    DEFF Research Database (Denmark)

    Gamst, Mette; Spoorendonk, Simon; Røpke, Stefan

    Aggregating formulations is a powerful approach for problems to take on tractable forms. Aggregation may lead to loss of information, i.e. the aggregated formulation may be an approximation of the original problem. In branch-and-bound context, aggregation can also complicate branching, e.g. when...... optimality cannot be guaranteed by branching on aggregated variables. We present a generic exact solution method to remedy the drawbacks of aggregation. It combines the original and aggregated formulations and applies Benders' decomposition. We apply the method to the Split Delivery Vehicle Routing Problem....

  15. Preparation of radiopharmaceutical formulations

    International Nuclear Information System (INIS)

    Simon, J.; Garlich, J.R.; Frank, R.K.; McMillan, K.

    1998-01-01

    Radiopharmaceutical formulations for complexes comprising at least one radionuclide complexed with a ligand, or its physiologically-acceptable salts thereof, especially 153 samarium-ethylenediaminetetramethylenephosphonic acid, which optionally contains a divalent metal ion, e.g. calcium, and is frozen, thawed, and then administered by injection. Alternatively, the radiopharmaceutical formulations must contain the divalent metal and are frozen only if the time before administration is sufficiently long to cause concern for radiolysis of the ligand. 2 figs., 9 tabs

  16. Tariff formulation and equalization

    International Nuclear Information System (INIS)

    Svartsund, Trond

    2003-01-01

    The primary goal of the transmission tariff is to provide for socioeconomic use of the transmission grid. The present tariff structure is basically right. The responsibility for the formulation of the tariff resides with the local grid owner. This must take place in agreement with the current regulations which are passed by the authorities. The formulation must be adaptable to the local requirements. EBL (Norwegian Electricity Industry Association) is content with the current regulations

  17. The effect of X-ray irradiation on the function and saliva composition of rat parotid and submandibular/sublingual glands

    International Nuclear Information System (INIS)

    Hashida, Tatsuo; Kamemoto, Hiromasa; Fuchihata, Hajime; Ooshima, Takashi

    1999-01-01

    Radiation therapy to the head and neck area frequently causes severe salivary gland dysfunction and xerostomia. Morphological studies of irradiated salivary glands have suggested that the submandibular/sublingual gland may be less radiosensitive than the parotid gland. The purpose of this study was to evaluate the effect of radiation on major salivary gland functions in rats with radiation-induced xerostomia. The effect of salivary gland irradiation on salivary function was examined in specific pathogen-free Sprague-Dawley rats. The animals were irradiated with a single exposure of either 22 Gy or 32 Gy. Stimulated saliva excretion time was measured for the parotid and submandibular/sublingual glands, and the total protein in saliva was analysed. Our results showed that the saliva flow rate and protein concentration of parotid saliva were significantly reduced in the 32 Gy-irradiated rats. (author)

  18. A Case of Sublingual Ranula That Responded Successfully to Localized Injection Treatment with OK-432 after Healing from Drug Induced Hypersensitivity Syndrome

    Directory of Open Access Journals (Sweden)

    Kunio Yoshizawa

    2016-01-01

    Full Text Available A ranula is a mucus retention cyst or pseudocyst caused by leakage of mucus from the sublingual gland and generally occurs in the oral floor. In addition, drug induced hypersensitivity syndrome (DIHS is a rare but well-recognized serious adverse effect characterized by fever, skin rashes, generalized lymphadenopathy, hepatitis, and hepatosplenomegaly and oral stomatitis. This paper presents the first case of successfully treated sublingual ranula with localized injection of OK-432 after healing from drug induced hypersensitivity syndrome, which has previously been unreported in the literature. We present the case of a 38-year-old Japanese woman with sublingual ranula that responded successfully to localized injection treatment with OK-432 after healing from drug induced hypersensitivity syndrome. She was affected with cutaneous myositis and interstitial lung disease when she was 26 years old. At the age 34 years, she received additional oral treatment of diaminodiphenyl-sulfone due to deterioration of the cutaneous myositis, which resulted in drug induced hypersensitivity syndrome (DIHS with severe oral stomatitis. Local injection of OK-432 to the ranula may be a very safe and useful treatment method even if the patient has a history of drug allergy and has connective tissue disease such as cutaneous myositis.

  19. Transdermal buprenorphine, opioid rotation to sublingual buprenorphine, and the avoidance of precipitated withdrawal: a review of the literature and demonstration in three chronic pain patients treated with butrans.

    Science.gov (United States)

    Kornfeld, Howard; Reetz, Heidi

    2015-01-01

    Buprenorphine is an opioid, used in the United States and abroad for both analgesia and addiction, with unique opioid receptor binding properties. There are several pharmacological features of buprenorphine that make it an emerging option for the long-term treatment of chronic pain-its respiratory suppression ceiling effect, its efficacy in neuropathic pain and hyperalgesic states, and its decreased suppression of the immune and endocrine systems compared with other long-acting opioids. Previous studies have shown that high-dose sublingual buprenorphine is an effective treatment of chronic pain patients not responding to other opioids. Guidelines for the introduction of sublingual buprenorphine, termed buprenorphine induction, include an opioid-free "withdrawal" period of 12-48 hours to avoid an anticipated and accelerated opioid withdrawal, a syndrome described in this article as precipitated withdrawal. The requirement of a period of opioid abstinence before buprenorphine use may present a significant barrier to its adoption for chronic pain. We present a case series of a novel method of sublingual buprenorphine introduction without an induction period, using the recently Food and Drug Administration-approved low-dose transdermal buprenorphine (Butrans; Purdue Pharma L.P.) as a bridge medication. In these cases, buprenorphine was started in opioid-dependent chronic noncancer pain patients who had taken short-acting opioid medications within hours of the initiation of the rotation. This method avoids the painful abstinence period and did not result in precipitated withdrawal or other significant adverse effects.

  20. Granulated decontamination formulations

    Science.gov (United States)

    Tucker, Mark D.

    2007-10-02

    A decontamination formulation and method of making that neutralizes the adverse health effects of both chemical and biological compounds, especially chemical warfare (CW) and biological warfare (BW) agents, and toxic industrial chemicals. The formulation provides solubilizing compounds that serve to effectively render the chemical and biological compounds, particularly CW and BW compounds, susceptible to attack, and at least one reactive compound that serves to attack (and detoxify or kill) the compound. The formulation includes at least one solubilizing agent, a reactive compound, a sorbent additive, and water. A highly adsorbent sorbent additive (e.g., amorphous silica, sorbitol, mannitol, etc.) is used to "dry out" one or more liquid ingredients into a dry, free-flowing powder that has an extended shelf life, and is more convenient to handle and mix in the field.

  1. Correction of vitamin D deficiency using sublingually administered vitamin D2 in a Crohn's disease patient with mal-absorption and a new ileostomy.

    Science.gov (United States)

    McCullough, Patrick; Heaney, Robert

    2017-10-01

    Vitamin D deficiency has been shown to be associated with many adverse health problems. Studies have shown that patients with Crohn's disease who have low vitamin D levels have a poorer quality of life than those with more adequate levels. It has also been shown that patients with mal-absorption problems have a difficult time achieving normal vitamin D levels in spite of aggressive supplementation, and that exposure to UVB radiation may be the most effective treatment option for these patients. We present a case in which 25-hydroxyvitamin D levels were normalized within 2 weeks in a severely vitamin D deficient patient with Crohn's disease with mal-absorption and a new ileostomy, utilizing sublingually administered vitamin D2. A 58 year-old white female was admitted with a new ileostomy following partial bowel resection due to complications from Crohn's disease. She was found to be severely vitamin D deficient at the time of admission, with a level of 6.1ng/ml on hospital day 3. Her treatment with vitamin D was delayed for a few days. She was initially treated with 5000 units of vitamin D3 orally twice a day for 3days (days 7-10). After discussion with the patient and obtaining her consent, vitamin D3 was stopped, and she was then treated with a total of 8 doses of 50,000 units of vitamin D2 administered sublingually. She was given the first 3 doses on alternating days (days 11, 13, 15), and then 5 more doses on consecutive days (days 17-21). The rise in her 25-hydroxyvitamin D level in response to treatment with sublingual vitamin D2 was significant. On day 10, after receiving 3days of orally administered vitamin D3, her level was 9.8ng/ml. One week later, after receiving 3 sublingual doses of vitamin D2, it rose to 20.3ng/ml. It was then measured on alternating days twice over the next 4days, and it rose to 45.5ng/ml, and then to 47.4ng/ml on the day of discharge to home. The major finding of this study is that sublingual administration of vitamin D2 appears to

  2. Determination of degradation products and process related impurities of asenapine maleate in asenapine sublingual tablets by UPLC

    Science.gov (United States)

    Kumar, Nitin; Sangeetha, D.; Kalyanraman, L.

    2017-11-01

    For determination of process related impurities and degradation products of asenapine maleate in asenapine sublingual Tablets, a reversed phase, stability indicating UPLC method was developed. Acetonitrile, methanol and potassium dihydrogen phosphate buffer with tetra-n- butyl ammonium hydrogen sulphate as ion pair (pH 2.2; 0.01 M) at flow rate of 0.2 ml/min were used in gradient elution mode. Separation was achieved by using acquity BEH Shield RP18 column (1.7 μm, 2.1 mm×100 mm) at 35 ºC. UV detection was performed at 228 nm. Subsequently the liquid chromatography method was validated as per ICH. The drug product was exposed to the stress conditions of acid hydrolysis, base hydrolysis, water hydrolysis, oxidative, thermal, and photolytic. In oxidative stress and thermal stress significant degradation was observed. All the degradation products were well separated from analyte peak and its impurities. Stability indicating nature of the method was proved by demonstrating the peak purity of Asenapine peak in all the stressed samples. The mass balance was found >95% for all the stress conditions. Based on method validation, the method was found specific, linear, accurate, precise, rugged and robust.

  3. Simultaneous quantitative determination of multiple bioactive markers in Ocimum sanctum obtained from different locations and its marketed herbal formulations using UPLC-ESI-MS/MS combined with principal component analysis.

    Science.gov (United States)

    Pandey, Renu; Chandra, Preeti; Srivastava, Mukesh; Mishra, D K; Kumar, Brijesh

    2015-01-01

    Ocimum sanctum L., with phenolic acids, flavonoids, propenyl phenols and terpenoids as active pharmacological constituents, is a popular medicinal herb and is present as an ingredient in many herbal formulations. Therefore, development of a reliable analytical method for simultaneous determination of the pharmacologically active constituents of O. sanctum is of high importance. To develop and validate a new, rapid, sensitive and selective UPLC-ESI/MS/MS method for simultaneous determination of 23 bioactive markers including phenolic acids, flavonoids, propenyl phenol and terpenoid in the leaf extract and marketed herbal formulations of O. sanctum. An UPLC-ESI/MS/MS method using negative electrospray ionisation (ESI) in multiple-reaction-monitoring (MRM) mode was used for simultaneous determination. Chromatographic separation was achieved on an Acquity UPLC BEH C18 -column using a gradient elution with 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Principal component analysis (PCA) was applied to correlate and discriminate eight geographical collections of O. sanctum based on quantitative data of the analytes. The developed method was validated as per International Conference on Harmonization guidelines and found to be accurate, with overall recovery in the range 95.09-104.84% (RSD ≤ 1.85%), precise (RSD ≤ 1.98%) and linear (r(2)  ≥ 0.9971) over the concentration range of 0.5-1000 ng/mL. Ursolic acid was found to be the most abundant marker in all the samples investigated, except for the marketed tablet. The method established is simple, rapid and sensitive, hence it can be reliably utilised for the quality control of O. sanctum and derived herbal formulations. Copyright © 2015 John Wiley & Sons, Ltd.

  4. Equivalência farmacêutica da formulação combinada de budesonida e formoterol em cápsula única com dispositivo inalador de pó Pharmaceutical equivalence of the combination formulation of budesonide and formoterol in a single capsule with a dry powder inhaler

    Directory of Open Access Journals (Sweden)

    Marina Andrade-Lima

    2012-12-01

    Full Text Available OBJETIVO: Avaliar a equivalência farmacêutica da formulação teste (associação fixa de budesonida e fumarato de formoterol em cápsula única dispensada com o dispositivo Aerocaps® em relação a uma formulação referência (budesonida e fumarato de formoterol em duas cápsulas distintas dispensadas com o dispositivo Aerolizer®. MÉTODOS: Estudo in vitro no qual foram realizadas identificação/quantificação dos ingredientes ativos por HPCL e determinação da uniformidade da dose liberada e da distribuição aerodinâmica das partículas das formulações teste e referência. RESULTADOS: Na formulação teste, o teor de budesonida e de formoterol foi de 111,0% e 103,8%, respectivamente, enquanto esse foi de 110,5% e 104,5% na formulação referência. Na formulação teste, a uniformidade das doses de budesonida e de formoterol foi de 293,2 µg e 10,2 µg, respectivamente, enquanto essa foi de 353,0 µg e 11,1 µg na formulação referência. Esses resultados estão dentro da faixa recomendada para esse tipo de formulação (75-125% da dose rotulada. A fração de partículas finas (OBJECTIVE: To evaluate the pharmaceutical equivalence of a test formulation (fixed-dose combination of budesonide and formoterol fumarate in a single capsule dispensed in an Aerocaps® inhaler in relation to a reference formulation (budesonide and formoterol fumarate in two separate capsules dispensed in an Aerolizer® inhaler. METHODS: This was an in vitro study in which we performed the identification/quantification of the active ingredients by HPLC and determined dose uniformity and aerodynamic particle size distribution in the test and reference formulations. RESULTS: In the test formulation, the content of budesonide and formoterol was 111.0% and 103.8%, respectively, compared with 110.5% and 104.5%, respectively, in the reference formulation. In the test formulation, dose uniformity regarding budesonide and formoterol was 293.2 µg and 10.2 µg

  5. Artificial intelligence in pharmaceutical product formulation: neural computing

    OpenAIRE

    Svetlana Ibrić; Jelena Petrović; Jelena Parojčić; Zorica Djurić

    2009-01-01

    The properties of a formulation are determined not only by the ratios in which the ingredients are combined but also by the processing conditions. Although the relationships between the ingredient levels, processing conditions, and product performance may be known anecdotally, they can rarely be quantified. In the past, formulators tended to use statistical techniques to model their formulations, relying on response surfaces to provide a mechanism for optimazation. However, the optimization b...

  6. 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.

  7. The influence of sublingual immunotherapy on several parameters of immunological response in children suffering from atopic asthma and allergic rhinitis depending on asthma features.

    Science.gov (United States)

    Ciepiela, Olga; Zawadzka-Krajewska, Anna; Kotuła, Iwona; Demkow, Urszula

    2014-01-01

    The clinical efficacy of sublingual immunotherapy (SLIT) has already been proven and is known to be high. Its influence on the immunological system of patients suffering from bronchial asthma was also examined. However, it is still unclear how the polysensitisation, coexistence of other atopic disease and asthma treatment step influence the response to treatment with specific immunotherapy. Herein we evaluate the impact of one-year SLIT on selected markers of immunological response depending on different individual and clinical factors of children suffering from atopic asthma and allergic rhinitis. Twenty-five patients aged 8.1 ± 3.1 years (range 5-15 years), 21 boys and 4 girls, suffering from asthma and allergic rhinitis with polysensitisation to seasonal and non-seasonal allergens, shortlisted for SLIT, were included in the study. Th1 cell and Th2 cell percentages, Bcl-2 expression in T cells, and basophil activation after allergen challenge (house dust mite and/or grass pollen antigen in solution used for skin prick tests) in peripheral blood were measured using flow cytometry. The association between clinical features of asthma and the influence of SLIT on immunological parameters was evaluated with exact Fisher test. No association between the influence of one-year sublingual immunotherapy on immunological system and patients' age, polysensitisation, asthma treatment step, or coexistence of any other atopic diseases was observed. However, an increase of the Th1 percentage in children sensitised against more than three allergens was found more often (at the limit of statistical significance) than in the group of children sensitised against three or less allergens. Based on our results, we cannot point to any subgroup isolated in the study, in which the response of the immunological system to sublingual immunotherapy is more satisfactory than any other. Nevertheless, the increase of Th1 cells may be more specific for polysensitised children.

  8. Systematic Equation Formulation

    DEFF Research Database (Denmark)

    Lindberg, Erik

    2007-01-01

    A tutorial giving a very simple introduction to the set-up of the equations used as a model for an electrical/electronic circuit. The aim is to find a method which is as simple and general as possible with respect to implementation in a computer program. The “Modified Nodal Approach”, MNA, and th......, and the “Controlled Source Approach”, CSA, for systematic equation formulation are investigated. It is suggested that the kernel of the P Spice program based on MNA is reprogrammed....

  9. Sequential Treatment Initiation with Timothy Grass and Ragweed Sublingual Immunotherapy Tablets Followed by Simultaneous Treatment Is Well Tolerated.

    Science.gov (United States)

    Maloney, Jennifer; Berman, Gary; Gagnon, Remi; Bernstein, David I; Nelson, Harold S; Kleine-Tebbe, Jörg; Kaur, Amarjot; Li, Qing; Nolte, Hendrik

    2016-01-01

    Dual treatment with grass and ragweed sublingual immunotherapy (SLIT) tablets has not been studied. To characterize the safety and tolerability of dual grass and ragweed SLIT-tablet administration. This open-label, multicenter trial (NCT02256553) enrolled North American adults (N = 102) allergic to grass and ragweed. The trial had 3 periods, each of 2 weeks duration. In period 1, subjects received once-daily timothy grass SLIT tablet (2800 bioequivalent allergen unit; Merck, Inc, Kenilworth, NJ/ALK, Hørsholm, Denmark). In period 2, subjects received a short ragweed SLIT tablet (12 Ambrosia artemisiifolia 1-U; Merck/ALK) every morning and a grass SLIT tablet every evening. In period 3, subjects received once-daily grass and ragweed SLIT tablets within 5 minutes (simultaneous intake). The primary end point was the proportion of subjects with 1 or more local swelling events in each period. Secondary end points were the proportion of subjects with 1 or more local adverse events (AEs), that discontinued the treatment because of AEs, and subjects with 1 or more local AEs requiring treatment. No severe swellings, systemic allergic reactions, asthma attacks, or reactions requiring epinephrine were reported. Most (99%) AEs were graded mild to moderate. The proportions of subjects with 1 or more local swelling events were 14%, 22%, and 15% for periods 1, 2, and 3, respectively. For periods 1, 2, and 3, the proportions of subjects with 1 or more local AEs were 71%, 69%, and 56%, respectively; the proportions discontinuing the treatment because of treatment-related AEs were 5%, 1%, and 2%, and the proportions with 1 or more local AEs requiring treatment were 4%, 4%, and 1%. In this trial, a 4-week sequential SLIT-tablet dosing schedule followed by simultaneous intake of timothy grass and ragweed tablets was well tolerated. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Cine MR enterography grading of small bowel peristalsis: evaluation of the antiperistaltic effectiveness of sublingual hyoscyamine sulfate.

    Science.gov (United States)

    Ghobrial, Peter M; Neuberger, Ilana; Guglielmo, Flavius F; Mitchell, Donald G; Parker, Laurence; O'Kane, Patrick L; Roth, Christopher G; Deshmukh, Sandeep P; Borowski, Allison

    2014-01-01

    To use a cine balanced steady-state free precession magnetic resonance enterography (cine MRE) pulse sequence to assess the effectiveness of a sublingual (SL) antiperistaltic agent, hyoscyamine sulfate. Institutional review board approval was granted with an exemption for informed consent in this Health Insurance Portability and Accountability Act-compliant, retrospective, single-institution study. Of the 288 MRE examinations performed between October 1, 2007 and January 15, 2011, 92 using SL hyoscyamine sulfate for antiperistalsis were included for review, each with cine MRE before and after medication. These 184 cine MRE data sets were randomized, blinded for treatment, and independently reviewed by five attending abdominal radiologists, who rated the degree of whole abdomen bowel motility on each cine MRE data set on a 5-point scale. Pre- and postmedication mean peristalsis ratings, standard deviation, mean difference, and treatment effect sizes were calculated. A repeated measures analysis of variance test was performed using a significance threshold of P = .05. Interobserver reliabilities were also calculated. Mean peristalsis ratings ranged 2.63-3.34 and 2.36-3.03, before and after medication administration, respectively. The mean differences ranged from 0.22 to 0.46, which are treatment effect sizes of 0.20 to 0.37. The decrease in peristalsis observed by the five reviewing radiologists after SL hyoscyamine sulfate administration was significant (df = 1/182, f = 7.35, P cine MRE sequences show decreased bowel peristalsis after the use of SL hyoscyamine sulfate, the small size of the observed treatment effect is likely insufficient to justify its use for MRE. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

  11. Sublingual Buprenorphine and Methadone Maintenance Treatment: A Three-Year Follow-Up of Quality of Life Assessment

    Directory of Open Access Journals (Sweden)

    Salvatore M. Giacomuzzi

    2005-01-01

    Full Text Available This study was conducted to compare long-term outcome effects on the quality of life (QOL of oral methadone with sublingual buprenorphine maintenance treatment. The QOL status of opioid-dependent patients was assessed using the German version (“Berlin Quality of Life Profile” of the Lancashire Quality of Life Profile. Physical symptoms were measured using the Opiate Withdrawal Scale (OWS. Urine tests were carried out randomly to detect additional consumption. In the first study period, 53 opioid-dependent subjects were enrolled and 25 could be reached after 3 years. The retention rate was 50% for methadone and 45% for buprenorphine (p = 0.786. Baseline values of the total sample (completers and noncompleters QOL and somatic complaints did not show significant differences between the two treatment groups. QOL characteristics at 6 months of treatment of the buprenorphine completer and noncompleter groups differed significantly regarding job (p = 0.013, family, and total score of physical symptoms (p = 0.002, in which the completer group showed the more favorable values. Concerning physical symptoms at 36 months, logistic regression revealed significantly less stomach cramps (p = 0.037 and fatigue and tiredness (p = 0.034 in buprenorphine compared to the methadone. Moreover, the buprenorphine-maintained group showed significantly less additional consumption of benzodiazepines (p = 0.015 compared with methadone participants. It is concluded that opioid addicts improved their QOL and health status when treated with methadone or buprenorphine. In summary, regarding QOL and health status, the present data indicate that buprenorphine is also a useful long-term alternative for maintenance treatment of opioid-dependent patients.

  12. Drug delivery and formulations.

    Science.gov (United States)

    Breitkreutz, Jörg; Boos, Joachim

    2011-01-01

    Paediatric drug delivery is a major challenge in drug development. Because of the heterogeneous nature of the patient group, ranging from newborns to adolescents, there is a need to use appropriate excipients, drug dosage forms and delivery devices for different age groups. So far, there is a lack of suitable and safe drug formulations for children, especially for the very young and seriously ill patients. The new EU legislation will enforce paediatric clinical trials and drug development. Current advances in paediatric drug delivery include interesting new concepts such as fast-dissolving drug formulations, including orodispersible tablets and oral thin strips (buccal wafers), and multiparticulate dosage forms based on mini-tabletting or pelletization technologies. Parenteral administration is likely to remain the first choice for children in the neonatal period and for emergency cases. Alternative routes of administration include transdermal, pulmonary and nasal drug delivery systems. A few products are already available on the market, but others still need further investigations and clinical proof of concept.

  13. Ether formulations of relativity

    International Nuclear Information System (INIS)

    Duffy, M.C.

    1980-01-01

    Contemporary ether theories are surveyed and criticised, especially those formally identical to orthodox Relativity. The historical development of Relativity, Special and General, in terms of an ether, is briefly indicated. Classical interpretations of Generalized Relativity using ether are compared to Euclidean formulations using a background space. The history of a sub-group of theories, formulating a 'new' Relativity involving modified transforms, is outlined. According to the theory with which they agree, recent supposed detections of drift are classified and criticised. Cosmological evidence suggesting an ether is mentioned. Only ether theories formally identical to Relativity have been published in depth. They stand criticised as being contrary to the positivist spirit. The history of mechanical analogues is traced, from Hartley's representing gravitating matter as spherical standing waves, to recent suggestions that vortex-sponge might model electromagnetic, quantum, uncertainty and faster-than-light phenomena. Contemporary theories are particular physical theories, themselves 'second interpretations' of a primary mathematical model. Mechanical analogues are auxiliary, not necessary, to other theory, disclosing relationships between classical and non-classical descriptions of assemblies charging state. The ether-relativity polemic, part of a broader dispute about relativity, is founded on mistaken conceptions of the roles of mathematical and physical models, mechanical analogues; and a distored view of history, which indicates that ether theories have become relativistic. (author)

  14. Screening of mucoadhesive vaginal gel formulations

    Directory of Open Access Journals (Sweden)

    Ana Ochoa Andrade

    2014-12-01

    Full Text Available Rational design of vaginal drug delivery formulations requires special attention to vehicle properties that optimize vaginal coating and retention. The aim of the present work was to perform a screening of mucoadhesive vaginal gels formulated with carbomer or carrageenan in binary combination with a second polymer (carbomer, guar or xanthan gum. The gels were characterised using in vitroadhesion, spreadability and leakage potential studies, as well as rheological measurements (stress and frequency sweep tests and the effect of dilution with simulated vaginal fluid (SVF on spreadability. Results were analysed using analysis of variance and multiple factor analysis. The combination of polymers enhanced adhesion of both primary gelling agents, carbomer and carrageenan. From the rheological point of view all formulations presented a similar behaviour, prevalently elastic and characterised by loss tangent values well below 1. No correlation between rheological and adhesion behaviour was found. Carbomer and carrageenan gels containing the highest percentage of xanthan gum displayed good in vitro mucoadhesion and spreadability, minimal leakage potential and high resistance to dilution. The positive results obtained with carrageenan-xanthan gum-based gels can encourage the use of natural biocompatible adjuvants in the composition of vaginal products, a formulation field that is currently under the synthetic domain.

  15. [Optimization of formulations for dietetic pastry products].

    Science.gov (United States)

    Villarroel, M; Uquiche, E; Brito, G; Cancino, M

    2000-03-01

    Optimized formulations of dietetic pastry products such as cake and sponge cake premixes were formulated using the surface response methodology. % Emulsifier agent and baking time were the selected independent variables for cake, as well as % emulsifier agent % chlorinated flour the variables selected for sponge cake. Three different level of each variable summing up thirteen experimental formulae of each product were assessed to optimize the variables that could have some influence in the sensory characteristics of these dietetic products. The total sensory quality was determined for both dietetic products using the composite scoring test and a panel of 18 trained judges. Looking at the contour graphic and considering economic aspects the best combination of variables for cake formulation was 2% emulsifier agent and 48 minutes for baking time, With respect to sponge cake, the best combination was 6% emulsifier agent and 48% chlorinated flour. Shelf life studies showed that both dietetic formulations remained stable during storage conditions of 75 days at 30 degrees C. During this period, significant differences in sensory characteristics were not found (p pastry products had good acceptability, and open up marketing opportunities for new products with potential health benefits to consumers.

  16. Vozy formule 1

    OpenAIRE

    Zbožínek, Adam

    2009-01-01

    Tato práce uvádí základní pravidla a předpoklady pro konstrukci a použití vozů formule 1. Hlavní zaměření je na aerodynamiku, která je nejdůležitější disciplínou v tomto motoristickém sportu, dále je tato práce zaměřena na základní faktory týkající se motoru vozu, kol, nové technologie KERS a provedení volantu. This work shows basic rules and conditions for construction and use of cars formula 1. The main part of this work focus on the aerodynamics which is the most important discipline of...

  17. Assessment of strategy formulation

    DEFF Research Database (Denmark)

    Acur, Nuran; Englyst, Linda

    2006-01-01

    of the success criteria through face-to-face interviews with 46 managers, workshops involving 40 managers, and two in-depth case studies. The success criteria have been slightly modified due to the empirical results, to yield the assessment tool. Findings – The resulting assessment tool integrates three generic...... approaches to strategy assessment, namely the goal-centred, comparative and improvement approaches, as found in the literature. Furthermore, it encompasses three phases of strategy formulation processes: strategic thinking, strategic planning and embedding of strategy. The tool reflects that the different......, but cases and managerial perceptions indicate that the need for accurate and detailed plans might be overrated in the literature, as implementation relies heavily on continuous improvement and empowerment. Concerning embedding, key aspects relate both to the goal-centred and improvement approaches, while...

  18. Efficacy of a House Dust Mite Sublingual Allergen Immunotherapy Tablet in Adults With Allergic Asthma

    DEFF Research Database (Denmark)

    Virchow, Johann Christian; Backer, Vibeke; Kuna, Piotr

    2016-01-01

    moderate or severe asthma exacerbation during the ICS reduction period. Secondary outcomes were deterioration in asthma symptoms, change in allergen-specific immunoglobulin G4 (IgG4), change in asthma control or asthma quality-of-life questionnaires, and adverse events. RESULTS: Among 834 randomized...... in allergen-specific IgG4. However, there was no significant difference for change in asthma control questionnaire or asthma quality-of-life questionnaire for either dose. There were no reports of severe systemic allergic reactions. The most frequent adverse events were mild to moderate oral pruritus (13...... corticosteroid (ICS) reduction period. DESIGN, SETTINGS, AND PARTICIPANTS: Double-blind, randomized, placebo-controlled trial conducted between August 2011 and April 2013 in 109 European trial sites. The trial included 834 adults with HDM allergy-related asthma not well controlled by ICS or combination products...

  19. Food-specific sublingual immunotherapy is well tolerated and safe in healthy dogs: a blind, randomized, placebo-controlled study.

