Sanz, Roser; Calpena, Ana C; Mallandrich, Mireia; Clares, Beatriz
2015-01-01
Topical administration is an appealing method for drug delivery due to its non-invasiveness, self-controlled application, avoidance of first-pass metabolism in the liver and reduction of systemic side effects compared to other conventional routes such as oral and parenteral. However, topical administration must overcome the permeable barriers that skin and mucosa represent for the drug to achieve its desired therapeutic effect. Penetration of drugs through human skin is mainly impaired by the stratum corneum- the uppermost keratinized skin layer. In contrast, the stratified squamous epithelium (a nonkeratinized tissue) represents the major physical barrier for transbuccal drug administration in humans. Different technologies have been studied to enhance the bioavailability or local effects of drugs administered through skin and buccal mucosa. Those technologies involve the use of physical or chemical enhancers and new dosage forms such as vesicles, cyclodextrins, nanoparticles and other complex systems. Combinations of these technologies may further increase drug delivery in some cases. As analgesia is one of the main therapeutic effects sought through topical administration, this paper focuses on the review of drug delivery systems to improve the topical and transdermal/transbuccal drug delivery of substances with known analgesic action. A discussion of their possibilities and limitations is also included.
Jelacic, Srdjan; Bowdle, Andrew; Nair, Bala G; Kusulos, Dolly; Bower, Lynnette; Togashi, Kei
2015-08-01
Many anesthetic drug errors result from vial or syringe swaps. Scanning the barcodes on vials before drug preparation, creating syringe labels that include barcodes, and scanning the syringe label barcodes before drug administration may help to prevent errors. In contrast, making syringe labels by hand that comply with the recommendations of regulatory agencies and standards-setting bodies is tedious and time consuming. A computerized system that uses vial barcodes and generates barcoded syringe labels could address both safety issues and labeling recommendations. We measured compliance of syringe labels in multiple operating rooms (ORs) with the recommendations of regulatory agencies and standards-setting bodies before and after the introduction of the Codonics Safe Label System (SLS). The Codonics SLS was then combined with Smart Anesthesia Manager software to create an anesthesia barcode drug administration system, which allowed us to measure the rate of scanning syringe label barcodes at the time of drug administration in 2 cardiothoracic ORs before and after introducing a coffee card incentive. Twelve attending cardiothoracic anesthesiologists and the OR satellite pharmacy participated. The use of the Codonics SLS drug labeling system resulted in >75% compliant syringe labels (95% confidence interval, 75%-98%). All syringe labels made using the Codonics SLS system were compliant. The average rate of scanning barcodes on syringe labels using Smart Anesthesia Manager was 25% (730 of 2976) over 13 weeks but increased to 58% (956 of 1645) over 8 weeks after introduction of a simple (coffee card) incentive (P < 0.001). An anesthesia barcode drug administration system resulted in a moderate rate of scanning syringe label barcodes at the time of drug administration. Further, adaptation of the system will be required to achieve a higher utilization rate.
Avidan, Alexander; Dotan, Koren; Weissman, Charles; Cohen, Matan J; Levin, Phillip D
2014-11-01
Data on drug administration are entered manually into anesthesia information management systems (AIMS). This study examined whether these data are accurate regarding drug name, dose administered, and time of administration, and whether the stage of anesthesia influences data accuracy. Real-time observational data on drug administration during elective operations were compared with computerized information on drug administration entered by anesthesiologists. A trained observer (K.D.) performed the observations. Data were collected during 57 operations which included 596 separate occasions of drug administration by 22 anesthesiologists. No AIMS records were found for 90 (15.1%) occasions of drug administration (omissions), while there were 11 (1.8%) AIMS records where drug administration was not observed. The AIMS and observer data matched for drug name on 495 of 596 (83.1%) occasions, for dose on 439 of 495 (92.5%) occasions, and for time on 476 of 495 (96.2%) occasions. Amongst the 90 omitted records, 34 (37.8%) were for vasoactive drugs with 24 (27.7%) for small doses of hypnotics. Omissions occurred mostly during maintenance: 50 of 153 (24.6%), followed by induction: 30 of 325 (9.2%) and emergence: 10 of 57 (17.5%) (P < 0.001). Time and dose inaccuracies occurred mainly during induction, followed by maintenance and emergence; time inaccuracies were 7/325 (8.3%), 10/203 (4.9%), and 0/57 (0%), respectively (P = 0.07), and dose inaccuracies were 15/325 (4.6%), 3/203 (1.5%), and 1/57 (1.7%), respectively (P = 0.11). The range of accuracy varies when anesthesiologists manually enter drug administration data into an AIMS. Charting omissions represent the largest cause of inaccuracy, principally by omissions of records for vasopressors and small doses of hypnotic drugs. Manually entered drug administration data are not without errors. Accuracy of entering drug administration data remains the responsibility of the anesthesiologist.
Merry, Alan F; Webster, Craig S; Hannam, Jacqueline; Mitchell, Simon J; Henderson, Robert; Reid, Papaarangi; Edwards, Kylie-Ellen; Jardim, Anisoara; Pak, Nick; Cooper, Jeremy; Hopley, Lara; Frampton, Chris; Short, Timothy G
2011-09-22
To clinically evaluate a new patented multimodal system (SAFERSleep) designed to reduce errors in the recording and administration of drugs in anaesthesia. Prospective randomised open label clinical trial. Five designated operating theatres in a major tertiary referral hospital. Eighty nine consenting anaesthetists managing 1075 cases in which there were 10,764 drug administrations. Use of the new system (which includes customised drug trays and purpose designed drug trolley drawers to promote a well organised anaesthetic workspace and aseptic technique; pre-filled syringes for commonly used anaesthetic drugs; large legible colour coded drug labels; a barcode reader linked to a computer, speakers, and touch screen to provide automatic auditory and visual verification of selected drugs immediately before each administration; automatic compilation of an anaesthetic record; an on-screen and audible warning if an antibiotic has not been administered within 15 minutes of the start of anaesthesia; and certain procedural rules-notably, scanning the label before each drug administration) versus conventional practice in drug administration with a manually compiled anaesthetic record. Primary: composite of errors in the recording and administration of intravenous drugs detected by direct observation and by detailed reconciliation of the contents of used drug vials against recorded administrations; and lapses in responding to an intermittent visual stimulus (vigilance latency task). Secondary: outcomes in patients; analyses of anaesthetists' tasks and assessments of workload; evaluation of the legibility of anaesthetic records; evaluation of compliance with the procedural rules of the new system; and questionnaire based ratings of the respective systems by participants. The overall mean rate of drug errors per 100 administrations was 9.1 (95% confidence interval 6.9 to 11.4) with the new system (one in 11 administrations) and 11.6 (9.3 to 13.9) with conventional methods (one
Mignani, Serge; El Kazzouli, Saïd; Bousmina, Mosto; Majoral, Jean-Pierre
2013-10-01
Drugs are introduced into the body by numerous routes such as enteral (oral, sublingual and rectum administration), parenteral (intravascular, intramuscular, subcutaneous and inhalation administration), or topical (skin and mucosal membranes). Each route has specific purposes, advantages and disadvantages. Today, the oral route remains the preferred one for different reasons such as ease and compliance by patients. Several nanoformulated drugs have been already approved by the FDA, such as Abelcet®, Doxil®, Abraxane® or Vivagel®(Starpharma) which is an anionic G4-poly(L-lysine)-type dendrimer showing potent topical vaginal microbicide activity. Numerous biochemical studies, as well as biological and pharmacological applications of both dendrimer based products (dendrimers as therapeutic compounds per se, like Vivagel®) and dendrimers as drug carriers (covalent conjugation or noncovalent encapsulation of drugs) were described. It is widely known that due to their outstanding physical and chemical properties, dendrimers afforded improvement of corresponding carried-drugs as dendrimer-drug complexes or conjugates (versus plain drug) such as biodistribution and pharmacokinetic behaviors. The purpose of this manuscript is to review the recent progresses of dendrimers as nanoscale drug delivery systems for the delivery of drugs using enteral, parenteral and topical routes. In particular, we focus our attention on the emerging and promising routes such as oral, transdermal, ocular and transmucosal routes using dendrimers as delivery systems. Copyright © 2013 Elsevier B.V. All rights reserved.
Drug Enforcement Administration
... de informacin confidencial --> DEA NEWS The Drug Enforcement Administration and Discovery Education name grand winner of Operation ... JUN 15 (Washington) The United States Drug Enforcement Administration, DEA Educational Foundation and Discovery Education awarded Porter ...
38 CFR 52.180 - Administration of drugs.
2010-07-01
... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Administration of drugs... of drugs. The program management must assist with the management of medication and have a system for disseminating drug information to participants and program staff. (a) Procedures. (1) The program management...
[Innovative therapeutic strategies for intravesical drug administration].
Moch, C; Salmon, D; Rome, P; Marginean, R; Pivot, C; Colombel, M; Pirot, F
2013-05-01
Perspectives for innovative pharmaceutical molecules and intravesical administration of pharmacological agents are presented in the present review carried out from a recent literature. This review of the literature was built by using the PubMed and ScienceDirect databases running 20keywords revealing 34publications between 1983 and 2012. The number of referenced articles on ScienceDirect has increased in recent years, highlighting the interest of scientists for intravesical drug administration and the relevance of innovating drug delivery systems. Different modalities of intravesical administration using physical (e.g., iontophoresis, electroporation) or chemical techniques (e.g., enzyme, solvent, nanoparticles, liposomes, hydrogels) based on novel formulation methods are reported. Finally, the development of biopharmaceuticals (e.g., bacillus Calmette-Guérin, interferon α) and gene therapies is also presented and analyzed in this review. The present review exhibits new development in the pipeline for emerging intravesical drug administration strategies. Knowledge of all these therapies allows practitioners to propose a specific and tailored treatment to each patient with limiting systemic side effects. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
Design of a RESTful web information system for drug prescription and administration.
Bianchi, Lorenzo; Paganelli, Federica; Pettenati, Maria Chiara; Turchi, Stefano; Ciofi, Lucia; Iadanza, Ernesto; Giuli, Dino
2014-05-01
Drug prescription and administration processes strongly impact on the occurrence of risks in medical settings for they can be sources of adverse drug events (ADEs). A properly engineered use of information and communication technologies has proven to be a promising approach to reduce these risks. In this study, we propose PHARMA, a web information system which supports healthcare staff in the secure cooperative execution of drug prescription, transcription and registration tasks. PHARMA allows the easy sharing and management of documents containing drug-related information (i.e., drug prescriptions, medical reports, screening), which is often inconsistent and scattered across different information systems and heterogeneous organization domains (e.g., departments, other hospital facilities). PHARMA enables users to access such information in a consistent and secure way, through the adoption of REST and web-oriented design paradigms and protocols. We describe the implementation of the PHARMA prototype, and we discuss the results of the usability evaluation that we carried out with the staff of a hospital in Florence, Italy.
2011-12-30
...] Food and Drug Administration Transparency Initiative: Food and Drug Administration Report on Good Guidance Practices: Improving Efficiency and Transparency; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice of availability; request for comments. SUMMARY: As part of the Transparency...
Rectal drug administration: clinical pharmacokinetic considerations.
de Boer, A G; Moolenaar, F; de Leede, L G; Breimer, D D
1982-01-01
The human rectum represents a body cavity in which drugs can be easily introduced and retained and from which absorption is well possible. There are important therapeutic reasons why it is sometimes preferable to give a drug rectally rather than orally, e.g. in cases of nausea and vomiting. Drawbacks of rectal drug administration include the interruption of absorption by defaecation and lack of patient acceptability. The mechanism of drug absorption from the rectum is probably no different to that in the upper part of the gastrointestinal tract, despite the fact that the physiological circumstances (e.g. pH, fluid content) differ substantially, Absorption from aqueous and alcoholic solutions may occur very rapidly, which has proved to be of considerable therapeutic value in the rapid suppression of acute convulsive attacks by diazepam (e.g. in children), but absorption from suppositories is generally slower and very much dependent on the nature of the suppository base, the use of surfactants or other additives, particle size of the active ingredient, etc. There is some evidence that hepatic first-pass elimination of high clearance drugs is partially avoided after rectal administration, e.g. lignocaine. This can be explained by the rectal venous blood supply: the upper part is connected with the portal system, whereas the lower part is directly connected with the systemic circulation. Plasma concentration data following rectal administration of representatives of several classes of drugs are reviewed: anticonvulsants, non-narcotic analgesics and non-steroidal anti-inflammatory agents, hypnosedatives and anaesthetics, strong analgesics, theophylline and derivatives, corticosteroids, antibacterial agents, thiazinamium, promethazine, hyoscine-N-butyl-bromide, streptokinase, progesterone, ergotamine tartrate and levodopa. Only limited number of cases has it been adequately shown that the rectal route of administration gives plasma concentrations which are comparable to
78 FR 69133 - Drug Enforcement Administration
2013-11-18
... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances..., California 94085, made application by renewal to the Drug Enforcement Administration (DEA) to be registered... Diversion Control, Drug Enforcement Administration. [FR Doc. 2013-27486 Filed 11-15-13; 8:45 am] BILLING...
[New drug development by innovative drug administration--"change" in pharmaceutical field].
Nagai, T
1997-11-01
New drug development can be made by providing products of higher "selectivity for the drug" for medical treatment. There are two ways for the approach to get higher "selectivity of drug": 1) discovery of new compounds with high selectivity of drug; 2) innovation of new drug administration, that is new formulation and/or method with high selectivity of drug by integration and harmonization of various hard/soft technologies. An extensive increase of biological information and advancement of surrounding science and technology may modify the situation as the latter overcomes the former in the 21 century. As the science and technology in the 21 century is said to be formed on "3H", that is, 1. hybrid; 2. hi-quality; 3. husbandry, the new drug development by innovative drug administration is exactly based on the science and technology of 3H. Its characteristic points are interdisciplinary/interfusion, international, of philosophy/ethics, and systems of hard/hard/heart. From these points of view, not only the advance of unit technology but also a revolution in thinking way should be "must" subjects. To organize this type of research well, a total research activity such as ROR (research on research) might take an important and efficient role. Here the key words are the "Optimization technology" and "Change in Pharmaceutical Fields." As some examples of new drug innovation, our trials on several topical mucosal adhesive dosage forms and parenteral administration of peptide drugs such as insulin and erythropoietin will be described.
Common errors of drug administration in infants: causes and avoidance.
Anderson, B J; Ellis, J F
1999-01-01
Drug administration errors are common in infants. Although the infant population has a high exposure to drugs, there are few data concerning pharmacokinetics or pharmacodynamics, or the influence of paediatric diseases on these processes. Children remain therapeutic orphans. Formulations are often suitable only for adults; in addition, the lack of maturation of drug elimination processes, alteration of body composition and influence of size render the calculation of drug doses complex in infants. The commonest drug administration error in infants is one of dose, and the commonest hospital site for this error is the intensive care unit. Drug errors are a consequence of system error, and preventive strategies are possible through system analysis. The goal of a zero drug error rate should be aggressively sought, with systems in place that aim to eliminate the effects of inevitable human error. This involves review of the entire system from drug manufacture to drug administration. The nuclear industry, telecommunications and air traffic control services all practise error reduction policies with zero error as a clear goal, not by finding fault in the individual, but by identifying faults in the system and building into that system mechanisms for picking up faults before they occur. Such policies could be adapted to medicine using interventions both specific (the production of formulations which are for children only and clearly labelled, regular audit by pharmacists, legible prescriptions, standardised dose tables) and general (paediatric drug trials, education programmes, nonpunitive error reporting) to reduce the number of errors made in giving medication to infants.
2010-04-29
...] Draft Guidance for Industry and Food and Drug Administration Staff; Food and Drug Administration and Industry Procedures for Section 513(g) Requests for Information Under the Federal Food, Drug, and Cosmetic... and Industry Procedures for Section 513(g) Requests for Information Under the Federal Food, Drug, and...
2012-04-06
...] Guidance for Industry and Food and Drug Administration Staff; Food and Drug Administration and Industry... Administration (FDA) is announcing the availability of the guidance entitled ``Guidance for Industry and Food and... written requests for single copies of the guidance document entitled ``Guidance for Industry and Food and...
Discrete-choice modelling of patient preferences for modes of drug administration.
Tetteh, Ebenezer Kwabena; Morris, Steve; Titcheneker-Hooker, Nigel
2017-12-01
The administration of (biologically-derived) drugs for various disease conditions involves consumption of resources that constitutes a direct monetary cost to healthcare payers and providers. An often ignored cost relates to a mismatch between patients' preferences and the mode of drug administration. The "intangible" benefits of giving patients what they want in terms of the mode of drug delivery is seldom considered. This study aims to evaluate, in monetary terms, end-user preferences for the non-monetary attributes of different modes of drug administration using a discrete-choice experiment. It provides empirical support to the notion that there are significant benefits from developing patient-friendly approaches to drug delivery. The gross benefits per patient per unit administration is in the same order of magnitude as the savings in resource costs of administering drugs. The study argues that, as long as the underlying manufacturing science is capable, a patient-centred approach to producing drug delivery systems should be encouraged and pursued.
Prudhviraj, G; Vaidya, Yogyata; Singh, Sachin Kumar; Yadav, Ankit Kumar; Kaur, Puneet; Gulati, Monica; Gowthamarajan, K
2015-11-01
Significant clinical success of colon targeted dosage forms has been limited by their inappropriate release profile at the target site. Their failure to release the drug completely in the colon may be attributed to changes in the colonic milieu because of pathological state, drug effect and psychological stress accompanying the diseased state or, a combination of these. Alteration in normal colonic pH and bacterial picture leads to incomplete release of drug from the designed delivery system. We report the effectiveness of a targeted delivery system wherein the constant replenishment of the colonic microbiota is achieved by concomitant administration of probiotics along with the polysaccharide based drug delivery system. Guar gum coated spheroids of sulfasalazine were prepared. In the dissolution studies, these spheroids showed markedly higher release in the simulated colonic fluid. In vivo experiments conducted in rats clearly demonstrated the therapeutic advantage of co-administration of probiotics with guar gum coated spheroids. Our results suggest that concomitant use of probiotics along with the polysaccharide based delivery systems can be a simple strategy to achieve satisfactory colon targeting of drugs. Copyright © 2015 Elsevier B.V. All rights reserved.
21 CFR 203.34 - Policies and procedures; administrative systems.
2010-04-01
... distribution security and audit system, including conducting random and for-cause audits of sales... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Policies and procedures; administrative systems...; administrative systems. Each manufacturer or authorized distributor of record that distributes drug samples shall...
2010-04-09
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0142] Drug and Medical Device Forum on Food and Drug Administration Drug and Device Requirements and Supplier Controls; Public Educational Forum AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public...
28 CFR 16.98 - Exemption of the Drug Enforcement Administration (DEA)-limited access.
2010-07-01
... Administration (DEA)-limited access. 16.98 Section 16.98 Judicial Administration DEPARTMENT OF JUSTICE PRODUCTION... Exemption of the Drug Enforcement Administration (DEA)—limited access. (a) The following systems of records.../Diversion Analysis and Detection System (ARCOS/DADS) (Justice/DEA-003) (2) Controlled Substances Act...
Administration costs of intravenous biologic drugs for rheumatoid arthritis
Soini, Erkki J; Leussu, Miina; Hallinen, Taru
2013-01-01
Background Cost-effectiveness studies explicitly reporting infusion times, drug-specific administration costs for infusions or real-payer intravenous drug cost are few in number. Yet, administration costs for infusions are needed in the health economic evaluations assessing intravenously-administered drugs. Objectives To estimate the drug-specific administration and total cost of biologic intravenous rheumatoid arthritis (RA) drugs in the adult population and to compare the obtained costs wit...
2011-08-16
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] 2011 Parenteral Drug Association/Food and Drug Administration Joint Public Conference; Quality and...: Notice of public conference. The Food and Drug Administration (FDA), in cosponsorship with Parenteral...
2011-05-04
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] 2011 Parenteral Drug Association/Food and Drug Administration Glass Quality Conference; Public Conference AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public conference. SUMMARY: The Food...
78 FR 20664 - Society of Clinical Research Associates-Food and Drug Administration: Food and Drug...
2013-04-05
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Society of Clinical Research Associates-Food and Drug Administration: Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical Practice AGENCY: Food and Drug...
2011-04-14
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0189] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Low Level Laser System for Aesthetic Use; Availability AGENCY: Food and Drug Administration, HHS...
2010-11-05
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2008-D-0275] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Full-Field Digital Mammography System; Availability AGENCY: Food and Drug Administration, HHS. [[Page...
2011-03-23
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0028] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Ovarian Adnexal Mass Assessment Score Test System; Availability AGENCY: Food and Drug Administration, HHS...
2011-02-07
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0645] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Contact Cooling System for Aesthetic Use; Availability AGENCY: Food and Drug Administration, HHS. ACTION...
2011-07-20
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0500] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Focused Ultrasound Stimulator System for Aesthetic Use; Availability AGENCY: Food and Drug Administration...
Ion-Responsive Drug Delivery Systems.
Yoshida, Takayuki; Shakushiro, Kohsuke; Sako, Kazuhiro
2018-02-08
Some kinds of cations and anions are contained in body fluids such as blood, interstitial fluid, gastrointestinal juice, and tears at relatively high concentration. Ionresponsive drug delivery is available to design the unique dosage formulations which provide optimized drug therapy with effective, safe and convenient dosing of drugs. The objective of the present review was to collect, summarize, and categorize recent research findings on ion-responsive drug delivery systems. Ions in body fluid/formulations caused structural changes of polymers/molecules contained in the formulations, allow formulations exhibit functions. The polymers/molecules responding to ions were ion-exchange resins/fibers, anionic or cationic polymers, polymers exhibiting transition at lower critical solution temperature, self-assemble supramolecular systems, peptides, and metalorganic frameworks. The functions of ion-responsive drug delivery systems were categorized to controlled drug release, site-specific drug release, in situ gelation, prolonged retention at the target sites, and enhancement of drug permeation. Administration of the formulations via oral, ophthalmic, transdermal, and nasal routes has showed significant advantages in the recent literatures. Many kinds of drug delivery systems responding to ions have been reported recently for several administration routes. Improvement and advancement of these systems can maximize drugs potential and contribute to patients in the world. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
2011-02-04
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Industry Exchange Workshop on Food and Drug Administration Drug and Device Requirements; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. SUMMARY: The Food and Drug...
Adverse Drug Event Monitoring at the Food and Drug Administration: Your Report Can Make a Difference
Ahmad, Syed Rizwanuddin
2003-01-01
The Food and Drug Administration (FDA) is responsible not only for approving drugs but also for monitoring their safety after they reach the market. The complete adverse event profile of a drug is not known at the time of approval because of the small sample size, short duration, and limited generalizability of pre-approval clinical trials. This report describes the FDA's postmarketing surveillance system, to which many clinicians submit reports of adverse drug events encountered while treati...
Evaluation of drug administration errors in a teaching hospital
Directory of Open Access Journals (Sweden)
Berdot Sarah
2012-03-01
Full Text Available Abstract Background Medication errors can occur at any of the three steps of the medication use process: prescribing, dispensing and administration. We aimed to determine the incidence, type and clinical importance of drug administration errors and to identify risk factors. Methods Prospective study based on disguised observation technique in four wards in a teaching hospital in Paris, France (800 beds. A pharmacist accompanied nurses and witnessed the preparation and administration of drugs to all patients during the three drug rounds on each of six days per ward. Main outcomes were number, type and clinical importance of errors and associated risk factors. Drug administration error rate was calculated with and without wrong time errors. Relationship between the occurrence of errors and potential risk factors were investigated using logistic regression models with random effects. Results Twenty-eight nurses caring for 108 patients were observed. Among 1501 opportunities for error, 415 administrations (430 errors with one or more errors were detected (27.6%. There were 312 wrong time errors, ten simultaneously with another type of error, resulting in an error rate without wrong time error of 7.5% (113/1501. The most frequently administered drugs were the cardiovascular drugs (425/1501, 28.3%. The highest risks of error in a drug administration were for dermatological drugs. No potentially life-threatening errors were witnessed and 6% of errors were classified as having a serious or significant impact on patients (mainly omission. In multivariate analysis, the occurrence of errors was associated with drug administration route, drug classification (ATC and the number of patient under the nurse's care. Conclusion Medication administration errors are frequent. The identification of its determinants helps to undertake designed interventions.
Estimating preferences for modes of drug administration: The case of US healthcare professionals.
Tetteh, Ebenezer K; Morris, Steve; Titchener-Hooker, Nigel
2018-01-01
There are hidden drug administration costs that arise from a mismatch between end-user preferences and how manufacturers choose to formulate their drug products for delivery to patients. The corollary of this is: there are "intangible benefits" from considering end-user preferences in manufacturing patient-friendly medicines. It is important then to have some idea of what pharmaceutical manufacturers should consider in making patient-friendly medicines and of the magnitude of the indirect benefits from doing so. This study aimed to evaluate preferences of healthcare professionals in the US for the non-monetary attributes of different modes of drug administration. It uses these preference orderings to compute a monetary valuation of the indirect benefits from making patient-friendly medicines. A survey collected choice preferences of a sample of 210 healthcare professionals in the US for two unlabelled drug options. These drugs were identical except in the levels of attributes of drug administration. Using the choice data collected, statistical models were estimated to compute gross welfare benefits, measured by the expected compensating variation, from making drugs in a more patient-friendly manner. The monetary value of end-user benefits from developing patient-friendly drug delivery systems is: (1) as large as the annual acquisition costs per full treatment episode for some biologic drugs; and (2) likely to fall in the "high end" of the distribution of the direct monetary costs of drug administration. An examination of end-user preferences should help manufacturers make more effective and efficient use of limited resources for innovations in drug delivery system, or manufacturing research in general. Copyright © 2017 Elsevier Inc. All rights reserved.