    Science.gov (United States)

    Maina, E; Pelst, M; Hesta, M; Cox, E

    2017-01-18

    Food allergies are increasing in prevalence but no treatment strategies are currently available to cure dogs with food allergy. Over the past decade, experimental food allergen-specific sublingual immunotherapy (FA-SLIT) has emerged as a potential treatment for food allergies in human medicine. However, FA-SLIT has not been investigated in dogs. Therefore, the objective of this study was to prospectively evaluate the safety, tolerability and dispenser sterility of FA-SLIT in healthy dogs before testing it in food allergic dogs. Eight experimental healthy beagle dogs, never orally exposed to peanut, were randomized in two groups to receive SLIT with peanut or placebo for 4 months. Subjects were monitored daily for local and systemic adverse effects. Blood samples for complete blood count and serum biochemistry, and urine for urinalysis were collected and the dogs' body weight was recorded at day 0, 35 and 119 of the SLIT treatment. Sera for the determination of peanut-specific IgG and IgE were collected at day 0, 35, 49, 70, 91, 105 and 119. Intradermal tests were performed before (day 0) and after (day 119) the experiment. The content of each dispenser used to administer treatment or placebo was tested for sterility after usage. In order to assess the presence or absence of sensitization, dogs were challenged 6 months after the end of the study with 2000 μg of peanut extract daily for 7 to 14 days. All dogs completed the study. The treatment did not provoke either local or systemic side-effects. Peanut-specific IgG significantly increased in treatment group. Even though a significant increase in peanut-specific IgE was also seen, intradermal tests were negative in all dogs before and after the experiment, and the challenge test did not trigger any adverse reactions in the treated dogs, which shows the protocol did not cause sensitization to peanut, but nevertheless primed the immune system as indicated by the humoral immune response. All dispenser solutions

  20. Baseline LAW Glass Formulation Testing

    International Nuclear Information System (INIS)

    Kruger, Albert A.; Mooers, Cavin; Bazemore, Gina; Pegg, Ian L.; Hight, Kenneth; Lai, Shan Tao; Buechele, Andrew; Rielley, Elizabeth; Gan, Hao; Muller, Isabelle S.; Cecil, Richard

    2013-01-01

    The major objective of the baseline glass formulation work was to develop and select glass formulations that are compliant with contractual and processing requirements for each of the LAW waste streams. Other objectives of the work included preparation and characterization of glasses with respect to the properties of interest, optimization of sulfate loading in the glasses, evaluation of ability to achieve waste loading limits, testing to demonstrate compatibility of glass melts with melter materials of construction, development of glass formulations to support ILAW qualification activities, and identification of glass formulation issues with respect to contract specifications and processing requirements

  1. Pharmacokinetics and bioavailability of oxycodone and acetaminophen following single-dose administration of MNK-795, a dual-layer biphasic IR/ER combination formulation, under fed and fasted conditions

    Directory of Open Access Journals (Sweden)

    Devarakonda K

    2014-08-01

    Full Text Available Krishna Devarakonda,1 Terri Morton,1 Rachel Margulis,2 Michael Giuliani,3 Thomas Barrett4 1Clinical Pharmacology and Pharmacokinetics, 2Clinical Operations, 3Research and Development, 4Clinical Affairs, Mallinckrodt Inc., Hazelwood, MO, USA Background: XARTEMIS™ XR (formerly MNK-795 is a combination oxycodone (OC and acetaminophen (APAP analgesic with both immediate-release and extended-release (ER components (ER OC/APAP. The tablets are designed with gastric-retentive ER oral delivery technology that releases the ER component at a controlled rate in the upper gastrointestinal tract. Because consumption of food has demonstrated an impact on the pharmacokinetics (PK of some marketed products using gastric-retentive ER oral delivery technology, a characterization of the effects of fed (high- and low-fat diets versus fasted conditions on the PK of ER OC/APAP was performed. Methods: This Phase I study used an open-label randomized single-dose three-period six-sequence crossover single-center design. Healthy adult participants (n=48 were randomized to receive two tablets of ER OC/APAP under three conditions: following a high-fat meal; following a low-fat meal; and fasted. Plasma concentration versus time data from predose throughout designated times up to 48 hours postdose was used to estimate the PK parameters of oxycodone and APAP. Results: Thirty-one participants completed all three treatment periods. Both oxycodone and APAP were rapidly absorbed under fasted conditions. Total oxycodone and APAP exposures (area under the plasma drug concentration-time curve [AUC] from ER OC/APAP were not significantly affected by food, and minimal changes to maximum observed plasma concentration for oxycodone and APAP were also noted. However, food marginally delayed the time to maximum observed plasma concentration of oxycodone and APAP. There was no indication that tolerability was affected by food. Conclusion: The findings from this study suggest that ER OC

  2. Quality of Artemisinin-Based Combination Formulations for Malaria Treatment: Prevalence and Risk Factors for Poor Quality Medicines in Public Facilities and Private Sector Drug Outlets in Enugu, Nigeria

    Science.gov (United States)

    Kaur, Harparkash; Allan, Elizabeth Louise; Mamadu, Ibrahim; Hall, Zoe; Ibe, Ogochukwu; El Sherbiny, Mohamed; van Wyk, Albert; Yeung, Shunmay; Swamidoss, Isabel; Green, Michael D.; Dwivedi, Prabha; Culzoni, Maria Julia; Clarke, Siân; Schellenberg, David; Fernández, Facundo M.; Onwujekwe, Obinna

    2015-01-01

    Background Artemisinin-based combination therapies are recommended by the World Health Organisation (WHO) as first-line treatment for Plasmodium falciparum malaria, yet medication must be of good quality for efficacious treatment. A recent meta-analysis reported 35% (796/2,296) of antimalarial drug samples from 21 Sub-Saharan African countries, purchased from outlets predominantly using convenience sampling, failed chemical content analysis. We used three sampling strategies to purchase artemisinin-containing antimalarials (ACAs) in Enugu metropolis, Nigeria, and compared the resulting quality estimates. Methods ACAs were purchased using three sampling approaches - convenience, mystery clients and overt, within a defined area and sampling frame in Enugu metropolis. The active pharmaceutical ingredients were assessed using high-performance liquid chromatography and confirmed by mass spectrometry at three independent laboratories. Results were expressed as percentage of APIs stated on the packaging and used to categorise each sample as acceptable quality, substandard, degraded, or falsified. Results Content analysis of 3024 samples purchased from 421 outlets using convenience (n=200), mystery (n=1,919) and overt (n=905) approaches, showed overall 90.8% ACAs to be of acceptable quality, 6.8% substandard, 1.3% degraded and 1.2% falsified. Convenience sampling yielded a significantly higher prevalence of poor quality ACAs, but was not evident by the mystery and overt sampling strategies both of which yielded results that were comparable between each other. Artesunate (n=135; 4 falsified) and dihydroartemisinin (n=14) monotherapy tablets, not recommended by WHO, were also identified. Conclusion Randomised sampling identified fewer falsified ACAs than previously reported by convenience approaches. Our findings emphasise the need for specific consideration to be given to sampling frame and sampling approach if representative information on drug quality is to be obtained

  3. OPTIMIZATION OF DIRECT COMPRESSION TABLET FORMULATIONS FOR USE IN TROPICAL COUNTRIES

    NARCIS (Netherlands)

    Bos, C. E.; BOLHUIS, G. K.; LERK, C. F.; de Boer, J. H.; DUINEVELD, C. A. A.; Smilde, A. K.; Doornbos, D. A.

    1991-01-01

    With the aid of a combined mixture- and factorial- design, 2 standard tablet formulations were selected suitable for use in tropical countries. The formulations were based on native ingredients or ingredients that are available worldwide. The selection of the standard formulations was based on both

  4. Towards a methodology to formulate sustainable diets for livestock: accounting for environmental impact in diet formulation.

    Science.gov (United States)

    Mackenzie, S G; Leinonen, I; Ferguson, N; Kyriazakis, I

    2016-05-28

    The objective of this study was to develop a novel methodology that enables pig diets to be formulated explicitly for environmental impact objectives using a Life Cycle Assessment (LCA) approach. To achieve this, the following methodological issues had to be addressed: (1) account for environmental impacts caused by both ingredient choice and nutrient excretion, (2) formulate diets for multiple environmental impact objectives and (3) allow flexibility to identify the optimal nutritional composition for each environmental impact objective. An LCA model based on Canadian pig farms was integrated into a diet formulation tool to compare the use of different ingredients in Eastern and Western Canada. By allowing the feed energy content to vary, it was possible to identify the optimum energy density for different environmental impact objectives, while accounting for the expected effect of energy density on feed intake. A least-cost diet was compared with diets formulated to minimise the following objectives: non-renewable resource use, acidification potential, eutrophication potential, global warming potential and a combined environmental impact score (using these four categories). The resulting environmental impacts were compared using parallel Monte Carlo simulations to account for shared uncertainty. When optimising diets to minimise a single environmental impact category, reductions in the said category were observed in all cases. However, this was at the expense of increasing the impact in other categories and higher dietary costs. The methodology can identify nutritional strategies to minimise environmental impacts, such as increasing the nutritional density of the diets, compared with the least-cost formulation.

  5. Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings.

    Science.gov (United States)

    Li, Jie; Li, Xin; Ren, Yu-Shan; Lv, Yuan-Yuan; Zhang, Jun-Sheng; Xu, Xiao-Li; Wang, Xian-Zhen; Yao, Jing-Chun; Zhang, Gui-Min; Liu, Zhong

    2017-01-01

    Although arctigenin ( AG ) has diverse bioactivities, such as anti-oxidant, anti-inflammatory, anti-cancer, immunoregulatory and neuroprotective activities, its pharmacokinetics have not been systematically evaluated. The purpose of this work was to identify the pharmacokinetic properties of AG via various experiments in vivo and in vitro . In this research, rats and beagle dogs were used to investigate the PK (pharmacokinetics, PK) profiles of AG with different drug-delivery manners, including intravenous (i.v), hypodermic injection (i.h), and sublingual (s.l) administration. The data shows that AG exhibited a strong absorption capacity in both rats and beagle dogs (absorption rate 100%), and a strong elimination ability ( t 1/2 beagle dog (25.9 ± 3.24%) > rat (15.7 ± 9%) > monkey (3.69 ± 0.12%). This systematic investigation of pharmacokinetic profiles of arctigenin (AG) in vivo and in vitro is worthy of further exploration.

  6. Novel Formulations for Antimicrobial Peptides

    Directory of Open Access Journals (Sweden)

    Ana Maria Carmona-Ribeiro

    2014-10-01

    Full Text Available Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy.

  7. Novel Formulations for Antimicrobial Peptides

    Science.gov (United States)

    Carmona-Ribeiro, Ana Maria; Carrasco, Letícia Dias de Melo

    2014-01-01

    Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy. PMID:25302615

  8. Fentanyl Sublingual Spray

    Science.gov (United States)

    ... medication, and who are tolerant (used to the effects of the medication) to narcotic pain medications. Fentanyl ... medications for seizures such as carbamazepine (Tegretol, Teril), oxcarbazepine (Trileptal), and phenytoin (Dilantin, Phenytek); modafinil (Provigil); nalbuphine; ...

  9. Evaluating higher doses of Shunthi - Guduchi formulations for safety in treatment of osteoarthritis knees: A Government of India NMITLI arthritis project

    OpenAIRE

    Arvind Chopra; Manjit Saluja; Girish Tillu; Anuradha Venugopalan; Gumdal Narsimulu; Sanjeev Sarmukaddam; Bhushan Patwardhan

    2012-01-01

    Background: Results of an exploratory trial suggested activity trends of Zingiber officinale-Tinopsora cordifolia (platform combination)-based formulations in the treatment of Osteoarthritis (OA) Knees. These formulations were "platform combination+Withania somnifera+Tribulus terrestris0" (formulation B) and "platform combination+Emblica officinale" (formulation C). This paper reports safety of these formulations when used in higher doses (1.5-2 times) along with Sallaki Guggul and Bhallataka...

  10. Dissolution Model Development: Formulation Effects and Filter Complications

    DEFF Research Database (Denmark)

    Berthelsen, Ragna; Holm, Rene; Jacobsen, Jette

    2016-01-01

    This study describes various complications related to sample preparation (filtration) during development of a dissolution method intended to discriminate among different fenofibrate immediate-release formulations. Several dissolution apparatus and sample preparation techniques were tested. The fl....... With the tested drug–formulation combination, the best in vivo–in vitro correlation was found after filtration of the dissolution samples through 0.45-μm hydrophobic PTFE membrane filters....

  11. Neonates need tailored drug formulations.

    Science.gov (United States)

    Allegaert, Karel

    2013-02-08

    Drugs are very strong tools used to improve outcome in neonates. Despite this fact and in contrast to tailored perfusion equipment, incubators or ventilators for neonates, we still commonly use drug formulations initially developed for adults. We would like to make the point that drug formulations given to neonates need to be tailored for this age group. Besides the obvious need to search for active compounds that take the pathophysiology of the newborn into account, this includes the dosage and formulation. The dosage or concentration should facilitate the administration of low amounts and be flexible since clearance is lower in neonates with additional extensive between-individual variability. Formulations need to be tailored for dosage variability in the low ranges and also to the clinical characteristics of neonates. A specific focus of interest during neonatal drug development therefore is a need to quantify and limit excipient exposure based on the available knowledge of their safety or toxicity. Until such tailored vials and formulations become available, compounding practices for drug formulations in neonates should be evaluated to guarantee the correct dosing, product stability and safety.

  12. Microcanonical formulation of quantum field theories

    International Nuclear Information System (INIS)

    Iwazaki, A.

    1984-03-01

    A microcanonical formulation of Euclidean quantum field theories is presented. In the formulation, correlation functions are given by a microcanonical ensemble average of fields. Furthermore, the perturbative equivalence of the formulation and the standard functional formulation is proved and the equipartition low is derived in our formulation. (author)

  13. FORMULATION AND EVALUATION OF ISONIAZID AND ETHAMBUTOL HYDROCHLORIDE COMBINATION TABLETS

    OpenAIRE

    Margret Chandira R; Jayakar B; Palanisamy P.

    2012-01-01

    Ethambutol hydrochloride and Isoniazid Drugs are used as Antituberculosis agents. It is mainly used in the initial Treatment of pulmonary tuberculosis. Here in present study compressed tablet of Ethambutol hydrochloride and Isoniazid prepared by using HPMC, HPC, and PVPK -30 as binders. Compressed tablets of Ethambutol hydrochloride and Isoniazid were prepared by wet granulation method. Among different trials of F1 to F9 with wet granulation, the trial F1 showed satisfactory in-vitro drug re...

  14. Tactile friction of topical formulations.

    Science.gov (United States)

    Skedung, L; Buraczewska-Norin, I; Dawood, N; Rutland, M W; Ringstad, L

    2016-02-01

    The tactile perception is essential for all types of topical formulations (cosmetic, pharmaceutical, medical device) and the possibility to predict the sensorial response by using instrumental methods instead of sensory testing would save time and cost at an early stage product development. Here, we report on an instrumental evaluation method using tactile friction measurements to estimate perceptual attributes of topical formulations. Friction was measured between an index finger and an artificial skin substrate after application of formulations using a force sensor. Both model formulations of liquid crystalline phase structures with significantly different tactile properties, as well as commercial pharmaceutical moisturizing creams being more tactile-similar, were investigated. Friction coefficients were calculated as the ratio of the friction force to the applied load. The structures of the model formulations and phase transitions as a result of water evaporation were identified using optical microscopy. The friction device could distinguish friction coefficients between the phase structures, as well as the commercial creams after spreading and absorption into the substrate. In addition, phase transitions resulting in alterations in the feel of the formulations could be detected. A correlation was established between skin hydration and friction coefficient, where hydrated skin gave rise to higher friction. Also a link between skin smoothening and finger friction was established for the commercial moisturizing creams, although further investigations are needed to analyse this and correlations with other sensorial attributes in more detail. The present investigation shows that tactile friction measurements have potential as an alternative or complement in the evaluation of perception of topical formulations. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Decontamination formulation with sorbent additive

    Science.gov (United States)

    Tucker; Mark D. , Comstock; Robert H.

    2007-10-16

    A decontamination formulation and method of making that neutralizes the adverse health effects of both chemical and biological compounds, especially chemical warfare (CW) and biological warfare (BW) agents, and toxic industrial chemicals. The formulation provides solubilizing compounds that serve to effectively render the chemical and biological compounds, particularly CW and BW compounds, susceptible to attack, and at least one reactive compound that serves to attack (and detoxify or kill) the compound. The formulation includes at least one solubilizing agent, a reactive compound, a bleaching activator, a sorbent additive, and water. The highly adsorbent, water-soluble sorbent additive (e.g., sorbitol or mannitol) is used to "dry out" one or more liquid ingredients, such as the liquid bleaching activator (e.g., propylene glycol diacetate or glycerol diacetate) and convert the activator into a dry, free-flowing powder that has an extended shelf life, and is more convenient to handle and mix in the field.

  16. Effect of two different sublingual dosages of vitamin B12 on cobalamin nutritional status in vegans and vegetarians with a marginal deficiency: A randomized controlled trial.

    Science.gov (United States)

    Del Bo', Cristian; Riso, Patrizia; Gardana, Claudio; Brusamolino, Antonella; Battezzati, Alberto; Ciappellano, Salvatore

    2018-02-15

    Vegetarians and vegans are more vulnerable to vitamin B 12 deficiency with severe risks of megaloblastic anemia, cognitive decline, neuropathy, and depression. An easy and simple method of supplementation consists of taking one weekly dosage of 2000 μg. However, single large oral doses of vitamin B 12 are poorly absorbed. The present research evaluates the ability of two different sublingual dosages of vitamin B 12 (350 μg/week vs 2000 μg/week) in improving cyanocobalamin (vitamin B 12 ) nutritional status in vegans and vegetarians with a marginal deficiency. A 12-week randomized, double-blind, controlled, parallel intervention trial was performed. Forty subjects with marginal vitamin B 12 deficiency were enrolled and randomly divided into two groups: test group Ld (low dose, 350 μg/week) and control group Hd (high dose, 2000 μg/week) vitamin B 12 supplementation. Blood samples were collected at baseline and after 15, 30, 60, and 90 days from the intervention for the determination of vitamin B 12 , related metabolic markers, and blood cell counts. Two-way analysis of variance showed a significant effect of time (P < 0.0001) and of time × treatment interaction (P = 0.012) on serum concentration of vitamin B 12 that increased after 90-day supplementation (Ld and Hd) compared to baseline. Both the supplements increased (P < 0.0001, time effect) the levels of holotranscobalamin, succinic acid, methionine and wellness parameter, while decreased (P < 0.0001, time effect) the levels of methylmalonic acid, homocysteine and folate compared to baseline. No difference was observed between groups (LdvsHd). No effect was detected for vitamin B 6 and blood cell count. In our experimental conditions, both supplements were able to restore adequate serum concentrations of vitamin B 12 and to improve the levels of related metabolic blood markers in subjects with a marginal deficiency. The results support the use of a sublingual dosage of 50 μg/day (350

  17. Curcumin nanodisks: formulation and characterization

    OpenAIRE

    Ghosh, Mistuni; Singh, Amareshwar T. K.; Xu, Wenwei; Sulchek, Todd; Gordon, Leo I.; Ryan, Robert O.

    2010-01-01

    Nanodisks (ND) are nanoscale, disk-shaped phospholipid bilayers whose edge is stabilized by apolipoproteins. In the present study, ND were formulated with the bioactive polyphenol, curcumin, at a 6:1 phospholipid:curcumin molar ratio. Atomic force microscopy revealed that curcumin-ND are particles with diameters

  18. Covariant Formulation of Hooke's Law.

    Science.gov (United States)

    Gron, O.

    1981-01-01

    Introducing a four-vector strain and a four-force stress, Hooke's law is written as a four-vector equation. This formulation is shown to clarify seemingly paradoxical results in connection with uniformly accelerated motion, and rotational motion with angular acceleration. (Author/JN)

  19. Hamiltonian formulation of the supermembrane

    International Nuclear Information System (INIS)

    Bergshoeff, E.; Sezgin, E.; Tanii, Y.

    1987-06-01

    The Hamiltonian formulation of the supermembrane theory in eleven dimensions is given. The covariant split of the first and second class constraints is exhibited, and their Dirac brackets are computed. Gauge conditions are imposed in such a way that the reparametrizations of the membrane with divergence free 2-vectors are unfixed. (author). 10 refs

  20. Evaporation and skin penetration characteristics of mosquito repellent formulations

    International Nuclear Information System (INIS)

    Reifenrath, W.G.; Hawkins, G.S.; Kurtz, M.S.

    1989-01-01

    Formulations of the mosquito repellent N,N-diethyl-3-methylbenzamide (deet) in combination with a variety of additives were developed to control repellent evaporation and percutaneous penetration. Deet was also formulated with the repellent dimethyl phthalate to study the interaction of the two compounds on the skin. The evaporation and penetration processes were evaluated on whole and split-thickness pig skin using radiolabeled repellents with an in vitro apparatus. Under essentially still air and air flow conditions, one of the deet formulations resulted in significantly reduced total evaporation and percutaneous penetration of deet as compared to unformulated repellent. When deet and dimethyl phthalate were combined, neither repellent affected the total amount of evaporation and penetration of the other compound. However, initial percutaneous penetration and evaporation rates were slightly less and decayed less rapidly than when both chemicals were tested separately at the same dose. These results indicated a degree of competition of the two compounds for the same avenues of loss

  1. Technical Status Report: Preliminary Glass Formulation Report for INEEL HAW

    International Nuclear Information System (INIS)

    Peeler, D.; Reamer, I.; Vienna, J.; Crum, J.A.

    1998-03-01

    This study was performed by a team comprising experts in glass chemistry, glass technology, and statistics at both SRTC and PNNL. This joint effort combined the strengths of each discipline and site to quickly develop a glass formulation for specific INEEL HAW

  2. Clinical pharmacology of novel anticancer agents : Focus on oral formulations

    NARCIS (Netherlands)

    de Weger, V.A.

    2017-01-01

    The taxanes paclitaxel and docetaxel have a low oral bioavailability, as a result of poor water solubility and high first-pass effect. The water-solubility could be improved by the development of solid dispersion formulations for oral use. In this thesis it is shown that the combination of the solid

  3. Formulation of Sustained-Release Diltiazem Matrix Tablets Using ...

    African Journals Online (AJOL)

    Formulation of Sustained-Release Diltiazem Matrix Tablets Using Hydrophilic Gum Blends. A Moin, H.G Shivakumar. Abstract. Purpose: To develop sustained release matrix tablets of diltiazem hydrochloride (DTZ) using karaya gum (K) alone or in combination with locust bean gum (LB) and hydroxypropyl methylcellulose ...

  4. Cleaning UF membranes with simple and formulated solutions

    NARCIS (Netherlands)

    Levitsky, I.; Duek, A.; Naim, R.; Arkhangelsky, E.; Gitis, V.

    2012-01-01

    The ultrafiltration membranes fouled by proteins are typically cleaned by consecutive soaking in alkali, surfactant and oxidizing solutions. We combined all three chemicals into a formulated cleaning agent and examined its efficiency to restore the water flux without damaging the membrane or

  5. Formulation and Optimization of the Seed Extracts of Glinus lotoides ...

    African Journals Online (AJOL)

    A two-factor-two-level factorial was designed to investigate the combined effects on formulation variable (amount of MCC) and processing variable [compression force (CF)] on tablet properties; crushing strength (H), friability (Fr), and disintegration time (DT). From the results of multiple linear regression analysis, surface ...

  6. Sublingual Immunotherapy with a Five-Grass Pollen Tablet in Adult Patients with Allergic Rhinitis: An Open, Prospective, Noninterventional, Multicenter Study

    Directory of Open Access Journals (Sweden)

    Oliver Pfaar

    2015-01-01

    Full Text Available Background. Although the safety and efficacy of sublingual immunotherapy (SLIT with a five-grass pollen tablet have been demonstrated in randomized clinical trials (RCTs, these outcomes must always be evaluated in real-life medical practice. Methods. In a prospective, open-label, noninterventional, “real-life” study in Germany, we evaluated the safety, tolerability, and effectiveness of SLIT with a five-grass pollen tablet in adults with grass-pollen-induced allergic rhinoconjunctivitis. Results. 808 adults were enrolled between September 2008 and December 2009. 35.3% of the participants experienced at least one adverse drug reaction (ADR, the most common of which were mild-to-moderate gastrointestinal and respiratory disorders. Serious ADRs considered causally related to SLIT treatment occurred in four patients. Overall, the five-grass pollen tablet was considered to have good or very good tolerability by most investigators and patients. Treatment was associated with the relief of nasal, ocular, and bronchial symptoms and decreased symptomatic medication use. However, interpretation of clinical improvements was limited by lower atmospheric grass pollen levels during the study season (relative to the preceding season. Conclusions. In a large population of patients treated in real-life medical practice, SLIT with a five-grass pollen tablet was safe and well tolerated. The patient-reported symptom relief suggests that SLIT was associated with clinical benefits.

  7. Langevin formulation of quantum dynamics

    International Nuclear Information System (INIS)

    Roncadelli, M.

    1989-03-01

    We first show that nonrelativistic quantum mechanics formulated at imaginary-(h/2 π) can formally be viewed as the Fokker-Planck description of a frictionless brownian motion, which occurs (in general) in an absorbing medium. We next offer a new formulation of quantum mechanics, which is basically the Langevin treatment of this brownian motion. Explicitly, we derive a noise-average representation for the transition probability W(X'',t''|X',t'), in terms of the solutions to a Langevin equation with a Gaussian white-noise. Upon analytic continuation back to real-(h/2 π),W(X'',t''|X',t') becomes the propagator of the original Schroedinger equation. Our approach allows for a straightforward application to quantum dynamical problems of the mathematical techniques of classical stochastic processes. Moreover, computer simulations of quantum mechanical systems can be carried out by using numerical programs based on the Langevin dynamics. (author). 19 refs, 1 tab

  8. Optimization of chlorphenesin emulgel formulation

    OpenAIRE

    Mohamed, Magdy I.

    2004-01-01

    This study was conducted to develop an emulgel formulation of chlorphenesin (CHL) using 2 types of gelling agents: hydroxypropylmethyl cellulose (HPMC) and Carbopol 934. The influence of the type of the gelling agent and the concentration of both the oil phase and emulsifying agent on the drug release from the prepared emulgels was investigated using a 23 factorial design. The prepared emulgels were evaluated for their physical appearance, rheological behavior, drug release, antifungal activi...

  9. Cumulative irritation potential of topical retinoid formulations.

    Science.gov (United States)

    Leyden, James J; Grossman, Rachel; Nighland, Marge

    2008-08-01

    Localized irritation can limit treatment success with topical retinoids such as tretinoin and adapalene. The factors that influence irritant reactions have been shown to include individual skin sensitivity, the particular retinoid and concentration used, and the vehicle formulation. To compare the cutaneous tolerability of tretinoin 0.04% microsphere gel (TMG) with that of adapalene 0.3% gel and a standard tretinoin 0.025% cream. The results of 2 randomized, investigator-blinded studies of 2 to 3 weeks' duration, which utilized a split-face method to compare cumulative irritation scores induced by topical retinoids in subjects with healthy skin, were combined. Study 1 compared TMG 0.04% with adapalene 0.3% gel over 2 weeks, while study 2 compared TMG 0.04% with tretinoin 0.025% cream over 3 weeks. In study 1, TMG 0.04% was associated with significantly lower cumulative scores for erythema, dryness, and burning/stinging than adapalene 0.3% gel. However, in study 2, there were no significant differences in cumulative irritation scores between TMG 0.04% and tretinoin 0.025% cream. Measurements of erythema by a chromameter showed no significant differences between the test formulations in either study. Cutaneous tolerance of TMG 0.04% on the face was superior to that of adapalene 0.3% gel and similar to that of a standard tretinoin cream containing a lower concentration of the drug (0.025%).

  10. Projecting India's energy requirements for policy formulation

    International Nuclear Information System (INIS)

    Parikh, Kirit S.; Karandikar, Vivek; Rana, Ashish; Dani, Prasanna

    2009-01-01

    Energy policy has to have a long-term perspective. To formulate it one needs to know the contours of energy requirements and options. Different approaches have been followed in literature, each with their own problems. A top down econometric approach provides little guidance on policies, while a bottom up approval requires too much knowledge and too many assumptions. Using top-down econometric approach for aggregate overall benchmarking and a detailed activity analysis model, Integrated Energy System Model, for a few large sectors, provides a unique combination for easing the difficulties of policy formulation. The model is described in this paper. Eleven alternate scenarios are built, designed to map out extreme points of feasible options. Results show that even after employing all domestic energy resource to their full potential, there will be a continued rise of fossil fuel use, continued importance of coal, and continued rise of import dependence. Energy efficiency emerges as a major option with a potential to reduce energy requirement by as much as 17%. Scenario results point towards pushing for development of alternative sources. (author)

  11. Grout formulations for nuclear-waste isolation

    International Nuclear Information System (INIS)

    Buck, A.D.; Mather, K.