Peker, Kemal; Inal, Abdullah; Sayar, Ilyas; Sahin, Murat; Gullu, Huriye; Inal, Duriye Gul; Isik, Arda
2013-01-01
Background: Intraperitoneal adhesion formation is a serious postsurgical issue. Adhesions develop after damage to the peritoneum by surgery, irradiation, infection or trauma. Objectives: Using a rat model, we compared the effectiveness of systemic and intraperitoneally administered common immunosuppressive drugs for prevention of postoperative intraperitoneal adhesions. Materials and Methods: Peritoneal adhesions were induced in 98 female Wistar-Albino rats by cecal abrasion and peritoneal excision. Rats were randomly separated into seven groups, each containing fourteen rats, and the standard experimental model was applied to all of rats. 14 days later, rats were euthanized, intraperitoneal adhesions were scored and tissues were examined histologically using hematoxylin/eosin and Masson’s trichrome staining. Results: Throughout the investigation, no animal died during or after surgery. In all of experimental groups, decrease in fibrosis was statistically significant. Decrease in fibrosis was most prominently in intraperitoneal tacrolimus group (P = 0.000), and decrease was least in intraperitoneal cyclosporine group (P = 0.022). Vascular proliferation was significantly decreased in all experimental groups (P < 0.05) except for systemic tacrolimus group (P = 0.139). Most prominent reduction in vascular proliferation was in intraperitoneal tacrolimus group (P = 0.000). Conclusions: Administration of immunosuppressive drugs is effective for prevention of intraperitoneal adhesions. PMID:24693396
[Evaluation of administration errors of injectable drugs in neonatology].
Cherif, A; Sayadi, M; Ben Hmida, H; Ben Ameur, K; Mestiri, K
2015-11-01
Use of injectable drugs in newborns represents more than 90% of prescriptions and requires special precautions in order to ensure more safety and efficiency. The aim of this study is to gather errors relating to the administration of injectable drugs and to suggest corrective actions. This descriptive and transversal study has evaluated 300 injectable drug administrations in a neonatology unit. Two hundred and sixty-one administrations have contained an error. Data are collected by direct observations of administrative act. Errors observed are: an inappropriate mixture (2.6% of cases); an incorrect delivery rate (33.7% of cases); incorrect dilutions (26.7% of cases); error in calculation of the dose to be injected (16.7% of cases); error while sampling small volumes (6.3% of cases); error or omission of administration schedule (1% of cases). These data have enabled us to evaluate administration of injectable drugs in neonatology. Different types of errors observed could be a source of therapeutic inefficiency, extended lengths of stay or iatrogenic drug. Following these observations, corrective actions have been undertaken by pharmacists and consist of: organizing training sessions for nursing; developing an explanatory guide for dilution and administration of injectable medicines, which was made available to the clinical service. Collaborative strategies doctor-nurse-pharmacist can help to reduce errors in the medication process especially during his administration. It permits improvement of injectable drugs use, offering more security and better efficiency and contribute to guarantee ideal therapy for patients. Copyright © 2015. Published by Elsevier Masson SAS.
Yang, Lucie; Krefting, Ira; Gorovets, Alex; Marzella, Louis; Kaiser, James; Boucher, Robert; Rieves, Dwaine
2012-10-01
In 2007, the Food and Drug Administration requested that manufacturers of all approved gadolinium-based contrast agents (GBCAs), drugs widely used in magnetic resonance imaging, use nearly identical text in their product labeling to describe the risk of nephrogenic systemic fibrosis (NSF). Accumulating information about NSF risks led to revision of the labeling text for all of these drugs in 2010. The present report summarizes the basis and purpose of this class-labeling approach and describes some of the related challenges, given the evolutionary nature of the NSF risk evidence. The class-labeling approach for presentation of product risk is designed to decrease the occurrence of NSF and to enhance the safe use of GBCAs in radiologic practice. © RSNA, 2012.
Spray-on transdermal drug delivery systems.
Ibrahim, Sarah A
2015-02-01
Transdermal drug delivery possesses superior advantages over other routes of administration, particularly minimizing first-pass metabolism. Transdermal drug delivery is challenged by the barrier nature of skin. Numerous technologies have been developed to overcome the relatively low skin permeability, including spray-on transdermal systems. A transdermal spray-on system (TSS) usually consists of a solution containing the drug, a volatile solvent and in many cases a chemical penetration enhancer. TSS promotes drug delivery via the complex interplay between solvent evaporation and drug-solvent drag into skin. The volatile solvent carries the drug into the upper layers of the stratum corneum, and as the volatile solvent evaporates, an increase in the thermodynamic activity of the drug occurs resulting in an increased drug loading in skin. TSS is easily applied, delivering flexible drug dosage and associated with lower incidence of skin irritation. TSS provides a fast-drying product where the volatile solvent enables uniform drug distribution with minimal vehicle deposition on skin. TSS ensures precise dose administration that is aesthetically appealing and eliminates concerns of residual drug associated with transdermal patches. Furthermore, it provides a better alternative to traditional transdermal products due to ease of product development and manufacturing.
Hasni, Nesrine; Ben Hamida, Emira; Ben Jeddou, Khouloud; Ben Hamida, Sarra; Ayadi, Imene; Ouahchi, Zeineb; Marrakchi, Zahra
2016-12-01
The medication iatrogenic risk is quite unevaluated in neonatology Objective: Assessment of errors that occurred during the preparation and administration of injectable medicines in a neonatal unit in order to implement corrective actions to reduce the occurrence of these errors. A prospective, observational study was performed in a neonatal unit over a period of one month. The practice of preparing and administering injectable medications were identified through a standardized data collection form. These practices were compared with summaries of the characteristics of each product (RCP) and the bibliography. One hundred preparations were observed of 13 different drugs. 85 errors during preparations and administration steps were detected. These errors were divided into preparation errors in 59% of cases such as changing the dilution protocol (32%), the use of bad solvent (11%) and administration errors in 41% of cases as errors timing of administration (18%) or omission of administration (9%). This study showed a high rate of errors during stages of preparation and administration of injectable drugs. In order to optimize the care of newborns and reduce the risk of medication errors, corrective actions have been implemented through the establishment of a quality assurance system which consisted of the development of injectable drugs preparation procedures, the introduction of a labeling system and staff training.
75 FR 15439 - Food and Drug Administration/Xavier University Global Medical Device Conference
2010-03-29
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Food and Drug Administration/Xavier University Global Medical Device Conference AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public conference. SUMMARY: The Food and Drug Administration (FDA...
78 FR 15957 - Food and Drug Administration/Xavier University Global Medical Device Conference
2013-03-13
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Food and Drug Administration/Xavier University Global Medical Device Conference AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public conference. SUMMARY: The Food and Drug Administration (FDA...
77 FR 10537 - Food and Drug Administration/Xavier University Global Medical Device Conference
2012-02-22
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Food and Drug Administration/Xavier University Global Medical Device Conference AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public conference. SUMMARY: The Food and Drug Administration (FDA...
Evaluation of drug administration errors in a teaching hospital
Berdot, Sarah; Sabatier, Brigitte; Gillaizeau, Florence; Caruba, Thibaut; Prognon, Patrice; Durieux, Pierre
2012-01-01
Abstract Background Medication errors can occur at any of the three steps of the medication use process: prescribing, dispensing and administration. We aimed to determine the incidence, type and clinical importance of drug administration errors and to identify risk factors. Methods Prospective study based on disguised observation technique in four wards in a teaching hospital in Paris, France (800 beds). A pharmacist accompanied nurses and witnessed the preparation and administration of drugs...
Solid‐in‐oil nanodispersions for transdermal drug delivery systems
Kitaoka, Momoko; Wakabayashi, Rie; Kamiya, Noriho
2016-01-01
Abstract Transdermal administration of drugs has advantages over conventional oral administration or administration using injection equipment. The route of administration reduces the opportunity for drug evacuation before systemic circulation, and enables long‐lasting drug administration at a modest body concentration. In addition, the skin is an attractive route for vaccination, because there are many immune cells in the skin. Recently, solid‐in‐oil nanodisperison (S/O) technique has demonstrated to deliver cosmetic and pharmaceutical bioactives efficiently through the skin. S/O nanodispersions are nanosized drug carriers designed to overcome the skin barrier. This review discusses the rationale for preparation of efficient and stable S/O nanodispersions, as well as application examples in cosmetic and pharmaceutical materials including vaccines. Drug administration using a patch is user‐friendly, and may improve patient compliance. The technique is a potent transcutaneous immunization method without needles. PMID:27529824
Food and Drug Administration Drug Approval Process: A History and Overview.
Williams, Christopher Ty
2016-03-01
In this article, the processing of investigational and new drug applications is described and the standard and expedited review processes are examined. The efforts of the US Food and Drug Administration to ensure greater agency transparency and fiscal responsibility and intensify oversight during the drug development and approval process are reviewed. Often attributed to a decrease in the number of uninsured adults, both the increase in prescription drug sales and the high costs associated with bringing a new drug to market highlight the necessity for a streamlined and cost-effective process to deliver these drugs safely and effectively. Copyright © 2016 Elsevier Inc. All rights reserved.
Drug overprescription in nursing homes: an empirical evaluation of administrative data.
Stroka, Magdalena A
2016-04-01
A widely discussed shortcoming of long-term care in nursing homes for the elderly is the inappropriate or suboptimal drug utilization, particularly of psychotropic drugs. Using administrative data from the largest sickness fund in Germany, this study was designed to estimate the effect of institutionalization on the drug intake of the frail elderly. Difference-in-differences propensity score matching techniques were used to compare drug prescriptions for the frail elderly who entered a nursing home with those who remained in the outpatient care system; findings suggest that nursing home residents receive more doses of antipsychotics, antidepressants, and analgesics. The potential overprescription correlates with estimated drug costs of about €87 million per year.
Subramaniam, B; Claudius, J S
1990-03-08
Cancer therapy using chemotherapeutic drugs frequently involves injection of the drug into the body through some intravenous mode of administration, viz, continuous (drip) infusion or single/multiple bolus injection(s). An understanding of the effect of the various modes of administration upon tumor penetration of drug is essential to rational design of drug therapy. This paper investigates drug penetration into a model tumor of slab geometry (between two capillaries) in which the overall transport rate of drug is limited by intra-tumor transport characterized by an effective diffusion coefficient. Employing the method of Finite Fourier Transforms (FFT), analytical solutions have been obtained for transient drug distribution in both the plasma and the tumor following three modes of administration, viz, continuous infusion, single bolus injection and equally-spaced equal-dose multiple bolus injections, of a given amount of drug. The qualitative trends exhibited by the plasma drug distribution profiles are consistent with reported experimental studies. Two concepts, viz, the dimensionless decay constant and the plasma/tumor drug concentration trajectories, are found to be particularly useful in the rational design of drug therapy. The dimensionless decay constant provides a measure of the rate of drug decay in the plasma relative to the rate of drug diffusion into the tumor and is thus characteristic of the tumor/drug system. The magnitude of this parameter dictates the choice of drug administration mode for minimizing drug decay in the plasma while simultaneously maximizing drug transport into the tumor. The concentration trajectories provide a measure of the plasma drug concentration relative to the tumor drug concentration at various times following injection. When the tumor drug concentration exceeds the plasma drug concentration, the drug will begin to diffuse out of the tumor. Knowledge of the time at which this diffusion reversal occurs is especially useful
Horibe, Megumi; Hane, Yuuki; Abe, Junko; Matsui, Toshinobu; Kato, Yamato; Ueda, Natsumi; Sasaoka, Sayaka; Motooka, Yumi; Hatahira, Haruna; Hasegawa, Shiori; Kinosada, Yasutomi; Hara, Hideaki; Nakamura, Mitsuhiro
2018-04-01
Postpartum depression is a mood disorder that commonly affects women during the early postpartum period. The objective of this study was to analyse the association of postpartum depression with drugs (including contraceptive devices and implants) with spontaneously reported adverse events reported in the US Food and Drug Administration Adverse Event Reporting System database. Retrospective study. Reports of postpartum depression events between 2004-2015 were analysed with a reporting odds ratio (ROR) algorithm. The Medical Dictionary for Regulatory Activities was used to identify postpartum depression. The reporting odds ratios (95% confidence intervals, CI) of levonorgestrel (an intrauterine device with progestogen), etonogestrel (a hormonal contraceptive implant), sertraline and drospirenone (an oral contraceptive) were 12.5 (8.7-18.0), 14.0 (8.5-22.8), 12.2 (6.5-23.1) and 5.4 (2.7-10.9) respectively. Among the drugs in the US Food and Drug Administration Adverse Event Reporting System database, the use of contraceptives or an intrauterine device with progestogen might convey risk for postpartum depression.
21 CFR 20.2 - Production of records by Food and Drug Administration employees.
2010-04-01
... upon an officer or employee of the Food and Drug Administration commanding the production of any record... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Production of records by Food and Drug Administration employees. 20.2 Section 20.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...
Solid-in-oil nanodispersions for transdermal drug delivery systems.
Kitaoka, Momoko; Wakabayashi, Rie; Kamiya, Noriho; Goto, Masahiro
2016-11-01
Transdermal administration of drugs has advantages over conventional oral administration or administration using injection equipment. The route of administration reduces the opportunity for drug evacuation before systemic circulation, and enables long-lasting drug administration at a modest body concentration. In addition, the skin is an attractive route for vaccination, because there are many immune cells in the skin. Recently, solid-in-oil nanodisperison (S/O) technique has demonstrated to deliver cosmetic and pharmaceutical bioactives efficiently through the skin. S/O nanodispersions are nanosized drug carriers designed to overcome the skin barrier. This review discusses the rationale for preparation of efficient and stable S/O nanodispersions, as well as application examples in cosmetic and pharmaceutical materials including vaccines. Drug administration using a patch is user-friendly, and may improve patient compliance. The technique is a potent transcutaneous immunization method without needles. © 2016 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
2010-09-16
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug Safety... and Central Nervous System Drugs Advisory Committee and the Drug Safety and Risk Management Advisory...
Polymer based drug delivery systems for mycobacterial infections.
Pandey, Rajesh; Khuller, G K
2004-07-01
In the last decade, polymer based technologies have found wide biomedical applications. Polymers, whether synthetic (e.g. polylactide-co-glycolide or PLG) or natural (e.g. alginate, chitosan etc.), have the property of encapsulating a diverse range of molecules of biological interest and bear distinct therapeutic advantages such as controlled release of drugs, protection against the premature degradation of drugs and reduction in drug toxicity. These are important considerations in the long-duration treatment of chronic infectious diseases such as tuberculosis in which patient non-compliance is the major obstacle to successful chemotherapy. Antitubercular drugs, singly or in combination, have been encapsulated in polymers to provide controlled drug release and the system also offers the flexibility of selecting various routes of administration such as oral, subcutaneous and aerosol. The present review highlights the approaches towards the preparation of polymeric antitubercular drug delivery systems, emphasizing how the route of administration may influence drug bioavailability as well as the chemotherapeutic efficacy. In addition, the pros and cons of the various delivery systems are also discussed.
2000-05-03
The Food and Drug Administration (FDA) is delaying until October 1, 2001, the effective date and reopening the administrative record to receive additional comments regarding certain requirements of a final rule published in the Federal Register of December 3, 1999 (64 FR 67720). The other provisions of the final rule become effective on December 4, 2000. The final rule implements the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA) and the FDA Modernization Act of 1997 (the Modernization Act). FDA is delaying the effective date for certain requirements relating to wholesale distribution of prescription drugs by distributors that are not authorized distributors of record. FDA is also delaying the effective date of another requirement that would prohibit blood centers functioning as "health care entities" to act as wholesale distributors of blood derivatives. The agency is taking this action to address numerous concerns about the provisions raised by affected parties.
Transdermal and Topical Drug Administration in the Treatment of Pain
Directory of Open Access Journals (Sweden)
Wojciech Leppert
2018-03-01
Full Text Available The comprehensive treatment of pain is multidimodal, with pharmacotherapy playing a key role. An effective therapy for pain depends on the intensity and type of pain, the patients’ age, comorbidities, and appropriate choice of analgesic, its dose and route of administration. This review is aimed at presenting current knowledge on analgesics administered by transdermal and topical routes for physicians, nurses, pharmacists, and other health care professionals dealing with patients suffering from pain. Analgesics administered transdermally or topically act through different mechanisms. Opioids administered transdermally are absorbed into vessels located in subcutaneous tissue and, subsequently, are conveyed in the blood to opioid receptors localized in the central and peripheral nervous system. Non–steroidal anti–inflammatory drugs (NSAIDs applied topically render analgesia mainly through a high concentration in the structures of the joint and a provision of local anti–inflammatory effects. Topically administered drugs such as lidocaine and capsaicin in patches, capsaicin in cream, EMLA cream, and creams containing antidepressants (i.e., doxepin, amitriptyline act mainly locally in tissues through receptors and/or ion channels. Transdermal and topical routes offer some advantages over systemic analgesic administration. Analgesics administered topically have a much better profile for adverse effects as they relieve local pain with minimal systemic effects. The transdermal route apart from the above-mentioned advantages and provision of long period of analgesia may be more convenient, especially for patients who are unable to take drugs orally. Topically and transdermally administered opioids are characterised by a lower risk of addiction compared to oral and parenteral routes.
Injectable In-Situ Gelling Controlled Release Drug Delivery System
Kulwant Singh; S. L. HariKumar
2012-01-01
The administration of poorly bioavailable drug through parenteral route is regarded the most efficient for drug delivery. Parenteral delivery provides rapid onset even for the drug with narrow therapeutic window, but to maintain the systemic drug level repeated installation are required which cause the patient discomfort. This can be overcome by designing the drug into a system, which control the drug release even through parenteral delivery, which improve patient compliance as well as pharma...
Bigi, Caterina; Tuccori, Marco; Bocci, Guido
2017-02-17
To analyze the Adverse Events Reporting System (AERS) database of the Food and Drug Administration (FDA), investigating the characteristics of pediatric adverse drug reactions (ADRs) and describing the effective participation of healthcare professionals in the reporting activity. Reports of ADRs were obtained from the FDA website. Only ADRs in pediatric subjects (divided by age, by country and by professional category) were included into the analysis. The drugs suspected as primary cause of the ADRs in pediatric subjects and their principal anatomic group according to the Anatomical Therapeutic Chemical classification system were considered. To classify the ADRs, the Medical Dictionary for Regularity Activities terminology was adopted. Between 2008 and 2012, FDA collected 113,077 ADRs in pediatric patients. Of the total pediatric ADR reports, those performed by medical doctors were 32%, followed by consumers (26%) and healthcare professionals (25%). Most of the ADR reports were related to the adolescent group (39%). Healthcare professionals resulted the category with the highest rate of ADR reports in neonates and infants. Drugs acting on nervous system and antineoplastic/immunomodulating agents were the most involved the pediatric ADR reports. Pyrexia, convulsion, vomiting and accidental overdose were the reactions more reported both from healthcare professionals and medical doctors. The present study describes the pediatric ADR reports of the FDA database through healthcare professional's perspective, describing the various aspects of pediatric pharmacovigilance.
Oral controlled release drug delivery system and Characterization of oral tablets; A review
Muhammad Zaman; Junaid Qureshi; Hira Ejaz; Rai Muhammad Sarfraz; Hafeez ullah Khan; Fazal Rehman Sajid; Muhammad Shafiq ur Rehman
2016-01-01
Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes dif...
75 FR 22412 - Food and Drug Administration/Xavier University Global Outsourcing Conference
2010-04-28
... Selection Process--the criteria a contract organization should use to consider saying no to a contract... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Food and Drug Administration/Xavier University Global Outsourcing Conference AGENCY: Food and Drug...
Recent trends in challenges and opportunities of Transdermal drug delivery system
P.M.Patil; P.D.Chaudhari; Jalpa K.Patel; K.A.Kedar; P.P.Katolkar
2012-01-01
Drug delivery system relates to the production of a drug, its delivery medium, and the way of administration. Drug delivery systems are even used for administering nitroglycerin. Transdermal drug delivery system is the system in which the delivery of the active ingredients of the drug occurs by the means of skin. Various types of transdermal patches are used. There are various methods to enhance the transdermal drug delivery system. But using microfabricated microneedles drugs are delivered v...
Hierarchical pulmonary target nanoparticles via inhaled administration for anticancer drug delivery.
Chen, Rui; Xu, Liu; Fan, Qin; Li, Man; Wang, Jingjing; Wu, Li; Li, Weidong; Duan, Jinao; Chen, Zhipeng
2017-11-01
Inhalation administration, compared with intravenous administration, significantly enhances chemotherapeutic drug exposure to the lung tissue and may increase the therapeutic effect for pulmonary anticancer. However, further identification of cancer cells after lung deposition of inhaled drugs is necessary to avoid side effects on normal lung tissue and to maximize drug efficacy. Moreover, as the action site of the major drug was intracellular organelles, drug target to the specific organelle is the final key for accurate drug delivery. Here, we designed a novel multifunctional nanoparticles (MNPs) for pulmonary antitumor and the material was well-designed for hierarchical target involved lung tissue target, cancer cell target, and mitochondrial target. The biodistribution in vivo determined by UHPLC-MS/MS method was employed to verify the drug concentration overwhelmingly increasing in lung tissue through inhaled administration compared with intravenous administration. Cellular uptake assay using A549 cells proved the efficient receptor-mediated cell endocytosis. Confocal laser scanning microscopy observation showed the location of MNPs in cells was mitochondria. All results confirmed the intelligent material can progressively play hierarchical target functions, which could induce more cell apoptosis related to mitochondrial damage. It provides a smart and efficient nanocarrier platform for hierarchical targeting of pulmonary anticancer drug. So far, this kind of material for pulmonary mitochondrial-target has not been seen in other reports.
21 CFR 20.120 - Records available in Food and Drug Administration Public Reading Rooms.
2010-04-01
... Public Reading Rooms. 20.120 Section 20.120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF....120 Records available in Food and Drug Administration Public Reading Rooms. (a) The Food and Drug Administration operates two public reading rooms. The Freedom of Information Staff's Public Reading Room is...
Radiopharmaceutical regulation and Food and Drug Administration policy.
Rotman, M; Laven, D; Levine, G
1996-04-01
The regulatory policy of the Food and Drug Administration (FDA) on radiopharmaceuticals flows from a rigid, traditional, drug-like interpretation of the FDC Act on the licensing of radiopharmaceuticals. This contributes to significant delays in the drug-approval process for radiopharmaceuticals, which are very costly to the nuclear medicine community and the American public. It seems that radiopharmaceuticals would be better characterized as molecular devices. Good generic rule-making principles include: use of a risk/benefit/cost analysis; intent based on sound science; performance standards prepared by outside experts; a definite need shown by the regulatory agency; to live with the consequences of any erroneous cost estimates; and design individual credential requirements so that additional training results in enhanced professional responsibility. When these common elements are applied to current FDA policy, it seems that the agency is out of sync with the stated goals for revitalizing federal regulatory policies as deemed necessary by the Clinton administration. Recent FDA rulings on positron-emission tomography, Patient Package inserts, and on medical device service accentuate the degree of such asynchronization. Radiopharmaceutical review and licensing flexibility could be dramatically improved by excluding radiopharmaceuticals from the drug category and reviewing them as separate entities. This new category would take into account their excellent record of safety and their lack of pharmacological action. Additionally, their evaluation of efficacy should be based on their ability to provide useful scintiphotos, data, or responses of the physiological system it portends to image, quantitate, or describe. To accomplish the goal of transforming the FDA's rigid, prescriptive policy into a streamlined flexible performance-based policy, the Council on Radionuclides and Radiopharmaceuticals proposal has been presented. In addition, it is suggested that the United
Sakloetsakun, Duangkamon; Dünnhaupt, Sarah; Barthelmes, Jan; Perera, Glen; Bernkop-Schnürch, Andreas
2013-10-01
The aim of the study is to develop a self-nanoemulsifying drug delivery system (SNEDDS) based on thiolated chitosan for oral insulin administration. The preparations were characterized by particle size, entrapment efficiency, stability and drug release. Serum insulin concentrations were determined after oral administration of all formulations. Insulin SNEDDS formulation was served as control. The optimized SNEDDS consists of 65% (w/w) miglyol 840, 25% (w/w) cremophor EL, 10% (w/w) co-solvents (a mixture of DMSO and glycerol). The formulations in the presence or absence of insulin (5mg/mL) were spherical with the size range between 80 and 160 nm. Entrapment efficiency of insulin increased significantly when the thiolated chitosan was employed (95.14±2.96%), in comparison to the insulin SNEDDS (80.38±1.22%). After 30 min, the in vitro release profile of insulin from the nanoemulsions was markedly increased compared to the control. In vivo results showed that insulin/thiolated chitosan SNEDDS displayed a significant increase in serum insulin (p-value=0.02) compared to oral insulin solution. A new strategy to combine SNEDDS and thiolated chitosan described in the study would therefore be a promising and innovative approach to improve oral bioavailability of insulin. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.
Systematic review of drug administration costs and implications for biopharmaceutical manufacturing.
Tetteh, Ebenezer; Morris, Stephen
2013-10-01
The acquisition costs of biologic drugs are often considered to be relatively high compared with those of nonbiologics. However, the total costs of delivering these drugs also depend on the cost of administration. Ignoring drug administration costs may distort resource allocation decisions because these affect cost effectiveness. The objectives of this systematic review were to develop a framework of drug administration costs that considers both the costs of physical administration and the associated proximal costs; and, as a case example, to use this framework to evaluate administration costs for biologics within the UK National Health Service (NHS). We reviewed literature that reported estimates of administration costs for biologics within the UK NHS to identify how these costs were quantified and to examine how differences in dosage forms and regimens influenced administration costs. The literature reviewed were identified by searching the Centre for Review and Dissemination Databases (DARE, NHS EED and HTA); EMBASE (The Excerpta Medica Database); MEDLINE (using the OVID interface); Econlit (EBSCO); Tufts Medical Center Cost Effectiveness Analysis (CEA) Registry; and Google Scholar. We identified 4,344 potentially relevant studies, of which 43 studies were selected for this systematic review. We extracted estimates of the administration costs of biologics from these studies. We found evidence of variation in the way that administration costs were measured, and that this affected the magnitude of costs reported, which could then influence cost effectiveness. Our findings suggested that manufacturers of biologic medicines should pay attention to formulation issues and their impact on administration costs, because these affect the total costs of healthcare delivery and cost effectiveness.
Oral controlled release drug delivery system and Characterization of oral tablets; A review
Directory of Open Access Journals (Sweden)
Muhammad Zaman
2016-01-01
Full Text Available Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes diffusion controlled drug delivery systems; dissolution controlled drug delivery systems, osmotically controlled drug delivery systems, ion-exchange controlled drug delivery systems, hydrodynamically balanced systems, multi-Particulate drug delivery systems and microencapsulated drug delivery system. The systems are formulated using different natural, semi-synthetic and synthetic polymers. The purpose of the review is to provide information about the orally controlled drug delivery system, polymers which are used to formulate these systems and characterizations of one of the most convenient dosage form which is the tablets.
A Comprehensive Review on: Transdermal drug delivery systems.
Kharat, Rekha; Bathe, Ritesh Suresh
2016-01-01
Transdermal drug delivery system was introduced to overcome the difficulties of drug delivery through oral route. Despite their relatively higher costs, transdermal delivery systems have proved advantageous for delivery of selected drugs, such as estrogens, testosterone, clonidine and nitro-glycerine. Transdermal delivery provides a leading edge over injectable and oral routes by increasing patient compliance and avoiding first pass metabolism respectively. Topical administration of therap...
Buccoadhesive drug delivery systems--extensive review on recent patents.
Pathan, Shadab A; Iqbal, Zeenat; Sahani, Jasjeet K; Talegaonkar, Sushma; Khar, Roop K; Ahmad, Farhan J
2008-01-01
Peroral administration of drugs, although most preferred by both clinicians and patients has several disadvantages such as hepatic first pass metabolism and enzymatic degradation within the GI tract, that prohibit oral administration of certain classes of drugs especially peptides and proteins. Consequently, other absorptive mucosae are considered as potential sites for administration of these drugs. Among the various transmucosal routes studied the buccal mucosa offers several advantages for controlled drug delivery for extended period of time. The mucosa is well supplied with both vascular and lymphatic drainage and first-pass metabolism in the liver and pre-systemic elimination in the gastrointestinal tract is avoided. The area is well suited for a retentive device and appears to be acceptable to the patient. With the right dosage form, design and formulation, the permeability and the local environment of the mucosa can be controlled and manipulated in order to accommodate drug permeation. Buccal drug delivery is thus a promising area for continued research with the aim of systemic and local delivery of orally inefficient drugs as well as feasible and attractive alternative for non-invasive delivery of potent protein and peptide drug molecules. Extensive review pertaining specifically to the patents relating to buccal drug delivery is currently available. However, many patents e.g. US patents 6, 585,997; US20030059376A1 etc. have been mentioned in few articles. It is the objective of this article to extensively review buccal drug delivery by discussing the recent patents available. Buccal dosage forms will also be reviewed with an emphasis on bioadhesive polymeric based delivery systems.
27 CFR 17.136 - Compliance with Food and Drug Administration requirements.
2010-04-01
... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Compliance with Food and Drug Administration requirements. 17.136 Section 17.136 Alcohol, Tobacco Products and Firearms ALCOHOL... Compliance with Food and Drug Administration requirements. A product is not a medicine, medicinal preparation...
Nanostructured lipid carriers system: recent advances in drug delivery.
Iqbal, Md Asif; Md, Shadab; Sahni, Jasjeet Kaur; Baboota, Sanjula; Dang, Shweta; Ali, Javed
2012-12-01
Nanostructured lipid carrier (NLC) is second generation smarter drug carrier system having solid matrix at room temperature. This carrier system is made up of physiological, biodegradable and biocompatible lipid materials and surfactants and is accepted by regulatory authorities for application in different drug delivery systems. The availability of many products in the market in short span of time reveals the success story of this delivery system. Since the introduction of the first product, around 30 NLC preparations are commercially available. NLC exhibit superior advantages over other colloidal carriers viz., nanoemulsions, polymeric nanoparticles, liposomes, SLN etc. and thus, have been explored to more extent in pharmaceutical technology. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes NLC versatile delivery system for various routes of administration. The present review gives insights on the definitions and characterization of NLC as colloidal carriers including the production techniques and suitable formulations. This review paper also highlights the importance of NLC in pharmaceutical applications for the various routes of drug delivery viz., topical, oral, pulmonary, ocular and parenteral administration and its future perspective as a pharmaceutical carrier.
Combined Transcriptomics and Metabolomics in a Rhesus Macaque Drug Administration Study
Directory of Open Access Journals (Sweden)
Kevin J. Lee
2014-10-01
Full Text Available We describe a multi-omic approach to understanding the effects that the anti-malarial drug pyrimethamine has on immune physiology in rhesus macaques (Macaca mulatta. Whole blood and bone marrow RNA-Seq and plasma metabolome profiles (each with over 15,000 features have been generated for five naïve individuals at up to seven time-points before, during and after three rounds of drug administration. Linear modelling and Bayesian network analyses are both considered, alongside investigations of the impact of statistical modeling strategies on biological inference. Individual macaques were found to be a major source of variance for both omic data types, and factoring individuals into subsequent modelling increases power to detect temporal effects. A major component of the whole blood transcriptome follows the bone marrow with a time-delay, while other components of variation are unique to each compartment. We demonstrate that pyrimethamine administration does impact both compartments throughout the experiment, but very limited perturbation of transcript or metabolite abundance following each round of drug exposure is observed. New insights into the mode of action of the drug are presented in the context of pyrimethamine’s predicted effect on suppression of cell division and metabolism in the immune system.
Ménétré, S; Weber, M; Socha, M; Le Tacon, S; May, I; Schweitzer, C; Demoré, B
2018-04-01
In hospitals, the nursing staff is often confronted with the problem of the preparation and administration of drugs for their pediatric patients because of the lack of indication, pediatric dosage, and appropriate galenic form. The goal of this study was to give an overview of the nurses' preparation habits in pediatric units and highlight their daily problems. This single-center prospective study was conducted through an observation of the nursing staff during the drug preparation process in medicine, surgery and intensive care units. We included 91 patients (55 boys and 36 girls), with an average age of 6.3 years (youngest child, 10 days old; oldest child, 18 years old). We observed a mean 2.16 drug preparations per patient [1-5]. We collected 197 observation reports regarding 66 injectable drugs and 131 oral drugs (71 liquid forms and 60 solid forms). The majority of these reports concerned central nervous system drugs (63/197), metabolism and digestive system drugs (50/197), and anti-infective drugs (46/197). The study highlights the nurses' difficulties: modification of the solid galenic forms, lack of knowledge on oral liquid form preservation or reconstitution methods, withdrawal of small volumes, and vague and noncompliant labeling. This study led to the creation of a specific working group for pediatrics. This multidisciplinary team meets on a regular basis to work toward improving the current habits to both simplify and secure drug administration to hospitalized children. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Financial Effect of a Drug Distribution Model Change on a Health System.
Turingan, Erin M; Mekoba, Bijan C; Eberwein, Samuel M; Roberts, Patricia A; Pappas, Ashley L; Cruz, Jennifer L; Amerine, Lindsey B
2017-06-01
Background: Drug manufacturers change distribution models based on patient safety and product integrity needs. These model changes can limit health-system access to medications, and the financial impact on health systems can be significant. Objective: The primary aim of this study was to determine the health-system financial impact of a manufacturer's change from open to limited distribution for bevacizumab (Avastin), rituximab (Rituxan), and trastuzumab (Herceptin). The secondary aim was to identify opportunities to shift administration to outpatient settings to support formulary change. Methods: To assess the financial impact on the health system, the cost minus discount was applied to total drug expenditure during a 1-year period after the distribution model change. The opportunity analysis was conducted for three institutions within the health system through chart review of each inpatient administration. Opportunity cost was the sum of the inpatient administration cost and outpatient administration margin. Results: The total drug expenditure for the study period was $26 427 263. By applying the cost minus discount, the financial effect of the distribution model change was $1 393 606. A total of 387 administrations were determined to be opportunities to be shifted to the outpatient setting. During the study period, the total opportunity cost was $1 766 049. Conclusion: Drug expenditure increased for the health system due to the drug distribution model change and loss of cost minus discount. The opportunity cost of shifting inpatient administrations could offset the increase in expenditure. It is recommended to restrict bevacizumab, rituximab, and trastuzumab through Pharmacy & Therapeutics Committees to outpatient use where clinically appropriate.
21 CFR 20.3 - Certification and authentication of Food and Drug Administration records.
2010-04-01
... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Certification and authentication of Food and Drug... authentication of Food and Drug Administration records. (a) Upon request, the Food and Drug Administration will... or for authentication of records shall be sent in writing to the Freedom of Information Staff (HFI-35...
The 2015 US Food and Drug Administration Pregnancy and Lactation Labeling Rule.
Brucker, Mary C; King, Tekoa L
2017-05-01
As of 2015, the US Food and Drug Administration (FDA) discontinued the pregnancy risk categories (ABCDX) that had been used to denote the putative safety of drugs for use among pregnant women. The ABCDX system has been replaced by the FDA Pregnancy and Lactation Labeling Rule (PLLR) that requires narrative text to describe risk information, clinical considerations, and background data for the drug. The new rule includes 3 overarching categories: 1) pregnancy, which includes labor and birth; 2) lactation; and 3) females and males of reproductive potential. This article reviews the key components of the PLLR and clinical implications, and provides resources for clinicians who prescribe drugs for women of reproductive age. © 2017 by the American College of Nurse-Midwives.
Film forming systems for topical and transdermal drug delivery
Directory of Open Access Journals (Sweden)
Kashmira Kathe
2017-11-01
Full Text Available Skin is considered as an important route of administration of drugs for both local and systemic effects. The effectiveness of topical therapy depends on the physicochemical properties of the drug and adherence of the patient to the treatment regimen as well as the system's ability to adhere to skin during the therapy so as to promote drug penetration through the skin barrier. Conventional formulations for topical and dermatological administration of drugs have certain limitations like poor adherence to skin, poor permeability and compromised patient compliance. For the treatment of diseases of body tissues and wounds, the drug has to be maintained at the site of treatment for an effective period of time. Topical film forming systems are such developing drug delivery systems meant for topical application to the skin, which adhere to the body, forming a thin transparent film and provide delivery of the active ingredients to the body tissue. These are intended for skin application as emollient or protective and for local action or transdermal penetration of medicament for systemic action. The transparency is an appreciable feature of this polymeric system which greatly influences the patient acceptance. In the current discussion, the film forming systems are described as a promising choice for topical and transdermal drug delivery. Further the various types of film forming systems (sprays/solutions, gels and emulsions along with their evaluation parameters have also been reviewed.
Setlow, Barry; Mendez, Ian A; Mitchell, Marci R; Simon, Nicholas W
2009-09-01
Drug-addicted individuals show high levels of impulsive choice, characterized by preference for small immediate over larger but delayed rewards. Although the causal relationship between chronic drug use and elevated impulsive choice in humans has been unclear, a small but growing body of literature over the past decade has shown that chronic drug administration in animal models can cause increases in impulsive choice, suggesting that a similar causal relationship may exist in human drug users. This article reviews this literature, with a particular focus on the effects of chronic cocaine administration, which have been most thoroughly characterized. The potential mechanisms of these effects are described in terms of drug-induced neural alterations in ventral striatal and prefrontal cortical brain systems. Some implications of this research for pharmacological treatment of drug-induced increases in impulsive choice are discussed, along with suggestions for future research in this area.
78 FR 30317 - Science Board to the Food and Drug Administration; Notice of Meeting
2013-05-22
... 24, 2013, from approximately 1 p.m. to 3:45 p.m. Location: Food and Drug Administration, White Oak..., Office of the Chief Scientist, Office of the Commissioner, Food and Drug Administration, White Oak Bldg... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001...
2013-05-06
...] Food and Drug Administration/International Society for Pharmaceutical Engineering Co-Sponsorship... Society of Pharmaceutical Engineering (ISPE), is announcing a conference entitled ``Redefining the `C' in CGMP: Creating, Implementing and Sustaining a Culture of Quality'' Pharmaceutical Quality System (ICH...
2011-10-04
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0247] Food and Drug Administration Transparency Initiative: Draft Proposals for Public Comment to Increase...: Food and Drug Administration, HHS. [[Page 61367
2012-02-27
... Oversight of PET Drug Products--Questions and Answers.'' The draft guidance provides questions and answers... assist that office in processing your requests. See the SUPPLEMENTARY INFORMATION section for electronic... PET Drug Products--Questions and Answers.'' In 1997, Congress passed the Food and Drug Administration...
Drug delivery systems with modified release for systemic and biophase bioavailability.
Leucuta, Sorin E
2012-11-01
This review describes the most important new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body. Drug delivery of these pharmaceutical formulations has the benefit of improving product efficacy and safety, as well as patient convenience and compliance. This paper describes the biopharmaceutical, pharmacokinetic, pharmacologic and technological principles in the design of drug delivery systems with modified release as well as the formulation criteria of prolonged and controlled release drug delivery systems. The paper presents pharmaceutical prolonged and controlled release dosage forms intended for different routes of administration: oral, ocular, transdermal, parenteral, pulmonary, mucoadhesive, but also orally fast dissolving tablets, gastroretentive drug delivery systems, colon-specific drug delivery systems, pulsatile drug delivery systems and carrier or ligand mediated transport for site specific or receptor drug targeting. Specific technologies are given on the dosage forms with modified release as well as examples of marketed products, and current research in these areas.
2013-03-06
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-D-0010] Guidance for Industry and Food and Drug Administration Staff: Investigational Device Exemption Guidance for Retinal Prostheses; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The...
Rahman, Md Motiur; Alatawi, Yasser; Cheng, Ning; Qian, Jingjing; Plotkina, Annya V; Peissig, Peggy L; Berg, Richard L; Page, David; Hansen, Richard A
2017-09-01
Despite the cost saving role of generic anti-epileptic drugs (AEDs), debate exists as to whether generic substitution of branded AEDs may lead to therapeutic failure and increased toxicity. This study compared adverse event (AE) reporting rates for brand vs. authorized generic (AG) vs. generic AEDs. Since AGs are pharmaceutically identical to brand but perceived as generics, the generic vs. AG comparison minimized potential bias against generics. Events reported to the U.S. Food and Drug Administration Adverse Event Reporting System between January 2004 to March 2015 with lamotrigine, carbamazepine, and oxcarbazepine listed as primary or secondary suspect were classified as brand, generic, or AG based on the manufacturer. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting of labeled AEs compared to reporting these events with all other drugs. The Breslow-Day statistic compared RORs across brand, AG, and other generics using a Bonferroni-corrected Pbrand and generics for all three drugs of interest (Breslow-Day Pbrands and generics have similar reporting rates after accounting for generic perception biases. Disproportional suicide reporting was observed for generics compared with AGs and brand, although this finding needs further study. Copyright © 2017 Elsevier B.V. All rights reserved.
Adverse Drug Events caused by Serious Medication Administration Errors
Sawarkar, Abhivyakti; Keohane, Carol A.; Maviglia, Saverio; Gandhi, Tejal K; Poon, Eric G
2013-01-01
OBJECTIVE To determine how often serious or life-threatening medication administration errors with the potential to cause patient harm (or potential adverse drug events) result in actual patient harm (or adverse drug events (ADEs)) in the hospital setting. DESIGN Retrospective chart review of clinical events that transpired following observed medication administration errors. BACKGROUND Medication errors are common at the medication administration stage for hospitalized patients. While many of these errors are considered capable of causing patient harm, it is not clear how often patients are actually harmed by these errors. METHODS In a previous study where 14,041 medication administrations in an acute-care hospital were directly observed, investigators discovered 1271 medication administration errors, of which 133 had the potential to cause serious or life-threatening harm to patients and were considered serious or life-threatening potential ADEs. In the current study, clinical reviewers conducted detailed chart reviews of cases where a serious or life-threatening potential ADE occurred to determine if an actual ADE developed following the potential ADE. Reviewers further assessed the severity of the ADE and attribution to the administration error. RESULTS Ten (7.5% [95% C.I. 6.98, 8.01]) actual adverse drug events or ADEs resulted from the 133 serious and life-threatening potential ADEs, of which 6 resulted in significant, three in serious, and one life threatening injury. Therefore 4 (3% [95% C.I. 2.12, 3.6]) serious and life threatening potential ADEs led to serious or life threatening ADEs. Half of the ten actual ADEs were caused by dosage or monitoring errors for anti-hypertensives. The life threatening ADE was caused by an error that was both a transcription and a timing error. CONCLUSION Potential ADEs at the medication administration stage can cause serious patient harm. Given previous estimates of serious or life-threatening potential ADE of 1.33 per 100
Adverse Drug Reactions Related to Drug Administration in Hospitalized Patients.
Gallelli, Luca; Siniscalchi, Antonio; Palleria, Caterina; Mumoli, Laura; Staltari, Orietta; Squillace, Aida; Maida, Francesca; Russo, Emilio; Gratteri, Santo; De Sarro, Giovambattista
2017-01-01
Drug treatment may be related to the development of adverse drug reactions (ADRs). In this paper, we evaluated the ADRs in patients admitted to Catanzaro Hospital. After we obtained the approval by local Ethical Committee, we performed a retrospective study on clinical records from March 01, 2013 to April 30, 2015. The association between drug and ADR or between drug and drug-drug-interactions (DDIs) was evaluated using the Naranjo's probability scale and Drug Interaction Probability Scale (DIPS), respectively. During the study period, we analyzed 2870 clinical records containing a total of 11,138 prescriptions, and we documented the development of 770 ADRs. The time of hospitalization was significantly higher (P<0.05) in women with ADRs (12.6 ± 1.2 days) with respect to men (11.8± 0.83 days). Using the Naranjo score, we documented a probable association in 78% of these reactions, while DIPS revealed that about 22% of ADRs were related to DDIs. Patients with ADRs received 3052 prescriptions on 11,138 (27.4%) having a mean of 6.1±0.29 drugs that was significantly higher (P<0.01) with respect to patients not experiencing ADRs (mean of 3.4±0.13 drugs). About 19% of ADRs were not diagnosed and were treated as new diseases. Our results indicate that drug administration induces the development of ADRs also during the hospitalization, particularly in elderly women. Moreover, we also documented that ADRs in some patients are under-diagnosed, therefore, it is important to motivate healthcare to report the ADRs in order to optimize the patients' safety. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Otic drug delivery systems: formulation principles and recent developments.
Liu, Xu; Li, Mingshuang; Smyth, Hugh; Zhang, Feng
2018-04-25
Disorders of the ear severely impact the quality of life of millions of people, but the treatment of these disorders is an ongoing, but often overlooked challenge particularly in terms of formulation design and product development. The prevalence of ear disorders has spurred significant efforts to develop new therapeutic agents, but perhaps less innovation has been applied to new drug delivery systems to improve the efficacy of ear disease treatments. This review provides a brief overview of physiology, major diseases, and current therapies used via the otic route of administration. The primary focuses are on the various administration routes and their formulation principles. The article also presents recent advances in otic drug deliveries as well as potential limitations. Otic drug delivery technology will likely evolve in the next decade and more efficient or specific treatments for ear disease will arise from the development of less invasive drug delivery methods, safe and highly controlled drug delivery systems, and biotechnology targeting therapies.
2011-05-13
... Tots Public-Private Partnership AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0005; FDA 225-09-0014] Memorandum of Understanding Between the Food and Drug Administration and the...
2013-04-05
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0345] Food and Drug Administration/National Institutes of Health/ National Science Foundation Public Workshop... public workshop; request for comments. SUMMARY: The Food and Drug Administration (FDA) is announcing its...
2011-07-21
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0530] Draft Guidance for Industry and Food and Drug Administration Staff; Mobile Medical Applications; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...
PLGA based drug delivery systems: Promising carriers for wound healing activity.
Chereddy, Kiran Kumar; Vandermeulen, Gaëlle; Préat, Véronique
2016-03-01
Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Current treatment options are limited and require repeated administrations which led to the development of new therapeutics to satisfy the unmet clinical needs. Many potent wound healing agents were discovered but most of them are fragile and/or sensitive to in vivo conditions. Poly(lactic-co-glycolic acid) (PLGA) is a widely used biodegradable polymer approved by food and drug administration and European medicines agency as an excipient for parenteral administrations. It is a well-established drug delivery system in various medical applications. The aim of the current review is to elaborate the applications of PLGA based drug delivery systems carrying different wound healing agents and also present PLGA itself as a wound healing promoter. PLGA carriers encapsulating drugs such as antibiotics, anti-inflammatory drugs, proteins/peptides, and nucleic acids targeting various phases/signaling cycles of wound healing, are discussed with examples. The combined therapeutic effects of PLGA and a loaded drug on wound healing are also mentioned. © 2016 by the Wound Healing Society.
2013-01-03
... Dependence; Public Hearing; Extension of Comment Period AGENCY: Food and Drug Administration, HHS. ACTION: Notification of public hearing; Extension of comment period. SUMMARY: The Food and Drug Administration (FDA) is... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 15 [Docket No...
2013-03-11
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-0168] Draft Guidance for Industry and Food and Drug Administration Staff: Recommendations for Labeling Medical...; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...
Franklin, Bryony Dean; O'Grady, Kara; Donyai, Parastou; Jacklin, Ann; Barber, Nick
2007-08-01
To assess the impact of a closed-loop electronic prescribing, automated dispensing, barcode patient identification and electronic medication administration record (EMAR) system on prescribing and administration errors, confirmation of patient identity before administration, and staff time. Before-and-after study in a surgical ward of a teaching hospital, involving patients and staff of that ward. Closed-loop electronic prescribing, automated dispensing, barcode patient identification and EMAR system. Percentage of new medication orders with a prescribing error, percentage of doses with medication administration errors (MAEs) and percentage given without checking patient identity. Time spent prescribing and providing a ward pharmacy service. Nursing time on medication tasks. Prescribing errors were identified in 3.8% of 2450 medication orders pre-intervention and 2.0% of 2353 orders afterwards (pMedical staff required 15 s to prescribe a regular inpatient drug pre-intervention and 39 s afterwards (p = 0.03; t test). Time spent providing a ward pharmacy service increased from 68 min to 98 min each weekday (p = 0.001; t test); 22% of drug charts were unavailable pre-intervention. Time per drug administration round decreased from 50 min to 40 min (p = 0.006; t test); nursing time on medication tasks outside of drug rounds increased from 21.1% to 28.7% (p = 0.006; chi(2) test). A closed-loop electronic prescribing, dispensing and barcode patient identification system reduced prescribing errors and MAEs, and increased confirmation of patient identity before administration. Time spent on medication-related tasks increased.
Lipid nanoparticles for administration of poorly water soluble neuroactive drugs.
Esposito, Elisabetta; Drechsler, Markus; Mariani, Paolo; Carducci, Federica; Servadio, Michela; Melancia, Francesca; Ratano, Patrizia; Campolongo, Patrizia; Trezza, Viviana; Cortesi, Rita; Nastruzzi, Claudio
2017-09-01
This study describes the potential of solid lipid nanoparticles and nanostructured lipid carriers as nano-formulations to administer to the central nervous system poorly water soluble drugs. Different neuroactive drugs, i.e. dimethylfumarate, retinyl palmitate, progesterone and the endocannabinoid hydrolysis inhibitor URB597 have been studied. Lipid nanoparticles constituted of tristearin or tristearin in association with gliceryl monoolein were produced. The nanoencapsulation strategy allowed to obtain biocompatible and non-toxic vehicles, able to increase the solubility of the considered neuroactive drugs. To improve URB597 targeting to the brain, stealth nanoparticles were produced modifying the SLN surface with polysorbate 80. A behavioural study was conducted in rats to test the ability of SLN containing URB597 given by intranasal administration to alter behaviours relevant to psychiatric disorders. URB597 maintained its activity after nanoencapsulation, suggesting the possibility to propose this kind of vehicle as alternative to unphysiological mixtures usually employed for animal and clinical studies.
2013-04-09
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Chapter I [Docket No. FDA-2013-N-0365] Establishment of a Public Docket for Administrative Detention Under the Food and Drug Administration Safety and Innovation Act AGENCY: Food and Drug Administration, HHS. ACTION: Establishment of...
2010-11-17
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0515] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...
2011-02-16
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0057] Draft Guidance for Industry and Food and Drug Administration Staff on Best Practices for Conducting and...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...