    1982-06-01

    It is imperative that control parameters for a grout mixture such as flow time, setting time, compressive strength, permeability, or combinations of these or of other properties be specified before a grout mixture is formulated and used. Once such parameters have been specified, it is possible to proportion a hydraulic cement-based grout mixture to meet the applicable requirements. This may be from experience or by trial mixtures or by both. While longevity of cemetitious mixtures in nonaggressive environments is known from history, satisfactory data involving specific mixtures in selected environments are still needed. Such testing is underway. While compatibility, especially long-term compatibility, of cemetitious mixtures with various rock types is also known, it is necessary to have such evidence for specific mixtures in contact with specific rocks in a selected environment or environments. Satisfactory grout mixtures may be proportioned using the standard practice set forth in Appendix A

  12. Histometría de la glándula sublingual de ratones (Mus musculus machos y hembras infectados con la cepa RAL del parásito de Chagas, Trypanosoma cruzi

    Directory of Open Access Journals (Sweden)

    Sérgio de Albuquerque

    2008-06-01

    Full Text Available Analizamos morfológica e histométricamente la glándula sublingual de ratones infectados con la cepa RAL del Trypanosoma cruzi, en machos y hembras. Usamos ratones albinos (Mus musculus, variedad Swiss, inoculados con 2x104 tripomastigotes sanguíneos de la cepa RAL del T. cruzi.. Sacrificamos los animales en el pico de la parasitemia (12º día y fijamos las glándulas sublinguales en ALFAC. Los cortes histológicos teñidos con HE fueron evaluados histométricamente (cariometría y estereología. La parasitemia fue más elevada en las hembras. Histopatológicamente, los "ácinos" (acini de los animales infectados eran menores, con escasa secreción, y conductos estriados menores. Los núcleos de las "medialunas" eran menores y había nidos de amastigotes en el citoplasma. Cariométricamente, los núcleos de los ácinos, medialunas y conductos estriados eran menores en los ratones infectados. Estereológicamente, los volúmenes relativos ocupados por ácinos y conductos estriados fueron menores e, inversamente, fue mayor el volumen para el tejido conjuntivo de los machos infectados. Las densidades de superficie de ácinos y conductos fueron mayores, y el diámetro y el espesor de la pared menores, en este grupo. Por otro lado, la densidad de ácinos fue menor, y las de los conductos estriados y tejido conjuntivo, fueron mayores en las hembras infectadas. Las densidades de superficie de ácinos y conductos estriados fueron mayores, mientras que el diámetro y espesor de la pared de los ácinos fueron menores (y las de los conductos estriados mayores, en este grupo. La cepa RAL del T. cruzi causó un cuadro general de atrofia general en la glándula sublingual, con numerosos nidos de parásitos.Histometry of the sublingual gland in male and female mice (Mus musculus infected with the RAL strain of the Chagas parasite, Trypanosoma cruzi. The aim of this work was to analyze histologically and histometrically the sublingual gland of mice infected

  13. Perfume formulation: words and chats.

    Science.gov (United States)

    Ellena, Céline

    2008-06-01

    What does it mean to create fragrances with materials from chemistry and/or from nature? How are they used to display their characteristic differences, their own personality? Is it easier to create with synthetic raw materials or with essential oils? This review explains why a perfume formulation corresponds in fact to a conversation, an interplay between synthetic and natural perfumery materials. A synthetic raw material carries a single information, and usually is very linear. Its smell is uniform, clear, and faithful. Natural raw materials, on the contrary, provide a strong, complex and generous image. While a synthetic material can be seen as a single word, a natural one such as rose oil could be compared to chatting: cold, warm, sticky, heavy, transparent, pepper, green, metallic, smooth, watery, fruity... full of information. Yet, if a very small amount of the natural material is used, nothing happens, the fragrance will not change. However, if a large amount is used, the rose oil will swallow up everything else. The fragrance will smell of nothing else except rose! To formulate a perfume is not to create a culinary recipe, with only dosing the ingredients in well-balanced amounts. To formulate rather means to flexibly knit materials together with a lively stitch, meeting or repelling each other, building a pleasant form, which is neither fixed, nor solid, nor rigid. A fragrance has an overall structure, which ranges from a clear sound, made up of stable, unique, and linear items, to a background chat, comfortable and reassuring. But that does, of course, not mean that there is only one way of creating a fragrance!

  14. Formulation of soy oil products

    Directory of Open Access Journals (Sweden)

    Woerfel, John B.

    1995-12-01

    Full Text Available The paper comments different formulations of soy oil products such as salad and cooking oils, margarine, shortenings, commercial shortenings, frying shortenings, and fluid shortenings. Hydrogenation and its influence on final products is also included.

    El trabajo presenta diferentes formulaciones a base de aceite de soja tales como aceites para ensalada y cocinado, margarina, grasas sólidas (shortenings, grasas sólidas comerciales, grasas sólidas para frituras y grasas fluidas. Hace también referencia al proceso de hidrogenación y a sus efectos en los productos finales.

  15. Formulation and Characterization of Sustained Release Floating ...

    African Journals Online (AJOL)

    Purpose: To formulate sustained release gastroretentive microballoons of metformin hydrochloride with the objective of improving its bioavailability. Methods: Microballoons of metformin hydrochloride were formulated by solvent evaporation and diffusion method using varying mixtures of hydroxypropyl methylcellulose ...

  16. Bioequivalence assessment of two formulations of ibuprofen

    KAUST Repository

    Al-Talla, Zeyad; Akrawi, Sabah H; Tolley, Luke T; Sioud, Salim H; Zaater, Mohammed F; Emwas, Abdul-Hamid M

    2011-01-01

    Background: This study assessed the relative bioavailability of two formulations of ibuprofen. The first formulation was Doloraz , produced by Al-Razi Pharmaceutical Company, Amman, Jordan. The second forumulation was Brufen , manufactured by Boots

  17. Modern approach to relativity theory (radar formulation)

    International Nuclear Information System (INIS)

    Strel'tsov, V.N.

    1991-01-01

    The main peculiarities of the radar formulation of the relativity theory are presented. This formulation operates with the retarded (light) distances and relativistic or radar length introduced on their basis. 21 refs.; 1 tab

  18. Quality of life improvement after a three-year course of sublingual immunotherapy in patients with house dust mite and grass pollen induced allergic rhinitis: results from real-life.

    Science.gov (United States)

    Novakova, Silviya Mihaylova; Staevska, Maria Toncheva; Novakova, Plamena Ivanova; Yoncheva, Manuela Dimitrova; Bratoycheva, Maria Stoykova; Musurlieva, Nina Mihaylova; Tzekov, Valeri Dimitrov; Nicolov, Dimitar Georgiev

    2017-09-29

    Along with its high prevalence, the burden of allergic rhinitis rests upon the serious impact on quality of life of patients. Allergic rhinitis is associated with impairments in daily activities, work and school performance, and practical problems. Patients suffer from sleep disorders and emotional problems. Тhe advantages of sublingual immunotherapy on quality of life have only recently begun to emerge. The objective of this prospective real-life study was to evaluate the effect of a three-year course of sublingual immunotherapy with house dust mite (HDM) and grass pollen extracts on quality of life in adults with allergic rhinitis. A total number of 191 adult patients [105 (54,979%) men; mean age 27.3 years (SD-6.14)] with moderate to severe allergic rhinitis and clinically relevant sensitization to house dust mites or grass pollen were prospectively evaluated in the course of management of their disease. Health-related quality of life was assessed by Rhinoconjunctivitis Quality of Life Questionnaire at baseline and after three-year course of sublingual immunotherapy. The mean overall Qol score assessed at baseline and at the end of the third year of treatment decreased significantly in patients treated with HDM extract (from 2.95 to 0.76) as well as with Grass pollen extract (from 2.83 to 1.22) (р life provided evidence that a three-year course of SLIT with HDM extract as well as with grass pollen extract significantly increased QoL in patients with allergic rhinitis.

  19. Formulation, Preparation, and Characterization of Polyurethane Foams

    Science.gov (United States)

    Pinto, Moises L.

    2010-01-01

    Preparation of laboratory-scale polyurethane foams is described with formulations that are easy to implement in experiments for undergraduate students. Particular attention is given to formulation aspects that are based on the main chemical reactions occurring in polyurethane production. This allows students to develop alternative formulations to…

  20. Performance Evaluation of Abrasive Grinding Wheel Formulated ...

    African Journals Online (AJOL)

    This paper presents a study on the formulation and manufacture of abrasive grinding wheel using locally formulated silicon carbide abrasive grains. Six local raw material substitutes were identified through pilot study and with the initial mix of the identified materials, a systematic search for an optimal formulation of silicon ...

  1. Optimization of chlorphenesin emulgel formulation.

    Science.gov (United States)

    Mohamed, Magdy I

    2004-10-11

    This study was conducted to develop an emulgel formulation of chlorphenesin (CHL) using 2 types of gelling agents: hydroxypropylmethyl cellulose (HPMC) and Carbopol 934. The influence of the type of the gelling agent and the concentration of both the oil phase and emulsifying agent on the drug release from the prepared emulgels was investigated using a 2(3) factorial design. The prepared emulgels were evaluated for their physical appearance, rheological behavior, drug release, antifungal activity, and stability. Commercially available CHL topical powder was used for comparison. All the prepared emulgels showed acceptable physical properties concerning color, homogeneity, consistency, spreadability, and pH value. They also exhibited higher drug release and antifungal activity than the CHL powder. It was found that the emulsifying agent concentration had the most pronounced effect on the drug release from the emulgels followed by the oil phase concentration and finally the type of the gelling agent. The drug release from all the emulgels was found to follow diffusion-controlled mechanism. Rheological studies revealed that the CHL emulgels exhibited a shear-thinning behavior with thixotropy. Stability studies showed that the physical appearance, rheological properties, drug release, and antifungal activity in all the prepared emulgels remained unchanged upon storage for 3 months. As a general conclusion, it was suggested that the CHL emulgel formulation prepared with HPMC with the oil phase concentration in its low level and emulsifying agent concentration in its high level was the formula of choice since it showed the highest drug release and antifungal activity.

  2. Evaluation of stability of allergen extracts for sublingual immunotherapy during transport under unfavourable temperature conditions with an innovative thermal insulating packaging.

    Science.gov (United States)

    Puccinelli, P; Natoli, V; Dell'albani, I; Scurati, S; Incorvaia, C; Barbieri, S; Masieri, S; Frati, F

    2013-10-01

    Many pharmaceutical and biotechnological products are temperature-sensitive and should normally be kept at a controlled temperature, particularly during transport, in order to prevent the loss of their stability and activity. Therefore, stability studies should be performed for temperature-sensitive products, considering product characteristics, typical environmental conditions, and anticipating environmental extremes that may occur during product transport in a specific country. Staloral products for sublingual immunotherapy are temperature sensitive and are labelled for maintenance under refrigerated conditions (2-8°C). Given the peculiar climatic context of Italy and the great temperature fluctuations that may occur during transport, this study was aimed at evaluating the impact of a new engineered thermal insulating packaging for Staloral. In particular, the purpose was to assess whether the new packaging could create a container condition able to preserve the stability and immunological activity of the product during the transport phase throughout Italy. The results showed that the range of temperatures that can affect the product, in the area surrounding the product packaging, may reach a peak of 63°C during transport under the most unfavourable climatic conditions, i.e. in a non-refrigerated van during the summer season, from the site of production in France to the patient's house in Catania, the city with the highest temperatures in Italy. However, the highest temperature reached inside the vaccine did not exceed 45°C over a period of about 2 h. The ELISA inhibition test on samples subjected to the extreme temperature conditions previously defined (45°C) showed an immunological activity higher than 75% of that initially measured and was comparable to those obtained with samples stored at controlled temperature (5°C). This means that, even in the worst case scenario, the structure of the allergen extracts is not influenced and the vaccine potency is

  3. Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings

    Directory of Open Access Journals (Sweden)

    Jie Li

    2017-06-01

    Full Text Available Although arctigenin (AG has diverse bioactivities, such as anti-oxidant, anti-inflammatory, anti-cancer, immunoregulatory and neuroprotective activities, its pharmacokinetics have not been systematically evaluated. The purpose of this work was to identify the pharmacokinetic properties of AG via various experiments in vivo and in vitro. In this research, rats and beagle dogs were used to investigate the PK (pharmacokinetics, PK profiles of AG with different drug-delivery manners, including intravenous (i.v, hypodermic injection (i.h, and sublingual (s.l administration. The data shows that AG exhibited a strong absorption capacity in both rats and beagle dogs (absorption rate < 1 h, a high absorption degree (absolute bioavailability > 100%, and a strong elimination ability (t1/2 < 2 h. The tissue distributions of AG at different time points after i.h showed that the distribution of AG in rat tissues is rapid (2.5 h to reach the peak and wide (detectable in almost all tissues and organs. The AG concentration in the intestine was the highest, followed by that in the heart, liver, pancreas, and kidney. In vitro, AG were incubated with human, monkey, beagle dog and rat liver microsomes. The concentrations of AG were detected by UPLC-MS/MS at different time points (from 0 min to 90 min. The percentages of AG remaining in four species’ liver microsomes were human (62 ± 6.36% > beagle dog (25.9 ± 3.24% > rat (15.7 ± 9% > monkey (3.69 ± 0.12%. This systematic investigation of pharmacokinetic profiles of arctigenin (AG in vivo and in vitro is worthy of further exploration.

  4. The influence of house dust mite sublingual immunotherapy on the TSLP-OX40L signaling pathway in patients with allergic rhinitis.

    Science.gov (United States)

    Meng, Qingxiang; Liu, Xiaolong; Li, Peng; He, Long; Xie, Jinghua; Gao, Xionghui; Wu, Xiaozhong; Su, Fang; Liang, Yong

    2016-08-01

    This study aimed to investigate the clinical efficacy of sublingual immunotherapy (SLIT) with house dust mite (HDM) extract and to examine T helper 2 (Th2)-type immune responses mediated by the thymic stromal lymphopoietin (TSLP-OX40L) signaling pathway in patients with moderate to severe allergic rhinitis (AR) after 12-month HDM SLIT. Forty-six cases of HDM-sensitized patients with persistent AR in southern China were enrolled in this study. Clinical efficacy of SLIT was assessed by determining the individual nasal symptom score (INSS) and total nasal symptom score (TNSS) after 12-month HDM SLIT. Moreover, the TSLP-OX40L signaling pathway was investigated through measurements of TSLP by enzyme-labeled immunosorbent assay (ELISA) and OX40L by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and flow cytometry. After 12 months of HDM SLIT, TNSS and INSS were significantly decreased overall compared with baseline values (p < 0.001). By the end of the 12-month HDM SLIT, TNSS had declined by ∼50% compared with baseline, and the corresponding level of TSLP in nasal lavage decreased significantly (p < 0.05). The level of OX40L messenger RNA (mRNA) in blood was markedly decreased significantly after 12-month HDM SLIT compared with baseline (t = 12.300, p < 0.05). Furthermore, significant decreases in OX40L expression on the surface of peripheral blood mononuclear cells (PBMCs) (t = 13.100, p < 0.05) and OX40L expression on the surface of CD11c+CD86+ cells in PBMCs (t = 9.946, p < 0.05) after 12-month HDM SLIT were observed. HDM SLIT downregulated Th2-type immune responses mediated by the TSLP-OX40L signaling pathway in patients with persistent moderate to severe AR. © 2016 ARS-AAOA, LLC.

  5. Urinary tract infections in women with stress urinary incontinence treated with transobturator suburethral tape and benefit gained from the sublingual polibacterial vaccine.

    Science.gov (United States)

    Lorenzo Gómez, María F; Collazos Robles, Rafael E; Virseda Rodríguez, Álvaro J; García Cenador, María B; Mirón Canelo, José A; Padilla Fernández, Bárbara

    2015-08-01

    Stress urinary incontinence (SUI) and recurrent urinary tract infections (RUTIs) are highly prevalent diseases. Our purpose was to investigate the relationship between RUTIs and surgical correction of SUI with transobturator suburethral tape (TOT) and to describe the benefit gained from a sublingual polibacterial preparation on RUTIs developed after TOT. A retrospective study was performed on 420 women who underwent TOT surgery due to SUI between April 2003 and October 2011. Group A: patients without urinary tract infections (UTIs) before TOT (n = 294). Group B: patients with UTIs before TOT (n = 126). age, personal history, number of UTIs/month prior to and after surgery, appearance of urgent urinary incontinence (UUI) with or without UTIs, response to International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) and Short Form 36 (SF-36) questionnaires. Group A: 85% dry; 5% UUI; 4% de novo UTIs with good response to antibiotics over 6 days. No RUTIs during the follow-up period, 2% with sporadic UTIs. Group B: 47.61% RUTIs; 52.39% sporadic UTIs; greater incidence of diabetes mellitus (p < 0.0025) and smoking (p < 0.0031) than group A. After TOT: 79.36% dry; 10% RUTIs. After treatment with antibiotics for 6 days and bacterial preparation for 3 months, 82% of patients did not have a UTI anymore. Postoperative cystourethrogram revealed 38% of nondiagnosed cystoceles before TOT. No patient had a postvoiding volume greater than 100 cm(3) after TOT. Improvement of ICIQ-SF (p < 0.001) and SF-36 (p < 0.0004) in both groups. After eliminating bias associated with the tape, the technique and the surgeon's skills, SUI correction may decrease the number of UTIs and improve the quality of life. UTIs disappeared in 82% of patients with RUTIs after TOT.

  6. Artificial intelligence in pharmaceutical product formulation: neural computing

    Directory of Open Access Journals (Sweden)

    Svetlana Ibrić

    2009-10-01

    Full Text Available The properties of a formulation are determined not only by the ratios in which the ingredients are combined but also by the processing conditions. Although the relationships between the ingredient levels, processing conditions, and product performance may be known anecdotally, they can rarely be quantified. In the past, formulators tended to use statistical techniques to model their formulations, relying on response surfaces to provide a mechanism for optimazation. However, the optimization by such a method can be misleading, especially if the formulation is complex. More recently, advances in mathematics and computer science have led to the development of alternative modeling and data mining techniques which work with a wider range of data sources: neural networks (an attempt to mimic the processing of the human brain; genetic algorithms (an attempt to mimic the evolutionary process by which biological systems self-organize and adapt, and fuzzy logic (an attempt to mimic the ability of the human brain to draw conclusions and generate responses based on incomplete or imprecise information. In this review the current technology will be examined, as well as its application in pharmaceutical formulation and processing. The challenges, benefits and future possibilities of neural computing will be discussed.

  7. Development and Evaluation of Herbal Formulations for Hair Growth

    Directory of Open Access Journals (Sweden)

    Lipi Purwal

    2008-01-01

    Full Text Available Hair formulation of Emblica officinalis (Euphorbiaceae, Bacopa, monnieri (Scrophulariaceae, Trigonella foenumgraecum (Leguminosae, Murraya koenigii (Rutaceae in various concentrations in the form of herbal oil were studied for their hair growth activity. Each drug was tested for their hair growth activity in a concentration range for 1-10% separately. Based on these results mixture of crude drugs Murraya koeniigi, leaf (Rutaceae, Bacopa monnieri, leaf (Scrophulariaceae, Trigonella foenumgraecum (Leguminosae, Murraya koenigii (Rutaceae were prepared in varying concentration in the form of herbal hair oil by three different oils preparation techniques and were tested for hair growth activity. The result revealed that the hair growth activity of each drug was found proportional to the concentration range tested. Similarly higher concentrations of drug in the formulation were found to have higher hair growth activities. But looking towards the formulation viscosity the maximum concentration of combined drug was found to be 30% at their maximum level. The formulation containing 7.5% of each drug used for the study and showed excellent hair growth activity with standard (2% minoxidil ethanolic solution by an enlargement of follicular size and prolongation of the anagen phase. It holds the promise of potent herbal alternative for minoxidil. Excellent results of hair growth were seen in formulation prepared by cloth pouch decoction method of oils preparation technique.

  8. Formulation development for PREPP concreted waste forms

    International Nuclear Information System (INIS)

    Neilson, R.M. Jr.; Welch, J.M.

    1984-05-01

    Analysis of variance and logistic regression techniques have been used to develop models describing the effects of formulation variables and their interactions on compressive strength, solidification, free-standing water, and workability of hydraulic cement grouts incorporating simulated Process Experimental Pilot Plant (PREPP) wastes. These models provide the basis for specifications of grout formulations to solidify these wastes. The experimental test matrix, formulation preparation, and test methods employed are described. The development of analytical models for formulation behavior and the conclusions drawn regarding appropriate formulation variable ranges are discussed. 13 references, 9 figures, 15 tables

  9. Suitability of different formulated carriers for sustaining microbial shelf life

    International Nuclear Information System (INIS)

    Tabassam, T.; Ali, A.

    2014-01-01

    Non-availability of a suitable carrier for bioinnoculant is a serious constraint for dissemination of biofertilizer technology in Pakistan. Present study was designed to formulate a suitable carrier from locally available cheap material and evaluate for shelf life by using locally isolated plant growth promoting rhizobacteria (PGPR) strains from maize rhizosphere. Different combinations of material were prepared using clay soil (35-50%), fly-ash (30-45%), press mud (5-15%) and lignite (5-15%). Clay soil (53% clay) was used for adhesion purpose but considering free of lump formation an important property of a good carrier, mixing 40% of soil with other material was found suitable. Using 40% of soil, six different treatments were formulated and physico-chemical characteristics were determined. Four combinations in the range of 40% clay, 30-40% fly-ash, 10-15% press mud and 10-15% lignitic coal were selected which had good adhesion capacity, moisture holding capacity, nutrient contents and investigated for microbial shelf life. Significant difference regarding microbial survival was observed between different formulations as well as between different incubation intervals. Among different carrier tested the FC-4 supported the maximum population of 33.5x10- 10.8x10 cfu g for MR-8 and 32.6x10 - 7.2x10 cfu g for MR-5. Results showed that the required population of PGPR was sustained in all the formulation tested up to six months of storage period. (author)

  10. Energy policy formulation for Pakistan

    International Nuclear Information System (INIS)

    Riaz, T.

    1981-01-01

    Pakistan is a low income, low energy consumption country. In view of the close interdependence between economic growth and energy consumption, she will need increasing energy supplies in order to maintain her economic growth. This paper develops an energy sector optimization model for the Pakistan economy, which consists of production models for five energy industries, ie oil, gas, coal, electricity (including electricity generated in nuclear power plants) and non-commercial fuels. The model is first used to forecast energy balances for the period 1975 - 2006. The model is then employed to formulate a long-term comprehensive energy policy for Pakistan. Finally the suggested policy is compared with the current official energy programme. (author)

  11. On Scalar Energy: Mathematical Formulation

    International Nuclear Information System (INIS)

    Hathout, A.M.

    2011-01-01

    A new kind of electromagnetic waves (EMW), which exists only in vacuum of the empty space, will be discussed and mathematically formulated in this paper. The mathematical existence of this energy was first proposed in a series of groundbreaking equations by Scottish Mathematician, James Clerk Maxwell, in the mid of 1800 and 39;s. This energy is called scalar energy. It is characterized by both particle and wave like. The waves of this energy are called longitudinal EMW to distinguish them from transverse EM, the kind we are familiar with in our daily life. Teslas name of this energy is scalar energy or zero point energy. It is aimed at this paper to explain more details and to verify the scalar EM concept in vacuum.

  12. Prophylactic Sublingual Immunization with Mycobacterium tuberculosis Subunit Vaccine Incorporating the Natural Killer T Cell Agonist Alpha-Galactosylceramide Enhances Protective Immunity to Limit Pulmonary and Extra-Pulmonary Bacterial Burden in Mice

    Directory of Open Access Journals (Sweden)

    Arshad Khan

    2017-12-01

    Full Text Available Infection by Mycobacterium tuberculosis (Mtb remains a major global concern and the available Bacillus Calmette-Guerin (BCG vaccine is poorly efficacious in adults. Therefore, alternative vaccines and delivery strategies focusing on Mtb antigens and appropriate immune stimulating adjuvants are needed to induce protective immunity targeted to the lungs, the primary sites of infections and pathology. We present here evidence in support of mucosal vaccination by the sublingual route in mice using the subunit Mtb antigens Ag85B and ESAT-6 adjuvanted with the glycolipid alpha-galactosylceramide (α-GalCer, a potent natural killer T (NKT cell agonist. Vaccinated animals exhibited strong antigen-specific CD4 and CD8 T cells responses in the spleen, cervical lymph nodes and lungs. In general, inclusion of the α-GalCer adjuvant significantly enhanced these responses that persisted over 50 days. Furthermore, aerosolized Mtb infection of vaccinated mice resulted in a significant reduction of bacterial load of the lungs and spleens as compared to levels seen in naïve controls or those vaccinated with subunit proteins, adjuvant , or BCG alone. The protection induced by the Mtb antigens and-GalCer vaccine through sublingual route correlated with a TH1-type immunity mediated by antigen-specific IFN-γ and IL-2 producing T cells.

  13. In vivo photoprotective effects of cosmetic formulations containing UV filters, vitamins, Ginkgo biloba and red algae extracts.

    Science.gov (United States)

    Mercurio, D G; Wagemaker, T A L; Alves, V M; Benevenuto, C G; Gaspar, L R; Maia Campos, P M B G

    2015-12-01

    The aim of this study was to assess the photoprotective effects of cosmetic formulations containing UV filters, red algae, Porphyra umbilicalis, extracts and combinations of the extract with vitamins and Ginkgo biloba through the use of in vivo preclinical studies. For this study, 4 groups of 4 hairless mice each were treated with topical formulations applied on the dorsum for 5 days as follows: group 1 - control (no treatment); group 2 - application of the formulation F (sunscreen formulation containing only UV filters); group 3 - application of the formulation FA (sunscreen formulation with red algae extract); and group 4 - application of the formulation FVGA (sunscreen formulation with red algae extract, G. biloba and vitamins A, C and E). The effects of these formulations were evaluated by determining the transepidermal water loss (TEWL) and erythema index. Apoptosis was detected by immunohistochemical staining with anti-p53 and anti-caspase-3 antibodies. The results showed that the formulations protected the skin from erythema when exposed to UV radiation. The group that received the formulation FVGA presented a greater TEWL than did the other groups, suggesting that this formulation was involved in cell renewal. Immunohistochemical analysis showed that UV radiation caused an increase in the expression of p53 and active caspase-3, confirming that the damage caused by UV radiation exposure led to apoptosis. The application of all formulations studied resulted in a statistically significant reduction in the expression of p53 and caspase-3, with a more pronounced effect observed following treatment with FA. In conclusion, extracts from the red algae P. umbilicalis could be considered effective ingredients to be used in sunscreen formulations. The combination of vitamins A, E, C and G. biloba along with red algae extracts can improve significantly the performance of the sunscreens, preventing UV-induced DNA damage and inflammation. Thus, they should be considered

  14. Summary compilation of shell element performance versus formulation.

    Energy Technology Data Exchange (ETDEWEB)

    Heinstein, Martin Wilhelm; Hales, Jason Dean (Idaho National Laboratory, Idaho Falls, ID); Breivik, Nicole L.; Key, Samuel W. (FMA Development, LLC, Great Falls, MT)

    2011-07-01

    This document compares the finite element shell formulations in the Sierra Solid Mechanics code. These are finite elements either currently in the Sierra simulation codes Presto and Adagio, or expected to be added to them in time. The list of elements are divided into traditional two-dimensional, plane stress shell finite elements, and three-dimensional solid finite elements that contain either modifications or additional terms designed to represent the bending stiffness expected to be found in shell formulations. These particular finite elements are formulated for finite deformation and inelastic material response, and, as such, are not based on some of the elegant formulations that can be found in an elastic, infinitesimal finite element setting. Each shell element is subjected to a series of 12 verification and validation test problems. The underlying purpose of the tests here is to identify the quality of both the spatially discrete finite element gradient operator and the spatially discrete finite element divergence operator. If the derivation of the finite element is proper, the discrete divergence operator is the transpose of the discrete gradient operator. An overall summary is provided from which one can rank, at least in an average sense, how well the individual formulations can be expected to perform in applications encountered year in and year out. A letter grade has been assigned albeit sometimes subjectively for each shell element and each test problem result. The number of A's, B's, C's, et cetera assigned have been totaled, and a grade point average (GPA) has been computed, based on a 4.0-system. These grades, combined with a comparison between the test problems and the application problem, can be used to guide an analyst to select the element with the best shell formulation.

  15. Cream formulation impact on topical administration of engineered colloidal nanoparticles.

    Directory of Open Access Journals (Sweden)

    Benedetta Santini

    Full Text Available In order to minimize the impact of systemic toxicity of drugs in the treatment of local acute and chronic inflammatory reactions, the achievement of reliable and efficient delivery of therapeutics in/through the skin is highly recommended. While the use of nanoparticles is now an established practice for drug intravenous targeted delivery, their transdermal penetration is still poorly understood and this important administration route remains almost unexplored. In the present study, we have synthesized magnetic (iron oxide nanoparticles (MNP coated with an amphiphilic polymer, developed a water-in-oil emulsion formulation for their topical administration and compared the skin penetration routes with the same nanoparticles deposited as a colloidal suspension. Transmission and scanning electron microscopies provided ultrastructural evidence that the amphiphilic nanoparticles (PMNP cream formulation allowed the efficient penetration through all the skin layers with a controllable kinetics compared to suspension formulation. In addition to the preferential follicular pathway, also the intracellular and intercellular routes were involved. PMNP that crossed all skin layers were quantified by inductively coupled plasma mass spectrometry. The obtained data suggests that combining PMNP amphiphilic character with cream formulation improves the intradermal penetration of nanoparticles. While PMNP administration in living mice via aqueous suspension resulted in preferential nanoparticle capture by phagocytes and migration to draining lymph nodes, cream formulation favored uptake by all the analyzed dermis cell types, including hematopoietic and non-hematopoietic. Unlike aqueous suspension, cream formulation also favored the maintenance of nanoparticles in the dermal architecture avoiding their dispersion and migration to draining lymph nodes via afferent lymphatics.

  16. Slag-based saltstone formulations

    International Nuclear Information System (INIS)

    Langton, C.A.

    1987-01-01

    Approximately 400 x 10 6 liters of low-level alkaline salt solution will be treated at the Savannah River Plant (SRP) Defense Waste Processing Facility (DWPF) prior to disposal in concrete vaults at SRP. Treatment involves removal of CS + and Sr +2 followed by solidification and stabilization of potential contaminants in saltstone, a hydrated ceramic waste form. Chromium, technetium, and nitrate releases from saltstone can be significantly reduced by substituting hydraulic blast furnace slag for portland cement in the formulation designs. Slag-based mixes are also compatible with Class F fly ash used in saltstone as a functional extender to control heat of hydration and reduce permeability. A monolithic waste form is produced by the hydration of the slag and fly ash. Soluble ion release (NO 3 - ) is controlled by the saltstone microstructure. Chromium and technetium are less leachable from slag mixes compared to cement-based waste forms because these species are chemically reduced to a lower valence state by ferrous iron in the slag and precipitated as relatively insoluble phases, such as CR(OH) 3 and TcO 2 . 5 refs., 4 figs., 4 tabs

  17. Slag-based saltstone formulations

    International Nuclear Information System (INIS)

    Langton, C.A.

    1987-08-01

    Approximately 400 x 10 6 L of low-level alkaline salt solution will be treated at the Savannah River Plant (SRP) Defense Waste Processing Facility (DWPF) prior to disposal in concrete vaults at SRP. Treatment involves removal of Cs + and Sr +2 , followed by solidification and stabilization of potential contaminants in saltstone, a hydrated ceramic wasteform. Chromium, technetium, and nitrate releases from saltstone can be significantly reduced by substituting hydraulic blast furnace slag for portland cement in the formulation designs. Slag-based mixes are also compatible with the Class F flyash used in saltstone as a functional extender to control heat of hydration and reduce permeability. (Class F flyash is also locally available at SRP.) A monolithic wasteform is produced by the hydration of the slag and flyash. Soluble ion release (NO 3- ) is controlled by the saltstone microstructure. Chromium and technetium are less leachable from slag mixes because these species are chemically reduced to a lower valence state by ferrous iron in the slag and are precipitated as relatively insoluble phases, such as Cr(OH) 3 and TcO 2 . 3 refs., 3 figs., 2 tabs

  18. Policy formulation of public acceptance

    International Nuclear Information System (INIS)

    Kasai, Akihiro

    1978-01-01

    Since 1970, the new policy formulation for public acceptance of the new consideration on the location of electric power generation has been set and applied. The planning and the enforcement being conducted by local public organizations for the local economic build-up with plant location and also the adjustement of the requirements for fishery are two main specific characters in this new policy. The background of this new public acceptance policy, the history and the actual problems about the compensation for the location of power generation plants are reviewed. One new proposal, being recommended by the Policy and Science Laboratory to MITI in 1977 is explained. This is based on the method of promoting the location of power generation plants by public participation placing the redevelopment of regional societies as its basis. The problems concerning the industrial structures in farm villages, fishing villages and the areas of commerce and industry should be systematized, and explained from the viewpoint of outside impact, the characteristics of local areas and the location problems in this new proposal. Finally, the location process and its effectiveness should be put in order. (Nakai, Y.)