International Nuclear Information System (INIS)
Gao Lei; Zhang Dianrui; Chen Minghui
2008-01-01
Formulation of poorly soluble drugs is a general intractable problem in pharmaceutical field, especially those compounds poorly soluble in both aqueous and organic media. It is difficult to resolve this problem using conventional formulation approaches, so many drugs are abandoned early in discovery. Nanocrystals, a new carrier-free colloidal drug delivery system with a particle size ranging from 100 to 1000 nm, is thought as a viable drug delivery strategy to develop the poorly soluble drugs, because of their simplicity in preparation and general applicability. In this article, the product techniques of the nanocrystals were reviewed and compared, the special features of drug nanocrystals were discussed. The researches on the application of the drug nanocrystals to various administration routes were described in detail. In addition, as introduced later, the nanocrystals could be easily scaled up, which was the prerequisite to the development of a delivery system as a market product
Brady, Oliver J; Slater, Hannah C; Pemberton-Ross, Peter; Wenger, Edward; Maude, Richard J; Ghani, Azra C; Penny, Melissa A; Gerardin, Jaline; White, Lisa J; Chitnis, Nakul; Aguas, Ricardo; Hay, Simon I; Smith, David L; Stuckey, Erin M; Okiro, Emelda A; Smith, Thomas A; Okell, Lucy C
2017-07-01
Mass drug administration for elimination of Plasmodium falciparum malaria is recommended by WHO in some settings. We used consensus modelling to understand how to optimise the effects of mass drug administration in areas with low malaria transmission. We collaborated with researchers doing field trials to establish a standard intervention scenario and standard transmission setting, and we input these parameters into four previously published models. We then varied the number of rounds of mass drug administration, coverage, duration, timing, importation of infection, and pre-administration transmission levels. The outcome of interest was the percentage reduction in annual mean prevalence of P falciparum parasite rate as measured by PCR in the third year after the final round of mass drug administration. The models predicted differing magnitude of the effects of mass drug administration, but consensus answers were reached for several factors. Mass drug administration was predicted to reduce transmission over a longer timescale than accounted for by the prophylactic effect alone. Percentage reduction in transmission was predicted to be higher and last longer at lower baseline transmission levels. Reduction in transmission resulting from mass drug administration was predicted to be temporary, and in the absence of scale-up of other interventions, such as vector control, transmission would return to pre-administration levels. The proportion of the population treated in a year was a key determinant of simulated effectiveness, irrespective of whether people are treated through high coverage in a single round or new individuals are reached by implementation of several rounds. Mass drug administration was predicted to be more effective if continued over 2 years rather than 1 year, and if done at the time of year when transmission is lowest. Mass drug administration has the potential to reduce transmission for a limited time, but is not an effective replacement for existing
Hyaluronan-decorated liposomes as drug delivery systems for cutaneous administration.
Franzé, Silvia; Marengo, Alessandro; Stella, Barbara; Minghetti, Paola; Arpicco, Silvia; Cilurzo, Francesco
2018-01-15
The work aimed to evaluate the feasibility to design hyaluronic acid (HA) decorated flexible liposomes to enhance the skin penetration of nifedipine. Egg phosphatidylcholine (e-PC) based transfersomes (Tween 80) and transethosomes (ethanol) were prepared. HA was reacted with 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (HA-DPPE) and two molar ratios (0.5 and 3%) of conjugate with respect to e-PC were tested. The presence of HA significantly increased the packing order of the bilayer (as verified by differential scanning calorimetry), reducing both the encapsulation efficiency and the flexibility of the decorated liposomes in a dose-dependent manner. In fact, at the highest HA content the constant of deformability (K, N/mm) increased and the carriers remained on the skin surface after topical application. The stiffening effect of HA was counterbalanced by the addition of ethanol as fluidizing agent that allowed to maintain the highest HA concentration, meanwhile reducing the K value of the vesicles. HA-transethosomes allowed a suitable nifedipine permeation (J ∼ 30 ng/cm 2 /h) and significantly improved the drug penetration, favouring the formation of a drug depot in the epidermis. These data suggest the potentialities of HA-transethosomes as drug delivery systems intended for the treatment of cutaneous pathologies and underline the importance of studying the effect of surface functionalization on carrier deformability to rationalize the design of such systems. Copyright © 2017 Elsevier B.V. All rights reserved.
2010-07-01
... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Federal Bureau of Investigation, Drug Enforcement Administration, Bureau of Alcohol, Tobacco, Firearms, and Explosives, Bureau of Prisons, Federal... Administrative Matters § 0.138 Federal Bureau of Investigation, Drug Enforcement Administration, Bureau of...
Ophthalmic Drug Delivery Systems for Antibiotherapy—A Review
Dubald, Marion; Bourgeois, Sandrine; Andrieu, Véronique; Fessi, Hatem
2018-01-01
The last fifty years, ophthalmic drug delivery research has made much progress, challenging scientists about the advantages and limitations of this drug delivery approach. Topical eye drops are the most commonly used formulation in ocular drug delivery. Despite the good tolerance for patients, this topical administration is only focus on the anterior ocular diseases and had a high precorneal loss of drugs due to the tears production and ocular barriers. Antibiotics are popularly used in solution or in ointment for the ophthalmic route. However, their local bioavailability needs to be improved in order to decrease the frequency of administrations and the side effects and to increase their therapeutic efficiency. For this purpose, sustained release forms for ophthalmic delivery of antibiotics were developed. This review briefly describes the ocular administration with the ocular barriers and the currently topical forms. It focuses on experimental results to bypass the limitations of ocular antibiotic delivery with new ocular technology as colloidal and in situ gelling systems or with the improvement of existing forms as implants and contact lenses. Nanotechnology is presently a promising drug delivery way to provide protection of antibiotics and improve pathway through ocular barriers and deliver drugs to specific target sites. PMID:29342879
Ophthalmic Drug Delivery Systems for Antibiotherapy—A Review
Directory of Open Access Journals (Sweden)
Marion Dubald
2018-01-01
Full Text Available The last fifty years, ophthalmic drug delivery research has made much progress, challenging scientists about the advantages and limitations of this drug delivery approach. Topical eye drops are the most commonly used formulation in ocular drug delivery. Despite the good tolerance for patients, this topical administration is only focus on the anterior ocular diseases and had a high precorneal loss of drugs due to the tears production and ocular barriers. Antibiotics are popularly used in solution or in ointment for the ophthalmic route. However, their local bioavailability needs to be improved in order to decrease the frequency of administrations and the side effects and to increase their therapeutic efficiency. For this purpose, sustained release forms for ophthalmic delivery of antibiotics were developed. This review briefly describes the ocular administration with the ocular barriers and the currently topical forms. It focuses on experimental results to bypass the limitations of ocular antibiotic delivery with new ocular technology as colloidal and in situ gelling systems or with the improvement of existing forms as implants and contact lenses. Nanotechnology is presently a promising drug delivery way to provide protection of antibiotics and improve pathway through ocular barriers and deliver drugs to specific target sites.
2010-04-05
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-D-0495] Draft Guidance for Industry and Food and Drug Administration Staff; Medical Devices; Neurological and Physical Medicine Device Guidance Documents; Availability AGENCY: Food and Drug Administration, HHS. ACTION...
76 FR 789 - Guidance for Industry and Food and Drug Administration Staff; Section 905(j) Reports...
2011-01-06
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0635] Guidance for Industry and Food and Drug Administration Staff; Section 905(j) Reports: Demonstrating Substantial Equivalence for Tobacco Products; Availability AGENCY: Food and Drug Administration, HHS. ACTION...
2011-08-16
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0514] Draft Guidance for Industry and Food and Drug Administration Staff; Procedures for Handling Section 522 Postmarket Surveillance Studies; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice...
2010-08-06
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0395] Draft Guidance for Industry and Food and Drug Administration Staff; Recommendations for Premarket Notifications for Lamotrigine and Zonisamide Assays; Availability AGENCY: Food and Drug Administration, HHS...
Cyclodextrins in drug carrier systems.
Uekama, K; Otagiri, M
1987-01-01
One of the important characteristics of cyclodextrins is the formation of an inclusion complex with a variety of drug molecules in solution and in the solid state. As a consequence of intensive basic research, exhaustive toxic studies, and realization of industrial production during the past decade, there seem to be no more barriers for the practical application of natural cyclodextrins in the biomedical field. Recently, a number of cyclodextrin derivatives and cyclodextrin polymers have been prepared to obtain better inclusion abilities than parent cyclodextrins. The natural cyclodextrins and their synthetic derivatives have been successfully utilized to improve various drug properties, such as solubility, dissolution and release rates, stability, or bioavailability. In addition, the enhancement of drug activity, selective transfer, or the reduction of side effects has been achieved by means of inclusion complexation. The drug-cyclodextrin complex is generally formed outside of the body and, after administration, it dissociates, releasing the drug into the organism in a fast and nearly uniform manner. In the biomedical application of cyclodextrins, therefore, particular attention should be directed to the magnitude of the stability constant of the inclusion complex. In the case of parenteral application, a rather limited amount of work has been done because the cyclodextrins in the drug carrier systems have to be more effectively designed to compete with various biological components in the circulatory system. However, the works published thus far apparently indicate that the inclusion phenomena of cyclodextrin analogs may allow the rational design of drug formulation and that the combination of molecular encapsulation with other carrier systems will become a very effective and valuable method for the development of a new drug delivery system in the near future.
Pinão, Sílvia Raquel das Neves
2016-01-01
The effectiveness of drug administration strongly depends on attainment of an effective drug concentration in the area to be treated, for a sufficient period of time. Nowadays, the most used drug administration method for many eye diseases is delivery through eye drops, although it is very inefficient and can lead to negative side effects. The use of soft contact lenses as drug delivery systems appeared as a promising alternative, due to the prolonged contact with the eye surface, high degree...
Nanoparticulate delivery systems for antiviral drugs.
Lembo, David; Cavalli, Roberta
2010-01-01
Nanomedicine opens new therapeutic avenues for attacking viral diseases and for improving treatment success rates. Nanoparticulate-based systems might change the release kinetics of antivirals, increase their bioavailability, improve their efficacy, restrict adverse drug side effects and reduce treatment costs. Moreover, they could permit the delivery of antiviral drugs to specific target sites and viral reservoirs in the body. These features are particularly relevant in viral diseases where high drug doses are needed, drugs are expensive and the success of a therapy is associated with a patient's adherence to the administration protocol. This review presents the current status in the emerging area of nanoparticulate delivery systems in antiviral therapy, providing their definition and description, and highlighting some peculiar features. The paper closes with a discussion on the future challenges that must be addressed before the potential of nanotechnology can be translated into safe and effective antiviral formulations for clinical use.
Polepalli Ramesh, Balaji; Belknap, Steven M; Li, Zuofeng; Frid, Nadya; West, Dennis P; Yu, Hong
2014-06-27
The Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) is a repository of spontaneously-reported adverse drug events (ADEs) for FDA-approved prescription drugs. FAERS reports include both structured reports and unstructured narratives. The narratives often include essential information for evaluation of the severity, causality, and description of ADEs that are not present in the structured data. The timely identification of unknown toxicities of prescription drugs is an important, unsolved problem. The objective of this study was to develop an annotated corpus of FAERS narratives and biomedical named entity tagger to automatically identify ADE related information in the FAERS narratives. We developed an annotation guideline and annotate medication information and adverse event related entities on 122 FAERS narratives comprising approximately 23,000 word tokens. A named entity tagger using supervised machine learning approaches was built for detecting medication information and adverse event entities using various categories of features. The annotated corpus had an agreement of over .9 Cohen's kappa for medication and adverse event entities. The best performing tagger achieves an overall performance of 0.73 F1 score for detection of medication, adverse event and other named entities. In this study, we developed an annotated corpus of FAERS narratives and machine learning based models for automatically extracting medication and adverse event information from the FAERS narratives. Our study is an important step towards enriching the FAERS data for postmarketing pharmacovigilance.
2013-02-13
... AGENCY: Food and Drug Administration, HHS. ACTION: Notification of public meeting. SUMMARY: The Food and Drug Administration (FDA) is providing public meeting registration information for two FSMA related... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 16, 106, 110...
2010-11-29
...] Guidance for Industry and Food and Drug Administration Staff; Blood Lancet Labeling; Availability AGENCY... announcing the availability of the guidance entitled ``Guidance for Industry and Food and Drug Administration... single copies of the guidance document entitled ``Guidance for Industry and Food and Drug Administration...
2010-06-25
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0076] (formerly Docket No. 2007D-0387) Guidance for Industry and Food and Drug Administration Staff; In Vitro Diagnostic Studies--Frequently Asked Questions; Availability AGENCY: Food and Drug Administration, HHS...
2010-09-02
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0367] Guidance for Industry and Food and Drug Administration Staff; Impact-Resistant Lenses: Questions and Answers; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...
2011-11-07
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0689] Draft Guidance for Industry and Food and Drug Administration Staff; De Novo Classification Process... for Industry and Food and Drug Administration Staff; De Novo Classification Process (Evaluation of...
2012-12-13
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1161] Draft Guidance for Industry and Food and Drug Administration Staff; Design Considerations for Devices Intended for Home Use; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The...
2013-01-24
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0847] Guidance for Industry and Food and Drug Administration Staff; Humanitarian Use Device (HUD) Designations... public comment ``Draft Guidance for Industry and Food and Drug Administration Staff on Humanitarian Use...
Mucoadhesive Buccal Drug Delivery System
Pooja P.Thakkar; Meghana J.Chaudhari; Ami M.Soni; Dharti P.Pandya; Darshan A.Modi
2012-01-01
The buccal region of the oral cavity is an attractive target for administration of the drug of choice,particularly in overcoming deficiencies associated with the latter mode of administration. Problems suchas high first-pass metabolism and drug degradation in the gastrointestinal environment can becircumvented by administering the drug via the buccal route. Mucoadhesion can be defined as a state inwhich two components, of which one is of biological origin are held together for extended period...
2012-06-20
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA 2012-D-0304] Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance... Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the...
FDA approves efavirenz. Food and Drug Administration.
Highleyman, L
1998-10-01
The Food and Drug Administration (FDA) approved DuPont Pharma's new non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (Sustiva, DMP-266). Efavirenz has shown promise in trials with over 2000 participants for up to 24 weeks, and early data suggests it may be as effective as protease inhibitors when used in a combination regimen. It is the first anti-HIV drug approved for once-daily dosing. Efavirenz is well tolerated, and the main side effects reported are dizziness, insomnia, abnormal dreams, and skin rash. Efavirenz has been approved for adults and children, but should not be used by pregnant women. Contact information is provided.
76 FR 44595 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting
2011-07-26
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug... Committee: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee...
Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A
2013-09-01
This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3: 1 morphine : oxycodone oral dose ratio yielded equivalent subjective and physiological effects in nondependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures - that is, a drug versus money and a drug versus drug procedure - were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater than those of high-dose morphine. The study demonstrated that a 3: 1 oral dose ratio of morphine : oxycodone was not equipotent in buprenorphine-dependent individuals. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest.
Frequency and determinants of drug administration errors in the intensive care unit
van den Bemt, PMLA; Fijn, R; van der Voort, PHJ; Gossen, AA; Egberts, TCG; Brouwers, JRBJ
Objective., The study aimed to identify both the frequency and the determinants of drug administration errors in the intensive care unit. Design: Administration errors were detected by using the disguised-observation technique (observation of medication administrations by nurses, without revealing
75 FR 12768 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting
2010-03-17
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...
78 FR 20328 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting
2013-04-04
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...
78 FR 63478 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting
2013-10-24
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...
75 FR 36428 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting
2010-06-25
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...
77 FR 20037 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting
2012-04-03
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...
76 FR 3912 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting
2011-01-21
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...
75 FR 17417 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting
2010-04-06
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...
78 FR 63481 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting
2013-10-24
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...
Immunological Risk of Injectable Drug Delivery Systems
Jiskoot, W.; van Schie, R.M.F.; Carstens, M.G.; Schellekens, H.
2009-01-01
Injectable drug delivery systems (DDS) such as particulate carriers and water-soluble polymers are being used and developed for a wide variety of therapeutic applications. However, a number of immunological risks with serious clinical implications are associated with administration of DDS. These
2012-02-01
...] Food and Drug Administration Transparency Initiative: Exploratory Program To Increase Access to the... entitled ``Food and Drug Administration Transparency Initiative: Exploratory Program to [[Page 5028
Franklin, Bryony Dean; O'Grady, Kara; Donyai, Parastou; Jacklin, Ann; Barber, Nick
2007-01-01
Objectives To assess the impact of a closed‐loop electronic prescribing, automated dispensing, barcode patient identification and electronic medication administration record (EMAR) system on prescribing and administration errors, confirmation of patient identity before administration, and staff time. Design, setting and participants Before‐and‐after study in a surgical ward of a teaching hospital, involving patients and staff of that ward. Intervention Closed‐loop electronic prescribing, automated dispensing, barcode patient identification and EMAR system. Main outcome measures Percentage of new medication orders with a prescribing error, percentage of doses with medication administration errors (MAEs) and percentage given without checking patient identity. Time spent prescribing and providing a ward pharmacy service. Nursing time on medication tasks. Results Prescribing errors were identified in 3.8% of 2450 medication orders pre‐intervention and 2.0% of 2353 orders afterwards (pMedical staff required 15 s to prescribe a regular inpatient drug pre‐intervention and 39 s afterwards (p = 0.03; t test). Time spent providing a ward pharmacy service increased from 68 min to 98 min each weekday (p = 0.001; t test); 22% of drug charts were unavailable pre‐intervention. Time per drug administration round decreased from 50 min to 40 min (p = 0.006; t test); nursing time on medication tasks outside of drug rounds increased from 21.1% to 28.7% (p = 0.006; χ2 test). Conclusions A closed‐loop electronic prescribing, dispensing and barcode patient identification system reduced prescribing errors and MAEs, and increased confirmation of patient identity before administration. Time spent on medication‐related tasks increased. PMID:17693676
2012-03-19
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0226...) audit report provides FDA a degree of assurance of compliance with basic and fundamental quality management system requirements for medical devices. \\1\\ The GHTF founding members auditing systems include...
1 Impact of praziquantel mass drug administration campaign on ...
African Journals Online (AJOL)
used to collect information on MDA uptake, knowledge of schistosomiasis, sources .... transmission and in which Praziquantel mass drug administration has been ..... MoHSW (2012) Tanzania Mainland Strategic Master Plan for the Neglected ...
76 FR 55928 - Food and Drug Administration Health Professional Organizations Conference
2011-09-09
...] Food and Drug Administration Health Professional Organizations Conference AGENCY: Food and Drug... conference for representatives of Health Professional Organizations. Dr. Margaret Hamburg, Commissioner of... person attending, the name of the organization, address, and telephone number. There is no registration...
Directory of Open Access Journals (Sweden)
Gisele de Lima
2009-03-01
Full Text Available Objective: To study solid medications for oral delivery on the formulary of Hospital Israelita Albert Einstein (HIAE, investigating the possibility of using these drugs through enteral feeding tubes, and recommending appropriate administration. Methods: Study carried out through survey of solid medications for oral delivery included on the formulary of HIAE, literature review, and analysis of medication monographs, manufacturer information and pharmacotechnical data of active ingredients and excipients. It was observed the factors that might hinder or complicate the administration of these drugs though enteral tubes, and was drawn an information chart with recommendations about drug administration in this context. Rresults: The study evaluated 234 medications; and the main problems of administering these drugs through enteral feeding tubes were as follows: changes in drug pharmacokinetics (38; gastrointestinal damage (9; risk of obstruction (40, drug-nutrient interactions (7; biological hazards (5 and no information (33. Cconclusions: Compiling this information helps the healthcare team to choose the appropriate pharmaceutical formulation for medications administered through enteral tubes, and may help identify adverse events related to this technique.
Investigation of the mechanisms of action behind Electromotive Drug Administration (EMDA)
DEFF Research Database (Denmark)
Kos, Bor; Vasquez, Juan Luis; Miklavčič, D
2016-01-01
Objective. Bladder cancer is a cause of considerable morbidity worldwide. Electromotive Drug Administration is a method that combines intravesical chemotherapy with local electric field application. Electroporation has been suggested among other mechanisms as having a possible role in the therapy......, so the goal of the present study was to investigate the electric fields present in the bladder wall during the treatment to determine which mechanisms might be involved. Material and Methods. Electromotive Drug Administration involves applying intravesical mitomycin C with direct current of 20 m...
Li, ChunYan; Huang, ZhiGang; Liu, ZheShuo; Ci, LiQian; Liu, ZhePeng; Liu, Yu; Yan, XueYing; Lu, WeiYue
Effective interaction between mucoadhesive drug delivery systems and mucin is the basis of effective local placement of drugs to play its therapeutic role after mucosal administration including vaginal use, which especially requires prolonged drug presence for the treatment of gynecological infectious diseases. Our previous report on phenylboronic acid-rich nanoparticles (PBNPs) demonstrated their strong interaction with mucin and mucin-sensitive release profiles of the model protein therapeutics interferon (IFN) in vitro, but their poor stability and obvious tendency to aggregate over time severely limited future application. In this study, sulfonate-modified PBNPs (PBNP-S) were designed as a stable mucoadhesive drug delivery system where the negative charges conferred by sulfonate groups prevented aggregation of nanoparticles and the phenylboronic acid groups ensured effective interaction with mucin over a wide pH range. Results suggested that PBNP-S were of spherical morphology with narrow size distribution (123.5 nm, polydispersity index 0.050), good stability over a wide pH range and 3-month storage and considerable in vitro mucoadhesion capability at vaginal pH as shown by mucin adsorption determination. IFN could be loaded to PBNP-S by physical adsorption with high encapsulation efficiency and released in a mucin-dependent manner in vitro. In vivo near-infrared fluorescent whole animal imaging and quantitative vaginal lavage followed by enzyme-linked immunosorbent assay (ELISA) assay of IFN demonstrated that PBNP-S could stay in the vagina and maintain intravaginal IFN level for much longer time than IFN solution (24 hours vs several hours) without obvious histological irritation to vaginal mucosa after vaginal administration to mice. In summary, good stability, easy loading and controllable release of protein therapeutics, in vitro and in vivo mucoadhesive properties and local safety of PBNP-S suggested it as a promising nanoscale mucoadhesive drug delivery
Energy Technology Data Exchange (ETDEWEB)
Tietze, Rainer; Jurgons, Roland; Lyer, Stefan; Schreiber, Eveline [Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-University Erlangen-Nuernberg, Waldstr. 1, 91054 Erlangen (Germany); Wiekhorst, Frank; Eberbeck, Dietmar; Richter, Heike; Steinhoff, Uwe; Trahms, Lutz [Physikalisch-Technische Bundesanstalt, Berlin (Germany); Alexiou, Christoph [Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-University Erlangen-Nuernberg, Waldstr. 1, 91054 Erlangen (Germany)], E-mail: C.Alexiou@web.de
2009-05-15
Magnetic nanoparticles have been investigated for biomedical applications for more than 30 years. The development of biocompatible nanosized drug delivery systems for specific targeting of therapeutics is imminent in medical research, especially for treating cancer and vascular diseases. We used drug-labeled magnetic iron oxide nanoparticles, which were attracted to an experimental tumor in rabbits with an external magnetic field (magnetic drug targeting, MDT). Aim of this study was to detect and quantify the biodistribution of the magnetic nanoparticles by magnetorelaxometry. The study shows higher amount of nanoparticles in the tumor after intraarterial application and MDT compared to intravenous administration.
Salk, Allison; Ehrenpreis, Eli D
2016-01-01
The Food and Drug Administration Adverse Event Reporting System (FAERS) is used for postmarketing pharmacovigilance. Our study sought to assess attitudes and usage of the FAERS among gastroenterology nurse practitioners (NPs) and physician assistants (PAs). A survey was administered at the August 2012 Principles of Gastroenterology for the Nurse Practitioner and Physician Assistant course, held in Chicago, IL. Of the 128 respondents, 123 (96%) reported a specialty in gastroenterology or hepatology and were included in analysis. Eighty-nine participants were NPs and 32 PAs, whereas 2 did not report their profession. Although 119 (98%) agreed or strongly agreed with the statement that accurately reporting adverse drug reactions is an important process to optimize patient safety, the majority of participants (54% NPs and 81% PAs) were unfamiliar with the FAERS. In addition, only 20% of NPs and 9% of PAs reported learning about the FAERS in NP or PA schooling. Our study shows enthusiasm among gastroenterology NPs and PAs for the reporting of adverse drug reactions, coupled with a lack of familiarity with the FAERS. This presents an opportunity for enhanced education about reporting of adverse drug reactions for gastroenterology NPs and PAs.
Assessment of knowledge of pediatric nurses related with drug administration and preparation.
Bülbül, Ali; Kunt, Ayşe; Selalmaz, Melek; Sözeri, Şehrinaz; Uslu, Sinan; Nuhoğlu, Asiye
2014-12-01
Aim of this study is to determine the levels of knowledge related with drug administration and drug administration errors of nurses who care for pediatric patients. The study data were obtained from the nurses who were working in the departments of pediatrics in two education and research hospitals in the province of İstanbul and who accepted to participate in the study. The questionnaire form of the study was established by the investigators in accordance with the experiences and literature information. A total of 31 questions related with drug preparation, calculation and administration together with the general working properties of the individual were filled out by face to face interview. The data were evaluated using percent and chi-square tests. The study was initiated after ethics committee approval was obtained from Şişli Hamidiye Etfal Education and Research Hospital (365/2013). The study was conducted with 98 nurses who accepted the questionnaire. The education levels of the participants were as follows: undergraduate (48%), high school (32.7%), associate degree (12.2%), master's degree (6.1%) and postgraduate (1%). It was found that 88.8% of the participants worked in a patient-centered fashion and 11.2% worked in a work-centered fashion. The frequency of interruption/distraction during preparation of treatment was found to be 92.9%. It was found that the frequency of checking by two people during preparation or administration of high risk drugs was 64.3% and the conditions under which drugs should be kept were found to known correctly with a rate of 76.5%. It was found that undergraduate healthcare workers were more successful in converting units (p= 0.000). It was found that powder weight of drugs was considered with a rate of 85.7% in calculation. Conclusively, it was found that nurses who worked in pediatric wards did not receive a standard education in terms of drug administration and preparation. It was found that undergraduate nurses were more
2012-07-31
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0524] Draft Guidance for Industry and Food and Drug Administration Staff; Acceptance and Filing Review for Premarket Approval Applications; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice...
2012-05-10
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0384] Draft Guidance for Industry and Food and Drug Administration Staff; Pediatric Information for X-Ray Imaging Device Premarket Notifications; Availability AGENCY: Food and Drug Administration, HHS. ACTION...
2012-03-09
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0167] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Norovirus Serological Reagents; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice...
Kuizenga, Merel H.; Vereecke, Hugo E. M.; Struys, Michel M. R. F.