  19. Hamiltonian formulation of reduced magnetohydrodynamics

    International Nuclear Information System (INIS)

    Morrison, P.J.; Hazeltine, R.D.

    1983-07-01

    Reduced magnetohydrodynamics (RMHD) has become a principal tool for understanding nonlinear processes, including disruptions, in tokamak plasmas. Although analytical studies of RMHD turbulence have been useful, the model's impressive ability to simulate tokamak fluid behavior has been revealed primarily by numerical solution. The present work describes a new analytical approach, not restricted to turbulent regimes, based on Hamiltonian field theory. It is shown that the nonlinear (ideal) RMHD system, in both its high-beta and low-beta versions, can be expressed in Hanmiltonian form. Thus a Poisson bracket, [ , ], is constructed such that each RMHD field quantitity, xi/sub i/, evolves according to xi/sub i/ = [xi/sub i/,H], where H is the total field energy. The new formulation makes RMHD accessible to the methodology of Hamiltonian mechanics; it has lead, in particular, to the recognition of new RMHD invariants and even exact, nonlinear RMHD solutions. A canonical version of the Poisson bracket, which requires the introduction of additional fields, leads to a nonlinear variational principle for time-dependent RMHD

  20. Formulation of disperse systems science and technology

    CERN Document Server

    Tadros, Tharwat F

    2014-01-01

    This book presents comprehensively the science and technology behind the formulation of disperse systems like emulsions, suspensions, foams and others. Starting with a general introduction, the book covers a broad range of topics like the role of different classes of surfactants, stability of disperse systems, formulation of different dispersions, evaluation of formulations and many more. Many examples are included, too. Written by the experienced author and editor Tharwart Tadros, this book is indispensable for every scientist working in the field.

  1. Formulated arthropod cadavers for pest suppression

    OpenAIRE

    2001-01-01

    Pesticidal and/or antimicrobial biological agent-infected arthropod cadavers are formulated by applying a coating agent once on the surface of the cadaver which either (a) prevents the cadavers from sticking together and/or rupturing or (b) acts as an adhesive for a powder or granule applied to the cadaver to prevent sticking and rupturing. The formulated cadavers maintain or improve infectivity, reproducibility, and survivability. The formulated cadavers can be partially desiccated to improv...

  2. Multiple excitation of supports - Part 1. Formulation

    International Nuclear Information System (INIS)

    Galeao, A.C.N.R.; Barbosa, H.J.C.

    1980-12-01

    The formulation and the solution of a simple specific problem of support movement are presented. The formulation is extended to the general case of infinitesimal elasticity where the approximated solutions are obtained by the variational formulation with spatial discretization by Finite Element Method. Finally, the present usual numerical techniques for the treatment of the resulting ordinary differential equations system are discused: Direct integration, Modal overlap, Spectral response. (E.G.) [pt

  3. Superspace formulation of new nonlinear sigma models

    International Nuclear Information System (INIS)

    Gates, S.J. Jr.

    1983-07-01

    The superspace formulation of two classes of supersymmetric nonlinear σ-models are presented. Two alternative N=1 superspace formulations are given for the d=2 supersymmetric nonlinear σ-models with Killing vector potentials: (a) formulation uses an active central charge and, (b) formulation uses a spurion superfield without inducing a classical breakdown of supersymmetry. The N=2 vector multiplet is used to construct a new class of d=4 nonlinear σ-models which when reduced to d=2 possess N=4 supersymmetry. Implications of these two classes of nonlinear σ-models for N>=4 superfield supergravity are discussed. (author)

  4. 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.

  5. CRYSTALLINE CERAMIC WASTE FORMS: REFERENCE FORMULATION REPORT

    Energy Technology Data Exchange (ETDEWEB)

    Brinkman, K.; Fox, K.; Marra, J.

    2012-05-15

    The research conducted in this work package is aimed at taking advantage of the long term thermodynamic stability of crystalline ceramics to create more durable waste forms (as compared to high level waste glass) in order to reduce the reliance on engineered and natural barrier systems. Durable ceramic waste forms that incorporate a wide range of radionuclides have the potential to broaden the available disposal options and to lower the storage and disposal costs associated with advanced fuel cycles. Assemblages of several titanate phases have been successfully demonstrated to incorporate radioactive waste elements, and the multiphase nature of these materials allows them to accommodate variation in the waste composition. Recent work has shown that they can be successfully produced from a melting and crystallization process. The objective of this report is to explain the design of ceramic host systems culminating in a reference ceramic formulation for use in subsequent studies on process optimization and melt property data assessment in support of FY13 melter demonstration testing. The waste stream used as the basis for the development and testing is a combination of the projected Cs/Sr separated stream, the Trivalent Actinide - Lanthanide Separation by Phosphorous reagent Extraction from Aqueous Komplexes (TALSPEAK) waste stream consisting of lanthanide fission products, the transition metal fission product waste stream resulting from the transuranic extraction (TRUEX) process, and a high molybdenum concentration with relatively low noble metal concentrations. In addition to the combined CS/LN/TM High Mo waste stream, variants without Mo and without Mo and Zr were also evaluated. Based on the results of fabricating and characterizing several simulated ceramic waste forms, two reference ceramic waste form compositions are recommended in this report. The first composition targets the CS/LN/TM combined waste stream with and without Mo. The second composition targets

  6. FORMULATION OF INDONESIAN PUBLIC HEALTH DEVELOPMENT INDEX

    Directory of Open Access Journals (Sweden)

    Puti Sari Hidayangsih

    2012-11-01

    Full Text Available The objective of formulation the Indonesian Public Health Development Index (IPHDI was to describe the successful development of public health based on composite several community-based health indicators. Cross sectional study design.The data analyzed was a combination of a nationwide survey covering Baseline Health Research (Riskesdas 2007, National Social Economic Survey (Susenas 2007 and the Village Potential (Podes in 2008. Selection of appropriate indicators included in IPHDI associated with LE at birth, selected on the basis of consensus expert team. When the indicator has the RSE (relative standard error value of less than 30% and the value was held for more than 75% of districts. then the indicator is a candidate in the calculation IPHDI. The team doing the analysis on 22 models of the combination of indicators. The number of indicators chat involved between 18 to 24. These models have been made and tested for correlation weighting of life expectancy each district. Results of correlation ranged from 0.314 to 0.512 and all models have a significance value p< 0.001. The model was chosen considering the variables that are considered priorities and values of correlation. IPHDI Highest value is 0.708959 (Magelang City, Central Java and the lowest is 0.247059 (Pegunungan Bintang district, Papua. Conclusion. IPHDI utilization is to know district who has severe health problems, resulting in enhancement programs that have intervened, resulting in focusing the target location, and became one of the parameters for the calculation of aid allocations fairly from center to the region. Key words: health indicators, Indonesian public health development index, life expectancy

  7. Glass Ceramic Formulation Data Package

    International Nuclear Information System (INIS)

    Crum, Jarrod V.; Rodriguez, Carmen P.; McCloy, John S.; Vienna, John D.; Chung, Chul-Woo

    2012-01-01

    A glass ceramic waste form is being developed for treatment of secondary waste streams generated by aqueous reprocessing of commercial used nuclear fuel (Crum et al. 2012b). The waste stream contains a mixture of transition metals, alkali, alkaline earths, and lanthanides, several of which exceed the solubility limits of a single phase borosilicate glass (Crum et al. 2009; Caurant et al. 2007). A multi-phase glass ceramic waste form allows incorporation of insoluble components of the waste by designed crystallization into durable heat tolerant phases. The glass ceramic formulation and processing targets the formation of the following three stable crystalline phases: (1) powellite (XMoO4) where X can be (Ca, Sr, Ba, and/or Ln), (2) oxyapatite Yx,Z(10-x)Si6O26 where Y is alkaline earth, Z is Ln, and (3) lanthanide borosilicate (Ln5BSi2O13). These three phases incorporate the waste components that are above the solubility limit of a single-phase borosilicate glass. The glass ceramic is designed to be a single phase melt, just like a borosilicate glass, and then crystallize upon slow cooling to form the targeted phases. The slow cooling schedule is based on the centerline cooling profile of a 2 foot diameter canister such as the Hanford High-Level Waste canister. Up to this point, crucible testing has been used for glass ceramic development, with cold crucible induction melter (CCIM) targeted as the ultimate processing technology for the waste form. Idaho National Laboratory (INL) will conduct a scaled CCIM test in FY2012 with a glass ceramic to demonstrate the processing behavior. This Data Package documents the laboratory studies of the glass ceramic composition to support the CCIM test. Pacific Northwest National Laboratory (PNNL) measured melt viscosity, electrical conductivity, and crystallization behavior upon cooling to identify a processing window (temperature range) for melter operation and cooling profiles necessary to crystallize the targeted phases in the

  8. Formulation, Characterization and Physicochemical Evaluation of Potassium Citrate Effervescent Tablets

    Directory of Open Access Journals (Sweden)

    Fatemeh Fattahi

    2013-02-01

    Full Text Available Purpose: The aim of this study was to design and formulation of potassium citrate effervescent tablet for reduction of calcium oxalate and urate kidney stones in patients suffering from kidney stones. Methods: In this study, 13 formulations were prepared from potassium citrate and effervescent base in different concentration. The flowability of powders and granules was studied. Then effervescent tablets were prepared by direct compression, fusion and wet granulation methods. The prepared tablets were evaluated for hardness, friability, effervescent time, pH, content uniformity. To amend taste of formulations, different flavoring agents were used and then panel test was done by using Latin Square method by 30 volunteers. Results: Formulations obtained from direct compression and fusion methods had good flow but low hardness. Wet granulation improves flowability and other physicochemical properties such as acceptable hardness, effervescence time ≤3 minutes, pH<6, friability < 1%, water percentage < 0.5% and accurate content uniformity. In panel test, both of combination flavors; (orange - lemon and (strawberry - raspberry had good acceptability. Conclusion: The prepared tablets by wet granulation method using PVP solution had more tablet hardness. It is a reproducible process and suitable to produce granules that are compressed into effervescent tablets due to larger agglomerates.

  9. An efficient algorithm for the generalized Foldy-Lax formulation

    Science.gov (United States)

    Huang, Kai; Li, Peijun; Zhao, Hongkai

    2013-02-01

    Consider the scattering of a time-harmonic plane wave incident on a two-scale heterogeneous medium, which consists of scatterers that are much smaller than the wavelength and extended scatterers that are comparable to the wavelength. In this work we treat those small scatterers as isotropic point scatterers and use a generalized Foldy-Lax formulation to model wave propagation and capture multiple scattering among point scatterers and extended scatterers. Our formulation is given as a coupled system, which combines the original Foldy-Lax formulation for the point scatterers and the regular boundary integral equation for the extended obstacle scatterers. The existence and uniqueness of the solution for the formulation is established in terms of physical parameters such as the scattering coefficient and the separation distances. Computationally, an efficient physically motivated Gauss-Seidel iterative method is proposed to solve the coupled system, where only a linear system of algebraic equations for point scatterers or a boundary integral equation for a single extended obstacle scatterer is required to solve at each step of iteration. The convergence of the iterative method is also characterized in terms of physical parameters. Numerical tests for the far-field patterns of scattered fields arising from uniformly or randomly distributed point scatterers and single or multiple extended obstacle scatterers are presented.

  10. Mixed hyperbolic-second-order-parabolic formulations of general relativity

    International Nuclear Information System (INIS)

    Paschalidis, Vasileios

    2008-01-01

    Two new formulations of general relativity are introduced. The first one is a parabolization of the Arnowitt-Deser-Misner formulation and is derived by the addition of combinations of the constraints and their derivatives to the right-hand side of the Arnowitt-Deser-Misner evolution equations. The desirable property of this modification is that it turns the surface of constraints into a local attractor because the constraint propagation equations become second-order parabolic independently of the gauge conditions employed. This system may be classified as mixed hyperbolic--second-order parabolic. The second formulation is a parabolization of the Kidder-Scheel-Teukolsky formulation and is a manifestly mixed strongly hyperbolic--second-order-parabolic set of equations, bearing thus resemblance to the compressible Navier-Stokes equations. As a first test, a stability analysis of flat space is carried out and it is shown that the first modification exponentially damps and smoothes all constraint-violating modes. These systems provide a new basis for constructing schemes for long-term and stable numerical integration of the Einstein field equations.

  11. An anisotropic elastoplastic constitutive formulation generalised for orthotropic materials

    Science.gov (United States)

    Mohd Nor, M. K.; Ma'at, N.; Ho, C. S.

    2018-03-01

    This paper presents a finite strain constitutive model to predict a complex elastoplastic deformation behaviour that involves very high pressures and shockwaves in orthotropic materials using an anisotropic Hill's yield criterion by means of the evolving structural tensors. The yield surface of this hyperelastic-plastic constitutive model is aligned uniquely within the principal stress space due to the combination of Mandel stress tensor and a new generalised orthotropic pressure. The formulation is developed in the isoclinic configuration and allows for a unique treatment for elastic and plastic orthotropy. An isotropic hardening is adopted to define the evolution of plastic orthotropy. The important feature of the proposed hyperelastic-plastic constitutive model is the introduction of anisotropic effect in the Mie-Gruneisen equation of state (EOS). The formulation is further combined with Grady spall failure model to predict spall failure in the materials. The proposed constitutive model is implemented as a new material model in the Lawrence Livermore National Laboratory (LLNL)-DYNA3D code of UTHM's version, named Material Type 92 (Mat92). The combination of the proposed stress tensor decomposition and the Mie-Gruneisen EOS requires some modifications in the code to reflect the formulation of the generalised orthotropic pressure. The validation approach is also presented in this paper for guidance purpose. The \\varvec{ψ} tensor used to define the alignment of the adopted yield surface is first validated. This is continued with an internal validation related to elastic isotropic, elastic orthotropic and elastic-plastic orthotropic of the proposed formulation before a comparison against range of plate impact test data at 234, 450 and {895 ms}^{-1} impact velocities is performed. A good agreement is obtained in each test.

  12. A New Resistance Formulation for Carbon Nanotubes

    Directory of Open Access Journals (Sweden)

    Ji-Huan He

    2008-01-01

    Full Text Available A new resistance formulation for carbon nanotubes is suggested using fractal approach. The new formulation is also valid for other nonmetal conductors including nerve fibers, conductive polymers, and molecular wires. Our theoretical prediction agrees well with experimental observation.

  13. Advanced Query Formulation in Deductive Databases.

    Science.gov (United States)

    Niemi, Timo; Jarvelin, Kalervo

    1992-01-01

    Discusses deductive databases and database management systems (DBMS) and introduces a framework for advanced query formulation for end users. Recursive processing is described, a sample extensional database is presented, query types are explained, and criteria for advanced query formulation from the end user's viewpoint are examined. (31…

  14. Aerosol formulation and clinical efficacy of bronchodilators

    NARCIS (Netherlands)

    Zanen, Pieter

    1998-01-01

    This thesis subject is the improvement of the formulation of inhaled aerosols. It is well known that the formulation of inhaled drugs is not optimal: the major part of the mass delivered does not reach the lower airways. This phenomenon is due to the particle size of the inhaled particles, which

  15. Hamiltonian formulation of anomaly free chiral bosons

    International Nuclear Information System (INIS)

    Abdalla, E.; Abdalla, M.C.B.; Devecchi, F.P.; Zadra, A.

    1988-01-01

    Starting out of an anomaly free Lagrangian formulation for chiral scalars, which a Wess-Zumino Term (to cancel the anomaly), we formulate the corresponding hamiltonian problem. Ther we use the (quantum) Siegel invariance to choose a particular, which turns out coincide with the obtained by Floreanini and Jackiw. (author) [pt

  16. Quality evaluation of extemporaneous delayed-release liquid formulations of lansoprazole.

    Science.gov (United States)

    Melkoumov, Alexandre; Soukrati, Amina; Elkin, Igor; Forest, Jean-Marc; Hildgen, Patrice; Leclair, Grégoire

    2011-11-01

    The quality attributes of extemporaneous delayed-release liquid formulations of lansoprazole for oral administration were evaluated. A novel liquid formulation (3 mg/mL) of Prevacid FasTab in an Ora-Blend vehicle was prepared and compared with the Prevacid FasTab 30 mg and Prevacid-sodium bicarbonate 1 M formulation (3 mg/mL). The latter formulation was combined with hydrochloric acid 0.1 N, and the remaining lansoprazole content was assayed by high-performance liquid chromatography (HPLC). A batch of delayed-release liquid formulation was prepared to evaluate content uniformity. For content assay, three samples were prepared for each evaluated condition and each sample was analyzed in triplicate by HPLC. The lansoprazole in the sodium bicarbonate formulation was extensively degraded by quantities of hydrochloric acid 0.1 N in excess of 100 mL. Storage time and temperature had a significant effect on lansoprazole stability in the Ora-Blend formulation. The drug remained stable for seven days when the formulation was stored at 4.5-5.5 °C, but storage at 21-22 °C or the reduction of pH with citric acid accelerated lansoprazole degradation. The amount of lansoprazole released from the Ora-Blend formulation during the buffer stage of the dissolution test decreased with increases in formulation storage time, in formulation storage temperature, and in the amount of lansoprazole released and degraded during the acid stage of the test. An extemporaneous formulation consisting of lansoprazole microgranules in Ora-Blend maintained acceptable quality attributes when stored for three days at 4.5-5.5 °C.

  17. Undefined cellulase formulations hinder scientific reproducibility.

    Science.gov (United States)

    Himmel, Michael E; Abbas, Charles A; Baker, John O; Bayer, Edward A; Bomble, Yannick J; Brunecky, Roman; Chen, Xiaowen; Felby, Claus; Jeoh, Tina; Kumar, Rajeev; McCleary, Barry V; Pletschke, Brett I; Tucker, Melvin P; Wyman, Charles E; Decker, Stephen R

    2017-01-01

    In the shadow of a burgeoning biomass-to-fuels industry, biological conversion of lignocellulose to fermentable sugars in a cost-effective manner is key to the success of second-generation and advanced biofuel production. For the effective comparison of one cellulase preparation to another, cellulase assays are typically carried out with one or more engineered cellulase formulations or natural exoproteomes of known performance serving as positive controls. When these formulations have unknown composition, as is the case with several widely used commercial products, it becomes impossible to compare or reproduce work done today to work done in the future, where, for example, such preparations may not be available. Therefore, being a critical tenet of science publishing, experimental reproducibility is endangered by the continued use of these undisclosed products. We propose the introduction of standard procedures and materials to produce specific and reproducible cellulase formulations. These formulations are to serve as yardsticks to measure improvements and performance of new cellulase formulations.

  18. Formulation of heat absorbing glasses

    Directory of Open Access Journals (Sweden)

    Álvarez-Casariego, Pedro

    1996-06-01

    Full Text Available In the thermal exchanges between buildings and environment, glazing is an element of major importance, for it largely influences the so-called Solar Heat Gain and Thermal Losses. These parameters can be modified by applying different type of coatings onto glass surface or by adding colorant compounds during glass melting. The latter is a cheaper way to control the Solar Heat Gain. The knowledge of the laws governing the interaction between colorant compounds and solar radiation, allows us to define glass formulations achieving specific aesthetic requirements and solar energy absorption. In this paper two examples of application of the modelling of glass colorants spectral absorptance are presented. First is addressed to obtaining a glass with high luminous transmittance and low solar energy transmittance, and the other one to obtaining a glass with neutral colour appearance and minimized solar energy transmittance. Calculation formulas are defined together with photometric properties so-obtained. These type of glasses are particularly suitable to be used as building and automotive glazing, for they retain the mechanical characteristics and possibilities of transformation of standard glass.

    En los intercambios de energía entre un edificio y el medio exterior, el vidrio es el elemento de mayor importancia, por su influencia en la Ganancia de Calor Solar y en las Pérdidas Térmicas. Estos parámetros pueden ser modificados mediante el depósito de capas sobre el vidrio o mediante la adición de compuestos absorbentes de la radiación solar. Esta última vía es la más económica para controlar la Ganancia de Calor Solar. El conocimiento de las leyes que gobiernan la interacción de los diversos colorantes con la radiación solar, permite definir formulaciones de vidrios con características especificas de tipo estético y de absorción energética. En este trabajo se presentan dos ejemplos de aplicación de esta modelización de las

  19. Canonical operator formulation of nonequilibrium thermodynamics

    International Nuclear Information System (INIS)

    Mehrafarin, M.

    1992-09-01

    A novel formulation of nonequilibrium thermodynamics is proposed which emphasises the fundamental role played by the Boltzmann constant k in fluctuations. The equivalence of this and the stochastic formulation is demonstrated. The k → 0 limit of this theory yields the classical deterministic description of nonequilibrium thermodynamics. The new formulation possesses unique features which bear two important results namely the thermodynamic uncertainty principle and the quantisation of entropy production rate. Such a theory becomes indispensable whenever fluctuations play a significant role. (author). 7 refs

  20. Application of UV Imaging in Formulation Development

    DEFF Research Database (Denmark)

    Sun, Yu; Østergaard, Jesper

    2017-01-01

    defining formulation behavior after exposure to the aqueous environments and pharmaceutical performance is critical in pharmaceutical development, manufacturing and quality control of drugs. UV imaging has been explored as a tool for qualitative and quantitative characterization of drug dissolution...... related to the structural properties of the drug substance or formulation can be monitored. UV imaging is a non-intrusive and simple-to-operate analytical technique which holds potential for providing a mechanistic foundation for formulation development. This review aims to cover applications of UV...

  1. Formulation of 11-dimensional supergravity in superspace

    International Nuclear Information System (INIS)

    Cremmer, E.; Ferrara, S.

    1980-01-01

    We formulate on-shell 11-dimensional supergravity in superspace and express its equations of motion in terms of purely geometrical quantities. All torsion and curvature components are solved in terms of a single superfield Wsub(rstu), totally antisymmetric in its (flat vector) indices. The dimensional reduction of this formulation is expected to be related to the superspace formulation of N = 8 extended supergravity and might explain the origin of the hidden (local) SU(8) and (global) E 7 symmetries present in this theory. (orig.)

  2. Comparação entre nifedipina por via sublingual e clonidina por via venosa no controle de hipertensão arterial peri-operatória em cirurgias de catarata

    Directory of Open Access Journals (Sweden)

    Stocche Renato Mestriner

    2002-01-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Estudo recente mostra que a clonidina por via venosa apresenta-se eficaz e segura no tratamento de crises hipertensivas durante cirurgia de catarata. Este estudo visa comparar o uso de nifedipina, droga amplamente utilizada por via sublingual, e clonidina por via venosa no controle da hipertensão arterial em cirurgias de catarata. MÉTODO: Setenta e cinco pacientes submetidos à facectomia foram distribuídos de forma aleatória e encoberta em: Grupo A, que recebeu nifedipina e Grupos C2 e C3, que receberam, respectivamente, 2 e 3 µg.kg-1 de clonidina por via venosa. Todos os pacientes apresentavam hipertensão arterial (PAS > 170 mmHg ou PAD > 110 mmHg. As PAS, PAD e freqüência cardíaca (FC foram medidas e comparadas nos momentos: 0 (antes do tratamento e de 2 em 2 minutos até o final do procedimento. Os eventos adversos foram anotados. RESULTADOS: Após o tratamento ocorreram diminuições da PAS e PAD nos 3 grupos (p <0,001. Houve controle da pressão arterial (<160 mmHg em 32%, 64% e 72% dos pacientes nos grupos A, C2 e C3, respectivamente (p < 0,05. No grupo C3 ocorreu maior incidência de efeitos colaterais que nos grupos C2 e A (p < 0,05. CONCLUSÕES:A clonidina por via venosa é mais eficaz que a nifedipina, por via sublingual, no controle de crises hipertensivas no peri-operatório de cirurgias de catarata. Contudo, a dose de 3 µg.kg-1 pode estar relacionada a efeitos colaterais, devendo-se iniciar o tratamento com 2 µg.kg-1.

  3. Carbamylated monomeric allergoids as a therapeutic option for sublingual immunotherapy of dust mite- and grass pollen-induced allergic rhinoconjunctivitis: a systematic review of published trials with a meta-analysis of treatment using Lais® tablets.

    Science.gov (United States)

    Mösges, R; Ritter, B; Kayoko, G; Allekotte, S

    2010-10-01

    Lais® allergoid tablets contain allergens that are modified by carbamylation. Due to their modified chemical structure, they are suitable for sublingual immunotherapy (SLIT) (13, 16, 17, 24). Based on their small molecule size of 12 to 40 kDa, they can be easily absorbed via the oral mucosa (1). In this review, we studied the efficacy of SLIT with carbamylated monomeric allergoid tablets in the treatment of grass pollen- and dust mite-induced allergic rhinoconjunctivitis on the basis of symptom and medication score improvements. Following a selective internet and databank search, six trials-some placebo-controlled-regarding the treatment of grass pollen- (n = 266) and dust mite-induced (n = 241) allergic rhinoconjunctivitis were used to draw conclusions regarding the clinical efficacy of allergoid tablets. The primary endpoints in these trials were decreases in the need for allergy medications and/or reductions in the occurrence of rhinoconjunctivitis symptoms. Data was recorded from patient diaries regarding their symptoms and medications used and conclusions were then drawn about the effectiveness and tolerabieity of Lais® tablets. The average improvement in symptom score in three trials of grass pollen allergy treatment was 34% in comparison to the placebo group. The treatment of dust mite-induced rhinoconjunctivitis produced an average symptom score improvement of 22% compared to the placebo or control groups. The intake of symptomatic rescue medication during allergoid tablet therapy declined. Treatment of grass pollen allergies and dust mite-induced rhinoconjunctivitis showed an average medication score improvement of 49% and 24%, respectively. Few side effects were documented in the trials and predominantly local effects were observed. Severe systemic side effects did not occur. On the basis of the trial results summarized in this review, we suggest that SLIT using Lais® sublingual tablets is an effective and well-tolerated form of treatment.

  4. Operadic formulation of topological vertex algebras and gerstenhaber or Batalin-Vilkovisky algebras

    International Nuclear Information System (INIS)

    Huang Yizhi

    1994-01-01

    We give the operadic formulation of (weak, strong) topological vertex algebras, which are variants of topological vertex operator algebras studied recently by Lian and Zuckerman. As an application, we obtain a conceptual and geometric construction of the Batalin-Vilkovisky algebraic structure (or the Gerstenhaber algebra structure) on the cohomology of a topological vertex algebra (or of a weak topological vertex algebra) by combining this operadic formulation with a theorem of Getzler (or of Cohen) which formulates Batalin-Vilkovisky algebras (or Gerstenhaber algebras) in terms of the homology of the framed little disk operad (or of the little disk operad). (orig.)

  5. Forecast Combinations

    OpenAIRE

    Timmermann, Allan G

    2005-01-01

    Forecast combinations have frequently been found in empirical studies to produce better forecasts on average than methods based on the ex-ante best individual forecasting model. Moreover, simple combinations that ignore correlations between forecast errors often dominate more refined combination schemes aimed at estimating the theoretically optimal combination weights. In this paper we analyse theoretically the factors that determine the advantages from combining forecasts (for example, the d...

  6. Chemical-Based Formulation Design: Virtual Experimentation

    DEFF Research Database (Denmark)

    Conte, Elisa; Gani, Rafiqul

    This paper presents a software, the virtual Product-Process Design laboratory (virtual PPD-lab) and the virtual experimental scenarios for design/verification of consumer oriented liquid formulated products where the software can be used. For example, the software can be employed for the design......, the additives and/or their mixtures (formulations). Therefore, the experimental resources can focus on a few candidate product formulations to find the best product. The virtual PPD-lab allows various options for experimentations related to design and/or verification of the product. For example, the selection...... design, model adaptation). All of the above helps to perform virtual experiments by blending chemicals together and observing their predicted behaviour. The paper will highlight the application of the virtual PPD-lab in the design and/or verification of different consumer products (paint formulation...

  7. Understanding Pesticide Risks: Toxicity and Formulation

    OpenAIRE

    Muntz, Helen; Miller, Rhonda; Alston, Diane

    2016-01-01

    This fact sheet provides information about pesticide risks to human health, primary means of pesticide exposure, standardized measures of pesticide toxicity, pesticide signal words and type of pesticide formulations.

  8. Emulsifying Formulation of Rosuvastatin Calcium for Improved ...

    African Journals Online (AJOL)

    solubility study, liquid formulations were prepared using LAS/Capryol 90: Maisine 35-1 as oil phase and. Tween 20 with ... evaluated for globule size, zeta potential, and emulsion properties. ..... surfactants which decreases the electrostatic.

  9. Drug Nanoparticle Formulation Using Ascorbic Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Kunikazu Moribe

    2011-01-01

    Full Text Available Drug nanoparticle formulation using ascorbic acid derivatives and its therapeutic uses have recently been introduced. Hydrophilic ascorbic acid derivatives such as ascorbyl glycoside have been used not only as antioxidants but also as food and pharmaceutical excipients. In addition to drug solubilization, drug nanoparticle formation was observed using ascorbyl glycoside. Hydrophobic ascorbic acid derivatives such as ascorbyl mono- and di-n-alkyl fatty acid derivatives are used either as drugs or carrier components. Ascorbyl n-alkyl fatty acid derivatives have been formulated as antioxidants or anticancer drugs for nanoparticle formulations such as micelles, microemulsions, and liposomes. ASC-P vesicles called aspasomes are submicron-sized particles that can encapsulate hydrophilic drugs. Several transdermal and injectable formulations of ascorbyl n-alkyl fatty acid derivatives were used, including ascorbyl palmitate.

  10. Dynamic psychiatry and the psychodynamic formulation

    African Journals Online (AJOL)

    processes and psychiatric disorders are biological, the range ... The formulation furthermore helps with the initial orientation towards the patient: it anticipates and predicts how the patient ..... contributed to problems with his sexual identity.

  11. Formulation of Thermosensitive Hydrogel Containing Cyclodextrin ...

    African Journals Online (AJOL)

    Materials. Chitosan (deacetylation degree, DDA = 80 %) was obtained from HiMedia Laboratories Pvt. ... Sterile formulations were ... Chilled β-GP aqueous solution (sterilized through ..... generally decreasing away from the center of the tumor.

  12. Current advances on polynomial resultant formulations

    Science.gov (United States)

    Sulaiman, Surajo; Aris, Nor'aini; Ahmad, Shamsatun Nahar

    2017-08-01

    Availability of computer algebra systems (CAS) lead to the resurrection of the resultant method for eliminating one or more variables from the polynomials system. The resultant matrix method has advantages over the Groebner basis and Ritt-Wu method due to their high complexity and storage requirement. This paper focuses on the current resultant matrix formulations and investigates their ability or otherwise towards producing optimal resultant matrices. A determinantal formula that gives exact resultant or a formulation that can minimize the presence of extraneous factors in the resultant formulation is often sought for when certain conditions that it exists can be determined. We present some applications of elimination theory via resultant formulations and examples are given to explain each of the presented settings.

  13. Formulation and Characterization of Biodegradable Medicated ...

    African Journals Online (AJOL)

    PEG)-600, tributyl citrate, PEG-200, PEG-300, PEG-400, PEG-4000, triethyl citrate and castor oil. The gum formulations were characterized for the following parameters: texture profile analysis (TPA), biodegradation, in vitro drug release using a ...

  14. A simplectic formulation of relativistic particle dynamics

    International Nuclear Information System (INIS)

    Tulczyjew, W.M.

    1976-12-01

    Particle mechanics is formulated in terms of symplectic relations and infinitesimal symplectic relations. Generating functions of symplectic relations are shown to be classical counterparts of Green's functions of wave mechanics. (orig.) [de

  15. A sympletic formulation of relativistic particle dynamics

    International Nuclear Information System (INIS)

    Tulczyjew, W.M.

    1977-01-01

    Particle mechanics is formulated in terms of sympletic relations and infinitesimal symplectic relations. Generating functions of symplectic relations are shown to be classical counterparts of Green's functions of wave mechanics. (author)

  16. Paclitaxel Albumin-stabilized Nanoparticle Formulation

    Science.gov (United States)

    This page contains brief information about paclitaxel albumin-stabilized nanoparticle formulation and a collection of links to more information about the use of this drug, research results, and ongoing clinical trials.

  17. The Boltzmann equation in the difference formulation

    Energy Technology Data Exchange (ETDEWEB)

    Szoke, Abraham [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Brooks III, Eugene D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-05-06

    First we recall the assumptions that are needed for the validity of the Boltzmann equation and for the validity of the compressible Euler equations. We then present the difference formulation of these equations and make a connection with the time-honored Chapman - Enskog expansion. We discuss the hydrodynamic limit and calculate the thermal conductivity of a monatomic gas, using a simplified approximation for the collision term. Our formulation is more consistent and simpler than the traditional derivation.

  18. Limitations of high dose carrier based formulations.

    Science.gov (United States)

    Yeung, Stewart; Traini, Daniela; Tweedie, Alan; Lewis, David; Church, Tanya; Young, Paul M

    2018-06-10

    This study was performed to investigate how increasing the active pharmaceutical ingredient (API) content within a formulation affects the dispersion of particles and the aerosol performance efficiency of a carrier based dry powder inhalable (DPI) formulation, using a custom dry powder inhaler (DPI) development rig. Five formulations with varying concentrations of API beclomethasone dipropionate (BDP) between 1% and 30% (w/w) were formulated as a multi-component carrier system containing coarse lactose and fine lactose with magnesium stearate. The morphology of the formulation and each component were investigated using scanning electron micrographs while the particle size was measured by laser diffraction. The aerosol performance, in terms of aerodynamic diameter, was assessed using the British pharmacopeia Apparatus E cascade impactor (Next generation impactor). Chemical analysis of the API was observed by high performance liquid chromatography (HPLC). Increasing the concentration of BDP in the blend resulted in increasing numbers and size of individual agglomerates and densely packed BDP multi-layers on the surface of the lactose carrier. BDP present within the multi-layer did not disperse as individual primary particles but as dense agglomerates, which led to a decrease in aerosol performance and increased percentage of BDP deposition within the Apparatus E induction port and pre-separator. As the BDP concentration in the blends increases, aerosol performance of the formulation decreases, in an inversely proportional manner. Concurrently, the percentage of API deposition in the induction port and pre-separator could also be linked to the amount of micronized particles (BDP and Micronized composite carrier) present in the formulation. The effect of such dose increase on the behaviour of aerosol dispersion was investigated to gain greater insight in the development and optimisation of higher dosed carrier-based formulations. Copyright © 2018 Elsevier B.V. All

  19. Chemicals-Based Formulation Design: Virtual Experimentations

    DEFF Research Database (Denmark)

    Conte, Elisa; Gani, Rafiqul

    2011-01-01

    This paper presents a systematic procedure for virtual experimentations related to the design of liquid formulated products. All the experiments that need to be performed when designing a liquid formulated product (lotion), such as ingredients selection and testing, solubility tests, property mea...... on the design of an insect repellent lotion will show that the software is an essential instrument in decision making, and that it reduces time and resources since experimental efforts can be focused on one or few product alternatives....

  20. Comments on alternate formulations for preequilibrium decay

    International Nuclear Information System (INIS)

    Blann, M.

    1978-01-01

    The physical and mathematical differences of several formulations for preequilibrium decay are discussed. Mathematical models and examples are presented or referred to in order to illustrate what the author believes to be errors in the exciton formulation as being due to improper inclusion of spectator effects. An earlier work of Gadioli et al. is reinterpreted, and quotations therein to work of the present author are corrected

  1. The coevent formulation of quantum theory

    International Nuclear Information System (INIS)

    Wallden, Petros

    2013-01-01

    Understanding quantum theory has been a subject of debate from its birth. Many different formulations and interpretations have been proposed. Here we examine a recent novel formulation, namely the coevents formulation. It is a histories formulation and has as starting point the Feynman path integral and the decoherence functional. The new ontology turns out to be that of a coarse-grained history. We start with a quantum measure defined on the space of histories, and the existence of zero covers rules out single-history as potential reality (the Kochen Specker theorem casted in histories form is a special case of a zero cover). We see that allowing coarse-grained histories as potential realities avoids the previous paradoxes, maintains deductive non-contextual logic (alas non-Boolean) and gives rise to a unique classical domain. Moreover, we can recover the probabilistic predictions of quantum theory with the use of the Cournot's principle. This formulation, being both a realist formulation and based on histories, is well suited conceptually for the purposes of quantum gravity and cosmology.

  2. An herbal formulation for hemorrhoids treatment

    Directory of Open Access Journals (Sweden)

    S. Dehdari

    2017-11-01

    Full Text Available Background and objectives: Hemorrhoids is the most painful rectal disease. Straining and pregnancy seem playing chief roles in the development of hemorrhoids. Symptoms of hemorrhoids may include bleeding, inflammation and pain. Despite current medical efforts, many discomforts of hemorrhoids have not been handled. The aim of the present study was to formulate and evaluate Itrifal-e muqil (IM tablet to achieve desired pharmaceutical properties. Method: Quality control tests of Allium ampeloperasum L, Commiphora mukul (Hook. ex Stocks Engl., Phyllanthus emblica L., Terminalia chebula Retz. and Terminalia bellerica Retz. were performed. Afterwards, different formulations were prepared and their physical properties were evaluated. Subsequently, the formulation was coated and its physicochemical characteristics were assessed. Result: All of the herbs demonstrated good results in quality control tests according to United State Pharmacopeia (USP. Formulation-1 that was completely prepared based on explained manufacturing process of IM in traditional medicine manuscripts did not show suitable pharmaceutical properties. Among different formulations, Formulation-3 that consisted of A. ampeloperasum, C. mukul, P. emblica, T. chebula and T. bellerica, displayed best outcomes through different tests. Conclusion: Modern pharmaceutical approaches can excellently be adapted for IM preparations.

  3. Anticancer Potential of Nutraceutical Formulations in MNU-induced Mammary Cancer in Sprague Dawley Rats.

    Science.gov (United States)

    Pitchaiah, Gummalla; Akula, Annapurna; Chandi, Vishala

    2017-01-01

    Nutraceuticals help in combating some of the major health problems of the century including cancer, and 'nutraceutical formulations' have led to the new era of medicine and health. To develop different nutraceutical formulations and to assess the anticancer potential of nutraceutical formulations in N-methyl-N-nitrosourea (MNU)-induced mammary cancer in Sprague Dawley rats. Different nutraceutical formulations were prepared using fine powders of amla, apple, garlic, onion, papaya, turmeric, and wheat grass with and without cow urine distillate. Total phenolic content, acute oral toxicity, and microbial load of nutraceutical formulations were assessed. The anticancer potential of nutraceutical formulations was evaluated against MNU-induced mammary cancer in female Sprague Dawley rats. Improvement in total phenolic content was significant ( P safe to use in animals. Microbial load was within the limits. Significant longer tumor-free days ( P apple, garlic, onion, papaya, turmeric, and wheat grass with and without cow urine distillate. Total phenolic content, acute oral toxicity, and microbial load of nutraceutical formulations were assessed. The anticancer potential of nutraceutical formulations was evaluated against MNU-induced mammary cancer in female Sprague Dawley rats. Improvement in total phenolic content was observed after self-fortification process. Toxicity studies showed that the nutraceutical formulations were safe to use in animals. Microbial load was within the limits. Longer tumor-free days, lower tumor incidence, lower tumor multiplicity and tumor burden were observed for nutraceutical formulation-treated groups. This suggests that combination of whole food-based nutraceuticals acted synergistically in the prevention of mammary cancer. Further, the process of fortification enhanced the anticancer potential of nutraceutical formulations. Abbreviations used: HMNU: N-methyl-N-nitrosourea, CAM: Complementary and Alternative Medicine, NF: Nutraceutical

  4. Formulation and quality control of a poly herbal tranquilizer syrup

    Directory of Open Access Journals (Sweden)

    2017-11-01

    Full Text Available Background and objectives: Herbal drugs are rapidly becoming popular in recent years as alternative therapies. Numerous poly herbal formulations, which are combinations of different herbal materials/extracts are being used for prevention or treatment of various disorders. The present research has been undertaken to formulate and evaluate the quality of a tranquilizing syrup based on Iranian traditional medicine references. Methods: A decoction containing Echium amoenum L., Lavandula spp. L., Melissa officinalis L., Cuscuta chinensis Lam, Vitis venifera L.,Prunus domestica and Alhagi camelorum Fisch.was prepared and then filtered. The filtrate was concentrated and different sweeteners and flavoring agents including, brown sugar, honey, masking flavor, sucralose, lemon and orange essential oil were examined to cover the unpleasant taste of the product caused by Cuscuta chinensis. Finally,sucralose was found to be beneficent to cover the unpleasant taste. The final product was evaluated physicochemically and microbiologically according to standard protocols. Results: The results of the quality control assessments demonstrated that the color, odor, microbial and physicochemical characteristics of the syrup were acceptable. Conclusion: The formulated syrup can be examined in in vivo and clinical studies as a tranquilizer with respect to its tranquilizing herbal content.

  5. The formulations and acceptance of herbal lip balm

    International Nuclear Information System (INIS)

    Seri Chempaka Mohd Yusof; Fazliana Mohd Saaya; Zainah Adam

    2006-01-01

    With increasing public concern on the presence of hazardous synthetic and chemical ingredients in cosmetic products, new efforts is gained to produce products using herbs as natural sources. Formulations of herbal lip balm was constructed with ingredients in specific percentages i.e. extracts of herbs, essential oils, honey and olive oil. The aim of this study is to obtain suitable formulations and combinations of essential oils and herbal extracts in herbal lip balm and to observe the influence of the ingredients to the acceptance of herbal lip balm. Acceptability of the formulations was determined through sensory evaluation using 30 members (female) of untrained panelists comprising staff of MINT for two weeks application. A 7 points hedonic rating scale was used. The attributes evaluated are aroma, colour, texture, taste, smoothness, spreading ability and overall acceptance. Natural pigment from Hibiscus sabdariffa L. was used as colorant that responsible for the red colour. Increased redness colour in lip balm scored higher value for the overall acceptability of the lip balm. The lip balm had the ability to moisten the lips and also reduced the mouth odour due to the presence of the essential oils and honey that had antibacterial and antioxidant properties. (Author)

  6. Formulation studies for mirtazapine orally disintegrating tablets.

    Science.gov (United States)

    Yıldız, Simay; Aytekin, Eren; Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Ünlü, Nurşen

    2016-01-01

    Orally disintegrating tablets (ODTs) recently have gained much attention to fulfill the needs for pediatric, geriatric, and psychiatric patients with dysphagia. Aim of this study was to develop new ODT formulations containing mirtazapine, an antidepressant drug molecule having bitter taste, by using simple and inexpensive preparation methods such as coacervation, direct compression and to compare their characteristics with those of reference product (Remereon SolTab). Coacervation method was chosen for taste masking of mirtazapine. In vitro characterization studies such as diameter and thickness, weight variation, tablet hardness, tablet friability and disintegration time were performed on tablet formulations. Wetting time and in vitro dissolution tests of developed ODTs also studied using 900 mL 0.1 N HCl medium, 900 mL pH 6.8 phosphate buffer or 900 mL pH 4.5 acetate buffer at 37 ± 0.2 °C as dissolution medium. Ratio of Eudragit® E-100 was chosen as 6% (w/w) since the dissolution profile of A1 (6% Eudragit® E-100) was found closer to the reference product than A2 (4% Eudragit® E-100) and A3 (8% Eudragit® E-100). Group D, E and F formulations were presented better results in terms of disintegration time. Dissolution results indicated that Group E and F formulations showed optimum properties in all three dissolution media. Formulations D1, D4, D5, E3, E4, F1 and F5 found suitable as ODT formulations due to their favorable disintegration times and dissolution profiles. Developed mirtazapine ODTs were found promising in terms of showing the similar characteristics to the original formulation.

  7. TURVA-2012: Formulation of radionuclide release scenarios

    International Nuclear Information System (INIS)

    Marcos, Nuria; Hjerpe, Thomas; Snellman, Margit; Ikonen, Ari; Smith, Paul

    2014-01-01

    TURVA-2012 is Posiva's safety case in support of the Preliminary Safety Analysis Report (PSAR) and application for a construction licence for a repository for disposal of spent nuclear fuel at the Olkiluoto site in south-western Finland. This paper gives a summary of the scenarios and the methodology followed in formulating them as described in TURVA-2012: Formulation of Radionuclide Release Scenarios (Posiva, 2013). The scenarios are further analysed in TURVA-2012: Assessment of Radionuclide Release Scenarios for the Repository System and TURVA-2012: Biosphere Assessment (Posiva, 2012a, 2012b). The formulation of scenarios takes into account the safety functions of the main barriers of the repository system and the uncertainties in the features, events, and processes (FEP) that may affect the entire disposal system (i.e. repository system plus the surface environment) from the emplacement of the first canister until the far future. In the report TURVA-2012: Performance Assessment (2012d), the performance of the engineered and natural barriers has been assessed against the loads expected during the evolution of the repository system and the site. Uncertainties have been identified and these are taken into account in the formulation of radionuclide release scenarios. The uncertainties in the FEP and evolution of the surface environment are taken into account in formulating the surface environment scenarios used ultimately in estimating radiation exposure. Formulating radionuclide release scenarios for the repository system links the reports Performance Assessment and Assessment of Radionuclide Release Scenarios for the Repository System. The formulation of radionuclide release scenarios for the surface environment brings together biosphere description and the surface environment FEP and is the link to the assessment of the surface environment scenarios summarised in TURVA-2012: Biosphere Assessment. (authors)

  8. Physical-Mechanical characterization of cosmetic formulations and correlation between instrumental measurements and sensorial properties.

    Science.gov (United States)

    Calixto, L S; Maia Campos, P M B G

    2017-10-01

    The correct choice of raw materials in the development of cosmetic formulations is essential for obtaining stable and pleasant skin care products. Therefore, rheological, texture and sensory analyses are important to understand the behaviour and stability of the formulations. In this context, the aim of this study was to develop cosmetic formulations containing or not (vehicle) UV filters and chicory root extract, to evaluate their stability as well as to characterize their physical and texture properties and correlate them with the sensory attributes. Four formulations containing organic UV filters and chicory extract, each alone or in combination, were developed and evaluated for 180 days with a cone and plate rheometer, a texture analyzer and consumer's sensorial analysis. Thus, the data obtained were correlated to observe the different influences. The developed formulations remained stable after 180 days regarding macroscopic aspects, organoleptic characteristics and pH values. The addition of the UV filters alone and in combination with the active substance resulted in significant increases in rheology properties, viscosity and consistency. The formulation with the active ingredient showed significant decreases in the texture parameters after 180 days, mainly due to its polysaccharide inulin. All formulations obtained high scores in sensorial parameters. A strong correlation was mainly found between spreadability and work of shear, and between the texture parameters. The raw materials strongly influenced the physical, texture and sensorial parameters. Finally, the UV filters showed a greater influence on the results of the formulations than the chicory root extract. In conclusion, the association of the mentioned methods allows the correct choice of ingredients and their combinations. © 2017 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  9. Lipid Based Formulations of Biopharmaceutics Classification System (BCS Class II Drugs: Strategy, Formulations, Methods and Saturation

    Directory of Open Access Journals (Sweden)

    Šoltýsová I.

    2016-12-01

    Full Text Available Active ingredients in pharmaceuticals differ by their physico-chemical properties and their bioavailability therefore varies. The most frequently used and most convenient way of administration of medicines is oral, however many drugs are little soluble in water. Thus they are not sufficiently effective and suitable for such administration. For this reason a system of lipid based formulations (LBF was developed. Series of formulations were prepared and tested in water and biorelevant media. On the basis of selection criteria, there were selected formulations with the best emulsification potential, good dispersion in the environment and physical stability. Samples of structurally different drugs included in the Class II of the Biopharmaceutics classification system (BCS were obtained, namely Griseofulvin, Glibenclamide, Carbamazepine, Haloperidol, Itraconazol, Triclosan, Praziquantel and Rifaximin, for testing of maximal saturation in formulations prepared from commercially available excipients. Methods were developed for preparation of formulations, observation of emulsification and its description, determination of maximum solubility of drug samples in the respective formulation and subsequent analysis. Saturation of formulations with drugs showed that formulations 80 % XA and 20 % Xh, 35 % XF and 65 % Xh were best able to dissolve the drugs which supports the hypothesis that it is desirable to identify limited series of formulations which could be generally applied for this purpose.

  10. DEVELOPMENT OF A CAST STONE FORMULATION FOR HANFORD TANK WASTES

    International Nuclear Information System (INIS)

    COOKE; ATTERIDGE; AVILA

    2005-01-01

    The U.S. Department of Energy (DOE) Hanford Site, the location of plutonium production for the US. nuclear weapons program, is the focal point of a broad range of waste remediation efforts. This presentation will describe a test program to develop a ''cast stoney'' formulation for the stabilization of certain Hanford tank wastes (Lockrem 2005). The program consisted of (1) a short series of tests with nonradioactive simulant to select preferred dry reagent formulations (DRF) and determine allowable liquid addition levels, (2) waste form performance testing on cast stone made from the DRF formulations using low-activity waste (LAW) simulant, (3) waste form performance testing on cast stone made from the preferred DRF using LAW, (4) waste form validation testing on a selected nominal cast stone formulation using the preferred DRF and LAW simulant, and (5) technetium ''getter'' testing with cast stone made with LAW simulant and with LAW. In addition, nitrate leaching observations were drawn from nitrate leachability data obtained in the course of waste form performance testing. The nitrate leachability index results are presented along with data on other performance criteria The results of this study led to the selection of a specific DRF. The key attributes of the DRF/waste loading combination considered were presence of ''bleed'' (or free) water, volume change on curing, compressive strength, maximum curing temperature, toxicity characteristic leaching testing, ANSYANS-16.1 (Measurement of the Leachability of Solidified Low-Level Radioactive Wastes by a Short-Term Test Procedure) leachability, and hydraulic conductivity. Important considerations included that the monoliths could be produced using readily available, low-cost reagents. The key results from each of these testing and evaluation activity categories will be summarized

  11. High-Level Waste Glass Formulation Model Sensitivity Study 2009 Glass Formulation Model Versus 1996 Glass Formulation Model

    International Nuclear Information System (INIS)

    Belsher, J.D.; Meinert, F.L.

    2009-01-01

    This document presents the differences between two HLW glass formulation models (GFM): The 1996 GFM and 2009 GFM. A glass formulation model is a collection of glass property correlations and associated limits, as well as model validity and solubility constraints; it uses the pretreated HLW feed composition to predict the amount and composition of glass forming additives necessary to produce acceptable HLW glass. The 2009 GFM presented in this report was constructed as a nonlinear optimization calculation based on updated glass property data and solubility limits described in PNNL-18501 (2009). Key mission drivers such as the total mass of HLW glass and waste oxide loading are compared between the two glass formulation models. In addition, a sensitivity study was performed within the 2009 GFM to determine the effect of relaxing various constraints on the predicted mass of the HLW glass.

  12. Formulation of Sustained-Release Diltiazem Matrix Tablets Using ...

    African Journals Online (AJOL)

    Erah

    surface, their drug release behavior appears simple, but ... matrix material for the formulation of ..... formulation F5 (,) and reference formulations. ( , □). 0. 50. 100. 150. 200. 250. 300. 0. 3. 6 .... Coviello T, Matricardi P, Marianecci C, Alhaique F.

  13. Formulation of lubricating grease using Beeswax thickener

    Science.gov (United States)

    Suhaila, N.; Japar, A.; Aizudin, M.; Aziz, A.; Najib Razali, Mohd

    2018-04-01

    The issues on environmental pollution has brought the industries to seek the alternative green solutions for lubricating grease formulation. The significant challenges in producing modified grease are in which considering the chosen thickener as one of the environmental friendly material. The main purposes of the current research were to formulate lubricant grease using different types of base oils and to study the effect of thickener on the formulated lubricant grease. Used oil and motor oil were used as the base oils for the grease preparation. Beeswax and Damar were used as thickener and additive. The grease is tested based on its consistency, stability and oil bleeding. The prepared greases achieved grease consistency of grade 2 and 3 except for grease with unfiltered used oil. Grease formulated with used oil and synthetic oil tend to harden and loss its lubricating ability under high temperature compared to motor oil’ grease. Grease modification using environmental friendly thickener were successfully formulated but it is considered as a low temperature grease as the beeswax have low melting point of 62°C-65°C.

  14. Bioequivalence assessment of two formulations of ibuprofen

    KAUST Repository

    Al-Talla, Zeyad

    2011-10-19

    Background: This study assessed the relative bioavailability of two formulations of ibuprofen. The first formulation was Doloraz , produced by Al-Razi Pharmaceutical Company, Amman, Jordan. The second forumulation was Brufen , manufactured by Boots Company, Nottingham, UK. Methods and results: A prestudy validation of ibuprofen demonstrated long-term stability, freeze-thaw stability, precision, and accuracy. Twenty-four healthy volunteers were enrolled in this study. After overnight fasting, the two formulations (test and reference) of ibuprofen (100 mg ibuprofen/5 mL suspension) were administered as a single dose on two treatment days separated by a one-week washout period. After dosing, serial blood samples were drawn for a period of 14 hours. Serum harvested from the blood samples was analyzed for the presence of ibuprofen by high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined from serum concentrations for both formulations. The 90% confidence intervals of the ln-transformed test/reference treatment ratios for peak plasma concentration and area under the concentration-time curve (AUC) parameters were found to be within the predetermined acceptable interval of 80%-125% set by the US Food and Drug Administration. Conclusion: Analysis of variance for peak plasma concentrations and AUC parameters showed no significant difference between the two formulations and, therefore, Doloraz was considered bioequivalent to Brufen. 2011 Al-Talla et al, publisher and licensee Dove Medical Press Ltd.

  15. Cast Stone Formulation At Higher Sodium Concentrations

    International Nuclear Information System (INIS)

    Fox, K. M.; Edwards, T. A.; Roberts, K. B.

    2013-01-01

    A low temperature waste form known as Cast Stone is being considered to provide supplemental Low Activity Waste (LAW) immobilization capacity for the Hanford site. Formulation of Cast Stone at high sodium concentrations is of interest since a significant reduction in the necessary volume of Cast Stone and subsequent disposal costs could be achieved if an acceptable waste form can be produced with a high sodium molarity salt solution combined with a high water to premix (or dry blend) ratio. The objectives of this study were to evaluate the factors involved with increasing the sodium concentration in Cast Stone, including production and performance properties and the retention and release of specific components of interest. Three factors were identified for the experimental matrix: the concentration of sodium in the simulated salt solution, the water to premix ratio, and the blast furnace slag portion of the premix. The salt solution simulants used in this study were formulated to represent the overall average waste composition. The cement, blast furnace slag, and fly ash were sourced from a supplier in the Hanford area in order to be representative. The test mixes were prepared in the laboratory and fresh properties were measured. Fresh density increased with increasing sodium molarity and with decreasing water to premix ratio, as expected given the individual densities of these components. Rheology measurements showed that all of the test mixes produced very fluid slurries. The fresh density and rheology data are of potential value in designing a future Cast Stone production facility. Standing water and density gradient testing showed that settling is not of particular concern for the high sodium compositions studied. Heat of hydration measurements may provide some insight into the reactions that occur within the test mixes, which may in turn be related to the properties and performance of the waste form. These measurements showed that increased sodium

  16. Cast Stone Formulation At Higher Sodium Concentrations

    International Nuclear Information System (INIS)

    Fox, K. M.; Roberts, K. A.; Edwards, T. B.

    2014-01-01

    A low temperature waste form known as Cast Stone is being considered to provide supplemental Low Activity Waste (LAW) immobilization capacity for the Hanford site. Formulation of Cast Stone at high sodium concentrations is of interest since a significant reduction in the necessary volume of Cast Stone and subsequent disposal costs could be achieved if an acceptable waste form can be produced with a high sodium molarity salt solution combined with a high water to premix (or dry blend) ratio. The objectives of this study were to evaluate the factors involved with increasing the sodium concentration in Cast Stone, including production and performance properties and the retention and release of specific components of interest. Three factors were identified for the experimental matrix: the concentration of sodium in the simulated salt solution, the water to premix ratio, and the blast furnace slag portion of the premix. The salt solution simulants used in this study were formulated to represent the overall average waste composition. The cement, blast furnace slag, and fly ash were sourced from a supplier in the Hanford area in order to be representative. The test mixes were prepared in the laboratory and fresh properties were measured. Fresh density increased with increasing sodium molarity and with decreasing water to premix ratio, as expected given the individual densities of these components. Rheology measurements showed that all of the test mixes produced very fluid slurries. The fresh density and rheology data are of potential value in designing a future Cast Stone production facility. Standing water and density gradient testing showed that settling is not of particular concern for the high sodium compositions studied. Heat of hydration measurements may provide some insight into the reactions that occur within the test mixes, which may in turn be related to the properties and performance of the waste form. These measurements showed that increased sodium

  17. Cast Stone Formulation At Higher Sodium Concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Fox, K. M. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Roberts, K. A. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Edwards, T. B. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2014-02-28

    A low temperature waste form known as Cast Stone is being considered to provide supplemental Low Activity Waste (LAW) immobilization capacity for the Hanford site. Formulation of Cast Stone at high sodium concentrations is of interest since a significant reduction in the necessary volume of Cast Stone and subsequent disposal costs could be achieved if an acceptable waste form can be produced with a high sodium molarity salt solution combined with a high water to premix (or dry blend) ratio. The objectives of this study were to evaluate the factors involved with increasing the sodium concentration in Cast Stone, including production and performance properties and the retention and release of specific components of interest. Three factors were identified for the experimental matrix: the concentration of sodium in the simulated salt solution, the water to premix ratio, and the blast furnace slag portion of the premix. The salt solution simulants used in this study were formulated to represent the overall average waste composition. The cement, blast furnace slag, and fly ash were sourced from a supplier in the Hanford area in order to be representative. The test mixes were prepared in the laboratory and fresh properties were measured. Fresh density increased with increasing sodium molarity and with decreasing water to premix ratio, as expected given the individual densities of these components. Rheology measurements showed that all of the test mixes produced very fluid slurries. The fresh density and rheology data are of potential value in designing a future Cast Stone production facility. Standing water and density gradient testing showed that settling is not of particular concern for the high sodium compositions studied. Heat of hydration measurements may provide some insight into the reactions that occur within the test mixes, which may in turn be related to the properties and performance of the waste form. These measurements showed that increased sodium

  18. Cast Stone Formulation At Higher Sodium Concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Fox, K. M.; Edwards, T. A.; Roberts, K. B.

    2013-10-02

    A low temperature waste form known as Cast Stone is being considered to provide supplemental Low Activity Waste (LAW) immobilization capacity for the Hanford site. Formulation of Cast Stone at high sodium concentrations is of interest since a significant reduction in the necessary volume of Cast Stone and subsequent disposal costs could be achieved if an acceptable waste form can be produced with a high sodium molarity salt solution combined with a high water to premix (or dry blend) ratio. The objectives of this study were to evaluate the factors involved with increasing the sodium concentration in Cast Stone, including production and performance properties and the retention and release of specific components of interest. Three factors were identified for the experimental matrix: the concentration of sodium in the simulated salt solution, the water to premix ratio, and the blast furnace slag portion of the premix. The salt solution simulants used in this study were formulated to represent the overall average waste composition. The cement, blast furnace slag, and fly ash were sourced from a supplier in the Hanford area in order to be representative. The test mixes were prepared in the laboratory and fresh properties were measured. Fresh density increased with increasing sodium molarity and with decreasing water to premix ratio, as expected given the individual densities of these components. Rheology measurements showed that all of the test mixes produced very fluid slurries. The fresh density and rheology data are of potential value in designing a future Cast Stone production facility. Standing water and density gradient testing showed that settling is not of particular concern for the high sodium compositions studied. Heat of hydration measurements may provide some insight into the reactions that occur within the test mixes, which may in turn be related to the properties and performance of the waste form. These measurements showed that increased sodium

  19. Cast Stone Formulation At Higher Sodium Concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Fox, K. M.; Roberts, K. A.; Edwards, T. B.