Purpose of review Drug administration might be optimized by incorporating pharmacokinetic-dynamic (PK/PD) principles and control engineering theories. This review gives an update of the actual status of target-controlled infusion (TCI) and closed-loop computer-controlled drug administration and the
2011-04-25
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2006-D-0094] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Topical Oxygen Chamber for Extremities; Availability AGENCY: Food and Drug Administration, HHS. ACTION...
2013-01-02
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0524] Guidance for Industry and Food and Drug Administration Staff; Acceptance and Filing Reviews for Premarket Approval Applications; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The...
2011-08-19
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0215] Draft Guidance for Industry and Food and Drug Administration Staff on In Vitro Companion Diagnostic Devices; Extension of Comment Period AGENCY: Food and Drug Administration, HHS. ACTION: Notice; extension...
2011-12-13
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0847] Draft Guidance for Industry and Food and Drug Administration Staff on Humanitarian Use Device Designations; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...
Directory of Open Access Journals (Sweden)
article editorial
2006-01-01
Full Text Available During the past 20 years advances in drug formulations and innovative routes of administration have been made. Our understanding of drug transport across tissues has increased. These changes have often resulted in improved patient adherence to the therapeutic regiment and pharmacologic response. The administration of drugs by transdermal or transmucosal routes offers the advantage of being relatively painless. Also, the potential for greater flexibility in a variety of clinical situations exists, often precluding the need to establish intravinus access which is a particular benefit for children. This statement focuses on the advantages and disadvantages of alternative routes of drug administration. Issues of particular importance in the care of pediatric patients especially factors that could lead to drug-relaxed toxicity or adverse responses are emphasized.Key words: drug formulation, pharmacoKINETICS, pharmacodynamics, drug, children.
Chitosan microspheres in novel drug delivery systems.
Mitra, Analava; Dey, Baishakhi
2011-07-01
The main aim in the drug therapy of any disease is to attain the desired therapeutic concentration of the drug in plasma or at the site of action and maintain it for the entire duration of treatment. A drug on being used in conventional dosage forms leads to unavoidable fluctuations in the drug concentration leading to under medication or overmedication and increased frequency of dose administration as well as poor patient compliance. To minimize drug degradation and loss, to prevent harmful side effects and to increase drug bioavailability various drug delivery and drug targeting systems are currently under development. Handling the treatment of severe disease conditions has necessitated the development of innovative ideas to modify drug delivery techniques. Drug targeting means delivery of the drug-loaded system to the site of interest. Drug carrier systems include polymers, micelles, microcapsules, liposomes and lipoproteins to name some. Different polymer carriers exert different effects on drug delivery. Synthetic polymers are usually non-biocompatible, non-biodegradable and expensive. Natural polymers such as chitin and chitosan are devoid of such problems. Chitosan comes from the deacetylation of chitin, a natural biopolymer originating from crustacean shells. Chitosan is a biocompatible, biodegradable, and nontoxic natural polymer with excellent film-forming ability. Being of cationic character, chitosan is able to react with polyanions giving rise to polyelectrolyte complexes. Hence chitosan has become a promising natural polymer for the preparation of microspheres/nanospheres and microcapsules. The techniques employed to microencapsulate with chitosan include ionotropic gelation, spray drying, emulsion phase separation, simple and complex coacervation. This review focuses on the preparation, characterization of chitosan microspheres and their role in novel drug delivery systems.
2012-03-19
... Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document... Drug Administration 21 CFR Part 866 Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Nucleic Acid-Based In Vitro Diagnostic Devices for the...
2011-05-20
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2006-D-0094] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls; Guidance Document... of the guidance entitled ``Guidance for Industry and Food and Drug Administration Staff; Class II...
2013-01-02
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1056] Guidance for Industry and Food and Drug Administration Staff; eCopy Program for Medical Device Submissions; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...
Hoffman, Keith B; Demakas, Andrea R; Dimbil, Mo; Tatonetti, Nicholas P; Erdman, Colin B
2014-11-01
The US Food and Drug Administration (FDA) uses the Adverse Event Reporting System (FAERS) to support post-marketing safety surveillance programs. Currently, almost one million case reports are submitted to FAERS each year, making it a vast repository of drug safety information. Sometimes cited as a limitation of FAERS, however, is the assumption that "stimulated reporting" of adverse events (AEs) occurs in response to warnings, alerts, and label changes that are issued by the FDA. To determine the extent of "stimulated reporting" in the modern-day FAERS database. One hundred drugs approved by the FDA between 2001 and 2010 were included in this analysis. FDA alerts were obtained by a comprehensive search of the FDA's MedWatch and main websites. Publicly available FAERS data were used to assess the "primary suspect" AE reporting pattern for up to four quarters before, and after, the issuance of an FDA alert. A few drugs did demonstrate "stimulated reporting" trends. A majority of the drugs, however, showed little evidence for significant reporting changes associated with the issuance of alerts. When we compared the percentage changes in reporting after an FDA alert with those after a sham "control alert", the overall reporting trends appeared to be quite similar. Of 100 drugs analyzed for short-term reporting trends, 21 real alerts and 25 sham alerts demonstrated an increase (greater than or equal to 1 %) in reporting. The long-term analysis of 91 drugs showed that 24 real alerts and 28 sham alerts demonstrated a greater than or equal to 1 % increase. Our results suggest that most of modern day FAERS reporting is not significantly affected by the issuance of FDA alerts.
Modeling of corneal and retinal pharmacokinetics after periocular drug administration.
Amrite, Aniruddha C; Edelhauser, Henry F; Kompella, Uday B
2008-01-01
the SD rat corneas. Similar pharmacokinetics models explain drug delivery to the cornea in rat and rabbit animal models. Retinal pharmacokinetics after periocular drug administration can be explained with a four-compartment (periocular space, choroid-containing transfer compartment, retina, and distribution compartment) model with elimination from the periocular space, retina, and choroid compartment. Inclusion of a dissolution-release step before the drug is available for absorption or elimination better explains retinal t(max). Good fits were obtained in both the BN (r = 0.99) and SD (r = 0.99) rats for retinal celecoxib using the same model; however, the parameter estimates differed. Corneal and retinal pharmacokinetics of small lipophilic molecules after periocular administration can be described by compartment models. The modeling analysis shows that (1) leak-back from the site of administration most likely contributes to the apparent lack of an increase phase in corneal concentrations; (2) elimination via the conjunctival or periocular blood and lymphatic systems contributes significantly to drug clearance after periocular injection; (3) corneal pharmacokinetics of small lipophilic molecules can be explained by using similar models in rats and rabbits; and (4) although there are differences in some retinal pharmacokinetics parameters between the pigmented and nonpigmented rats, the physiological basis of these differences has yet to be ascertained.
DEFF Research Database (Denmark)
Enemark, Stig
2014-01-01
Land administration systems are the operational tool for conceptualizing rights, restrictions and responsibilities (RRRs) in land. Each of the rights, restrictions and responsibilities encompasses a human rights dimension that relates to the overall national land policies and should be unfolded...... as more than just rhetoric. This paper attempts to analyse the aspects of human rights in relation to land administration systems with a special focus on developing countries struggling to build adequate systems for governing the rights, restrictions and responsibilities in land. Human rights....... This relates to national political arrangements and standards for good governance and land administration systems are highly instrumental in this regard. This paper introduces the relation between land administration and human rights. It is argued that human rights and land administration are closely linked...
2012-03-09
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2002-D-0094; (formerly Docket No. 02D-0049)] Guidance for the Public, Food and Drug Administration (FDA) Advisory... Food and Drug Administration (FDA) is announcing the availability of a guidance for the public, FDA...
2012-08-13
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0523] Draft Guidance for Industry and Food and Drug Administration Staff; Refuse To Accept Policy for 510(k)s; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...
International Nuclear Information System (INIS)
Gulyas, Balazs; Halldin, Christer; Sandell, Johan; Farde, Lars; Sovago, Judit; Cselenyi, Zsolt; Vas, Adam; Kiss, Bela; Karpati, Egon
2002-01-01
Direct information on the distribution of a drug requires measurements in various tissues. Such data have until now been obtained in animals, or have indirectly been calculated from plasma measurements in humans using mathematical models. Here we suggest the use of positron emission tomography (PET) as a method to obtain direct measurements of drug distribution in the human body. The distribution in body and brain of vinpocetine, a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases, was followed after oral administration. Vinpocetine was labelled with carbon-11 and radioactivity was measured by PET in stomach, liver, brain and kidney in six healthy volunteers. The radioactivity in blood and urine as well as the fractions of [ 11 C]vinpocetine and labelled metabolites in plasma were also determined. After oral administration, [ 11 C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the administration of the labelled drug. Brain distribution was heterogeneous, similar to the distribution previously reported after intravenous administration. These findings indicate that vinpocetine, administered orally in humans, readily enters the bloodstream from the stomach and gastrointestinal tract and, consequently, passes the blood-brain barrier and enters the brain. Radioactivity from [ 11 C]vinpocetine was also demonstrated in the kidneys and in urine, indicating that at least a part of the radioactive drug and labelled metabolites is eliminated from the body through the kidneys. This study is the first to demonstrate that PET might be a useful, direct and non-invasive tool to study the distribution and pharmacokinetics of orally
Gulyás, Balázs; Halldin, Christer; Sóvágó, Judit; Sandell, Johan; Cselényi, Zsolt; Vas, Adám; Kiss, Béla; Kárpáti, Egon; Farde, Lars
2002-08-01
Direct information on the distribution of a drug requires measurements in various tissues. Such data have until now been obtained in animals, or have indirectly been calculated from plasma measurements in humans using mathematical models. Here we suggest the use of positron emission tomography (PET) as a method to obtain direct measurements of drug distribution in the human body. The distribution in body and brain of vinpocetine, a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases, was followed after oral administration. Vinpocetine was labelled with carbon-11 and radioactivity was measured by PET in stomach, liver, brain and kidney in six healthy volunteers. The radioactivity in blood and urine as well as the fractions of [(11)C]vinpocetine and labelled metabolites in plasma were also determined. After oral administration, [(11)C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the administration of the labelled drug. Brain distribution was heterogeneous, similar to the distribution previously reported after intravenous administration. These findings indicate that vinpocetine, administered orally in humans, readily enters the bloodstream from the stomach and gastrointestinal tract and, consequently, passes the blood-brain barrier and enters the brain. Radioactivity from [(11)C]vinpocetine was also demonstrated in the kidneys and in urine, indicating that at least a part of the radioactive drug and labelled metabolites is eliminated from the body through the kidneys. This study is the first to demonstrate that PET might be a useful, direct and non-invasive tool to study the distribution and pharmacokinetics of orally
2010-04-22
...] (formerly Docket No. 02D-0049) Draft Guidance for the Public, Food and Drug Administration Advisory Committee Members, and Food and Drug Administration Staff: Public Availability of Advisory Committee Members... and Drug Administration Amendments Act of 2007, Public Law No. 110-85), and section 701 (21 U.S.C. 371...
2010-07-28
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0495] Draft Guidance for Industry and Food and Drug Administration Staff; Medical Devices; Neurological and Physical Medicine Device Guidance Document; Reopening of Comment Period AGENCY: Food and Drug...
2013-02-19
...] Draft Guidance for Industry and Food and Drug Administration Staff; Providing Information About... Guidance for Industry and Food and Drug Administration Staff: Providing Information About Pediatric Uses of...ComplianceRegulatoryInformation/default.htm . To receive ``Draft Guidance for Industry and Food and Drug...
Nanotechnology-Based Drug Delivery Systems for Treatment of Tuberculosis--A Review.
da Silva, Patricia Bento; de Freitas, Eduardo Sinésio; Bernegossi, Jessica; Gonçalez, Maíra Lima; Sato, Mariana Rillo; Leite, Clarice Queico Fujimura; Pavan, Fernando Rogério; Chorilli, Marlus
2016-02-01
Tuberculosis (TB) is an infectious and transmissible disease that is caused by Mycobacterium tuberculosis and primarily affects the lungs, although it can affect other organs and systems. The pulmonary presentation of TB, in addition to being more frequent, is also the most relevant to public health because it is primarily responsible for the transmission of the disease. The to their low World Health Organization (WHO) recommends a combined therapeutic regimen of several drugs, such as rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA) and ethambutol (ETB). These drugs have low plasma levels after oral administration, due to their low water solubility, poor permeability and ability to be rapidly metabolized by the liver and at high concentrations. Furthermore, they have short t₁/₂ (only 1-4 hours) indicating a short residence in the plasma and the need for multiple high doses, which can result in neurotoxicity and hepatotoxicity. Nanotechnology drug delivery systems have considerable potential for the treatment of TB. The systems can also be designed to allow for the sustained release of drugs from the matrix and drug delivery to a specific target. These properties of the systems enable the improvement of the bioavailability of drugs, can reduce the dosage and frequency of administration, and may solve the problem of non-adherence to prescribed therapy, which is a major obstacle to the control of TB. The purpose of this study was to systematically review nanotechnology-based drug delivery systems for the treatment of TB.
DEFF Research Database (Denmark)
Kisoka, William J.; Simonsen, Paul Erik; Malecela, Mwelecele N.
2014-01-01
BACKGROUND: In most countries of Sub-Saharan Africa, control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole. Treatment coverages are however often suboptimal for programmes to reach the goal of transmission interrupt......BACKGROUND: In most countries of Sub-Saharan Africa, control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole. Treatment coverages are however often suboptimal for programmes to reach the goal of transmission...
2011-10-03
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0689] Draft Guidance for Industry and Food and Drug Administration Staff; De Novo Classification Process... appropriate, and other forms of information technology. Draft Guidance for Industry and Food and Drug...
Buccal mucosa as a route for systemic drug delivery: a review.
Shojaei, A H
1998-01-01
Within the oral mucosal cavity, the buccal region offers an attractive route of administration for systemic drug delivery. The mucosa has a rich blood supply and it is relatively permeable. It is the objective of this article to review buccal drug delivery by discussing the structure and environment of the oral mucosa and the experimental methods used in assessing buccal drug permeation/absorption. Buccal dosage forms will also be reviewed with an emphasis on bioadhesive polymeric based delivery systems
Drug delivery from the oral cavity: a focus on mucoadhesive buccal drug delivery systems.
Shinkar, Dattatraya Manohar; Dhake, Avinash Sridhar; Setty, Chitral Mallikarjuna
2012-01-01
Since the early 1980s the concept of mucoadhesion has gained considerable interest in pharmaceutical technology. The various advantages associated with these systems made buccal drug delivery as a novel route of drug administration. It prolongs the residence time of the dosage form at the site of application. These systems remain in close contact with the absorption tissue, the mucous membrane, and thus contribute to improved and/or better therapeutic performance of the drug and of both local and systemic effects. This review highlights the anatomy and structure of oral mucosa, mechanism and theories of mucoadhesion, factors affecting mucoadhesion, characteristics and properties of desired mucoadhesive polymers, various types of dosage forms, and general considerations in design of mucoadhesive buccal dosage forms, permeation enhancers, and evaluation methods. Over the past few decades the mucoadhesive buccal drug delivery system has received a great deal of attention to develop mucoadhesive dosage forms to enable the prolonged retention at the site of action, providing a controlled release of drug for improved therapeutic outcome. Mucoadhesive drug delivery gives facility to include a permeation enhancer/enzyme inhibitor or pHmodifier in the formulation and versatility in designing as multidirectional or unidirectional release systems for local and systemic action. Local delivery to tissues of the oral cavity has a number of applications, including treatment of local conditions such as periodontal disease, bacterial and fungal infections, and aphthous stomatitis and vesiculo bullous diseases. For the treatment of chronic diseases, the mucoadhesive buccal drug delivery system allows easily accessibility and is generally well-accepted for administeringdrugs by systemic action.
2010-06-03
... Administration and the International Anesthesia Research Society for the Safety of Key Inhaled and Intravenous Drugs in Pediatrics Public-Private Partnership AGENCY: Food and Drug Administration, HHS. ACTION: Notice... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0004...
Drug delivery system and breast cancer cells
Colone, Marisa; Kaliappan, Subramanian; Calcabrini, Annarica; Tortora, Mariarosaria; Cavalieri, Francesca; Stringaro, Annarita
2016-06-01
Recently, nanomedicine has received increasing attention for its ability to improve the efficacy of cancer therapeutics. Nanosized polymer therapeutic agents offer the advantage of prolonged circulation in the blood stream, targeting to specific sites, improved efficacy and reduced side effects. In this way, local, controlled delivery of the drug will be achieved with the advantage of a high concentration of drug release at the target site while keeping the systemic concentration of the drug low, thus reducing side effects due to bioaccumulation. Various drug delivery systems such as nanoparticles, liposomes, microparticles and implants have been demonstrated to significantly enhance the preventive/therapeutic efficacy of many drugs by increasing their bioavailability and targetability. As these carriers significantly increase the therapeutic effect of drugs, their administration would become less cost effective in the near future. The purpose of our research work is to develop a delivery system for breast cancer cells using a microvector of drugs. These results highlight the potential uses of these responsive platforms suited for biomedical and pharmaceutical applications. At the request of all authors of the paper an updated version was published on 12 July 2016. The manuscript was prepared and submitted without Dr. Francesca Cavalieri's contribution and her name was added without her consent. Her name has been removed in the updated and re-published article.
2012-11-23
...; Establishment of a Public Docket AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is establishing a public docket for information pertaining to FDA's... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1090...
2012-10-17
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1056] Draft Guidance for Industry and Food and Drug Administration Staff; eCopy Program for Medical Device Submissions; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...
Hernán Pérez de la Ossa, D; Ligresti, A; Gil-Alegre, M E; Aberturas, M R; Molpeceres, J; Di Marzo, V; Torres Suárez, A I
2012-08-10
Cannabinoids show promise for the treatment of various medical conditions such as emesis, anorexia, pain, cancer, multiple sclerosis, Parkinson's disease and glaucoma. However, their high lipohilicity and instability complicate their handling and dosing, and restrict their use as pharmaceuticals. The objective of the present work was to assess the feasibility of developing cannabinoid loaded poly-ε-caprolactone (PCL) microparticles prepared by the oil-in-water emulsion-solvent evaporation technique as a suitable dosage form for their administration. Spherical microparticles with a size range of 20-50 μm, and high entrapment efficiency (around 100%) were obtained. Cannabidiol (CBD) dissolved in the polymeric matrix of the microspheres was slowly released in vitro within 10 days. In vitro cell viability studies demonstrated the antitumoral activity of CBD released from microparticles. After 4 and 7 days of incubation, CBD in microspheres significantly inhibited the growth of MDA-MB-231 cells by 60% as compared to the 50% attained with free drug. The results suggest that PCL microparticles could be an alternative delivery system for long-term cannabinoid administration, showing potential therapeutic advantages over free drug. Copyright © 2012 Elsevier B.V. All rights reserved.
Energy Technology Data Exchange (ETDEWEB)
Gulyas, Balazs [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 171 76 Stockholm (Sweden); Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm (Sweden); Halldin, Christer; Sandell, Johan; Farde, Lars [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 171 76 Stockholm (Sweden); Sovago, Judit; Cselenyi, Zsolt [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 171 76 Stockholm (Sweden); Department of Neurology, Faculty of Medicine, University of Debrecen, Debrecen (Hungary); Vas, Adam; Kiss, Bela; Karpati, Egon [Chemical Works of Gedeon Richter Ltd., Budapest (Hungary)
2002-08-01
Direct information on the distribution of a drug requires measurements in various tissues. Such data have until now been obtained in animals, or have indirectly been calculated from plasma measurements in humans using mathematical models. Here we suggest the use of positron emission tomography (PET) as a method to obtain direct measurements of drug distribution in the human body. The distribution in body and brain of vinpocetine, a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases, was followed after oral administration. Vinpocetine was labelled with carbon-11 and radioactivity was measured by PET in stomach, liver, brain and kidney in six healthy volunteers. The radioactivity in blood and urine as well as the fractions of [{sup 11}C]vinpocetine and labelled metabolites in plasma were also determined. After oral administration, [{sup 11}C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the administration of the labelled drug. Brain distribution was heterogeneous, similar to the distribution previously reported after intravenous administration. These findings indicate that vinpocetine, administered orally in humans, readily enters the bloodstream from the stomach and gastrointestinal tract and, consequently, passes the blood-brain barrier and enters the brain. Radioactivity from [{sup 11}C]vinpocetine was also demonstrated in the kidneys and in urine, indicating that at least a part of the radioactive drug and labelled metabolites is eliminated from the body through the kidneys. This study is the first to demonstrate that PET might be a useful, direct and non-invasive tool to study the distribution and
2011-07-21
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0149] (Formerly 2007D-0309) Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Electrocardiograph Electrodes; Availability AGENCY: Food and Drug...
Transferosomes - A vesicular transdermal delivery system for enhanced drug permeation
Directory of Open Access Journals (Sweden)
Reshmy Rajan
2011-01-01
Full Text Available Transdermal administration of drugs is generally limited by the barrier function of the skin. Vesicular systems are one of the most controversial methods for transdermal delivery of active substances. The interest in designing transdermal delivery systems was relaunched after the discovery of elastic vesicles like transferosomes, ethosomes, cubosomes, phytosomes, etc. This paper presents the composition, mechanisms of penetration, manufacturing and characterization methods of transferosomes as transdermal delivery systems of active substances. For a drug to be absorbed and distributed into organs and tissues and eliminated from the body, it must pass through one or more biological membranes/barriers at various locations. Such a movement of drug across the membrane is called as drug transport. For the drugs to be delivered to the body, they should cross the membranous barrier. The concept of these delivery systems was designed in an attempt to concentrate the drug in the tissues of interest, while reducing the amount of drug in the remaining tissues. Hence, surrounding tissues are not affected by the drug. In addition, loss of drug does not happen due to localization of drug, leading to get maximum efficacy of the medication. Therefore, the phospholipid based carrier systems are of considerable interest in this era.
2013-06-19
... inspections, and drive safety and quality throughout the supply chain. Implementation of these authorities... authorities granted to FDA under Title VII and their importance in ensuring drug safety, effectiveness, and.... FDA-2013-N-0683, FDA-2013-N-0684, and FDA-2013-N-0685] Food and Drug Administration Safety and...
Evaluating the administration costs of biologic drugs: development of a cost algorithm.
Tetteh, Ebenezer K; Morris, Stephen
2014-12-01
Biologic drugs, as with all other medical technologies, are subject to a number of regulatory, marketing, reimbursement (financing) and other demand-restricting hurdles applied by healthcare payers. One example is the routine use of cost-effectiveness analyses or health technology assessments to determine which medical technologies offer value-for-money. The manner in which these assessments are conducted suggests that, holding all else equal, the economic value of biologic drugs may be determined by how much is spent on administering these drugs or trade-offs between drug acquisition and administration costs. Yet, on the supply-side, it seems very little attention is given to how manufacturing and formulation choices affect healthcare delivery costs. This paper evaluates variations in the administration costs of biologic drugs, taking care to ensure consistent inclusion of all relevant cost resources. From this, it develops a regression-based algorithm with which manufacturers could possibly predict, during process development, how their manufacturing and formulation choices may impact on the healthcare delivery costs of their products.
21 CFR 864.3260 - OTC test sample collection systems for drugs of abuse testing.
2010-04-01
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false OTC test sample collection systems for drugs of abuse testing. 864.3260 Section 864.3260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology...
Logrip, Marian L.; Zorrilla, Eric P.; Koob, George F.
2011-01-01
Drug abuse and dependence present significant health burdens for our society, affecting roughly 10% of the population. Stress likely contributes to the development and persistence of drug use; for example, rates of substance dependence are elevated among individuals diagnosed with post-traumatic stress disorder (PTSD). Thus, understanding the interaction between stress and drug use, and associated neuroadaptations, is key for developing therapies to combat substance use disorders. For this purpose, many rodent models of the effects of stress exposure on substance use have been developed; the models can be classified according to three categories of stress exposure: developmental, adult nonsocial, and adult social. The present review addresses preclinical findings on the effect of each type of trauma on responses to and self-administration of drugs of abuse by focusing on a key exemplar for each category. In addition, the potential efficacy of targeting neuropeptide systems that have been implicated in stress responses and stress system neuroadaptation in order to treat comorbid PTSD and substance abuse will be discussed. PMID:21782834
Nanotechnology-based drug delivery systems
Directory of Open Access Journals (Sweden)
Singh Baljit
2007-12-01
Full Text Available Abstract Nanoparticles hold tremendous potential as an effective drug delivery system. In this review we discussed recent developments in nanotechnology for drug delivery. To overcome the problems of gene and drug delivery, nanotechnology has gained interest in recent years. Nanosystems with different compositions and biological properties have been extensively investigated for drug and gene delivery applications. To achieve efficient drug delivery it is important to understand the interactions of nanomaterials with the biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signalling involved in pathobiology of the disease under consideration. Several anti-cancer drugs including paclitaxel, doxorubicin, 5-fluorouracil and dexamethasone have been successfully formulated using nanomaterials. Quantom dots, chitosan, Polylactic/glycolic acid (PLGA and PLGA-based nanoparticles have also been used for in vitro RNAi delivery. Brain cancer is one of the most difficult malignancies to detect and treat mainly because of the difficulty in getting imaging and therapeutic agents past the blood-brain barrier and into the brain. Anti-cancer drugs such as loperamide and doxorubicin bound to nanomaterials have been shown to cross the intact blood-brain barrier and released at therapeutic concentrations in the brain. The use of nanomaterials including peptide-based nanotubes to target the vascular endothelial growth factor (VEGF receptor and cell adhesion molecules like integrins, cadherins and selectins, is a new approach to control disease progression.