    2013-09-17

    A low temperature waste form known as Cast Stone is being considered to provide supplemental Low Activity Waste (LAW) immobilization capacity for the Hanford site. Formulation of Cast Stone at high sodium concentrations is of interest since a significant reduction in the necessary volume of Cast Stone and subsequent disposal costs could be achieved if an acceptable waste form can be produced with a high sodium molarity salt solution combined with a high water to premix (or dry blend) ratio. The objectives of this study were to evaluate the factors involved with increasing the sodium concentration in Cast Stone, including production and performance properties and the retention and release of specific components of interest. Three factors were identified for the experimental matrix: the concentration of sodium in the simulated salt solution, the water to premix ratio, and the blast furnace slag portion of the premix. The salt solution simulants used in this study were formulated to represent the overall average waste composition. The cement, blast furnace slag, and fly ash were sourced from a supplier in the Hanford area in order to be representative. The test mixes were prepared in the laboratory and fresh properties were measured. Fresh density increased with increasing sodium molarity and with decreasing water to premix ratio, as expected given the individual densities of these components. Rheology measurements showed that all of the test mixes produced very fluid slurries. The fresh density and rheology data are of potential value in designing a future Cast Stone production facility. Standing water and density gradient testing showed that settling is not of particular concern for the high sodium compositions studied. Heat of hydration measurements may provide some insight into the reactions that occur within the test mixes, which may in turn be related to the properties and performance of the waste form. These measurements showed that increased sodium

  20. Cyclodextrins as excipients in tablet formulations.

    Science.gov (United States)

    Conceição, Jaime; Adeoye, Oluwatomide; Cabral-Marques, Helena Maria; Lobo, José Manuel Sousa

    2018-04-22

    This paper aims to provide a critical review of cyclodextrins as excipients in tablet formulations, highlighting: (i) the principal pharmaceutical applications of cyclodextrins; (ii) the most relevant technological aspects in pharmaceutical formulation development; and (iii) the actual regulatory status of cyclodextrins. Moreover, several illustrative examples are presented. Cyclodextrins can be used as complexing excipients in tablet formulations for low-dose drugs. By contrast, for medium-dose drugs and/or when the complexation efficiency is low, the methods to enhance the complexation efficiency play a key part in reducing the cyclodextrin quantity. In addition, these compounds are used as fillers, disintegrants, binders and multifunctional direct compression excipients of the tablets. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. STRATEGY FORMULATION PROCESS AND INNOVATION PERFORMANCE NEXUS

    Directory of Open Access Journals (Sweden)

    Chijioke Nwachukwu

    2018-03-01

    Full Text Available The purpose of this study is to examine the link between strategy formulation process and innovation performance indicators in microfinance banks in Nigeria (MFBs. 100 employees of leading microfinance banks were randomly selected for this study. 80 questionnaires were returned but only 76 were found usable for the analysis. Regression analysis technique was used in examining the nature of the relationships of the variables and for hypotheses testing. The authors used exploratory factor analysis and Cronbach's alpha to test for the validity and reliability of the questionnaires. The results show that strategy formulation process has a positive effect on process innovation performance, product innovation performance and marketing innovation performance. Thus, all the three hypotheses tested were supported. The authors, therefore, concludes that a systematic strategy formulation process is necessary for firms to achieve and sustain process innovation performance, product innovation performance and marketing innovation performance. This study proposed suggestion for further studies.

  2. Formulating viscous hydrodynamics for large velocity gradients

    International Nuclear Information System (INIS)

    Pratt, Scott

    2008-01-01

    Viscous corrections to relativistic hydrodynamics, which are usually formulated for small velocity gradients, have recently been extended from Navier-Stokes formulations to a class of treatments based on Israel-Stewart equations. Israel-Stewart treatments, which treat the spatial components of the stress-energy tensor τ ij as dynamical objects, introduce new parameters, such as the relaxation times describing nonequilibrium behavior of the elements τ ij . By considering linear response theory and entropy constraints, we show how the additional parameters are related to fluctuations of τ ij . Furthermore, the Israel-Stewart parameters are analyzed for their ability to provide stable and physical solutions for sound waves. Finally, it is shown how these parameters, which are naturally described by correlation functions in real time, might be constrained by lattice calculations, which are based on path-integral formulations in imaginary time

  3. RAACFDb: Rheumatoid arthritis ayurvedic classical formulations database.

    Science.gov (United States)

    Mohamed Thoufic Ali, A M; Agrawal, Aakash; Sajitha Lulu, S; Mohana Priya, A; Vino, S

    2017-02-02

    In the past years, the treatment of rheumatoid arthritis (RA) has undergone remarkable changes in all therapeutic modes. The present newfangled care in clinical research is to determine and to pick a new track for better treatment options for RA. Recent ethnopharmacological investigations revealed that traditional herbal remedies are the most preferred modality of complementary and alternative medicine (CAM). However, several ayurvedic modes of treatments and formulations for RA are not much studied and documented from Indian traditional system of medicine. Therefore, this directed us to develop an integrated database, RAACFDb (acronym: Rheumatoid Arthritis Ayurvedic Classical Formulations Database) by consolidating data from the repository of Vedic Samhita - The Ayurveda to retrieve the available formulations information easily. Literature data was gathered using several search engines and from ayurvedic practitioners for loading information in the database. In order to represent the collected information about classical ayurvedic formulations, an integrated database is constructed and implemented on a MySQL and PHP back-end. The database is supported by describing all the ayurvedic classical formulations for the treatment rheumatoid arthritis. It includes composition, usage, plant parts used, active ingredients present in the composition and their structures. The prime objective is to locate ayurvedic formulations proven to be quite successful and highly effective among the patients with reduced side effects. The database (freely available at www.beta.vit.ac.in/raacfdb/index.html) hopefully enables easy access for clinical researchers and students to discover novel leads with reduced side effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Triptans and migraine: advances in use, administration, formulation, and development.

    Science.gov (United States)

    Macone, Amanda E; Perloff, Michael D

    2017-03-01

    Recent triptan development has focused on new administration methods and formulations, triptan combination therapies, treatment in menstrually related migraines, and novel serotonin receptor subtype agonists (5HTf). Areas covered: Clinical triptan research related to migraine was reviewed, analyzing EMBASE and PUBMED data bases from 01/01/2011 to 06/29/2016, with a focus on clinical trials of class 1 or 2 level of evidence. There have been advances in drug combination therapies, as well as administration devices that aid in ease of use, increase efficacy, and decrease adverse reactions. Some new agents and devices have similar or less efficacy compared to previous generic triptan formulations. New agents have action at the 5HTf receptor subtype, and avoid vascular side effects of classic 5Ht1b/d agonists, however adverse reactions may limit their clinic use. Long half-life triptans, frovatriptan and naratriptan, do appear to have good benefit in menstral related migraine. Expert opinion: Recent advances in triptan development can offer some advantages to migraine therapy and patient preferences, but have a much higher cost compared to individual generic triptan agents. In the coming years, triptan advances with high efficacy, limiting ADRs and cost are welcomed, in this regard the 5HT1b/d triptans are already well established.

  5. Affine group formulation of the Standard Model coupled to gravity

    Energy Technology Data Exchange (ETDEWEB)

    Chou, Ching-Yi, E-mail: l2897107@mail.ncku.edu.tw [Department of Physics, National Cheng Kung University, Taiwan (China); Ita, Eyo, E-mail: ita@usna.edu [Department of Physics, US Naval Academy, Annapolis, MD (United States); Soo, Chopin, E-mail: cpsoo@mail.ncku.edu.tw [Department of Physics, National Cheng Kung University, Taiwan (China)

    2014-04-15

    In this work we apply the affine group formalism for four dimensional gravity of Lorentzian signature, which is based on Klauder’s affine algebraic program, to the formulation of the Hamiltonian constraint of the interaction of matter and all forces, including gravity with non-vanishing cosmological constant Λ, as an affine Lie algebra. We use the hermitian action of fermions coupled to gravitation and Yang–Mills theory to find the density weight one fermionic super-Hamiltonian constraint. This term, combined with the Yang–Mills and Higgs energy densities, are composed with York’s integrated time functional. The result, when combined with the imaginary part of the Chern–Simons functional Q, forms the affine commutation relation with the volume element V(x). Affine algebraic quantization of gravitation and matter on equal footing implies a fundamental uncertainty relation which is predicated upon a non-vanishing cosmological constant. -- Highlights: •Wheeler–DeWitt equation (WDW) quantized as affine algebra, realizing Klauder’s program. •WDW formulated for interaction of matter and all forces, including gravity, as affine algebra. •WDW features Hermitian generators in spite of fermionic content: Standard Model addressed. •Constructed a family of physical states for the full, coupled theory via affine coherent states. •Fundamental uncertainty relation, predicated on non-vanishing cosmological constant.

  6. Formulation and stability testing of photolabile drugs.

    Science.gov (United States)

    Tønnesen, H H

    2001-08-28

    Exposure of a drug to irradiation can influence the stability of the formulation, leading to changes in the physicochemical properties of the product. The influence of excipients of frequently used stabilizers is often difficult to predict and, therefore, stability testing of the final preparation is important. The selection of a protective packaging must be based on knowledge about the wavelength causing the instability. Details on drug photoreactivity will also be helpful in order to minimize side-effects and/or optimize drug targeting by developing photoresponsive drug delivery systems. This review focuses on practical problems related to formulation and stability testing of photolabile drugs.

  7. An exact approach for aggregated formulations

    DEFF Research Database (Denmark)

    Gamst, Mette; Spoorendonk, Simon

    Aggregating formulations is a powerful approach for transforming problems into taking more tractable forms. Aggregated formulations can, though, have drawbacks: some information may get lost in the aggregation and { put in a branch-and-bound context { branching may become very di_cult and even....... The paper includes general considerations on types of problems for which the method is of particular interest. Furthermore, we prove the correctness of the procedure and consider how to include extensions such as cutting planes and advanced branching strategies....

  8. Quaternionic formulation of the exact parity model

    Energy Technology Data Exchange (ETDEWEB)

    Brumby, S.P.; Foot, R.; Volkas, R.R.

    1996-02-28

    The exact parity model (EPM) is a simple extension of the standard model which reinstates parity invariance as an unbroken symmetry of nature. The mirror matter sector of the model can interact with ordinary matter through gauge boson mixing, Higgs boson mixing and, if neutrinos are massive, through neutrino mixing. The last effect has experimental support through the observed solar and atmospheric neutrino anomalies. In the paper it is shown that the exact parity model can be formulated in a quaternionic framework. This suggests that the idea of mirror matter and exact parity may have profound implications for the mathematical formulation of quantum theory. 13 refs.

  9. Quaternionic formulation of the exact parity model

    International Nuclear Information System (INIS)

    Brumby, S.P.; Foot, R.; Volkas, R.R.

    1996-01-01

    The exact parity model (EPM) is a simple extension of the standard model which reinstates parity invariance as an unbroken symmetry of nature. The mirror matter sector of the model can interact with ordinary matter through gauge boson mixing, Higgs boson mixing and, if neutrinos are massive, through neutrino mixing. The last effect has experimental support through the observed solar and atmospheric neutrino anomalies. In the paper it is shown that the exact parity model can be formulated in a quaternionic framework. This suggests that the idea of mirror matter and exact parity may have profound implications for the mathematical formulation of quantum theory. 13 refs

  10. Formulation of Sodium Alginate Nanospheres Containing ...

    African Journals Online (AJOL)

    Purpose: The aim of this work was to formulate sodium alginate nanospheres of amphotericin B by controlled gellification method and to evaluate the role of the nanospheres as a “passive carrier” in targeted antifungal therapy. Methods: Sodium alginate nanospheres of amphotericin B were prepared by controlled ...

  11. Facile Colorimetric Determination of Duloxetine in Formulations ...

    African Journals Online (AJOL)

    ... the determination of duloxetine hydrochloride (DX). Methods: Ion-pair spectrophotometric method was employed for the determination of duloxetine hydrochloride (DX) in bulk and pharmaceutical formulations using acidic dye methyl orange (MO) as ion-pairing agent at pH 4 (phthalate buffer). The yellow ion-pair complex ...

  12. Engaged Problem Formulation in IS Research

    DEFF Research Database (Denmark)

    Nielsen, Peter Axel; Persson, John Stouby

    2016-01-01

    problems requires a more substantial engagement with the different stakeholders, especially when their problems are ill structured and situated in complex organizational settings. On this basis, we present an engaged approach to formulating IS problems with, not for, IS practitioners. We have come...

  13. Effects of Methionine Containing Paracetamol Formulation on ...

    African Journals Online (AJOL)

    Effects of Methionine Containing Paracetamol Formulation on Serum Vitamins and Trace Elements in Male Rats. AA Iyanda, JI Anetor, DP Oparinde, FAA Adeniyi. Abstract. Methionine is an effective antidote in the treatment of paracetamol-induced toxicity but at large doses it has been reported to induce or aggravate a ...

  14. State-Space Formulation for Circuit Analysis

    Science.gov (United States)

    Martinez-Marin, T.

    2010-01-01

    This paper presents a new state-space approach for temporal analysis of electrical circuits. The method systematically obtains the state-space formulation of nondegenerate linear networks without using concepts of topology. It employs nodal/mesh systematic analysis to reduce the number of undesired variables. This approach helps students to…

  15. Yang-Mills formulation of interacting strings

    International Nuclear Information System (INIS)

    Chan Hongmo; Tsou Sheungtsun

    1988-06-01

    A suggestion that the theory of interacting open bosonic string be reformulated as a generalised Yang-Mills theory is further elucidated. Moreover, a serious reservation regarding the ordering of operators in the earlier 'proof' of equivalence between the new and standard formulations is now removed. (author)

  16. Initial value formulation of higher derivative gravity

    International Nuclear Information System (INIS)

    Noakes, D.R.

    1983-01-01

    The initial value problem is considered for the conformally coupled scalar field and higher derivative gravity, by expressing the equations of each theory in harmonic coordinates. For each theory it is shown that the (vacuum) equations can take the form of a diagonal hyperbolic system with constraints on the initial data. Consequently these theories possess well-posed initial value formulations

  17. Release Properties of Paracetamol Granulationa Formulated with ...

    African Journals Online (AJOL)

    Theobroma cacao gum, TCG was derived as a dry powder from fresh fruits of Theobroma cacao. Various granulations of paracetamol were prepared with TCG at the concentrations of 0.5 – 4% w/w. Similar formulations were prepared using sodium carboxymethyl cellulose, SCMC and acacia gums as standards. In each ...

  18. Probabilites in the general boundary formulation

    Energy Technology Data Exchange (ETDEWEB)

    Oeckl, Robert [Instituto de Matematicas, UNAM, Campus Morelia, C.P. 58190, Morelia, Michoacan (Mexico)

    2007-05-15

    We give an introductory account of the general boundary formulation of quantum theory. We refine its probability interpretation and emphasize a conceptual and historical perspective. We give motivations from quantum gravity and illustrate them with a scenario for describing gravitons in quantum gravity.

  19. On fictitious domain formulations for Maxwell's equations

    DEFF Research Database (Denmark)

    Dahmen, W.; Jensen, Torben Klint; Urban, K.

    2003-01-01

    We consider fictitious domain-Lagrange multiplier formulations for variational problems in the space H(curl: Omega) derived from Maxwell's equations. Boundary conditions and the divergence constraint are imposed weakly by using Lagrange multipliers. Both the time dependent and time harmonic formu...

  20. Necessity of rethinking oral pediatric formulations

    DEFF Research Database (Denmark)

    Bar-Shalom, Daniel

    2014-01-01

    by all patient groups, is needed, and an automated compounding concept is proposed. The finishing of the formulation is done at the dispensing pharmacy using an automated process. The individual components (pudding-like carrier, microencapsulated drug, and the dispensing robot and its software...

  1. Lagrangian formulation of classical BMT-theory

    International Nuclear Information System (INIS)

    Pupasov-Maksimov, Andrey; Deriglazov, Alexei; Guzman, Walberto

    2013-01-01

    Full text: The most popular classical theory of electron has been formulated by Bargmann, Michel and Telegdi (BMT) in 1959. The BMT equations give classical relativistic description of a charged particle with spin and anomalous magnetic momentum moving in homogeneous electro-magnetic field. This allows to study spin dynamics of polarized beams in uniform fields. In particular, first experimental measurements of muon anomalous magnetic momentum were done using changing of helicity predicted by BMT equations. Surprisingly enough, a systematic formulation and the analysis of the BMT theory are absent in literature. In the present work we particularly fill this gap by deducing Lagrangian formulation (variational problem) for BMT equations. Various equivalent forms of Lagrangian will be discussed in details. An advantage of the obtained classical model is that the Lagrangian action describes a relativistic spinning particle without Grassmann variables, for both free and interacting cases. This implies also the possibility of canonical quantization. In the interacting case, an arbitrary electromagnetic background may be considered, which generalizes the BMT theory formulated to the case of homogeneous fields. The classical model has two local symmetries, which gives an interesting example of constrained classical dynamics. It is surprising, that the case of vanishing anomalous part of the magnetic momentum is naturally highlighted in our construction. (author)

  2. A parcel formulation for Hamiltonian layer models

    NARCIS (Netherlands)

    Bokhove, Onno; Oliver, M.

    Starting from the three-dimensional hydrostatic primitive equations, we derive Hamiltonian N-layer models with isentropic tropospheric and isentropic or isothermal stratospheric layers. Our construction employs a new parcel Hamiltonian formulation which describes the fluid as a continuum of

  3. Clinical pharmacology of novel anticancer drug formulations

    NARCIS (Netherlands)

    Stuurman, F.E.

    2013-01-01

    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The

  4. Comparative evaluation of organic formulations of Pseudomonas ...

    African Journals Online (AJOL)

    An experiment was conducted in the laboratory and farm of the Department of Biotechnology, Gauhati University, to explore the potentiality of various organic formulations of Pseudomonas fluorescens (Pf) and to manage bacterial wilt disease of brinjal (Solanum melongena L.) under local conditions. Different organic ...

  5. Formulation and evaluation and terbutaline sulphate and ...

    African Journals Online (AJOL)

    We report the use of low rugosity lactose, product of controlled crystallization of this carrier, in the formulation of terbutaline sulphate and beclomethasone dipropionate dry powder inhalers. The deposition patterns obtained with inhalation mixtures consisting of the modified lactose and each of the micronised drugs ...

  6. Development and Evaluation of Topical Gabapentin Formulations

    Directory of Open Access Journals (Sweden)

    Christopher J. Martin

    2017-08-01

    Full Text Available Topical delivery of gabapentin is desirable to treat peripheral neuropathic pain conditions whilst avoiding systemic side effects. To date, reports of topical gabapentin delivery in vitro have been variable and dependent on the skin model employed, primarily involving rodent and porcine models. In this study a variety of topical gabapentin formulations were investigated, including Carbopol® hydrogels containing various permeation enhancers, and a range of proprietary bases including a compounded Lipoderm® formulation; furthermore microneedle facilitated delivery was used as a positive control. Critically, permeation of gabapentin across a human epidermal membrane in vitro was assessed using Franz-type diffusion cells. Subsequently this data was contextualised within the wider scope of the literature. Although reports of topical gabapentin delivery have been shown to vary, largely dependent upon the skin model used, this study demonstrated that 6% (w/w gabapentin 0.75% (w/w Carbopol® hydrogels containing 5% (w/w DMSO or 70% (w/w ethanol and a compounded 10% (w/w gabapentin Lipoderm® formulation were able to facilitate permeation of the molecule across human skin. Further pre-clinical and clinical studies are required to investigate the topical delivery performance and pharmacodynamic actions of prospective formulations.

  7. Development and Evaluation of Topical Gabapentin Formulations

    Science.gov (United States)

    Alcock, Natalie; Hiom, Sarah; Birchall, James C.

    2017-01-01

    Topical delivery of gabapentin is desirable to treat peripheral neuropathic pain conditions whilst avoiding systemic side effects. To date, reports of topical gabapentin delivery in vitro have been variable and dependent on the skin model employed, primarily involving rodent and porcine models. In this study a variety of topical gabapentin formulations were investigated, including Carbopol® hydrogels containing various permeation enhancers, and a range of proprietary bases including a compounded Lipoderm® formulation; furthermore microneedle facilitated delivery was used as a positive control. Critically, permeation of gabapentin across a human epidermal membrane in vitro was assessed using Franz-type diffusion cells. Subsequently this data was contextualised within the wider scope of the literature. Although reports of topical gabapentin delivery have been shown to vary, largely dependent upon the skin model used, this study demonstrated that 6% (w/w) gabapentin 0.75% (w/w) Carbopol® hydrogels containing 5% (w/w) DMSO or 70% (w/w) ethanol and a compounded 10% (w/w) gabapentin Lipoderm® formulation were able to facilitate permeation of the molecule across human skin. Further pre-clinical and clinical studies are required to investigate the topical delivery performance and pharmacodynamic actions of prospective formulations. PMID:28867811

  8. Engaged Problem Formulation in IS Research

    DEFF Research Database (Denmark)

    Nielsen, Peter Axel; Persson, John Stouby

    2016-01-01

    “Is this the problem?”: the question that haunts many information systems (IS) researchers when they pursue work relevant to both practice and research. Nevertheless, a deliberate answer to this question requires more than simply asking the involved IS practitioners. Deliberately formulating...

  9. Kit systems for granulated decontamination formulations

    Science.gov (United States)

    Tucker, Mark D.

    2010-07-06

    A decontamination formulation and method of making that neutralizes the adverse health effects of both chemical and biological compounds, especially chemical warfare (CW) and biological warfare (BW) agents, and toxic industrial chemicals. The formulation provides solubilizing compounds that serve to effectively render the chemical and biological compounds, particularly CW and BW compounds, susceptible to attack, and at least one reactive compound that serves to attack (and detoxify or kill) the compound. The formulation includes at least one solubilizing agent, a reactive compound, a sorbent additive, and water. A highly adsorbent sorbent additive (e.g., amorphous silica, sorbitol, mannitol, etc.) is used to "dry out" one or more liquid ingredients into a dry, free-flowing powder that has an extended shelf life, and is more convenient to handle and mix in the field. The formulation can be pre-mixed and pre-packaged as a multi-part kit system, where one or more of the parts are packaged in a powdered, granulated form for ease of handling and mixing in the field.

  10. Application of UV Imaging in Formulation Development.

    Science.gov (United States)

    Sun, Yu; Østergaard, Jesper

    2017-05-01

    Efficient drug delivery is dependent on the drug substance dissolving in the body fluids, being released from dosage forms and transported to the site of action. A fundamental understanding of the interplay between the physicochemical properties of the active compound and pharmaceutical excipients defining formulation behavior after exposure to the aqueous environments and pharmaceutical performance is critical in pharmaceutical development, manufacturing and quality control of drugs. UV imaging has been explored as a tool for qualitative and quantitative characterization of drug dissolution and release with the characteristic feature of providing real-time visualization of the solution phase drug transport in the vicinity of the formulation. Events occurring during drug dissolution and release, such as polymer swelling, drug precipitation/recrystallization, or solvent-mediated phase transitions related to the structural properties of the drug substance or formulation can be monitored. UV imaging is a non-intrusive and simple-to-operate analytical technique which holds potential for providing a mechanistic foundation for formulation development. This review aims to cover applications of UV imaging in the early and late phase pharmaceutical development with a special focus on the relation between structural properties and performance. Potential areas of future advancement and application are also discussed.

  11. The Hamiltonian of Einstein affine-metric formulation of general relativity

    International Nuclear Information System (INIS)

    Kiriushcheva, N.; Kuzmin, S.V.

    2010-01-01

    It is shown that the Hamiltonian of the Einstein affine-metric (first-order) formulation of General Relativity (GR) leads to a constraint structure that allows the restoration of its unique gauge invariance, four-diffeomorphism, without the need of any field dependent redefinition of gauge parameters as in the case of the second-order formulation. In the second-order formulation of ADM gravity the need for such a redefinition is the result of the non-canonical change of variables (Xiv:0809.0097). For the first-order formulation, the necessity of such a redefinition ''to correspond to diffeomorphism invariance'' (reported by Ghalati, arXiv:0901.3344) is just an artifact of using the Henneaux-Teitelboim-Zanelli ansatz (Nucl. Phys. B 332:169, 1990), which is sensitive to the choice of linear combination of tertiary constraints. This ansatz cannot be used as an algorithm for finding a gauge invariance, which is a unique property of a physical system, and it should not be affected by different choices of linear combinations of non-primary first class constraints. The algorithm of Castellani (Ann. Phys. 143:357, 1982) is free from such a deficiency and it leads directly to four-diffeomorphism invariance for first, as well as for second-order Hamiltonian formulations of GR. The distinct role of primary first class constraints, the effect of considering different linear combinations of constraints, the canonical transformations of phase-space variables, and their interplay are discussed in some detail for Hamiltonians of the second- and first-order formulations of metric GR. The first-order formulation of Einstein-Cartan theory, which is the classical background of Loop Quantum Gravity, is also discussed. (orig.)

  12. Bioequivalence assessment of two formulations of ibuprofen

    Directory of Open Access Journals (Sweden)

    Al-Talla ZA

    2011-10-01

    Full Text Available Zeyad A Al-Talla1, Sabah H Akrawi2, Luke T Tolley3, Salim H Sioud1, Mohammed F Zaater4, Abdul-Hamid M Emwas1 1Analytical and NMR Core Laboratories, King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudia Arabia; 2College of Pharmacy, Al-Ain University, Al-Ain, United Arab Emirates; 3Department of Chemistry and Biochemistry, Southern Illinois University Carbondale, Carbondale, IL, USA; 4Department of Chemistry, Jordan University of Science and Technology, Jordan University of Science and Technology, Irbid, Jordan Background: This study assessed the relative bioavailability of two formulations of ibuprofen. The first formulation was Doloraz®, produced by Al-Razi Pharmaceutical Company, Amman, Jordan. The second forumulation was Brufen®, manufactured by Boots Company, Nottingham, UK. Methods and results: A prestudy validation of ibuprofen demonstrated long-term stability, freeze-thaw stability, precision, and accuracy. Twenty-four healthy volunteers were enrolled in this study. After overnight fasting, the two formulations (test and reference of ibuprofen (100 mg ibuprofen/5 mL suspension were administered as a single dose on two treatment days separated by a one-week washout period. After dosing, serial blood samples were drawn for a period of 14 hours. Serum harvested from the blood samples was analyzed for the presence of ibuprofen by high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined from serum concentrations for both formulations. The 90% confidence intervals of the ln-transformed test/reference treatment ratios for peak plasma concentration and area under the concentration-time curve (AUC parameters were found to be within the predetermined acceptable interval of 80%–125% set by the US Food and Drug Administration. Conclusion: Analysis of variance for peak plasma concentrations and AUC parameters showed no significant difference between the two formulations and

  13. Topical formulations with superoxide dismutase: influence of formulation composition on physical stability and enzymatic activity.

    Science.gov (United States)

    Di Mambro, Valéria M; Borin, Maria F; Fonseca, Maria J V

    2003-04-24

    Three different topical formulations were supplemented with superoxide dismutase (SOD) and evaluated concerning physical and chemical stabilities in order to determine the most stable formulation that would maintain SOD activity. Physical stability was evaluated by storing the formulation at room temperature, and at 37 and 45 degrees C for 28 days. Samples were collected at 7-day intervals for assessment of rheological behavior. Chemical stability was evaluated by the measurement of enzymatic activity in formulations stored at room temperature and at 45 degrees C for 75 days. The formulations showed a pseudoplastic behavior, with a flow index of less than 1. There was no significant difference in the initial values of flow index, hysteresis loop or minimum apparent viscosity. The simple emulsion and the one stabilized with hydroxyethylcellulose showed decreased viscosity by the 21st day and with higher temperature, but no significant changes concerning the presence of SOD. Although there were no significant changes concerning storage time or temperature, the formulation stabilized with hydroxyethylcellulose showed a marked loss of SOD activity. The addition of SOD to the formulations studied did not affect their physical stability. Simple emulsions or emulsions stabilized with carboxypolymethylene seem to be better bases for enzyme addition than emulsion stabilized with hydroxyethylcellulose.

  14. Improved detection of fill-in using sublingual nitroglycerin in technetium-99m tetrofosmin exercise/rest single photon emission computed tomography one day protocol for old myocardial infarction

    International Nuclear Information System (INIS)

    Miyanaga, Hajime; Kunieda, Yasufumi; Oguni, Atsuhiko; Kamitani, Tadaaki; Kawasaki, Shingo; Takahashi, Toru

    1999-01-01

    Twenty-one patients with old myocardial infarction underwent repeated 99m Tc-tetrofosmin ( 99m Tc) exercise/rest same day protocols with and without the administration of sublingual nitroglycerin (NTG) 5 min before the second injection of 99m Tc for rest SPECT. Twelve of these patients also underwent ordinary exercise/redistribution 201 Tl SPECT. The control study protocol images showed decreased uptake of 99m Tc on exercise in 157 of 420 segments and the presence of fill-in at rest in 58 segments. Images obtained with administration of NTG showed decreased uptake of 99m Tc on exercise in 163 of 420 segments and fill-in in 74 segments at rest. The frequency of fill-in was greater in the NTG protocol than in the control protocol. The segments were scored as different grades according to 99m Tc uptake between 2 protocols. Fill-in was only present or more remarkable in 31 segments in the NTG protocol than in the control protocol. Fill-in was only present or more remarkable in 10 segments in the control protocol than in the NTG protocol. In the NTG protocol, the mean defect score of the exercise images, calculated from the bull's eye image automatically, was higher than that of the rest images. The mean severity score of the exercise images, also calculated from the bull's eye image automatically, was likewise higher than that of the rest images, whereas the mean severity score of the stress images and rest images in the control protocol was not significantly different. Moreover, the mean defect score and severity score of the rest images from the NTG protocol were significantly lower than those obtained from the control protocol. Sublingual NTG administration before the injection of 99m Tc-tetrofosmin at the rest study in the one day exercise/rest studies enhanced fill-in, so may enhance the detection of viable myocardium, allowing more informed decisions regarding cardiac revascularization in patients with chronic coronary artery disease. (K.H.)

  15. Influence of different formulations and granulation techniques on dissolution of folic acid in film coated tablets

    Directory of Open Access Journals (Sweden)

    Ljiljana Krsteska

    2011-07-01

    Full Text Available The vitamin folic acid has received considerable attention because of it′s role in decreasing risk of neural tube birth defects, and it′s potential role in reducing risks of cardiovascular and psychiatric diseases. We evaluated compositions of 5 different formulations in terms of meeting the USP standard for dissolution and disintegration .However all the examined formulations had met the disintegration test but only 3 formulations had met the dissolution requirements to release 75 % of the active ingredient in 45 minutes. The maximum value of dissolution of 97.52 % in S5 composition was achieved by combination of certain excipients (combination of hydrophilic and hydrophobic filler and suitable wetting agent and wet high shear mixing granulation technique, resulting with optimize release of the active substance.

  16. combination Dictionary

    African Journals Online (AJOL)

    rbr

    of the idiomatic expression as a whole" (Crystal 2003: 225-226). Idiomatic .... nations and idioms.11 Nonetheless, free combinations of words have not been .... those who thronged Emmett place last night wanted to see the film, and they.

  17. Winning Combinations

    DEFF Research Database (Denmark)

    Criscuolo, Paola; Laursen, Keld; Reichstein, Toke

    2018-01-01

    examine the effectiveness of different combinations of knowledge sources for achieving innovative performance. We suggest that combinations involving integrative search strategies – combining internal and external knowledge – are the most likely to generate product and process innovation. In this context......, we present the idea that cognitively distant knowledge sources are helpful for innovation only when used in conjunction with knowledge sources that are closer to the focal firm. We also find important differences between product and process innovation, with the former associated with broader searches......Searching for the most rewarding sources of innovative ideas remains a key challenge in management of technological innovation. Yet, little is known about which combinations of internal and external knowledge sources are triggers for innovation. Extending theories about searching for innovation, we...

  18. Fatty acid-based formulations for wood protection against mold and sapstain

    Science.gov (United States)

    Carol A. Clausen; Robert D. Coleman; Vina W. Yang

    2010-01-01

    Safer, highly effective biocides providing long-term protection of mold growth on wood-based materials is of interest to the wood protection industry. Moldicide formulations containing synergistic combinations of ingredients derived from natural sources are commonly recognized as a promising approach for the next generation of wood protectants. Although fatty acid (FA...

  19. Effective pesticide nano formulations and their bacterial degradation

    Science.gov (United States)

    Ramadass, M.; Thiagarajan, P.

    2017-11-01

    The use of chemical pesticides for agricultural pest control and the consequent damage to the ecosystem at air, water and soil levels has become a factor of common knowledge. This alarming trend has led to research and development in the area of nanoformulations to achieve the end use of pest control with very low concentrations of pesticides. Such formulations are being proven to be as effective as traditional formulations due to their inherent ability to achieve controlled delivery of their respective active ingredients. The end result is a successful pest control with minimum environmental damage. Despite this, certain organic groups, that form the essential structural constituents of these pesticides, are not readily degraded due to their complex nature. They continue to persist, accumulate and biomagnify in the environment leading to short and long term hazards. In this context, it has been noted that certain common genera of bacteria such as Bacillus, Pseudomonas, Flavobacterium, Sphingomonas, Brevibacterium, Burkholderia, etc possess the inherent ability to utilise specific chemical groups in the pesticides as their sole source of either carbon and / or nitrogen and consequently achieve their conversion into non-toxic end products. A potential bioremediation process is thus slowly gaining popularity and being implemented on a pilot scale. However, large scale successful pesticide microbial remediation will involve experimentation with several combinations of a variety of nano pesticide formulations with different genera of bacteria under optimised conditions. Such studies will throw light on the precise genus and species of bacteria that may degrade the required groups of pesticides, for environmental damage control in the long run.

  20. Supramolecular curcumin-barium prodrugs for formulating with ceramic particles.

    Science.gov (United States)

    Kamalasanan, Kaladhar; Anupriya; Deepa, M K; Sharma, Chandra P

    2014-10-01

    A simple and stable curcumin-ceramic combined formulation was developed with an aim to improve curcumin stability and release profile in the presence of reactive ceramic particles for potential dental and orthopedic applications. For that, curcumin was complexed with barium (Ba(2+)) to prepare curcumin-barium (BaCur) complex. Upon removal of the unbound curcumin and Ba(2+) by dialysis, a water-soluble BaCur complex was obtained. The complex was showing [M+1](+) peak at 10,000-20,000 with multiple fractionation peaks of MALDI-TOF-MS studies, showed that the complex was a supramolecular multimer. The (1)H NMR and FTIR studies revealed that, divalent Ba(2+) interacted predominantly through di-phenolic groups of curcumin to form an end-to-end complex resulted in supramolecular multimer. The overall crystallinity of the BaCur was lower than curcumin as per XRD analysis. The complexation of Ba(2+) to curcumin did not degrade curcumin as per HPLC studies. The fluorescence spectrum was blue shifted upon Ba(2+) complexation with curcumin. Monodisperse nanoparticles with size less than 200dnm was formed, out of the supramolecular complex upon dialysis, as per DLS, and upon loading into pluronic micelles the size was remaining in similar order of magnitude as per DLS and AFM studies. Stability of the curcumin was improved greater than 50% after complexation with Ba(2+) as per UV/Vis spectroscopy. Loading of the supramloecular nanoparticles into pluronic micelles had further improved the stability of curcumin to approx. 70% in water. These BaCur supramolecule nanoparticles can be considered as a new class of prodrugs with improved solubility and stability. Subsequently, ceramic nanoparticles with varying chemical composition were prepared for changing the material surface reactivity in terms of the increase in, degradability, surface pH and protein adsorption. Further, these ceramic particles were combined with curcumin prodrug formulations and optimized the curcumin release

  1. Local normal vector field formulation for periodic scattering problems formulated in the spectral domain

    NARCIS (Netherlands)

    van Beurden, M.C.; Setija, Irwan

    2017-01-01

    We present two adapted formulations, one tailored to isotropic media and one for general anisotropic media, of the normal vector field framework previously introduced to improve convergence near arbitrarily shaped material interfaces in spectral simulation methods for periodic scattering geometries.

  2. Formulation of Pine Tar Antidandruff Shampoo Assessment and Comparison With Some Commercial Formulations

    Directory of Open Access Journals (Sweden)

    M. Gharavi

    1990-07-01

    Full Text Available In this study a pine tar shampoo as a new antidandruff formulation is presented. Assessment of antidandruff preparations has been hampered by the lack of standardized schedules, and reliable methods of evaluation.Some antidandruff agents such as : Zinc pyri-thione pine tar, selenium sulphide and (sulfure were used in shampoos. Samples were coded as numbers 1,2 formulated by us and 3,4 formulated commercially. The grading scheme based on 10 point scale, and corneocyte count was carried out on 50 selected volunte¬ers. Corneocyte count and fungal study proved that pine tor shampoo is effective against pityrosporum ovale. Draize lest was used for determination of the irritancy potential of the samples. Results showed that samples numbered 1,2 were relatively innocous in comparison with the others. I urthermore,s kin sensitination test on rabbit also confirmed the results obtained by Draize test. Consumer judgments proved that all formulations were acceptable.

  3. Design and formulation of nano-sized spray dried efavirenz. Part I: Influence of formulation parameters

    CSIR Research Space (South Africa)

    Katata, L

    2012-10-01

    Full Text Available statistical design with an L8 orthogonal array, was implemented to optimise the formulation parameters of PCL-EFV nanoparticles. The types of sugar (lactose or trehalose), surfactant concentration and solvent (dichloromethane and ethyl acetate) were chosen...

  4. Consistency of canonical formulation of Horava gravity

    International Nuclear Information System (INIS)

    Soo, Chopin

    2011-01-01

    Both the non-projectable and projectable version of Horava gravity face serious challenges. In the non-projectable version, the constraint algebra is seemingly inconsistent. The projectable version lacks a local Hamiltonian constraint, thus allowing for an extra graviton mode which can be problematic. A new formulation (based on arXiv:1007.1563) of Horava gravity which is naturally realized as a representation of the master constraint algebra (instead of the Dirac algebra) studied by loop quantum gravity researchers is presented. This formulation yields a consistent canonical theory with first class constraints; and captures the essence of Horava gravity in retaining only spatial diffeomorphisms as the physically relevant non-trivial gauge symmetry. At the same time the local Hamiltonian constraint is equivalently enforced by the master constraint.

  5. Formulation of diclofenac for dermal delivery.

    Science.gov (United States)

    Goh, Choon Fu; Lane, Majella E

    2014-10-01

    Diclofenac (DF) was first synthesized in the 1960's and is currently available as ophthalmic, oral, parenteral, rectal and skin preparations. This review focuses on the administration of DF to the skin. As a member of the non-steroidal anti-inflammatory (NSAID) group of drugs the primary indications of DF are for the management of inflammation and pain but it is also used to treat actinic keratosis. The specific aims of this paper are to: (i) provide an overview of the pharmacokinetics and metabolism of DF following oral and topical administration; (ii) examine critically the various formulation approaches which have been investigated to enhance dermal delivery of DF; and (iii) identify new formulation strategies for enhanced DF skin penetration. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Consistency of canonical formulation of Horava gravity

    Energy Technology Data Exchange (ETDEWEB)

    Soo, Chopin, E-mail: cpsoo@mail.ncku.edu.tw [Department of Physics, National Cheng Kung University, Tainan, Taiwan (China)

    2011-09-22

    Both the non-projectable and projectable version of Horava gravity face serious challenges. In the non-projectable version, the constraint algebra is seemingly inconsistent. The projectable version lacks a local Hamiltonian constraint, thus allowing for an extra graviton mode which can be problematic. A new formulation (based on arXiv:1007.1563) of Horava gravity which is naturally realized as a representation of the master constraint algebra (instead of the Dirac algebra) studied by loop quantum gravity researchers is presented. This formulation yields a consistent canonical theory with first class constraints; and captures the essence of Horava gravity in retaining only spatial diffeomorphisms as the physically relevant non-trivial gauge symmetry. At the same time the local Hamiltonian constraint is equivalently enforced by the master constraint.

  7. Principles of ration formulation for ruminants

    International Nuclear Information System (INIS)

    Jayasuriya, M.C.N.

    2002-01-01

    Feeding standards as practiced in developed countries could be misleading when non-conventional feed resources are used in formulating rations for ruminant livestock in developing countries. They tend to reject the poor quality feeds that are available in vast quantities. The non-availability of good quality forage throughout the year and the need to optimise the efficiency of utilisation of locally available feed resources have lead to the application of basic nutritional principles when considering ration formulation. The alternative approach to the use of feeding standards would be to ensure that the production system matches the available resources. The development of feed supplementation strategies based on locally available feed resources require the understanding of the relative roles and nutrient needs of the two-compartment system represented by the micro-organisms in the rumen and the host animal. (author)

  8. Spray drying formulation of amorphous solid dispersions.

    Science.gov (United States)

    Singh, Abhishek; Van den Mooter, Guy

    2016-05-01

    Spray drying is a well-established manufacturing technique which can be used to formulate amorphous solid dispersions (ASDs) which is an effective strategy to deliver poorly water soluble drugs (PWSDs). However, the inherently complex nature of the spray drying process coupled with specific characteristics of ASDs makes it an interesting area to explore. Numerous diverse factors interact in an inter-dependent manner to determine the final product properties. This review discusses the basic background of ASDs, various formulation and process variables influencing the critical quality attributes (CQAs) of the ASDs and aspects of downstream processing. Also various aspects of spray drying such as instrumentation, thermodynamics, drying kinetics, particle formation process and scale-up challenges are included. Recent advances in the spray-based drying techniques are mentioned along with some future avenues where major research thrust is needed. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Canonical formulation of general-relativistic theories

    International Nuclear Information System (INIS)

    Bergmann, P.G.

    1987-01-01

    With the birth of quantum field theory in the late twenties physicists decided that nature could not be half classical and half quantum, and that the gravitational field ought to be quanticized, just as the electromagnetic field had been. One could accept the group of differomorphisms as a fundamental characteristic of general relativity (and indeed of all general-relativistic theories), and proceed to construct a quantum field-theory that was adapted to that group. Quantization would be attempted by way of a Hamiltonian formulation of the (classical) theory, and quantum commutation relations be patterned after the Poisson brackets arising in that formulation. This program is usually called the canonical quantization program, whereas the weak-field approach is known as covariant quantization. The first steps, conceived entirely within the framework of the classical theory, turned out to be beset with technical and conceptual difficulties, which today are essentially resolved. In this paper the author traces out these initial steps

  10. Evaluation of dermatological effects of cosmetic formulations containing Saccharomyces cerevisiae extract and vitamins.

    Science.gov (United States)

    Gaspar, L R; Camargo, F B; Gianeti, M D; Maia Campos, P M B G

    2008-11-01

    Saccharomyces cerevisiae extract (SCE) is used in cosmetics since it can act in oxidative stress and improve skin conditions. This study investigated dermatological effects of cosmetic formulations containing SCE and/or vitamins A, C and E. The formulation studied was supplemented or not (F1: vehicle) with vitamins A, C and E esters (F2) or with SCE (F3) or with the combination of vitamins and SCE (F4). Formulations were patch tested on back skin of volunteers. For efficacy studies, formulations were applied on volunteers and transepidermal water loss (TEWL), skin moisture (SM), skin microrelief (SMR) and free radicals protection were analysed after 3h, 15 and 30 days of application. Volunteers were also asked about efficacy perception. It was observed that F4 provoked a slight erythema in one volunteer. All formulations enhanced forearm SM. Only F3 and F4 presented long term effects on SMR and showed higher texture values; F3 had the highest brightness values. Our results suggest that vitamins and SCE showed effects in SM and SMR. Only formulations containing SC had long term effects in the improvement of SMR. Thus, these kinds of evaluations are very important in cosmetics development to evaluate the best risk and benefit correlation.

  11. A comparison of Fick and Maxwell-Stefan diffusion formulations in PEMFC gas diffusion layers

    Science.gov (United States)

    Lindstrom, Michael; Wetton, Brian

    2017-01-01

    This paper explores the mathematical formulations of Fick and Maxwell-Stefan diffusion in the context of polymer electrolyte membrane fuel cell cathode gas diffusion layers. The simple Fick law with a diagonal diffusion matrix is an approximation of Maxwell-Stefan. Formulations of diffusion combined with mass-averaged Darcy flow are considered for three component gases. For this application, the formulations can be compared computationally in a simple, one dimensional setting. Despite the models' seemingly different structure, it is observed that the predictions of the formulations are very similar on the cathode when air is used as oxidant. The two formulations give quite different results when the Nitrogen in the air oxidant is replaced by helium (this is often done as a diagnostic for fuel cells designs). The two formulations also give quite different results for the anode with a dilute Hydrogen stream. These results give direction to when Maxwell-Stefan diffusion, which is more complicated to implement computationally in many codes, should be used in fuel cell simulations.

  12. Planar multibody dynamics formulation, programming and applications

    CERN Document Server

    Nikravesh, Parviz E

    2007-01-01

    Introduction Multibody Mechanical Systems Types of Analyses Methods of Formulation Computer Programming Application Examples Unit System Remarks Preliminaries Reference Axes Scalars and Vectors Matrices Vector, Array, and Matrix Differentiation Equations and Expressions Remarks Problems Fundamentals of Kinematics A Particle Kinematics of a Rigid Body Definitions Remarks Problems Fundamentals of Dynamics Newton's Laws of Motion Dynamics of a Body Force Elements Applied Forces Reaction Force Remarks Problems Point-Coordinates: Kinematics Multipoint

  13. Alternative formulations of the electricity tax

    International Nuclear Information System (INIS)

    2003-01-01

    According to EFTA's surveillance authority ESA, the current form of the electricity tax may have a competition distorting effect since only the industry and a few other sectors are exempt from it. This document discusses four alternative formulations of the electricity tax: same tax for all business sectors and households, defining a maximum payment for each firm, introduce a tax on power transmission, or have taxation only on power used for heating.

  14. Formulation and Evaluation of Bioadhesive Cyproheptadine Tablets ...

    African Journals Online (AJOL)

    Results: The shear stress of 3 % solution of HPMC was greater than that of an equivalent concentration of Carbopol 934P. The values of K, n, R2 and detachment force for the optimized formulation (F0) were 0.269, 0.696, 0.964 and 0.066 Newton (N), respectively, and showed good correlation with the predicted values, thus ...

  15. Ising formulations of many NP problems

    OpenAIRE

    Lucas, Andrew

    2013-01-01

    We provide Ising formulations for many NP-complete and NP-hard problems, including all of Karp's 21 NP-complete problems. This collects and extends mappings to the Ising model from partitioning, covering and satisfiability. In each case, the required number of spins is at most cubic in the size of the problem. This work may be useful in designing adiabatic quantum optimization algorithms.

  16. Ising formulations of many NP problems

    Directory of Open Access Journals (Sweden)

    Andrew eLucas

    2014-02-01

    Full Text Available We provide Ising formulations for many NP-complete and NP-hard problems, including all of Karp's 21 NP-complete problems. This collects and extends mappings to the Ising model from partitioning, covering and satisfiability. In each case, the required number of spins is at most cubic in the size of the problem. This work may be useful in designing adiabatic quantum optimization algorithms.

  17. Microcanonical ensemble formulation of lattice gauge theory

    International Nuclear Information System (INIS)

    Callaway, D.J.E.; Rahman, A.

    1982-01-01

    A new formulation of lattice gauge theory without explicit path integrals or sums is obtained by using the microcanonical ensemble of statistical mechanics. Expectation values in the new formalism are calculated by solving a large set of coupled, nonlinear, ordinary differential equations. The average plaquette for compact electrodynamics calculated in this fashion agrees with standard Monte Carlo results. Possible advantages of the microcanonical method in applications to fermionic systems are discussed

  18. Path Integral Formulation of Anomalous Diffusion Processes

    OpenAIRE

    Friedrich, Rudolf; Eule, Stephan

    2011-01-01

    We present the path integral formulation of a broad class of generalized diffusion processes. Employing the path integral we derive exact expressions for the path probability densities and joint probability distributions for the class of processes under consideration. We show that Continuous Time Random Walks (CTRWs) are included in our framework. A closed expression for the path probability distribution of CTRWs is found in terms of their waiting time distribution as the solution of a Dyson ...

  19. FORMULATION AND EVALUATION OF A HERBAL SHAMPOO

    OpenAIRE

    Gouri Kumar Dash* and Noor Husna Nazirah Binti A. Razak

    2017-01-01

    The study was aimed at formulating and evaluating a complete herbal shampoo containing only traditionally used plant materials. The shampoo contained extracts of Hibiscus rosa-sinensis, Azadirachta indica, Trigonella foenumgraecum, Phyllanthus emblica, Sapindus mukorossi, Acacia concinna and fresh juice of Aloe vera. The physicochemical parameters such as colour, clarity, pH, skin irritation, percentage of solid contents, dirt dispersion, foaming ability and foam stability, wetting time and c...

  20. Prednisone raw material characterization and formulation development

    OpenAIRE

    Leonardo Henrique Toehwé; Livia Deris Prado; Helvécio Vinícius Antunes Rocha

    2018-01-01

    ABSTRACT Solid dosage forms for oral use, particularly tablets, are the most highly used dosage forms in therapy because they are easily administered, have high productivity and relatively low cost and provide a more stable drug to form a semi-solid net. Numerous parameters influence the quality of the final dosage form. In this study, the dissolution profile of 20-mg prednisone tablets bioequivalent to the reference product and three test formulations were evaluated using stability testing. ...

  1. SO(9,1) invariant matrix formulation of a supermembrane

    International Nuclear Information System (INIS)

    Fujikawa, K.; Okuyama, K.

    1998-01-01

    An SO(9,1) invariant formulation of an 11-dimensional supermembrane is presented by combining an SO(10,1) invariant treatment of reparametrization symmetry with an SO(9,1) invariant θ R = 0 gauge of κ-symmetry. The Lagrangian thus defined consists of polynomials in dynamical variables (up to quartic terms in X μ and up to the eighth power in θ), and reparametrization BRST symmetry is manifest. The area preserving diffeomorphism is consistently incorporated and the area preserving gauge symmetry is made explicit. The SO(9,1) invariant theory contains terms which cannot be induced by a naive dimensional reduction of higher-dimensional supersymmetric Yang-Mills theory. The SO(9,1) invariant Hamiltonian and the generator of area preserving diffeomorphism together with the supercharge are matrix regularized by applying the standard procedure. As an application of the present formulation, we evaluate the possible central charges in superalgebra both in the path integral and in the canonical (Dirac) formalism, and we find only the two-form charge [ X μ , X ν ]. (orig.)

  2. An Investigation of Optimum NLC-Sunscreen Formulation Using Taguchi Analysis

    Directory of Open Access Journals (Sweden)

    Pao Chi Chen

    2013-01-01

    Full Text Available This study used three kinds of wax and three kinds of oil, with fixed mixture ratio including UV-blocking materials of ethylhexyl methoxycinnamate, oxybenzone, and avobenzone, and applied hot high-pressure homogenization process to prepare nanolipid sunscreen formulations. The measured particle size of the sunscreen formulations was 100~300 nm around PDI of 0.2 having a moderate polydisperse system. The distribution of zeta potential was −50 mV to −35 mV, showing a stable system. The UV light-absorbing range of 9 groups of sunscreen formulations was 275 nm~380 nm ranging within UVA and UVB. The rheological analysis found that the viscosity change is shear, thinning exhibiting colloid behavior. Taguchi analysis found that the optimum combinations are the carnauba wax and the blackcurrant oil combination for crystallinity and the beeswax and CPG oil for UV absorption. In addition, UV-blocking ability shows that the SPF was 51.5 and PFA was three stars for SU9 formulation. Finally, the effect of temperature on the properties of sunscreen formulations was also explored.

  3. [Exploration of how to formulate guidelines on post-marketing traditional Chinese medicine surveillance].

    Science.gov (United States)

    Zhang, Wen; Xie, Yan-Ming; Yu, Wen-Ya

    2013-09-01

    Combining the world health organization's (WHO), the United States and the European union's relevant laws and guidelines on post-marketing drug surveillance to judge the status of post-marketing surveillance of traditional Chinese medicine(TCM) in China. We found that due to the late start of post-marketing surveillance of traditional Chinese medicine, the appropriate guidelines are yet to be developed. Hence, hospitals, enterprises and research institutions do not have a shared foundation from which to compare their research results. Therefore there is an urgent need to formulate such post-marketing surveillance guidelines. This paper has used as guidance various technical documents such as, "procedures to formulate national standards" and "testing methods of management in formulating traditional Chinese medicine standards" and has combined these to produce a version of post-marketing surveillance particular to Chinese medicine in China. How to formulate these guidelines is discussed and procedures and methods to formulate technical specifications are introduced. These provide a reference for future technical specifications and will assist in the development of TCM.

  4. Novel sublingual low-dose zolpidem tablet reduces latency to sleep onset following spontaneous middle-of-the-night awakening in insomnia in a randomized, double-blind, placebo-controlled, outpatient study.

    Science.gov (United States)

    Roth, Thomas; Krystal, Andrew; Steinberg, Frank J; Singh, Nikhilesh N; Moline, Margaret

    2013-02-01

    To evaluate efficacy and safety of 3.5-mg zolpidem tartrate sublingual tablets (ZST) on latency to sleep onset after middle-of-the-night (MOTN) awakenings in patients with insomnia characterized by difficulty returning to sleep after MOTN awakenings. Multicenter randomized, double-blind, placebo-controlled, parallel-group. Outpatient. There were 295 adults (median age 43 y; 68.1% female) with primary insomnia and difficulty returning to sleep after MOTN awakenings (three or more MOTN awakenings/wk during screening). After a 2-wk, single-blind placebo eligibility period, participants were randomized 1:1 to as-needed MOTN dosing with 3.5 mg ZST or placebo for 28 nights. An interactive voice response system determined if the study drug could be taken and recorded sleep/wake efficacy measures. ZST significantly (P Zolpidem Tartrate Tablet in Adult Patients with Insomnia" http://www.clinicaltrials.gov/ct2/show/NCT00466193?spons=%22Transcept+Pharmaceuticals%22&spons_ex=Y&rank=2

  5. [ANALYSIS OF BACKGROUNDS AND LEVEL OF UNDERSTANDING OF TREATMENT OF POOR ADHERENCE AND DROPOUT CASES ON SUBLINGUAL IMMUNOTHERAPY FOR JAPANESE CEDAR POLLINOSIS IN THE FIRST FOLLOW-UP YEAR].

    Science.gov (United States)

    Kikkawa, Sayaka; Kamijo, Atsushi; Nakagome, Kazuyuki; Soma, Tomoyuki; Kobayashi, Takehito; Uchida, Yoshitaka; Morita, Eiji; Nagata, Makoto; Inoue, Tomoe; Kase, Yasuhiro

    We considered the factors of poor adherence to and dropout from sublingual immunotherapy (SLIT) by verifying patient backgrounds 1 year after start of treatment. We recruited 38 patients who began SLIT between November 2014 and September 2015. We analyzed their attributes and level of understanding of the treatment, and conducted a self-reported survey on factors behind dropout cases and poor adherence cases. Four patients dropped out 1 year after start of treatment. Three left for reasons related to anxiety about side effects. There were five cases of poor adherence. There was no significant difference between good adherence, poor adherence, and dropout regarding level of understanding of the treatment (p=0.59). In the comparison between good and poor adherence groups, except four dropout patients, the adherence tended to be poor in patients with short duration of disease, smoking patients, and young patients. Continuous rate of SLIT achieved about 90%, suggesting relatively high level of adherence. It appears possible that anxiety related to side effects could be a factor affecting dropout from SLIT. There was no significant difference regarding level of understanding of the treatment. The adherence tended to be poor in patients with short duration of disease, smoking patients, and young patients.

  6. Trigger chemistries for better industrial formulations.

    Science.gov (United States)

    Wang, Hsuan-Chin; Zhang, Yanfeng; Possanza, Catherine M; Zimmerman, Steven C; Cheng, Jianjun; Moore, Jeffrey S; Harris, Keith; Katz, Joshua S

    2015-04-01

    In recent years, innovations and consumer demands have led to increasingly complex liquid formulations. These growing complexities have provided industrial players and their customers access to new markets through product differentiation, improved performance, and compatibility/stability with other products. One strategy for enabling more complex formulations is the use of active encapsulation. When encapsulation is employed, strategies are required to effect the release of the active at the desired location and time of action. One particular route that has received significant academic research effort is the employment of triggers to induce active release upon a specific stimulus, though little has translated for industrial use to date. To address emerging industrial formulation needs, in this review, we discuss areas of trigger release chemistries and their applications specifically as relevant to industrial use. We focus the discussion on the use of heat, light, shear, and pH triggers as applied in several model polymeric systems for inducing active release. The goal is that through this review trends will emerge for how technologies can be better developed to maximize their value through industrial adaptation.

  7. What is Quantum Mechanics? A Minimal Formulation

    Science.gov (United States)

    Friedberg, R.; Hohenberg, P. C.

    2018-03-01

    This paper presents a minimal formulation of nonrelativistic quantum mechanics, by which is meant a formulation which describes the theory in a succinct, self-contained, clear, unambiguous and of course correct manner. The bulk of the presentation is the so-called "microscopic theory", applicable to any closed system S of arbitrary size N, using concepts referring to S alone, without resort to external apparatus or external agents. An example of a similar minimal microscopic theory is the standard formulation of classical mechanics, which serves as the template for a minimal quantum theory. The only substantive assumption required is the replacement of the classical Euclidean phase space by Hilbert space in the quantum case, with the attendant all-important phenomenon of quantum incompatibility. Two fundamental theorems of Hilbert space, the Kochen-Specker-Bell theorem and Gleason's theorem, then lead inevitably to the well-known Born probability rule. For both classical and quantum mechanics, questions of physical implementation and experimental verification of the predictions of the theories are the domain of the macroscopic theory, which is argued to be a special case or application of the more general microscopic theory.

  8. Development of formulation device for periodontal disease.

    Science.gov (United States)

    Sato, Yasuhiko; Oba, Takuma; Watanabe, Norio; Danjo, Kazumi

    2012-01-01

    In addition to providing standard surgical treatment that removes the plaque and infected tissues, medications that can regenerate periodontal tissue are also required in the treatment of periodontal disease. As a form of regenerative medication, various growth factors are expected to be used while treating periodontal disease. A protein-like growth factor is often developed as a lyophilized product with dissolution liquid, considering its instability in the solution state. We have clarified that the formulation for periodontal disease needs to be viscous. When the lyophilized product was dissolved using a sticky solution, various problems were encountered, difficulty in dissolving and air bubbles, for example, and some efforts were needed to prepare the formulation. In this research, to identify the problem of preparing a viscous formulation, a lyophilized product (placebo) and sticky liquid were prepared by using vial and ampoule as the conventional containers. Based on these problems, a prototype administration device was developed, and its functionality was confirmed. As a result, it was suggested that the device with a useful mixing system that could shorten the preparation time was developed.