Bijarania, Sunil Kumar; Saini, Sushma Kumari; Verma, Sanjay; Kaur, Sukhwinder
2017-05-01
To develop standard operational protocol (SOP) on oral drug administration and checklist to assess the implementation of the developed SOP. In this prospective methodological study, SOPs were developed in five phases. In the first phase, the preliminary draft of SOPs and checklists were prepared based on literature review, assessment of current practices and focus group discussion (FGD) with bedside working nurses. In the second phase, content validity was checked with the help of Delphi technique (12 experts). Total four drafts were prepared in stages and necessary modifications were made as per suggestions after each Delphi round. Fourth Delphi round was performed after conducting a pilot study. In the fourth phase, all bedside nurses were trained as per SOPs and asked to practice accordingly and observation of thirty oral drug administrations in children was done to check reliability of checklists for implementation of SOPs. In Phase-V, 7 FGDs were conducted with bedside nurses to assess the effectiveness of SOPs. The Content Validity Index (CVI) of SOP and checklists was 99.77%. Overall standardized Cronbach's alpha was calculated as 0.94. All the nurses felt that the SOP is useful. Valid and feasible SOP for drug administration to children through oral route along with valid and reliable checklist were developed. It is recommended to use this document for drug administration to children.
2011-12-28
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0893] Draft Guidance for Industry and Food and Drug Administration Staff; Center for Devices and Radiological... appropriate, and other forms of information technology. Draft Guidance for Industry and Food and Drug...
2010-11-10
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0514] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document... Administration (FDA) is announcing the availability of the guidance entitled ``Class II Special Controls Guidance...
2013-01-02
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0523] Guidance for Industry and Food and Drug Administration Staff; Refuse To Accept Policy for 510(k)s; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...
2011-03-08
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2008-D-0457] Guidance for Industry and Food and Drug Administration Staff; Clinical Investigations of Devices Indicated... other electrical continence devices; protective garment for incontinence; surgical mesh; electrosurgical...
Administrative litigation systems in Europe
Directory of Open Access Journals (Sweden)
Cătălin-Silviu Săraru
2017-06-01
Full Text Available The article, analyzing the administrative litigation in the comparative law, groups the existing types of administrative litigation into four major systems, namely: a States with administrative jurisdictions who have the State Council on top, administrative body with consultative and judicial role (the French system; b States with administrative jurisdictions completely separated from the active and consultative administrations (the German system; c States with administrative jurisdictions included in the judicial system; d States with no administrative jurisdiction (English system. The administrative contentious systems analyzed have developed in line with historical evolution and legal traditions and have been continually adapted to the realities existing in each state. The manner in which the administrative contentious is regulated in a State reflects the degree of democratization of that country, the extent to which the citizen enjoys legal safeguards to defend himself against abuses by public authorities. The scientific novelty of this article is to capture the latest trends in the evolution of the administrative contentious systems analyzed. This study aims to provide an easy working tool for reforming administrative litigation on comparative law in states with young democracy. In the research we used the comparative method, the historical and the logical method.
Enhancing food safety: the role of the Food and Drug Administration
National Research Council Canada - National Science Library
Wallace, Robert B; Oria, Maria
2010-01-01
.... Food and Drug Administration's abilities to discover potential threats to food safety and prevent outbreaks of foodborne illness are hampered by impediments to efficient use of its limited resources...
Drug Enforcement Administration.
Department of Justice, Washington, DC.
This fact sheet contains information relating to drug abuse and abusers; drug traffic legislation; law enforcement; and descriptions of commonly used narcotics, stimulants, depressants, and hallucinogens. Also included is a short but explicit listing of audiovisual aids, an annotated bibliography, and drug identification pictures. The booklet…
Samaranayake, N R; Cheung, S T D; Cheng, K; Lai, K; Chui, W C M; Cheung, B M Y
2014-06-01
We assessed the effects of a bar-code assisted medication administration system used without the support of computerised prescribing (stand-alone BCMA), on the dispensing process and its users. The stand-alone BCMA system was implemented in one ward of a teaching hospital. The number of dispensing steps, dispensing time and potential dispensing errors (PDEs) were directly observed one month before and eight months after the intervention. Attitudes of pharmacy and nursing staff were assessed using a questionnaire (Likert scale) and interviews. Among 1291 and 471 drug items observed before and after the introduction of the technology respectively, the number of dispensing steps increased from five to eight and time (standard deviation) to dispense one drug item by one staff personnel increased from 0.8 (0.09) to 1.5 (0.12) min. Among 2828 and 471 drug items observed before and after the intervention respectively, the number of PDEs increased significantly (Psystem offered less benefit to the dispensing process (9/16). Nursing staff perceived the system as useful in improving the accuracy of drug administration (7/10). Implementing a stand-alone BCMA system may slow down and complicate the dispensing process. Nursing staff believe the stand-alone BCMA system could improve the drug administration process but pharmacy staff believes the technology would be more helpful if supported by computerised prescribing. However, periodical assessments are needed to identify weaknesses in the process after implementation, and all users should be educated on the benefits of using this technology. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Poly(lactic-co-glycolic) acid drug delivery systems through transdermal pathway: an overview.
Naves, Lucas; Dhand, Chetna; Almeida, Luis; Rajamani, Lakshminarayanan; Ramakrishna, Seeram; Soares, Graça
2017-05-01
In past few decades, scientists have made tremendous advancement in the field of drug delivery systems (DDS), through transdermal pathway, as the skin represents a ready and large surface area for delivering drugs. Efforts are in progress to design efficient transdermal DDS that support sustained drug release at the targeted area for longer duration in the recommended therapeutic window without producing side-effects. Poly(lactic-co-glycolic acid) (PLGA) is one of the most promising Food and Drug Administration approved synthetic polymers in designing versatile drug delivery carriers for different drug administration routes, including transdermal drug delivery. The present review provides a brief introduction over the transdermal drug delivery and PLGA as a material in context to its role in designing drug delivery vehicles. Attempts are made to compile literatures over PLGA-based drug delivery vehicles, including microneedles, nanoparticles, and nanofibers and their role in transdermal drug delivery of different therapeutic agents. Different nanostructure evaluation techniques with their working principles are briefly explained.
Drugs and Polymers for Delivery Systems in OA Joints: Clinical Needs and Opportunities
Directory of Open Access Journals (Sweden)
Maarten Janssen
2014-03-01
Full Text Available Osteoarthritis (OA is a big burden of disease worldwide and one of the most common causes of disability in the adult population. Currently applied therapies consist of physical therapy, oral medication, intra-articular injections, and surgical interventions, with the main goal being to reduce pain and improve function and quality of life. Intra-articular (IA administration of drugs has potential benefits in OA treatment because it minimizes systemic bioavailability and side effects associated with oral administration of drugs without compromising the therapeutic effect in the joint. However, IA drug residence time is short and there is a clinical need for a vehicle that is able to provide a sustained release long enough for IA therapy to fulfill its promise. This review summarizes the use of different polymeric systems and the incorporated drugs for IA drug delivery in the osteoarthritic joint with a primary focus on clinical needs and opportunities.
Profile of drug administration errors in anesthesia among anesthesiologists from Santa Catarina
Directory of Open Access Journals (Sweden)
Thomas Rolf Erdmann
2016-02-01
Full Text Available INTRODUCTION: Anesthesiology is the only medical specialty that prescribes, dilutes, and administers drugs without conferral by another professional. Adding to the high frequency of drug administration, a propitious scenario to errors is created. OBJECTIVE: Access the prevalence of drug administration errors during anesthesia among anesthesiologists from Santa Catarina, the circumstances in which they occurred, and possible associated factors. MATERIALS AND METHODS: An electronic questionnaire was sent to all anesthesiologists from Sociedade de Anestesiologia do Estado de Santa Catarina, with direct or multiple choice questions on responder demographics and anesthesia practice profile; prevalence of errors, type and consequence of error; and factors that may have contributed to the errors. RESULTS: Of the respondents, 91.8% reported they had committed administration errors, adding the total error of 274 and mean of 4.7 (6.9 errors per respondent. The most common error was replacement (68.4%, followed by dose error (49.1%, and omission (35%. Only 7% of respondents reported neuraxial administration error. Regarding circumstances of errors, they mainly occurred in the morning (32.7%, in anesthesia maintenance (49%, with 47.8% without harm to the patient and 1.75% with the highest morbidity and irreversible damage, and 87.3% of cases with immediate identification. As for possible contributing factors, the most frequent were distraction and fatigue (64.9% and misreading of labels, ampoules, or syringes (54.4%. CONCLUSION: Most respondents committed more than one error in anesthesia administration, mainly justified as a distraction or fatigue, and of low gravity.
Development of an opioid self-administration assay to study drug seeking in zebrafish.
Bossé, Gabriel D; Peterson, Randall T
2017-09-29
The zebrafish (Danio rerio) has become an excellent tool to study mental health disorders, due to its physiological and genetic similarity to humans, ease of genetic manipulation, and feasibility of small molecule screening. Zebrafish have been shown to exhibit characteristics of addiction to drugs of abuse in non-contingent assays, including conditioned place preference, but contingent assays have been limited to a single assay for alcohol consumption. Using inexpensive electronic, mechanical, and optical components, we developed an automated opioid self-administration assay for zebrafish, enabling us to measure drug seeking and gain insight into the underlying biological pathways. Zebrafish trained in the assay for five days exhibited robust self-administration, which was dependent on the function of the μ-opioid receptor. In addition, a progressive ratio protocol was used to test conditioned animals for motivation. Furthermore, conditioned fish continued to seek the drug despite an adverse consequence and showed signs of stress and anxiety upon withdrawal of the drug. Finally, we validated our assay by confirming that self-administration in zebrafish is dependent on several of the same molecular pathways as in other animal models. Given the ease and throughput of this assay, it will enable identification of important biological pathways regulating drug seeking and could lead to the development of new therapeutic molecules to treat addiction. Copyright © 2017 Elsevier B.V. All rights reserved.
2010-09-23
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0459] Draft Guidance for Industry and Food and Drug Administration Staff; Establishing the Performance Characteristics of In Vitro Diagnostic Devices for the Detection of Helicobacter pylori; Availability AGENCY: Food...
40 CFR 23.10 - Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act.
2010-07-01
... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act. 23.10 Section 23.10 Protection of Environment ENVIRONMENTAL... action under the Federal Food, Drug, and Cosmetic Act. Unless the Administrator otherwise explicitly...
Default Drug Doses in Anesthesia Information Management Systems.
Rodriquez, Luis I; Smaka, Todd J; Mahla, Michael; Epstein, Richard H
2017-07-01
In the United States, anesthesia information management systems (AIMS) are well established, especially within academic practices. Many hospitals are replacing their stand-alone AIMS during migration to an enterprise-wide electronic health record. This presents an opportunity to review choices made during the original implementation, based on actual usage. One area amenable to this informatics approach is the configuration in the AIMS of quick buttons for typical drug doses. The use of such short cuts, as opposed to manual typing of doses, simplifies and may improve the accuracy of drug documentation within the AIMS. We analyzed administration data from 3 different institutions, 2 of which had empirically configured default doses, and one in which defaults had not been set up. Our first hypothesis was that most (ie, >50%) of drugs would need at least one change to the existing defaults. Our second hypothesis was that for most (>50%) drugs, the 4 most common doses at the site lacking defaults would be included among the most common doses at the 2 sites with defaults. If true, this would suggest that having default doses did not affect the typical administration behavior of providers. The frequency distribution of doses for all drugs was determined, and the 4 most common doses representing at least 5% of total administrations for each drug were identified. The appropriateness of the current defaults was determined by the number of changes (0-4) required to match actual usage at the 2 hospitals with defaults. At the institution without defaults, the most frequent doses for the 20 most commonly administered drugs were compared with the default doses at the other institutions. At the 2 institutions with defaults, 84.7% and 77.5% of drugs required at least 1 change in the default drug doses (P default drug doses, 100% of the 20 most commonly administered doses (representing ≥5% of use for that drug) were included in the most commonly administered doses at the other 2
Directory of Open Access Journals (Sweden)
Li CY
2016-11-01
Full Text Available ChunYan Li,1 ZhiGang Huang,2 ZheShuo Liu,1 LiQian Ci,3 ZhePeng Liu,3 Yu Liu,2 XueYing Yan,1 WeiYue Lu2 1School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 2Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, 3School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China Abstract: Effective interaction between mucoadhesive drug delivery systems and mucin is the basis of effective local placement of drugs to play its therapeutic role after mucosal administration including vaginal use, which especially requires prolonged drug presence for the treatment of gynecological infectious diseases. Our previous report on phenylboronic acid-rich nanoparticles (PBNPs demonstrated their strong interaction with mucin and mucin-sensitive release profiles of the model protein therapeutics interferon (IFN in vitro, but their poor stability and obvious tendency to aggregate over time severely limited future application. In this study, sulfonate-modified PBNPs (PBNP-S were designed as a stable mucoadhesive drug delivery system where the negative charges conferred by sulfonate groups prevented aggregation of nanoparticles and the phenylboronic acid groups ensured effective interaction with mucin over a wide pH range. Results suggested that PBNP-S were of spherical morphology with narrow size distribution (123.5 nm, polydispersity index 0.050, good stability over a wide pH range and 3-month storage and considerable in vitro mucoadhesion capability at vaginal pH as shown by mucin adsorption determination. IFN could be loaded to PBNP-S by physical adsorption with high encapsulation efficiency and released in a mucin-dependent manner in vitro. In vivo near-infrared fluorescent whole animal imaging and quantitative vaginal lavage followed by enzyme-linked immunosorbent assay (ELISA assay of
Cornell, Erika; Kwa, Michael; Paller, Amy S; Xu, Shuai
2018-03-01
Despite their ubiquitous use and several recent health controversies involving cosmetics and personal care products for children, the Food and Drug Administration has little oversight of these products and relies on consumer-submitted adverse event reports. We assessed the recently released Center for Food Safety and Applied Nutrition's Adverse Event Reporting System database for adverse event reports submitted to the Food and Drug Administration for baby personal care products and to determine whether useful insights can be derived. We extracted the Center for Food Safety and Applied Nutrition's Adverse Event Reporting System data file from 2004 to 2016 and examined the subset classified according to the Food and Drug Administration-designated product class as a baby product. Events were manually categorized into product type and symptom type to assess for trends. Only 166 total adverse events were reported to the Food and Drug Administration for baby products from 2004 to 2016. The majority of reports indicated rash or other skin reaction; 46% of reported events led to a health care visit. Pediatric dermatologists should consider submitting cosmetics and personal care product adverse event reports and encouraging consumers to do so likewise in situations in which a product adversely affects a child's health. © 2018 Wiley Periodicals, Inc.
The Drug Reimbursement Decision-Making System in Iran.
Ansaripour, Amir; Uyl-de Groot, Carin A; Steenhoek, Adri; Redekop, William K
2014-05-01
Previous studies of health policies in Iran have not focused exclusively on the drug reimbursement process. The aim of this study was to describe the entire drug reimbursement process and the stakeholders, and discuss issues faced by policymakers. Review of documents describing the administrative rules and directives of stakeholders, supplemented by published statistics and interviews with experts and policymakers. Iran has a systematic process for the assessment, appraisal, and judgment of drug reimbursements. The two most important organizations in this process are the Food and Drug Organization, which considers clinical effectiveness, safety, and economic issues, and the Supreme Council of Health Insurance, which considers various criteria, including budget impact and cost-effectiveness. Ultimately, the Iranian Cabinet approves a drug and recommends its use to all health insurance organizations. Reimbursed drugs account for about 53.5% of all available drugs and 77.3% of drug expenditures. Despite its strengths, the system faces various issues, including conflicting stakeholder aims, lengthy decision-making duration, limited access to decision-making details, and rigidity in the assessment process. The Iranian drug reimbursement system uses decision-making criteria and a structured approach similar to those in other countries. Important shortcomings in the system include out-of-pocket contributions due to lengthy decision making, lack of transparency, and conflicting interests among stakeholders. Iranian policymakers should consider a number of ways to remedy these problems, such as case studies of individual drugs and closer examination of experiences in other countries. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.
Norman, Jessica L; Fixen, Danielle R; Saseen, Joseph J; Saba, Laura M; Linnebur, Sunny A
2017-01-01
Women have higher morning serum zolpidem concentrations than men after taking an evening dose, potentially leading to increased risk of harm. On 19 April 2013, the United States Food and Drug Administration required labeling changes for zolpidem, recommending an initial dose of no greater than 5 mg (immediate release) or 6.25 mg (controlled release) per night in women. The primary objective of this study was to compare prescribing practices before and after the 2013 zolpidem labeling change. A secondary objective was to evaluate serious adverse events potentially related to zolpidem. Electronic medical records of adults receiving care through the University of Colorado Health system were accessed for study inclusion if patients were provided a first-time prescription for zolpidem either prior to or after the Food and Drug Administration labeling change. Patients were randomly chosen from eight strata based on age, gender, and date of zolpidem initiation (before/after the labeling change). Demographic and zolpidem prescribing data were collected. Low-dose zolpidem was considered 5 mg (immediate release) or 6.25 mg (controlled release) daily or less. Documentation of potentially related serious adverse events within the patients' records was also evaluated. A total of 400 patients were included in the study. The overall percentage of patients prescribed low-dose zolpidem increased from 44% to 58% after the labeling change (p = 0.0020). In a pre-specified subgroup analysis, the percentage of patients prescribed low-dose zolpidem increased in all groups, including young men (38%-50%, p = 0.23), elderly men (34%-40%, p = 0.53), and elderly women (60%-74%, p = 0.14), but the change was only significant in young women (42%-70%, p = 0.0045). After Food and Drug Administration-mandated labeling changes for zolpidem in 2013, the percentage of overall patients in our health system, and specifically young women, with initial prescriptions for low
2012-04-19
...: Notice. The Food and Drug Administration (FDA) is announcing a meeting for patients, caregivers..., caregivers, independent patient advocates, and patient advocate groups that seek to: Educate and inform... of patients? (2) What methodological and practical issues should FDA consider as it develops its...
2010-06-10
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0281] Draft Guidance for Industry and Food and Drug Administration Staff; ```Harmful and Potentially Harmful... Food, Drug, and Cosmetic Act.'' This draft guidance provides written guidance to industry and FDA staff...
Peptide and protein delivery using new drug delivery systems.
Jain, Ashish; Jain, Aviral; Gulbake, Arvind; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K
2013-01-01
Pharmaceutical and biotechnological research sorts protein drug delivery systems by importance based on their various therapeutic applications. The effective and potent action of the proteins/peptides makes them the drugs of choice for the treatment of numerous diseases. Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate target-specific protein carriers. Many efforts have been made for effective delivery of proteins/peptidal drugs through various routes of administrations for successful therapeutic effects. Nanoparticles made of biodegradable polymers such as poly lactic acid, polycaprolactone, poly(lactic-co-glycolic acid), the poly(fumaric-co-sebacic) anhydride chitosan, and modified chitosan, as well as solid lipids, have shown great potential in the delivery of proteins/peptidal drugs. Moreover, scientists also have used liposomes, PEGylated liposomes, niosomes, and aquasomes, among others, for peptidal drug delivery. They also have developed hydrogels and transdermal drug delivery systems for peptidal drug delivery. A receptor-mediated delivery system is another attractive strategy to overcome the limitation in drug absorption that enables the transcytosis of the protein across the epithelial barrier. Modification such as PEGnology is applied to various proteins and peptides of the desired protein and peptides also increases the circulating life, solubility and stability, pharmacokinetic properties, and antigenicity of protein. This review focuses on various approaches for effective protein/peptidal drug delivery, with special emphasis on insulin delivery.
RBAC Administration in Distributed Systems
Dekker, M.A.C.; Crampton, J.; Etalle, Sandro
2007-01-01
Despite a large body of literature on the administration of RBAC policies in centralized systems, the problem of the administration of a distributed system has hardly been addressed. We present a formal system for modelling a distributed RBAC system and its administration. We define two basic
Blok, C. de; Schilp, J.; Wagner, C.
2013-01-01
Objectives: To evaluate the implementation of a four-year national patient safety program concerning the parenteral drug administration process in the Netherlands. Methods: Structuring the preparation and administration process of parenteral drugs reduces the number of medication errors. A
Pro Linux System Administration
Turnbull, James
2009-01-01
We can all be Linux experts, provided we invest the time in learning the craft of Linux administration. Pro Linux System Administration makes it easy for small to medium--sized businesses to enter the world of zero--cost software running on Linux and covers all the distros you might want to use, including Red Hat, Ubuntu, Debian, and CentOS. Authors, and systems infrastructure experts James Turnbull, Peter Lieverdink, and Dennis Matotek take a layered, component--based approach to open source business systems, while training system administrators as the builders of business infrastructure. If
Buccal Mucosa as A Route for Systemic Drug Delivery: A Review
Dhaval A. Pate; M. R. Pate; K. R. Pate; N. M. Pate
2012-01-01
Within the oral mucosal cavity, the buccal region offers an attractive route of administration for systemic drug delivery. The mucosa has a rich blood supply and it is relatively permeable. It is the objective of this article to review buccal drug delivery by discussing the structure and environment of the oral mucosa and the experimental methods used in assessing buccal drug permeation/absorption. Buccal dosage forms will also be reviewed with an emphasis on bioadhesive polymeric based deliv...
2010-04-29
...] Draft Guidance for Industry and Food and Drug Administration Staff; User Fees for 513(g); Requests for... the Internet. To receive ``Draft Guidance for Industry and Food and Drug Administration Staff; User... and Industry Procedures for Section 513(g) Requests for Information under the Federal Food, Drug, and...
Kirschenbaum, Bonnie E
2009-12-15
To discuss the role of restricted drug distribution systems in the implementation of risk evaluation and mitigation strategies (REMS), health-system pharmacists' concerns associated with the use of specialty pharmacies and other restricted drug distribution systems, reimbursement policies for high-cost specialty drugs, supply chain models for traditional and specialty drugs, and emerging trends in the management of and reimbursement for specialty pharmaceuticals. Restricted drug distribution systems established by pharmaceutical manufacturers, specialty pharmacies, or other specialty suppliers may be a component of REMS, which are required by the Food and Drug Administration for the management of known or potential serious risks from certain drugs. Concerns of health-system pharmacists using specialty suppliers include access to pharmaceuticals, operational challenges, product integrity, financial implications, continuity of care, and patient safety. An ambulatory care patient taking a specialty drug product from home to a hospital outpatient clinic or inpatient setting for administration, a practice known as "brown bagging," raises concerns about product integrity and institutional liability. An institution's finances, tolerance for liability, and ability to skillfully manage the processes involved often determine its choice between an approach that prohibits brown bagging but is costly and one that permits the practice under certain conditions and is less costly. The recent shift from a traditional supply chain model to a specialty pharmacy supply chain model for high-cost pharmaceuticals has the potential to increase pharmaceutical costs for health systems. A dialogue is needed between health-system pharmacists and group purchasing organizations to address the latter's role in mitigating the financial implications of this change and to help clarify the safety issues. Some health plans have shifted part of the cost of expensive drugs to patients by establishing a
Shi, Zhenqi; Zhang, Qizhi; Jiang, Xinguo
2005-01-31
The aim of this paper is to establish a novel method to calculate the extent and amount of drug transported to brain after administration. The cerebrospinal fluid (CSF) was chosen as the target region. The intranasal administration of meptazinol hydrochloride (MEP) was chosen as the model administration and intravenous administration was selected as reference. According to formula transform, the extent was measured by the equation of X(A)CSF, infinity/X0 = Cl(CSF) AUC(0-->infinity)CSF/X0 and the drug amount was calculated by multiplying the dose with the extent. The drug clearance in CSF (Cl(CSF)) was calculated by a method, in which a certain volume of MEP solution was injected directly into rat cistern magna and then clearance was assessed as the reciprocal of the zeroth moment of a CSF level-time curve normalized for dose. In order to testify the accurateness of the method, 14C-sucrose was chosen as reference because of its impermeable characteristic across blood-brain barrier (BBB). It was found out that the MEP concentrations in plasma and CSF after intranasal administration did not show significant difference with those after intravenous administration. However, the extent and amount of MEP transported to CSF was significantly lower compared with those to plasma after these two administrations. In conclusion, the method can be applied to measure the extent and amount of drug transported to CSF, which would be useful to evaluate brain-targeting drug delivery.
Sex differences in the self-administration of cannabinoids and other drugs of abuse.
Fattore, Liana; Fadda, Paola; Fratta, Walter
2009-12-01
Many studies have provided evidence for important sex-dependent differences in the origins, outcomes and treatment of drug abuse and dependence. Preclinical studies typically have employed animal models of addiction, such as oral or intravenous self-administration, to untangle the environmental, neurobiological and genetic factors that contribute to the shift from occasional, recreational use to compulsive, uncontrolled intake of drugs. Craving and relapse of drug seeking in abstinent individuals have also been found to differ between men and women. Identification of the neurobiological basis of craving and drug dependence continues to pose a challenge to addiction research. Significant sex differences are emerging in substance-abuse-related behavior, which has increased the demand for research on how drug consumption may have different causes, progression and consequences in men and women. In keeping with epidemiological data in humans, differences between the two sexes in drug seeking and intake have been well-documented in animal studies, with most recent findings related to abuse of cannabinoids. Clinical and preclinical findings indicate that sex and gonadal hormones may account for individual differences in susceptibility to the reinforcing effects of addictive substances, and that differences in vulnerability to drug abuse may be mediated by the same biological mechanisms. This review focuses on the differences between males and females in relation to drug self-administration and how such behavior may be affected by hormonal status.
Wing, Deborah A; Powers, Barbara; Hickok, Durlin
2010-04-01
The process for drug approval in the United States is complex and time-consuming. There are comparatively few drugs with U.S. Food and Drug Administration (FDA)-approved indications for obstetric use in this country at this time; however, several are under development. We review the process for drug approval and recount the approval histories of obstetric drugs reviewed in the recent past. We also outline the current status of two progestational agents that are under development. For a variety of reasons, including a small market compared with others such as cardiology or oncology, and the potential of being drawn into medical-legal litigation, sponsors are disinclined to pursue drug development for obstetric purposes in this country. We compare the procedures for review and approval of drugs in the United States with those in Europe, and note that recent changes within the FDA may result in not only more drugs being approved but also changes in labeling of already approved drugs. Special programs to facilitate drug development and reforms to modernize the process and improve safety are discussed. These may result in changes in labeling of already approved drugs. Obstacles such as funding and liability are also discussed.