  9. Numerical simulation using vorticity-vector potential formulation

    Science.gov (United States)

    Tokunaga, Hiroshi

    1993-01-01

    An accurate and efficient computational method is needed for three-dimensional incompressible viscous flows in engineering applications. On solving the turbulent shear flows directly or using the subgrid scale model, it is indispensable to resolve the small scale fluid motions as well as the large scale motions. From this point of view, the pseudo-spectral method is used so far as the computational method. However, the finite difference or the finite element methods are widely applied for computing the flow with practical importance since these methods are easily applied to the flows with complex geometric configurations. However, there exist several problems in applying the finite difference method to direct and large eddy simulations. Accuracy is one of most important problems. This point was already addressed by the present author on the direct simulations on the instability of the plane Poiseuille flow and also on the transition to turbulence. In order to obtain high efficiency, the multi-grid Poisson solver is combined with the higher-order, accurate finite difference method. The formulation method is also one of the most important problems in applying the finite difference method to the incompressible turbulent flows. The three-dimensional Navier-Stokes equations have been solved so far in the primitive variables formulation. One of the major difficulties of this method is the rigorous satisfaction of the equation of continuity. In general, the staggered grid is used for the satisfaction of the solenoidal condition for the velocity field at the wall boundary. However, the velocity field satisfies the equation of continuity automatically in the vorticity-vector potential formulation. From this point of view, the vorticity-vector potential method was extended to the generalized coordinate system. In the present article, we adopt the vorticity-vector potential formulation, the generalized coordinate system, and the 4th-order accurate difference method as the

  10. Hydrazine levels in formulations of hydralazine, isoniazid, and phenelzine over a 2-year period.

    Science.gov (United States)

    Lovering, E G; Matsui, F; Curran, N M; Robertson, D L; Sears, R W

    1983-08-01

    Hydrazine levels in formulations of hydralazine, isoniazid, and phenelzine have been measured over a 2-year period under ambient conditions and under temperature and humidity stress. Hydralazine tablets are stable under ambient conditions, but the hydrazine level in an injectable formulation increased from 4.5 to 10 micrograms/ml over a 23-month period. Isoniazid tablets are also stable, but hydrazine levels in an elixir and a pyridoxine combination product doubled to 44 micrograms/ml and 19 micrograms/tablet, respectively. Levels in phenelzine tablets appeared to remain constant at approximately 60 micrograms/tablet, with considerable tablet-to-tablet variation.

  11. Extensive preclinical investigation of polymersomal formulation of doxorubicin versus Doxil-mimic formulation.

    Science.gov (United States)

    Alibolandi, Mona; Abnous, Khalil; Mohammadi, Marzieh; Hadizadeh, Farzin; Sadeghi, Fatemeh; Taghavi, Sahar; Jaafari, Mahmoud Reza; Ramezani, Mohammad

    2017-10-28

    Due to the severe cardiotoxicity of doxorubicin, its usage is limited. This shortcoming could be overcome by modifying pharmacokinetics of the drugs via preparation of various nanoplatforms. Doxil, a well-known FDA-approved nanoplatform of doxorubicin as antineoplastic agent, is frequently used in clinics in order to reduce cardiotoxicity of doxorubicin. Since Doxil shows some shortcomings in clinics including hand and food syndrome and very slow release pattern thus, there is a demand for the development and preparation of new doxorubicin nanoformulation with fewer side effects. The new formulation of the doxorubicin, synthesized previously by our group was extensively examined in the current study. This new formulation is doxorubicin encapsulated in PEG-PLGA polymersomes (PolyDOX). The main aim of the study was to compare the distribution and treatment efficacy of a new doxorubicin-polymersomal formulation (PolyDOX) with regular liposomal formulation (Doxil-mimic) in murine colon adenocarcinoma model. Additionally, the pathological, hematological changes, pharmacodynamics, biodistribution, tolerated dose and survival rate in vivo were evaluated and compared. Murine colon cancer model was induced by subcutaneous inoculation of BALB/c mice with C26 cells. Afterwards, either Doxil-mimic or PolyDOX was administered intravenously. The obtained results from biodistribution study showed a remarkable difference in the distribution of drugs in murine organs. In this regard, Doxil-mimic exhibited prolonged (48h) presence within liver tissues while PolyDOX preferentially accumulate in tumor and the presence in liver 48h post-treatment was significantly lower than that of Doxil-mimic. Obtained results demonstrated comparable final length of life for mice receiving either Doxil-mimic or PolyDOX formulations whereas tolerated dose of mice receiving Doxil-mimic was remarkably higher than those receiving PolyDOX. Therapeutic efficacy of formulation in term of tumor growth rate

  12. Role reductants in dilute chemical decontamination formulations

    Energy Technology Data Exchange (ETDEWEB)

    Ranganathan, S. [Univ. of New Brunswick (Canada). Dept. of Chemical Engineering; Srinivasan, M.P.; Narasimhan, S.V. [Bhabha Atomic Research Centre (BARC), Trombay, Mumbai (India). Water and Steam Chemistry Lab.; Raghavan, P.S. [Madras Christian Coll., Chennai (India); Gopalan, R. [Madras Christian Coll., Chennai (India). Dept. of Chemistry

    2004-10-01

    Iron(III) oxides are the major corrosion products formed in boiling water reactors. The iron(III) oxides are of two types, namely hematite ({alpha}-Fe{sub 2}O{sub 3}) and maghemite ({gamma}-Fe{sub 2}O{sub 3}). The dissolution of these oxides is in no way simple because of the labile nature of the Fe(III)-O bond towards the chelants. The leaching of metal ions is partially controlled by reductive dissolution. In order to understand the role of the reductant, it is essential to study the dissolution behaviour of a system like Fe{sub 2}O{sub 3}, which does not contain any Fe{sup 2+} in the crystal lattice. The present study was carried out with {gamma}-Fe{sub 2}O{sub 3} and dilute chemical decontamination (DCD) formulations containing ascorbic acid and citric acid with the addition of Fe(II)-L as a reductant. The chelants used for the dissolution process were nitrilotriacetic acid, 2,6-pyridinedicorboxylic acid and ethylenediaminetetraacetic acid. The {gamma}-Fe{sub 2}O{sub 3} was chosen since the earlier studies revealed that the dissolution kinetics of {alpha}-Fe{sub 2}O{sub 3} is slow and it is difficult to dissolve even by strong complexing agents, whereas {gamma}-Fe{sub 2}O{sub 3} dissolution is comparatively easier. This is due to the structural difference between these two oxides. The studies also revealed that the dissolution was partly influenced by the nature of the chelating agents but mainly controlled by the power of the reductants used in the formulation. The dissolution behaviour of {gamma}-Fe{sub 2}O{sub 3} under various experimental conditions is discussed and compared with that of magnetite in order to arrive at a suitable mechanism for the dissolution of iron oxides and emphasize the role of reductants in DCD formulations. (orig.)

  13. Random path formulation of nonrelativistic quantum mechanics

    International Nuclear Information System (INIS)

    Roncadelli, M.

    1993-01-01

    Quantum amplitudes satisfy (almost) the same calculus that probabilities obey in the theory of classical stochastic diffusion processes. As a consequence of this structural analogy, a new formulation of (nonrelativistic) quantum mechanics naturally arises as the quantum counterpart of the Langevin description of (classical) stochastic diffusion processes. Quantum fluctuations are simulated here by a Fresnel white noise (FWN), which is a (real) white noise with imaginary diffusion constant, whose functional (pseudo) measure yields the amplitude distribution for its configurations. Central to this approach is the idea that classical dynamical trajectories in configuration space are perturbed by the FWN. Hence, a single (arbitrary) classical dynamical path gets replaced by a family of quantum random paths (QRPs) - one for each FWN sample - all originating from the same space-time point (x', t'). The QRPs are the basic objects of the present formulation and are given by a Langevin equation with the FWN, whose drift is controlled by a (arbitrary) solution to the classical Hamilton-Jacobi equation. So, our approach is manifestly based on classical dynamics. Now, a transition amplitude is associated with each QRP: it gives the amplitude that a particle starting from (x', t') will reach (x'', t'') by travelling just along the considered QRP. The quantum mechanical propagator (x'', t'' modul x', t') then emerges as the FWN average of the transition amplitude along a QRP. Thus, quantum mechanics looks like classical mechanics as perturbed by the FWN. The general structure of this formulation is discussed in detail, along with some practical and conceptual implications. (author). 14 refs

  14. Oral matrix tablet formulations for concomitant controlled release of anti-tubercular drugs: design and in vitro evaluations.

    Science.gov (United States)

    Hiremath, Praveen S; Saha, Ranendra N

    2008-10-01

    The aim of the present investigation was to develop controlled release (C.R.) matrix tablet formulations of rifampicin and isoniazid combination, to study the design parameters and to evaluate in vitro release characteristics. In the present study, a series of formulations were developed with different release rates and duration using hydrophilic polymers hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC). The duration of rifampicin and isoniazid release could be tailored by varying the polymer type, polymer ratio and processing techniques. Further, Eudragit L100-55 was incorporated in the matrix tablets to compensate for the pH-dependent release of rifampicin. Rifampicin was found to follow linear release profile with time from HPMC formulations. In case of formulations with HPC, there was an initial higher release in simulated gastric fluid (SGF) followed by zero order release profiles in simulated intestinal fluid (SIFsp) for rifampicin. The release of isoniazid was found to be predominantly by diffusion mechanism in case of HPMC formulations, and with HPC formulations release was due to combination of diffusion and erosion. The initial release was sufficiently higher for rifampicin from HPC thus ruling out the need to incorporate a separate loading dose. The initial release was sufficiently higher for isoniazid in all formulations. Thus, with the use of suitable polymer or polymer combinations and with the proper optimization of the processing techniques it was possible to design the C.R. formulations of rifampicin and isoniazid combination that could provide the sufficient initial release and release extension up to 24h for both the drugs despite of the wide variations in their physicochemical properties.

  15. Formulation of optimal international freight transport objective

    Directory of Open Access Journals (Sweden)

    A. Jarašūnienė

    2002-10-01

    Full Text Available To increase the attraction of Lithuania as a transit country striving to promote carriers' border crossing activities and facilitate customs clearance procedures as well as freight delivery to clients it is necessary to identify the main obstacles, to analyse them and to select adequate measures and means for their elimination. Therefore, on the basis of the formulation of transport freight management objective, as well as basing on the assessment of indeterminacy of external impacts, it would be possible to deduce the main causes of idle time of transport means in customs, to estimate the dependence of service time in proportion to transport flow.

  16. Variational formulation of the Gardner's restacking algorithm

    International Nuclear Information System (INIS)

    Dodin, I.Y.; Fisch, N.J.

    2004-01-01

    The incompressibility of the phase flow of Hamiltonian wave-plasma interactions restrains the class of realizable wave-driven transformations of the particle distribution. After the interaction, the distribution remains composed of the original phase-space elements, or local densities, which are only rearranged (''restacked'') by the wave. A variational formalism is developed to study the corresponding limitations on the energy and momentum transfer. A case of particular interest is a toroidal plasma immersed in a dc magnetic field. The restacking algorithm by Gardner [Phys. Fluids 6, 839 (1963)] is formulated precisely. The minimum energy state for a plasma with a given current is determined

  17. Canonical formulation of IIB D-branes

    International Nuclear Information System (INIS)

    Kamimura, K.

    1998-01-01

    We find Wess-Zumino actions for kappa invariant type IIB D-branes in explicit forms. A simple and compact expression is obtained by the use of spinor variables which are defined as power series of differential forms. Using the Wess-Zumino actions we develop the canonical formulation and find the complete set of the constraint equations for generic type IIB Dp-branes. The conserved global supersymmetry charges are determined and the algebra containing the central charges can be obtained explicitly. (orig.)

  18. A geometric formulation of exceptional field theory

    Energy Technology Data Exchange (ETDEWEB)

    Bosque, Pascal du [Arnold Sommerfeld Center for Theoretical Physics,Department für Physik, Ludwig-Maximilians-Universität München,Theresienstraße 37, 80333 München (Germany); Max-Planck-Institut für Physik, Werner-Heisenberg-Institut, Föhringer Ring 6, 80805 München (Germany); Hassler, Falk [Department of Physics and Astronomy, University of North Carolina, Phillips Hall, CB #3255, 120 E. Cameron Ave., Chapel Hill, NC 27599-3255 (United States); City University of New York, The Graduate Center, 365 Fifth Avenue, New York, NY 10016 (United States); Department of Physics, Columbia University, Pupin Hall, 550 West 120th St., New York, NY 10027 (United States); Lüst, Dieter [Arnold Sommerfeld Center for Theoretical Physics,Department für Physik, Ludwig-Maximilians-Universität München,Theresienstraße 37, 80333 München (Germany); Max-Planck-Institut für Physik, Werner-Heisenberg-Institut, Föhringer Ring 6, 80805 München (Germany); Malek, Emanuel [Arnold Sommerfeld Center for Theoretical Physics,Department für Physik, Ludwig-Maximilians-Universität München,Theresienstraße 37, 80333 München (Germany)

    2017-03-01

    We formulate the full bosonic SL(5) exceptional field theory in a coordinate-invariant manner. Thereby we interpret the 10-dimensional extended space as a manifold with SL(5)×ℝ{sup +}-structure. We show that the algebra of generalised diffeomorphisms closes subject to a set of closure constraints which are reminiscent of the quadratic and linear constraints of maximal seven-dimensional gauged supergravities, as well as the section condition. We construct an action for the full bosonic SL(5) exceptional field theory, even when the SL(5)×ℝ{sup +}-structure is not locally flat.

  19. Forecast combinations

    OpenAIRE

    Aiolfi, Marco; Capistrán, Carlos; Timmermann, Allan

    2010-01-01

    We consider combinations of subjective survey forecasts and model-based forecasts from linear and non-linear univariate specifications as well as multivariate factor-augmented models. Empirical results suggest that a simple equal-weighted average of survey forecasts outperform the best model-based forecasts for a majority of macroeconomic variables and forecast horizons. Additional improvements can in some cases be gained by using a simple equal-weighted average of survey and model-based fore...

  20. Preparation and characterization of Slow Release Formulations of ...

    African Journals Online (AJOL)

    alginate beads and characterize the resulting slow release formulations (SRFs) using scanning electron microscopy (SEM), and Fourier Transform infrared spectroscopy (FTIR). Two sets of formulations were made by extrusion into 0.25 M calcium ...

  1. Combined homicide

    Directory of Open Access Journals (Sweden)

    Slović Živana

    2017-01-01

    Full Text Available Introduction: Combined homicide is a combination of two or more different modes of killing. These homicides occur when multiple perpetrators have different mode of killing, to hide the true manner of death, or when an initially unsuccessful attack with one weapon is abandoned and changed by another mode which is more successful, or due to availability of weapons at the scene of homicide, or unexpected appearance of possible eyewitness, or else. Case report: This case report is about 65-year old woman who was found in her residence on the floor next to the bed lying on her back with two kitchen knives in her neck. Autopsy revealed an abrasion on the frontal part of the neck and a bruise of the soft tissues of the neck with a double fracture of both greater horns of the hyoid bone and a fracture of both superior horns of the thyroid cartilage. The cause of death was exsanguination into right half of the thoracic cavity from the left subclavian artery which was cut, on the spot of stab wound in the neck. Conclusion: Hemorrhage in the soft tissue near broken hyoid bone and thyroid cartilage indicate that the victim was first strangulated and then stabbed with kitchen knives. Combined homicides are caused by one or more killers in order to accelerate the killing, or to be sure to provide the fatal outcome. This case is also interesting because the killer left weapon in the victim's neck.

  2. Formulation of humic-based soil conditioners

    Science.gov (United States)

    Amanova, M. A.; Mamytova, G. A.; Mamytova, B. A.; Kydralieva, K. A.; Jorobekova, Sh. J.

    2009-04-01

    The goal of the study is to prepare soil conditioners (SC) able to carry out the following functions: (i) the chemical conditioning of soil mainly comprising the adjustment of pH, (ii) the balancing of inorganic nutrients, (iii) the physical conditioning of soil mainly comprising the improvement of water permeability, air permeability and water retention properties, and (iv) improvement of the ecological system concerning of useful microorganisms activity in the soil. The SC was made of a mixture of inorganic ingredients, a chemical composition and physical and chemical properties of which promoted improvement of physical characteristic of soil and enrichment by its mineral nutritious elements. In addition to aforesaid ingredients, this soil conditioner contains agronomical-valued groups of microorganisms having the function promoting the growth of the crop. As organic component of SC humic acids (HA) was used. HA serve many major functions that result in better soil and plant health. In soil, HA can increase microbial and mycorrhizal activity while enhancing nutrient uptake by plant roots. HA work as a catalyst by stimulating root and plant growth, it may enhance enzymatic activity that in turn accelerates cell division which can lead to increased yields. HA can help to increase crop yields, seed germination, and much more. In short, humic acids helps keep healthy plants health. The first stage goal was to evaluate mineral and organic ingredients for formulation of SC. Soil conditioners assessed included ash and slag. The use of slags has been largelly used in agriculture as a source of lime and phosphoric acid. The silicic acid of slags reduces Al-acitivity thus, promoting a better assimilation of P-fertilizer by plants. Additionally, silicic acid is also known to improve soil moisture capacity, thus enhancing soil water availability to plants. Physico-chemical characteristics of ash and slag were determined, as a total - about 20 samples. Results include

  3. Conference report: formulating better medicines for children: 4th European Paediatric Formulation Initiative conference.

    Science.gov (United States)

    Walsh, Jennifer; Mills, Simon

    2013-01-01

    The fourth annual European Paediatric Formulation Initiative (EuPFI) conference on Formulating Better Medicines for Children was held on 19-20 September 2012 at the Institute of Molecular Genetics Congress Centre, Prague, Czech Republic. The 2-day conference concentrated on the latest advances, challenges and opportunities for developing medicinal products and administration devices for pediatric use, both from European and US perspectives. It was aimed specifically at providing exposure to emerging practical applications, and for illustrating remedies utilized by pediatric drug-development teams to overcome hurdles faced in developing medicines for pediatric patients. The conference format included plenary talks, focus sessions on each of the EuPFI work streams (extemporaneous preparations, excipients, pediatric administration devices, taste masking and taste assessment, age-appropriate formulations), case studies, soapbox sessions and a parallel poster display. This conference report summarizes the keynote lectures and also gives a flavor of other presentations and posters from the conference.

  4. Grid refinement model in lattice Boltzmann method for stream function-vorticity formulations

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Myung Seob [Dept. of Mechanical Engineering, Dongyang Mirae University, Seoul (Korea, Republic of)

    2015-03-15

    In this study, we present a grid refinement model in the lattice Boltzmann method (LBM) for two-dimensional incompressible fluid flow. That is, the model combines the desirable features of the lattice Boltzmann method and stream function-vorticity formulations. In order to obtain an accurate result, very fine grid (or lattice) is required near the solid boundary. Therefore, the grid refinement model is used in the lattice Boltzmann method for stream function-vorticity formulation. This approach is more efficient in that it can obtain the same accurate solution as that in single-block approach even if few lattices are used for computation. In order to validate the grid refinement approach for the stream function-vorticity formulation, the numerical simulations of lid-driven cavity flows were performed and good results were obtained.

  5. Fundamental study on formulation design of skin care products by modeling of tactile sensation.

    Science.gov (United States)

    Akiyama, Yoko; Mishima, Fumihito; Nishijima, Shigehiro

    2013-01-01

    The objective of this study is to construct a method to quantify and formulate the human tactile sensation. We have tried to indicate the sensory scores of tactile sensation as a combination of the physical values of skin care products. Consequently, the extracted principle factors of the sensory properties could be related to the physical values by multiple regression analysis. For the next step, we investigated the physical mechanism of tactile sensation, and proposed a method to formulate the sensory properties. A method to formulate the sensory properties of skin care products was constructed based on the relation between sensory values, principal factors, physical values and composition. The method was verified by sensory evaluation.

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

    African Journals Online (AJOL)

    A coating layer was then applied with a mixture of HPMC, ethylcellulose, shellac, and HPMC phthalate. The effect of several formulation variables on in vitro drug release was studied; furthermore, the drug release kinetics of the optimized formulation was evaluated. The in vivo pharmacokinetics of the optimized formulation ...

  7. Super-Group Field Cosmology in Batalin-Vilkovisky Formulation

    Science.gov (United States)

    Upadhyay, Sudhaker

    2016-09-01

    In this paper we study the third quantized super-group field cosmology, a model in multiverse scenario, in Batalin-Vilkovisky (BV) formulation. Further, we propose the superfield/super-antifield dependent BRST symmetry transformations. Within this formulation we establish connection between the two different solutions of the quantum master equation within the BV formulation.

  8. Standardization Of A Siddha Formulation Amukkara Curanam By ...

    African Journals Online (AJOL)

    Amukkara curanam, a Siddha formulation, currently used in all types of gastric disorders, rheumatic pain, insomnia and sexual insufficiency, was investigated for the estimation of the marker compounds, withaferine A and piperine contents in a prepared standard formulation and a commercial formulation by using HPTLC ...

  9. Studies on the antimicrobial properties of formulated creams and ...

    African Journals Online (AJOL)

    Their performances were compared with those of standard antiseptic creams and ointments. The results of agar diffusion studies on cream and ointment formulations revealed that the topical bases used to disperse the medicaments could significantly affect the antimicrobial effectiveness of the formulation. Formulations ...

  10. Formulation and method for preparing gels comprising hydrous aluminum oxide

    Science.gov (United States)

    Collins, Jack L.

    2014-06-17

    Formulations useful for preparing hydrous aluminum oxide gels contain a metal salt including aluminum, an organic base, and a complexing agent. Methods for preparing gels containing hydrous aluminum oxide include heating a formulation to a temperature sufficient to induce gel formation, where the formulation contains a metal salt including aluminum, an organic base, and a complexing agent.

  11. Herbal antihyperlipidemic formulation of cocoa tea: Preparation and ...

    African Journals Online (AJOL)

    Purpose: To prepare and characterize a formulation containing an ethanol extract of Camellia ptilophylla leaves (cocoa tea), with a focus on antihyperlipidemic and anti-obesity activities. Methods: An aloe vera–based formulation of an ethanol extract of cocoa tea (C. ptilophylla) was prepared. The formulation was given ...

  12. A displacement based FE formulation for steady state problems

    NARCIS (Netherlands)

    Yu, Y.

    2005-01-01

    In this thesis a new displacement based formulation is developed for elasto-plastic deformations in steady state problems. In this formulation the displacements are the primary variables, which is in contrast to the more common formulations in terms of the velocities as the primary variables. In a

  13. Animal Diet Formulation with Floating Price

    Directory of Open Access Journals (Sweden)

    S.H Nasseri

    2016-12-01

    Full Text Available In the process of milk production, the highest cost relates to animal feed. Based on reports provided by the experts, around seventy percent of dairy livestock costs included feed costs. In order to minimize the total price of livestock feed, according to the limits of feed sources in each region or season, and also the transportation and maintenance costs and ultimately milk price reduction, optimization of the livestock nutrition program is an essential issue. Because of the uncertainty and lack of precision in the optimal food ration done with existing methods based on linear programming, there is a need to use appropriate methods to meet this purpose. Therefore, in this study formulation of completely mixed nutrient diets of dairy cows is done by using a fuzzy linear programming in early lactation. Application of fuzzy optimization method and floating price make it possible to formulate and change the completely mixed diets with adequate safety margins. Therefore, applications of fuzzy methods in feed rations of dairy cattle are recommended to optimize the diets. Obviously, it would be useful to design suitable software, which provides the possibility of using floating prices to set feed rations by the use of fuzzy optimization method.

  14. The covariant formulation of f ( T ) gravity

    International Nuclear Information System (INIS)

    Krššák, Martin; Saridakis, Emmanuel N

    2016-01-01

    We show that the well-known problem of frame dependence and violation of local Lorentz invariance in the usual formulation of f ( T ) gravity is a consequence of neglecting the role of spin connection. We re-formulate f ( T ) gravity starting from, instead of the ‘pure tetrad’ teleparallel gravity, the covariant teleparallel gravity, using both the tetrad and the spin connection as dynamical variables, resulting in a fully covariant, consistent, and frame-independent version of f ( T ) gravity, which does not suffer from the notorious problems of the usual, pure tetrad, f ( T ) theory. We present the method to extract solutions for the most physically important cases, such as the Minkowski, the Friedmann–Robertson–Walker (FRW) and the spherically symmetric ones. We show that in covariant f ( T ) gravity we are allowed to use an arbitrary tetrad in an arbitrary coordinate system along with the corresponding spin connection, resulting always in the same physically relevant field equations. (paper)

  15. Comparison of different formulations of vitamin D

    International Nuclear Information System (INIS)

    Rashid, H.M.F.; Khalil, K.

    2017-01-01

    Vitamin D Deficiency (VDD) is responsible for a wide spectrum of clinical diseases and vitamin D deficiency prevalence is frightening in most parts of the world including Pakistan. Therefore, supplementations of vitamin D are used in the population at high risk for the prevention and the treatment of vitamin D deficiency. Vitamin D supplementation comes in various formulations both oral and intramuscular. Cholecalciferol is the most commonly used preparation which is given through these routes of administration. There is need to study the fact that how much vitamin D levels are raised after administration of these different formulations as this can be a pivotal factor in determining dosage and route of vitamin D3. Methods: This cross-sectional study conducted on 320 cases and compared the efficacy of various Vitamin D3 preparations in raising Vitamin D levels conducted in Department of Endocrinology and Metabolism, Services Hospital, Lahore from February to July, 2016. Blood serum was drawn for vitamin D level in the cases at the time of presentation and after treatment. Results: Three hundred and twenty patients were enrolled in study and divided into four groups (A, B, C, D). There was no significant difference between groups (A, B, C, D) in change in vitamin d levels after 3 months of treatment (p-Value 0.446). Conclusion: Different preparations of vitamin D are equally effective in raising vitamin D levels at 12 weeks. However, there is a need to conduct large scale studies to further validate these results. (author)

  16. Statistical formulation of gravitational radiation reaction

    International Nuclear Information System (INIS)

    Schutz, B.F.

    1980-01-01

    A new formulation of the radiation-reaction problem is proposed, which is simpler than alternatives which have been used before. The new approach is based on the initial-value problem, uses approximations which need be uniformly valid only in compact regions of space-time, and makes no time-asymmetric assumptions (no a priori introduction of retarded potentials or outgoing-wave asymptotic conditions). It defines radiation reaction to be the expected evolution of a source obtained by averaging over a statistical ensemble of initial conditions. The ensemble is chosen to reflect one's complete lack of information (in real systems) about the initial data for the radiation field. The approach is applied to the simple case of a weak-field, slow-motion source in general relativity, where it yields the usual expressions for radiation reaction when the gauge is chosen properly. There is a discussion of gauge freedom, and another of the necessity of taking into account reaction corrections to the particle-conservation equation. The analogy with the second law of thermodynamics is very close, and suggests that the electromagnetic and thermodynamic arrows of time are the same. Because the formulation is based on the usual initial-value problem, it has no spurious ''runaway'' solutions

  17. Terbinafine: novel formulations that potentiate antifungal activities.

    Science.gov (United States)

    Ma, Y; Chen, X; Guan, S

    2015-03-01

    Terbinafine, an orally and topically active antifungal agent, has been available for the treatment of dermatophytic infections and onychomycosis for more than a decade. In addition, oral administration has been shown to be associated with drug-drug interactions, hepatotoxicity, low concentration at the infected sites, gastrointestinal and systemic side effects and other adverse effects. Since topical drug delivery can provide higher patient compliance, allow immediate access to the infected site and reduce unwanted systemic drug exposure, an improved topical drug delivery approach with high permeability, sustained release and prolonged retainment could overcome the limitations and side effects caused by oral administration. Conventional topical formulations cannot keep the drug in the targeted sites for a long duration of time and hence a novel drug delivery that can avoid the side effects while still providing sustained efficacy in treatment should be developed. This brief review of novel formulations based on polymers and nanostructure carriers provides insight into the efficacy and topical delivery of terbinafine. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

  18. Stabilisation de la formule des traces tordue

    CERN Document Server

    Moeglin, Colette

    2016-01-01

    Ce travail en deux volumes donne la preuve de la stabilisation de la formule des trace tordue. Stabiliser la formule des traces tordue est la méthode la plus puissante connue actuellement pour comprendre l'action naturelle du groupe des points adéliques d'un groupe réductif, tordue par un automorphisme, sur les formes automorphes de carré intégrable de ce groupe. Cette compréhension se fait en réduisant le problème, suivant les idées de Langlands, à des groupes plus petits munis d'un certain nombre de données auxiliaires; c'est ce que l'on appelle les données endoscopiques. L'analogue non tordu a été résolu par J. Arthur et dans ce livre on suit la stratégie de celui-ci. Publier ce travail sous forme de livre permet de le rendre le plus complet possible. Les auteurs ont repris la théorie de l'endoscopie tordue développée par R. Kottwitz et D. Shelstad et par J.-P. Labesse. Ils donnent tous les arguments des démonstrations même si nombre d'entre eux se trouvent déjà dans les travaux d'Ar...

  19. Factors for formulating strategies for environmental restoration

    International Nuclear Information System (INIS)

    1998-07-01

    This publication focusses on factors which are important for formulating a strategy for environmental restoration. In parallel to this effort, the IAEA has conducted activities in related areas which have been reported in companion reports dealing with (1) the characterization of radioactively contaminated sites for remediation purposes and (2) available technology for cleanup and remediation of radioactively contaminated sites. Additionally, follow-up activities will focus on two other areas, viz. planning and management options for cleanup of contaminated groundwater, and post-restoration monitoring of decommissioned sites. In a separate initiative the IAEA has developed preliminary guidance on radiological criteria for determining when cleanup action is needed and for deciding on when areas have been cleaned up to a sufficient extent. It is also concerned with radioactive contamination of soils, groundwaters, structures and biota which may have the potential for harm to people. It is intended that it will serve as an important source of information and data on the key factors to be considered in the formulation of an environmental restoration strategy

  20. Development and stability studies of sunscreen cream formulations containing three photo-protective filters

    Directory of Open Access Journals (Sweden)

    Slim Smaoui

    2017-02-01

    Full Text Available The present study aimed to formulate and subsequently evaluate sunscreen cream (W/O/W emulsion containing three photo-protective filters: benzophenone-3, ethylhexyl methoxycinnamate and titanium dioxide at different percentages. Formulations were stored at 8, 25 and 40 °C for four weeks to investigate their stability. Color, centrifugation, liquefaction, phase separation, pH and Sun Protection Factor (SPF of sunscreen cream formulations were determined. The microbiological stability of the creams was also evaluated and the organoleptic quality was carried out for 28 days. Interestingly, the combination of 7% Benzophenone-3, 7% Ethylhexyl methoxycinnamate and 6% Titanium dioxide preserved physicochemical properties of the product and was efficient against the development of different spoilage microorganisms as well as aerobic plate counts, Pseudomonas aeruginosa, Staphylococcus aureus, and yeast and mold counts. Furthermore, a good stability was observed for all formulations throughout the experimental period. The newly formulated sunscreen cream was proved to exhibit a number of promising properties and attributes that might open new opportunities for the development of more efficient, safe, and cost-effective skin-care, cosmetic, and pharmaceutical products.