Food and Drug Administration Evaluation and Cigarette Smoking Risk Perceptions
Kaufman, Annette R.; Waters, Erika A.; Parascandola, Mark; Augustson, Erik M.; Bansal-Travers, Maansi; Hyland, Andrew; Cummings, K. Michael
2011-01-01
Objectives: To examine the relationship between a belief about Food and Drug Administration (FDA) safety evaluation of cigarettes and smoking risk perceptions. Methods: A nationally representative, random-digit-dialed telephone survey of 1046 adult current cigarette smokers. Results: Smokers reporting that the FDA does not evaluate cigarettes for…
Directory of Open Access Journals (Sweden)
Nélida Barrueco
2008-03-01
Full Text Available Introducción: la vía oral de administración de medicamentos es la vía más cómoda, segura y económica. Sin embargo, pueden existir interacciones con otros fármacos o con alimentos que alteren la eficacia y seguridad de los mismos. Objetivo: desarrollar un programa de información dirigido a enfermeros y enfermeras sobre la administración de medicamentos por vía oral. Método: se seleccionan los medicamentos más utilizados en el área de cardiología pediátrica, revisándose para cada principio activo la administración en relación con alimentos o productos medicinales y otros aspectos relacionados con la administración por vía oral. Resultados: se elabora una tabla informativa sobre un total de 28 principios activos. Discusión: Los farmacéuticos de hospital se han integrado recientemente en los equipos multidisciplinares y desde esta posición tienen la oportunidad de desarrollar diferentes programas de atención farmacéutica, educación sanitaria e información encaminadas a prevenir problemas relacionados con los medicamentos, aumentar su uso seguro y disminuir los riesgos asociados a cualquier tratamiento farmacológico. Las prescripciones médicas generalmente no indican el horario y la forma de administración de los medicamentos, dejando a enfermeros y enfermeras la responsabilidad de su organización. Por esto deben estar informados de cómo y cuándo se deben administrar los medicamentos, lo que permite garantizar su uso seguro y disminuir los riesgos asociados al tratamiento.Background: The easiest, safest and cheapest way to administrate drugs is by mouth (PO. Nevertheless, there may be interactions, either with other drugs or with food, which can modify efficacy and security of the drug itself. Objective: the development of a nursing information program about the administration of drugs PO. Method: we selected the most used drugs corresponding to the pediatric cardiology area, looking for the best administration
Prescription Drug Promotion from 2001-2014: Data from the U.S. Food and Drug Administration.
Directory of Open Access Journals (Sweden)
Helen W Sullivan
Full Text Available The volume of prescription drug promotion over time is often measured by assessing changes in ad spending. However, this method obscures the fact that some types of advertising are more expensive than others. Another way to measure the changes in prescription drug promotion over time is to assess the number of promotional pieces submitted to the U.S. Food and Drug Administration (FDA. Form FDA 2253 collects information such as the date submitted and the type of material submitted. We analyzed data from Forms FDA 2253 received from 2001-2014. We examined the frequency of submissions by audience (consumer and healthcare professional and type of promotional material. There was a noted increase in prescription drug promotion submissions across all media in the early 2000s. Although non-Internet promotion submissions have since plateaued, Internet promotion continued to increase. These results can help public health advocates and regulators focus attention and resources.
2013-02-11
... on the sources of L. monocytogenes contamination, the effects of individual manufacturing and/or... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1182] Draft Joint Food and Drug Administration/Health Canada Quantitative Assessment of the Risk of...
2011-08-09
... selection inclusion and exclusion criteria section. The revisions define and differentiate the required... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0428] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document...
2010-09-28
... method comparison section and the sample selection inclusion and exclusion criteria section. The... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0428] Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...
76 FR 78931 - Food and Drug Administration Rare Disease Patient Advocacy Day; Notice of Meeting
2011-12-20
... Administration, HHS. ACTION: Notice. The Food and Drug Administration's (FDA) Office of Orphan Products... educate the rare disease community on the FDA regulatory processes. This educational meeting will consist...
Directory of Open Access Journals (Sweden)
Axel Newe
Full Text Available The analysis of electronic health records for an automated detection of adverse drug reactions is an approach to solve the problems that arise from traditional methods like spontaneous reporting or manual chart review. Algorithms addressing this task should be modeled on the criteria for a standardized case causality assessment defined by the World Health Organization. One of these criteria is the temporal relationship between drug intake and the occurrence of a reaction or a laboratory test abnormality. Appropriate data that would allow for developing or validating related algorithms is not publicly available, though.In order to provide such data, retrospective routine data of drug administrations and temporally corresponding laboratory observations from a university clinic were extracted, transformed and evaluated by experts in terms of a reasonable time relationship between drug administration and lab value alteration.The result is a data corpus of 400 episodes of normalized laboratory parameter values in temporal context with drug administrations. Each episode has been manually classified whether it contains data that might indicate a temporal correlation between the drug administration and the change of the lab value course, whether such a change is not observable or whether a decision between those two options is not possible due to the data. In addition, each episode has been assigned a concordance value which indicates how difficult it is to assess. This is the first open data corpus of a computable ground truth of temporal correlations between drug administration and lab value alterations.The main purpose of this data corpus is the provision of data for further research and the provision of a ground truth which allows for comparing the outcome of other assessments of this data with the outcome of assessments made by human experts. It can serve as a contribution towards systematic, computerized ADR detection in retrospective data. With
2011-05-18
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 866 [Docket No. FDA-2011-D-0102] Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: In Vitro Diagnostic Devices for Bacillus Species Detection AGENCY: Food and...
Prohibited or regulated? LSD psychotherapy and the United States Food and Drug Administration.
Oram, Matthew
2016-09-01
Over the 1950s and early 1960s, the use of the hallucinogenic drug lysergic acid diethylamide (LSD) to facilitate psychotherapy was a promising field of psychiatric research in the USA. However, during the 1960s, research began to decline, before coming to a complete halt in the mid-1970s. This has commonly been explained through the increase in prohibitive federal regulations during the 1960s that aimed to curb the growing recreational use of the drug. However, closely examining the Food and Drug Administration's regulation of LSD research in the 1960s will reveal that not only was LSD research never prohibited, but that the administration supported research to a greater degree than has been recognized. Instead, the decline in research reflected more complex changes in the regulation of pharmaceutical research and development. © The Author(s) 2016.
Adelstein, Tom
2007-01-01
If you're an experienced system administrator looking to acquire Linux skills, or a seasoned Linux user facing a new challenge, Linux System Administration offers practical knowledge for managing a complete range of Linux systems and servers. The book summarizes the steps you need to build everything from standalone SOHO hubs, web servers, and LAN servers to load-balanced clusters and servers consolidated through virtualization. Along the way, you'll learn about all of the tools you need to set up and maintain these working environments. Linux is now a standard corporate platform with user
International Nuclear Information System (INIS)
Hofer, M.; Pospisil, M.; Netikova, J.; Hola, J.; Znojil, V.; Vacha, J.
1995-01-01
The authors have recently demonstrated that a combined administration of dipyridamole and adenosine monophosphate to mice induces radioprotective effects in terms of postirradiation hematopoietic recovery in animals irradiated with a single dose. The aim of the present experiments was to investigate the radioprotective ability of the drug combination under conditions of fractionated radiation. It was shown that administration of the drugs either 15 or 60 min before each of the five daily 3-Gy doses of gamma radiation enhances hematopoietic recovery and survival of mice exposed to an additional 'top-up' dose of 3.5 Gy. Furthermore, it was ascertained that administration of the drugs 60 min prior to irradiation is more effective than administration of the drugs 15 min prior to irradiation. Due to the evidence that administration of the drugs 15 min prior to irradiation protects the organism mainly via mechanisms of systemic hypoxia while the pretreatment 60 min before irradiation avoids the role of hypoxia and mainly induces cell proliferation effects, the present results suggest a more protective role of mechanisms stimulating hematopoiesis under conditions of fractionated radiation. The data may provide a basis for more rational use of radioprotection in fractionated radiation techniques. (author) 1 tab., 1 fig., 25 refs
Balap, Aishwarya; Atre, Bhagyashri; Lohidasan, Sathiyanarayanan; Sinnathambi, Arulmozhi; Mahadik, Kakasaheb
2016-05-13
Andrographis paniculata Nees (Acanthacae) is commonly used medicinal plant in the traditional. Unani and Ayurvedic medicinal systems. It has broad range of pharmacological effects such as hepatoprotective, antioxidant, antivenom, antifertility, inhibition of replication of the HIV virus, antimalarial, antifungal, antibacterial, antidiabetic, suppression of various cancer cells and anti-inflammatory properties. Andrographolide (AN) is one of the active constituent of the A. paniculata Nees extract (APE). They have been found in many traditional herbal formulations in India and proven to be effective as anti-inflammatory drug To evaluate the pharmacokinetic and pharmacodynamic (anti-arthritic) herb-drug interactions of A. paniculata Nees extract (APE) and pure andrographolide (AN) with etoricoxib (ETO) after oral co-administration in wistar rats. After oral co-administration of APE (200mg/Kg) and AN (60mg/kg) with ETO (10mg/kg) in rats, drug concentrations in plasma were determined using HPLC method. The main pharmacokinetic parameters of Cmax, tmax, t1/2, MRT, Vd, CL, and AUC were calculated by non-compartment model. Change in paw volume, mechanical nociceptive threshold, mechanical hyperalgesia, histopathology and hematological parameters were evaluated to study antiarthritic activity. Co-administration of ETO with APE and pure AN decreased systemic exposure level of each compound in vivo. The Cmax, AUC, t1/2 of ETO was decreased whereas Vd and CL of ETO was increased significantly after co-administration of ETO with pure AN and APE. In pharmacodynamic study, ETO alone and ETO+APE (10+200mg/kg) groups exhibited significant synergistic anti-arthritic activity as compared to groups ETO+AN, APE and AN alone. The results obtained from this study suggested that ETO, APE and pure AN existed pharmacokinetic herb-drug interactions in rat which is correlated with anti-arthritic study. Physicians and patients using A. paniculata should have the knowledge about its possible
2011-10-18
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0529] Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small Business... amounts on small business, as set forth in the FDA Food Safety Modernization Act (FSMA). In particular...
2011-08-01
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0529] Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small Business... burden of fee amounts on small business, as set forth in the FDA Food Safety Modernization Act (FSMA...
DILEMMAS OF COMMUNITY-DIRECTED MASS DRUG ADMINISTRATION FOR LYMPHATIC FILARIASIS CONTROL
DEFF Research Database (Denmark)
Kisoka, William; Mushi, Declare; Meyrowitsch, Dan W.
2017-01-01
There has in recent years been a growing interest in the social significance of global health policy and associated interventions. This paper is concerned with neglected tropical disease control, which prescribes annual mass drug administration to interrupt transmission of, among others, lymphati...
A clinical perspective on mucoadhesive buccal drug delivery systems
Gilhotra, Ritu M; Ikram, Mohd; Srivastava, Sunny; Gilhotra, Neeraj
2014-01-01
Mucoadhesion can be defined as a state in which two components, of which one is of biological origin, are held together for extended periods of time by the help of interfacial forces. Among the various transmucosal routes, buccal mucosa has excellent accessibility and relatively immobile mucosa, hence suitable for administration of retentive dosage form. The objective of this paper is to review the works done so far in the field of mucoadhesive buccal drug delivery systems (MBDDS), with a clinical perspective. Starting with a brief introduction of the mucoadhesive drug delivery systems, oral mucosa, and the theories of mucoadhesion, this article then proceeds to cover the works done so far in the field of MBDDS, categorizing them on the basis of ailments they are meant to cure. Additionally, we focus on the various patents, recent advancements, and challenges as well as the future prospects for mucoadhesive buccal drug delivery systems. PMID:24683406
Modular reservoir concept for MEMS-based transdermal drug delivery systems
International Nuclear Information System (INIS)
Cantwell, Cara T; Wei, Pinghung; Ziaie, Babak; Rao, Masaru P
2014-01-01
While MEMS-based transdermal drug delivery device development efforts have typically focused on tightly-integrated solutions, we propose an alternate conception based upon a novel, modular drug reservoir approach. By decoupling the drug storage functionality from the rest of the delivery system, this approach seeks to minimize cold chain storage volume, enhance compatibility with conventional pharmaceutical practices, and allow independent optimization of reservoir device design, materials, and fabrication. Herein, we report the design, fabrication, and preliminary characterization of modular reservoirs that demonstrate the virtue of this approach within the application context of transdermal insulin administration for diabetes management. (technical note)
Modular reservoir concept for MEMS-based transdermal drug delivery systems
Cantwell, Cara T.; Wei, Pinghung; Ziaie, Babak; Rao, Masaru P.
2014-11-01
While MEMS-based transdermal drug delivery device development efforts have typically focused on tightly-integrated solutions, we propose an alternate conception based upon a novel, modular drug reservoir approach. By decoupling the drug storage functionality from the rest of the delivery system, this approach seeks to minimize cold chain storage volume, enhance compatibility with conventional pharmaceutical practices, and allow independent optimization of reservoir device design, materials, and fabrication. Herein, we report the design, fabrication, and preliminary characterization of modular reservoirs that demonstrate the virtue of this approach within the application context of transdermal insulin administration for diabetes management.
Dry Powder Inhalers: A Focus on Advancements in Novel Drug Delivery Systems
Directory of Open Access Journals (Sweden)
Piyush Mehta
2016-01-01
Full Text Available Administration of drug molecules by inhalation route for treatment of respiratory diseases has the ability to deliver drugs, hormones, nucleic acids, steroids, proteins, and peptides, particularly to the site of action, improving the efficacy of the treatment and consequently lessening adverse effects of the treatment. Numerous inhalation delivery systems have been developed and studied to treat respiratory diseases such as asthma, COPD, and other pulmonary infections. The progress of disciplines such as biomaterials science, nanotechnology, particle engineering, molecular biology, and cell biology permits further improvement of the treatment capability. The present review analyzes modern therapeutic approaches of inhaled drugs with special emphasis on novel drug delivery system for treatment of various respiratory diseases.
Directory of Open Access Journals (Sweden)
Jason Charng
2016-01-01
Full Text Available Objective. To examine whether retinal electrophysiology is a useful surrogate marker of drug penetrance into the central nervous system (CNS. Materials and Methods. Brain and retinal electrophysiology were assessed with full-field visually evoked potentials and electroretinograms in conscious and anaesthetised rats following systemic or local administrations of centrally penetrant (muscimol or nonpenetrant (isoguvacine compounds. Results. Local injections into the eye/brain bypassed the blood neural barriers and produced changes in retinal/brain responses for both drugs. In conscious animals, systemic administration of muscimol resulted in retinal and brain biopotential changes, whereas systemic delivery of isoguvacine did not. General anaesthesia confounded these outcomes. Conclusions. Retinal electrophysiology, when recorded in conscious animals, shows promise as a viable biomarker of drug penetration into the CNS. In contrast, when conducted under anaesthetised conditions confounds can be induced in both cortical and retinal electrophysiological recordings.
2012-04-06
...] Guidance for Industry and Food and Drug Administration Staff; User Fees for 513(g) Requests for Information... Administration (FDA) is announcing the availability of the guidance entitled ``Guidance for Industry and Food and... ``Guidance for Industry and Food and Drug Administration Staff; User Fees for 513(g) Requests for Information...
Seidling, Hanna M; Stützle, Marion; Hoppe-Tichy, Torsten; Allenet, Benoît; Bedouch, Pierrick; Bonnabry, Pascal; Coleman, Jamie J; Fernandez-Llimos, Fernando; Lovis, Christian; Rei, Maria Jose; Störzinger, Dominic; Taylor, Lenka A; Pontefract, Sarah K; van den Bemt, Patricia M L A; van der Sijs, Heleen; Haefeli, Walter E
2016-04-01
While evidence on implementation of medication safety strategies is increasing, reasons for selecting and relinquishing distinct strategies and details on implementation are typically not shared in published literature. We aimed to collect and structure expert information resulting from implementing medication safety strategies to provide advice for decision-makers. Medication safety experts with clinical expertise from thirteen hospitals throughout twelve European and North American countries shared their experience in workshop meetings, on-site-visits and remote structured interviews. We performed an expert-based, in-depth assessment of implementation of best-practice strategies to improve drug prescribing and drug administration. Workflow, variability and recommended medication safety strategies in drug prescribing and drug administration processes. According to the experts, institutions chose strategies that targeted process steps known to be particularly error-prone in the respective setting. Often, the selection was channeled by local constraints such as the e-health equipment and critically modulated by national context factors. In our study, the experts favored electronic prescribing with clinical decision support and medication reconciliation as most promising interventions. They agreed that self-assessment and introduction of medication safety boards were crucial to satisfy the setting-specific differences and foster successful implementation. While general evidence for implementation of strategies to improve medication safety exists, successful selection and adaptation of a distinct strategy requires a thorough knowledge of the institute-specific constraints and an ongoing monitoring and adjustment of the implemented measures.
Lee, Seung-Ju; Kim, Sae Woong; Chung, Hesson; Park, Yeong Taek; Choi, Young Wook; Cho, Yong-Hyun; Yoon, Moon Soo
2005-10-01
Many reports have shown that the efficacy of intravesical therapy for bladder cancer is in part limited by the poor penetration of drugs into the urothelium. The present study evaluated the effect of glyceryl monooleate (GMO) on the absorption of intravesically administered paclitaxel in a rabbit model of bladder cancer. Urine, plasma, and tissue pharmacokinetics were determined in rabbits treated for 120 min with paclitaxel (500 microg/20 ml) by intravesical instillation. Two formulations of GMO/paclitaxel were evaluated using different proportions of water, 15 and 30%, and Taxol was used as a control. Animals were observed for clinical signs of toxicity and necropsy was performed. 120 min after instillation, the bladder was emptied and excised. In the urine, paclitaxel concentration was decreased by 39.6 and 41.2% in the two experimental groups and by 25.2% in the control group. The paclitaxel concentrations in the urothelium were 53 and 56% of the urine concentration in both experimental groups, but 11% in the control group. The concentration then declined exponentially in the underlying capillary-perfused tissues, reaching equilibrium at a depth of 1,400-1,700 microm. The plasma concentrations were extremely low compared with concentrations in urine and bladder tissues and were not associated with clinical toxicity. We conclude that GMO has a significantly increased bioadhesiveness to bladder mucosa. Therefore, intravesical administration of GMO/paclitaxel/water provides a significant advantage for drugs targeting the bladder tissue, and paclitaxel represents a viable option for intravesical bladder cancer therapy. Copyright 2005 S. Karger AG, Basel.
2013-02-12
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0124... metrics. With that in mind, FDA would like input on the following issues: What metrics do manufacturers... been suggested as a potentially useful approach to expanding manufacturing capacity and preventing...
FDA publishes conflict of interest rules for clinical trials. Food and Drug Administration.
James, J S
1998-03-06
The Food and Drug Administration (FDA) published new rules defining conflict of interests between drug companies and medical researchers and clinicians. Certain financial arrangements will need to be disclosed, although the FDA estimates that only one to ten percent of pharmaceutical companies will need to submit disclosures for one or more of their investigators. The purpose of the new rule is to prevent bias in safety and efficacy studies of drugs and medical devices. The full rule is published in the Federal Register.
2010-11-12
... annually from approximately 25 application holders. FDA professionals familiar with Dear Health Care... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0319] Draft Guidance for Industry and Food and Drug Administration Staff on Dear Health Care Provider Letters...
1995-07-01
Chiron Corporation and Hoffman-LaRoche announced a filing of a New Drug Application with the Food and Drug Administration (FDA) to market Vitrasert, its intraocular implant which delivers ganciclovir directly to the eye for treatment of CMV retinitis. Clinical trials show that Vitrasert offers a clinical improvement versus intravenous ganciclovir in further delaying progression of CMV retinitis in the treated eye. One study reported that the median time to progression of CMV retinitis was 186 days for eyes receiving Vitrasert compared to 72 days for eyes receiving intravenous ganciclovir therapy. Chiron's intraocular implant contains ganciclovir embedded in a polymer-based system that slowly releases the drug into the eye for up to eight months. Two additional trials are underway. For further information contact the Professional Services Group at Chiron Corporation at (800) 244-7668, select 2.
Christiansen, Martin Lau; Holm, Rene; Abrahamsson, Bertil; Jacobsen, Jette; Kristensen, Jakob; Andersen, Jens Rikardt; Müllertz, Anette
2016-03-10
Positive food effects may be observed for low aqueous soluble compounds, these effects could potentially be circumvented using lipid based formulations. However, as all compounds are not chemically stable in lipid based systems, alternative dosage regimes could be investigated to evade the stability issue. The two aims for this present study were therefore; i) to investigate if a nutritional drink, Fresubin Energy®, could induce food effect in humans for the poorly soluble compound cinnarizine; and ii) to investigate if co-administration of a self-nano-emulsifying drug delivery systems (SNEDDS) with a conventional cinnarizine tablet could reduce the observed food-effect. A commercial conventional cinnarizine tablet was dosed to 10 healthy volunteers in a cross-over design in both fasted and fed state, with and without co-administration of a SNEDDS, with a one week wash-out period between dosing. The fed state was induced using a nutritional drink (Fresubin Energy®) and gastric emptying was assessed by administration of paracetamol as a marker. The pharmacokinetic analysis showed that the nutritional drink delayed the uptake and increased the fraction of absorbed cinnarizine, indicative of a food effect on the compound. This was in agreement with a previous dog study and indicates that the nutritional drink can be used for inducing the same level of food effect in humans. Though not statistically significant, the co-administration of SNEDDS exhibited a tendency towards a reduction of the observed food effect and an increased absorption of cinnarizine in the fasted state; based upon the individual ratios, which was not reflected in the mean data. However, the co-administration of SNEEDS in the fasted state, also induce a slower gastric emptying rate, which was observed as a delayed tmax for both cinnarizine and paracetamol. Copyright © 2016 Elsevier B.V. All rights reserved.
van den Bemt, P M L A; Robertz, R; de Jong, A L; van Roon, E N; Leufkens, H G M
BACKGROUND: Medication errors can result in harm, unless barriers to prevent them are present. Drug administration errors are less likely to be prevented, because they occur in the last stage of the drug distribution process. This is especially the case in non-alert patients, as patients often form
Acute antidepressant drug administration and autobiographical memory recall
DEFF Research Database (Denmark)
Papadatou-Pastou, Marietta; Miskowiak, Kamilla W; Williams, J Mark G
2012-01-01
Antidepressants affect memory and neural responses to emotionally valenced stimuli in healthy volunteers. However, it is unclear whether this extends to autobiographical memory for personally experienced events. The current study investigated the effects of acute administration of the antidepress...... of reboxetine on emotional memory extends to recall of personally experienced events. Such effects may be relevant to the cognitive improvements found with recovery from depression and with the mechanism of action of contemporary antidepressant drugs.......Antidepressants affect memory and neural responses to emotionally valenced stimuli in healthy volunteers. However, it is unclear whether this extends to autobiographical memory for personally experienced events. The current study investigated the effects of acute administration...... in the processing of positive versus negative memories was reduced following reboxetine compared with placebo in the left frontal lobe (extending into the insula) and the right superior temporal gyrus. This was paired with increased memory speed in volunteers given reboxetine versus placebo. The effect...
5-FU Metabolism in Cancer and Orally-Administrable 5-FU Drugs
Directory of Open Access Journals (Sweden)
Iwao Sasaki
2010-09-01
Full Text Available 5-Fluorouracil (5-FU is a key anticancer drug that for its broad antitumor activity, as well as for its synergism with other anticancer drugs, has been used to treat various types of malignancies. In chemotherapeutic regimens, 5-FU has been combined with oxaliplatin, irinotecan and other drugs as a continuous intravenous infusion. Recent clinical chemotherapy studies have shown that several of the regimens with oral 5-FU drugs are not inferior compared to those involving continuous 5-FU infusion chemotherapy, and it is probable that in some regimens continuous 5-FU infusion can be replaced by oral 5-FU drugs. Historically, both the pharmaceutical industry and academia in Japan have been involved in the development of oral 5-FU drugs, and this review will focus on the current knowledge of 5-FU anabolism and catabolism, and the available information about the various orally-administrable 5-FU drugs, including UFT, S-1 and capecitabine. Clinical studies comparing the efficacy and adverse events of S-1 and capecitabine have been reported, and the accumulated results should be utilized to optimize the treatment of cancer patients. On the other hand, it is essential to elucidate the pharmacokinetic mechanism of each of the newly-developed drugs, to correctly select the drugs for each patient in the clinical setting, and to further develop optimized drug derivatives.
2010-04-01
... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Testing and research conducted by or with funds... Categories of Records § 20.105 Testing and research conducted by or with funds provided by the Food and Drug Administration. (a) Any list that may be prepared by the Food and Drug Administration of testing and research...
System administrator`s guide to CDPS. Version 1.0
Energy Technology Data Exchange (ETDEWEB)
Didier, B.T.; Portwood, M.H.
1994-05-01
The System Administrator`s Guide to CDPS is intended for those responsible for setting up and maintaining the hardware and software of a Common Mapping Standard (CMS) Date Production System (CDPS) installation. This guide assists the system administrator in performing typical administrative functions. It is not intended to replace the Ultrix Documentation Set that should be available for a DCPS installation. The Ultrix Documentation Set will be required to provide details on referenced Ultrix commands as well as procedures for performing Ultrix maintenance functions. There are six major sections in this guide. Section 1 introduces the system administrator to CDPS and describes the assumptions that are made by this guide. Section 2 describes the CDPS platform configuration. Section 3 describes the platform preparation that is required to install the CDPS software. Section 4 describes the CPS software and its installation procedures. Section 5 describes the CDS software and its installation procedures. Section 6 describes various operation and maintenance procedures. Four appendices are also provided. Appendix A contains a list of used acronyms. Appendix B provides a terse description of common Ultrix commands that are used in administrative functions. Appendix C provides sample CPS and CDS configuration files. Appendix D provides a required list and a recommended list of Ultrix software subsets for installation on a CDPS platform.
Palmer, Brian C.; DeLouise, Lisa A.
2017-01-01
Transdermal drug delivery systems have been around for decades, and current technologies (e.g. patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases. PMID:27983701
Palmer, Brian C; DeLouise, Lisa A
2016-12-15
Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.
Carrier-Based Drug Delivery System for Treatment of Acne
Vyas, Amber; Kumar Sonker, Avinesh
2014-01-01
Approximately 95% of the population suffers at some point in their lifetime from acne vulgaris. Acne is a multifactorial disease of the pilosebaceous unit. This inflammatory skin disorder is most common in adolescents but also affects neonates, prepubescent children, and adults. Topical conventional systems are associated with various side effects. Novel drug delivery systems have been used to reduce the side effect of drugs commonly used in the topical treatment of acne. Topical treatment of acne with active pharmaceutical ingredients (API) makes direct contact with the target site before entering the systemic circulation which reduces the systemic side effect of the parenteral or oral administration of drug. The objective of the present review is to discuss the conventional delivery systems available for acne, their drawbacks, and limitations. The advantages, disadvantages, and outcome of using various carrier-based delivery systems like liposomes, niosomes, solid lipid nanoparticles, and so forth, are explained. This paper emphasizes approaches to overcome the drawbacks and limitations associated with the conventional system and the advances and application that are poised to further enhance the efficacy of topical acne formulations, offering the possibility of simplified dosing regimen that may improve treatment outcomes using novel delivery system. PMID:24688376
Directory of Open Access Journals (Sweden)
Sladjana Eftimova
2015-07-01
Full Text Available The structure of the legal system, through history until today mostly depends on law and policy which is conducted by the country. In European countries, there is position for historical and cultural conceptions for administrative judicature, differences and similarity that leave mark for solving administrative disputes. The obligation – an internal judicial reform to be established in legal system, is conducted by each of the countries after the breaking down and division of Social Federative Republic of Yugoslavia or SFRY due to following the European law for constitution of legitimacy and constitutionality of acts as well as implementing of independent administrative judicature. Analyze of the current condition regarding the independency and objectiveness of the judicature is necessary in our country and it is important to be seen how the conditions for working of the administrative judicature can be improved.
Prospects for the control of neglected tropical diseases by mass drug administration
Smits, Henk L.
2009-01-01
The prospects for the control of neglected tropical diseases, including soil-transmitted helminthiasis, shistosomiasis, lymphatic filariasis, onchocerciasis and trachoma, through mass drug administration, are exemplified by the elimination of the trachoma as a public-health problem in Morocco. In
Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease.
Gunay, Mine Silindir; Ozer, A Yekta; Chalon, Sylvie
2016-01-01
Although a variety of therapeutic approaches are available for the treatment of Parkinson's disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson's disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α -synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson's disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson's Disease therapy and reduce its side effects.
Application of in situ polymerization for design and development of oral drug delivery systems.
Ngwuluka, Ndidi
2010-12-01
Although preformed polymers are commercially available for use in the design and development of drug delivery systems, in situ polymerization has also been employed. In situ polymerization affords the platform to tailor and optimize the drug delivery properties of polymers. This review brings to light the benefits of in situ polymerization for oral drug delivery and the possibilities it provides to overcome the challenges of oral route of administration.
Application of In Situ Polymerization for Design and Development of Oral Drug Delivery Systems
Ngwuluka, Ndidi
2010-01-01
Although preformed polymers are commercially available for use in the design and development of drug delivery systems, in situ polymerization has also been employed. In situ polymerization affords the platform to tailor and optimize the drug delivery properties of polymers. This review brings to light the benefits of in situ polymerization for oral drug delivery and the possibilities it provides to overcome the challenges of oral route of administration.
Sharifi, N; Ozgoli, S; Ramezani, A
2017-06-01
Mixed immunotherapy and chemotherapy of tumours is one of the most efficient ways to improve cancer treatment strategies. However, it is important to 'design' an effective treatment programme which can optimize the ways of combining immunotherapy and chemotherapy to diminish their imminent side effects. Control engineering techniques could be used for this. The method of multiple model predictive controller (MMPC) is applied to the modified Stepanova model to induce the best combination of drugs scheduling under a better health criteria profile. The proposed MMPC is a feedback scheme that can perform global optimization for both tumour volume and immune competent cell density by performing multiple constraints. Although current studies usually assume that immunotherapy has no side effect, this paper presents a new method of mixed drug administration by employing MMPC, which implements several constraints for chemotherapy and immunotherapy by considering both drug toxicity and autoimmune. With designed controller we need maximum 57% and 28% of full dosage of drugs for chemotherapy and immunotherapy in some instances, respectively. Therefore, through the proposed controller less dosage of drugs are needed, which contribute to suitable results with a perceptible reduction in medicine side effects. It is observed that in the presence of MMPC, the amount of required drugs is minimized, while the tumour volume is reduced. The efficiency of the presented method has been illustrated through simulations, as the system from an initial condition in the malignant region of the state space (macroscopic tumour volume) transfers into the benign region (microscopic tumour volume) in which the immune system can control tumour growth. Copyright © 2017 Elsevier B.V. All rights reserved.
Cardiovascular outcomes and systemic anti-inflammatory drugs in patients with severe psoriasis
DEFF Research Database (Denmark)
Ahlehoff, O; Skov, L; Gislason, G
2014-01-01
BACKGROUND: Psoriasis is a common disease and is associated with cardiovascular diseases. Systemic anti-inflammatory drugs may reduce risk of cardiovascular events. We therefore examined the rate of cardiovascular events, i.e. cardiovascular death, myocardial infarction and stroke, in patients...... with severe psoriasis treated with systemic anti-inflammatory drugs. METHODS: Individual-level linkage of administrative registries was used to perform a longitudinal nationwide cohort study. Time-dependent multivariable adjusted Cox regression was used to estimate hazard ratios (HRs) with 95% confidence...... intervals (CIs) of cardiovascular events associated with use of biological drugs, methotrexate, cyclosporine, retinoids and other antipsoriatic therapies, including topical treatments, phototherapy and climate therapy. RESULTS: A total of 6902 patients (9662 treatment exposures) with a maximum follow...
Directory of Open Access Journals (Sweden)
Brian C. Palmer
2016-12-01
Full Text Available Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.
From Composition to Cure: A Systems Engineering Approach to Anticancer Drug Carriers.
MacEwan, Sarah R; Chilkoti, Ashutosh
2017-06-06
The molecular complexity and heterogeneity of cancer has led to a persistent, and as yet unsolved, challenge to develop cures for this disease. The pharmaceutical industry focuses the bulk of its efforts on the development of new drugs, but an alternative approach is to improve the delivery of existing drugs with drug carriers that can manipulate when, where, and how a drug exerts its therapeutic effect. For the treatment of solid tumors, systemically delivered drug carriers face significant challenges that are imposed by the pathophysiological barriers that lie between their site of administration and their site of therapeutic action in the tumor. Furthermore, drug carriers face additional challenges in their translation from preclinical validation to clinical approval and adoption. Addressing this diverse network of challenges requires a systems engineering approach for the rational design of optimized carriers that have a realistic prospect for translation from the laboratory to the patient. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Schneider, Lon S
2014-03-01
The February 2013 Food and Drug Administration (FDA) draft guidance for developing drugs for early-stage Alzheimer's disease (AD) creates certain challenges as they guide toward the use of one cognitive outcome to gain accelerated marketing approval for preclinical AD drugs, and a composite clinical scale - the Clinical Dementia Rating Scale in particular - for the primary outcome for prodromal AD clinical trials. In light of the developing knowledge regarding early stage diagnoses and clinical trials outcomes, we recommend that FDA describe its requirements for validating preclinical AD diagnoses for drug development purposes, maintain the principle for requiring coprimary outcomes, and encourage the advancement of outcomes for early stage AD trials. The principles for drug development for early stage AD should not differ from those for clinical AD, especially as the diagnoses of prodromal and early AD impinge on each other. The FDA should not recommend that a composite scale be used as a sole primary efficacy outcome to support a marketing claim unless it requires that the cognitive and functional components of such a scale are demonstrated to be individually meaningful. The current draft guidelines may inadvertently constrain efforts to better assess the clinical effects of new drugs and inhibit innovation in an area where evidence-based clinical research practices are still evolving. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Pro Python System Administration
Sileika, R
2010-01-01
As time goes on, system administrators are presented with increasingly complicated challenges. In the early days, a team of engineers might have had to look after one or two systems. These days, one engineer can administer hundreds or thousands of systems. System administrators are gradually replacing their tools with more advanced and flexible ones. One of the choices is Python. Structurally, Python is a modern, high-level language with a very clean syntax. Python comes with many built-in libraries that can make automation tasks easier. It also has extensive set of third-party libraries and a
Directory of Open Access Journals (Sweden)
Axel Newe
2016-03-01
Full Text Available According to the World Health Organization, one of the criteria for the standardized assessment of case causality in adverse drug reactions is the temporal relationship between the intake of a drug and the occurrence of a reaction or a laboratory test abnormality. This article presents and describes an algorithm for the detection of a reasonable temporal correlation between the administration of a drug and the alteration of a laboratory value course. The algorithm is designed to process normalized lab values and is therefore universally applicable. It has a sensitivity of 0.932 for the detection of lab value courses that show changes in temporal correlation with the administration of a drug and it has a specificity of 0.967 for the detection of lab value courses that show no changes. Therefore, the algorithm is appropriate to screen the data of electronic health records and to support human experts in revealing adverse drug reactions. A reference implementation in Python programming language is available.
Yu, Jingjing; Zhou, Zhu; Tay-Sontheimer, Jessica; Levy, Rene H; Ragueneau-Majlessi, Isabelle
2018-03-23
A total of 103 drugs (including 14 combination drugs) were approved by the U.S. Food and Drug Administration from 2013 to 2016. Pharmacokinetic-based drug interaction profiles were analyzed using the University of Washington Drug Interaction Database and the clinical relevance of these observations was characterized based on information from New Drug Application reviews. CYP3A was identified as a major contributor to clinical drug-drug interactions (DDIs), involved in approximately 2/3 of all interactions. Transporters (alone or with enzymes) were found to participate in about half of all interactions, although most of these were weak-to-moderate interactions. When considered as victims, eight new molecular entities (NMEs; cobimetinib, ibrutnib, isavuconazole, ivabradine, naloxegol, paritaprevir, simeprevir, and venetoclax) were identified as sensitive substrates of CYP3A, two NMEs (pirfenidone and tasimelteon) were sensitive substrates of CYP1A2, one NME (dasabuvir) was a sensitive substrate of CYP2C8, one NME (eliglustat) was a sensitive substrate of CYP2D6, and one NME (grazoprevir) was a sensitive substrate of OATP1B1/3 (with changes in exposure greater than 5-fold when co-administered with a strong inhibitor). Interestingly, approximately 75% of identified CYP3A substrates were also substrates of P-gp. As perpetrators, most clinical DDIs involved weak-to-moderate inhibition or induction, with only two drugs (Viekira Pak and idelalisib) showing strong inhibition of CYP3A, and one NME (lumacaftor) considered as a strong CYP3A inducer. Among drugs with large changes in exposure (≥ 5-fold), whether as victim or perpetrator, the most represented therapeutic classes were antivirals and oncology drugs, suggesting a significant risk of clinical DDIs in these patient populations. The American Society for Pharmacology and Experimental Therapeutics.
TRANSDERMAL DRUG DELIVERY SYSTEM: REVIEW
Vishvakarama Prabhakar; Agarwal Shivendra; Sharma Ritika; Saurabh Sharma
2012-01-01
Various new technologies have been developed for the transdermal delivery of some important drugs. Today about 74% of drugs are taken orally and are found not to be as effective as desired. To improve such characters transdermal drug delivery system was emerged. Drug delivery through the skin to achieve a systemic effect of a drug is commonly known as transdermal drug delivery and differs from traditional topical drug delivery. Transdermal drug delivery systems (TDDS) are dosage forms involve...
Directory of Open Access Journals (Sweden)
Jessica L Norman
2017-05-01
Full Text Available Background: Women have higher morning serum zolpidem concentrations than men after taking an evening dose, potentially leading to increased risk of harm. On 19 April 2013, the United States Food and Drug Administration required labeling changes for zolpidem, recommending an initial dose of no greater than 5 mg (immediate release or 6.25 mg (controlled release per night in women. Objectives: The primary objective of this study was to compare prescribing practices before and after the 2013 zolpidem labeling change. A secondary objective was to evaluate serious adverse events potentially related to zolpidem. Methods: Electronic medical records of adults receiving care through the University of Colorado Health system were accessed for study inclusion if patients were provided a first-time prescription for zolpidem either prior to or after the Food and Drug Administration labeling change. Patients were randomly chosen from eight strata based on age, gender, and date of zolpidem initiation (before/after the labeling change. Demographic and zolpidem prescribing data were collected. Low-dose zolpidem was considered 5 mg (immediate release or 6.25 mg (controlled release daily or less. Documentation of potentially related serious adverse events within the patients’ records was also evaluated. Results: A total of 400 patients were included in the study. The overall percentage of patients prescribed low-dose zolpidem increased from 44% to 58% after the labeling change (p = 0.0020. In a pre-specified subgroup analysis, the percentage of patients prescribed low-dose zolpidem increased in all groups, including young men (38%–50%, p = 0.23, elderly men (34%–40%, p = 0.53, and elderly women (60%–74%, p = 0.14, but the change was only significant in young women (42%–70%, p = 0.0045. Conclusion: After Food and Drug Administration–mandated labeling changes for zolpidem in 2013, the percentage of overall patients in our health
Gamma- scintigraphy in the evaluation of drug delivery systems
International Nuclear Information System (INIS)
Shahhosseini, S.; Beiki, D.; Eftekhari, M.
2003-01-01
Gamma-scintigraphy is applied extensively in the development and evaluation of pharmaceutical delivery systems, particularly for monitoring formulations in the gastrointestinal and respiratory tracts. The radiolabelling is generally achieved by the incorporation of an appropriate radionuclide such as technetium-99m or indium-111 into the formulation or by addition of a non- radioactive isotope such as samarium-152 followed by neutron activation of the final product. Drug delivery systems can be tested in vitro using various techniques like dissolution rate. Since in vitro testing methods are not predictive of in vivo results, such systems should be evaluated in vivo using animal models, especially oral dosage forms. Altered gastrointestinal transit due to individual variation, physiologic factors, or the presence of food may influence bioavailability. Distribution or drug release may be premature or delayed in vivo. Similarly, altered deposition or clearance from other routes of administration such as nasal, ocular, or inhalation may explain drug absorption anomalies. Therefore, there is a growing tendency for new drug delivery systems to be tested, whenever possible, in human subjects in a so called phase 1 clinical evaluation. Gamma- scintigraphy combined with knowledge of physiological and dosage from design can help to identify some of these variables. the resulting insight can be used to accelerate the formulation development process and to ensure success in early clinical trials
2013-09-06
.... Food and beverages will be available for purchase by participants during the workshop breaks. If you....regulations.gov . It may be viewed at the Division of Dockets Management (HFA-305), Food and Drug... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001...
Drug reaction with eosinophilia and systemic symptoms without skin rash.
Sasidharanpillai, Sarita; Binitha, Manikoth P; Manikath, Neeraj; Janardhanan, Anisha K
2015-01-01
Drug reaction with eosinophilia and systemic symptoms (DRESS) or drug hypersensitivity syndrome is considered as a severe cutaneous adverse drug reaction which is most commonly precipitated by aromatic anticonvulsants, lamotrigine, dapsone, allopurinol, minocycline, and salazopyrin. Its clinical manifestations are often variable. On rare occasions, it can present with only systemic involvement without any cutaneous features. A complete drug history is of paramount importance in making an early diagnosis. We report the case of a male patient who presented with fever, lymphadenopathy, hepatosplenomegaly, and hepatitis, 2 weeks after starting salazopyrin. The presence of atypical lymphocytes in the peripheral smear was indicative of a viral infection or a hematological dyscrasia. Bone marrow examination revealed a normocellular marrow with an increase in eosinophil precursors. Investigations for the common causes for fever and hepatitis were negative. The presence of eosinophilia, the temporal relationship of the symptoms with the initiation of treatment with salazopyrin, and the marked improvement on withdrawal of the drug along with the administration of systemic corticosteroids, were features consistent with the diagnosis of DRESS. With the incidence of this condition showing a rising trend, it is important for the clinician to be aware of its variable manifestations, as a delay in diagnosis and treatment can be fatal.
The history and contemporary challenges of the US Food and Drug Administration.
Borchers, Andrea T; Hagie, Frank; Keen, Carl L; Gershwin, M Eric
2007-01-01
The year 2006 marks the 100th anniversary of the regulatory agency now known as the US Food and Drug Administration (FDA), the first consumer protection agency of the federal government and arguably the most influential regulatory agency in the world. The FDA thus plays an integral role in the use of pharmaceuticals, not only in the United States but worldwide. The goal of this review was to present an overview of the FDA and place its current role in the perspectives of history and contemporary needs. Relevant materials for this review were identified through a search of the English-language literature indexed on MEDLINE (through 2006) using the main search terms United States Food and Drug Administration, FDA, history of the FDA, drug approvals, drug legislation, and FDA legislation. Results from the initial searches were then explored further. The statute that created the bureau which later became the FDA established this agency to prohibit interstate commerce of adulterated foods, drinks, and drugs. The Food, Drug, and Cosmetic Act that replaced it in 1938, and subsequent food and drug laws and amendments, expanded the FDA's responsibilities to cosmetics, medical devices, biological products, and radiation-emitting products. These amendments have also established the FDA as a mainly preventive regulatory agency that relies chiefly on pre-market control. As such, the FDA has played an important role in shaping the modern pharmaceutical industry by making the scientific approach and the clinical trial process the standard for establishing safety and efficacy and by making rigorous scientific analysis the predominant component of the process for pharmaceutical regulation. As shown in this review, the evolution of the FDA can be described as a series of "crisis-legislation-adaptation" cycles: a public health crisis promoted the passage of congressional legislation, which was then followed by implementation of the law by the FDA. However, the crises the FDA faces
Understanding land administration systems
DEFF Research Database (Denmark)
P. Williamson, Ian; Enemark, Stig; Wallace, Judy
2008-01-01
This paper introduces basic land administration theory and highlights four key concepts that are fundamental to understanding modern land administration systems - firstly the land management paradigm and its influence on the land administration framework, secondly the role that the cadastre plays...... in contributing to sustainable development, thirdly the changing nature of ownership and the role of land markets, and lastly a land management vision that promotes land administration in support of sustainable development and spatial enablement of society. We present here the first part of the paper. The second...
Application of three-dimensional printing for colon targeted drug delivery systems.
Charbe, Nitin B; McCarron, Paul A; Lane, Majella E; Tambuwala, Murtaza M
2017-01-01
Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems.
Drug delivery systems based on biocompatible imino-chitosan hydrogels for local anticancer therapy.
Ailincai, Daniela; Tartau Mititelu, Liliana; Marin, Luminita
2018-11-01
A series of drug delivery systems were prepared by chitosan hydrogelation with citral in the presence of an antineoplastic drug: 5-fluorouracil. The dynamic covalent chemistry of the imine linkage allowed the obtaining of supramolecular tridimensional architectures in which the drug has been homogenously dispersed. Fourier-transform infrared spectroscopy (FTIR), wide-angle X-ray diffraction (WXRD) and polarized light microscopy (POM) measurements were used in order to follow the hydrogelation and drug encapsulation processes. The ability of the prepared systems to release the drug has been investigated by UV-Vis spectroscopy using a calibration curve and by fitting the results with different mathematic models. To mimic the behavior of the hydrogel matrix in bio-environmental conditions in view of applications, their enzymatic degradability was monitored in the presence of lysozyme. The in vivo side effects of the systems, in terms of their influence on the blood elements, biochemical and immune parameters were monitored on white Swiss mice by intraperitoneal administration of the injectable obtained hydrogels. All the characteristics of the obtained systems, such as micro-porous morphology, uniform drug encapsulation, enzymatic degradability, lack of side effects, other than the one of the drug itself, along with their ability to release the drug in a sustained manner proved that these material meet the requirements for the development of drug delivery systems, making them suitable for being applied in intraperitoneal chemotherapy.
Directory of Open Access Journals (Sweden)
Fulvio ePlescia
2013-06-01
Full Text Available Increasing evidence focuses on acetaldehyde (ACD as the mediator of the rewarding and motivational properties of ethanol. Indeed, ACD stimulates dopamine release in the nucleus accumbens and it is self-administered under different conditions. Besides the dopaminergic transmission, the endocannabinoid system has been reported to play an important role in ethanol central effects, modulating primary alcohol rewarding effect, drug-seeking and relapse behaviour. Drug motivational properties are highlighted in operant paradigms which include response-contingent punishment, a behavioural equivalent of compulsive drug use despite adverse consequences.The aim of this study was thus to characterize ACD motivational and rewarding properties employing an operant-conflict paradigm in which rats, trained to lever press in order to get ACD solution (0.9%, undergo extinction, reinstatement and conflict sessions, according to a modified Geller-Seifter procedur. Furthermore the role played by CB1 receptor system in modulating ACD-induced effects were investigated through the administration of CB1 receptor antagonist, AM281 (1 mg/kg, i.p. during the extinction-, relapse- and conflict experiments.Our results indicate that ACD is able to induce and maintain an operant behaviour, a high number of responses during extinction, an increase in the lever presses during the reinstatement phase, and a higher emission of punished responses during the conflict experiments, when compared to controls.The administration of AM281 is able to decrease ACD-seeking behaviour during extinction, the number of lever presses during reinstatement and to strongly decrease the punished responses for ACD. Our data strengthen the idea that ACD may be responsible for the central effects of ethanol, and pinpoint at the CB1 system as one of the neural substrates underlying its addictive properties.
Understanding land administration systems
DEFF Research Database (Denmark)
P. Williamson, Ian; Enemark, Stig; Wallace, Judy
2008-01-01
This paper introduces basic land administration theory and highlights four key concepts that are fundamental to understanding modern land administration systems. Readers may recall the first part of the paper in October issue of Coordinates. Here is the concluding part that focuses on the changing...
[Professional practice evaluation of injectable drug preparation and administration in neonatology].
Morin, P; Guillois, B; Gloanec, L; Chatelier, N; Saint-Lorant, G
2017-09-01
Adverse drug events are a daily concern in neonatology departments. The aim of this study was to assess the professional practices of preparation and administration of injectable forms of medications in neonatology. A professional practice evaluation with regard to the preparation and administration of various injectable forms of medications in different neonatology units within a given department was conducted by a pharmacy intern based on an assessment grid comprising ten criteria. Following an initial assessment, the results were presented to the care team, which validated the corrective measures put forward by a multiprofessional work group. A second assessment was conducted following the same methodology. Fifty of the department's 76 pediatric nurses were assessed during the first round of the audit and 21 during the second round. Two improvement priorities were identified: taking account of the dead volume of medication in needles and syringe hubs, together with complete identification of syringes used to administer medication. During the second round, these two aspects were improved, progressing from 38% to 100% and from 59% to 89%, respectively. To improve drug administration in neonatology and consequently, to improve patient safety, professional practice evaluation is an essential tool that requires close collaboration between the paramedical team, physicians and pharmacists. Its main value lies in the mobilization of the entire team around the subject in question, hence generating improved understanding and application of corrective measures. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
LeBlanc, Kimberly H; Maidment, Nigel T; Ostlund, Sean B
2014-11-01
The incentive sensitization theory of addiction posits that repeated exposure to drugs of abuse, like cocaine, can lead to long-term adaptations in the neural circuits that support motivated behavior, providing an account of pathological drug-seeking behavior. Although pre-clinical findings provide strong support for this theory, much remains unknown about the conditions that support incentive sensitization. The current study examined whether the mode of cocaine administration is an important factor governing that drug's long-term impact on behavior. Separate groups of rats were allowed either to self-administer intravenous cocaine or were given an equivalent number and distribution of unsignaled cocaine or saline infusions. During the subsequent test of incentive motivation (Pavlovian-to-instrumental transfer), we found that rats with a history of cocaine self-administration showed strong cue-evoked food seeking, in contrast to rats given unsignaled cocaine or saline. This finding indicates that the manner in which cocaine is administered can determine its lasting behavioral effects, suggesting that subjective experiences during drug use play a critical role in the addiction process. Our findings may therefore have important implications for the study and treatment of compulsive drug seeking. © 2013 Society for the Study of Addiction.
Bartel, Sylvia B; Tyler, Timothy G; Power, Luci A
2018-02-15
Results of a study to evaluate the effectiveness of a recently introduced closed system drug-transfer device (CSTD) in reducing surface contamination during compounding and simulated administration of antineoplastic hazardous drugs (AHDs) are reported. Wipe samples were collected from 6 predetermined surfaces in compounding and infusion areas of 13 U.S. cancer centers to establish preexisting levels of surface contamination by 2 marker AHDs (cyclophosphamide and fluorouracil). Stainless steel templates were placed over the 6 previously sampled surfaces, and the marker drugs were compounded and infused per a specific protocol using all components of the CSTD. Wipe samples were collected from the templates after completion of tasks and analyzed for both marker AHDs. Aggregated results of wipe sampling to detect preexisting contamination at the 13 study sites showed that overall, 66.7% of samples (104 of 156) had detectable levels of at least 1 marker AHD; subsequent testing after CSTD use per protocol found a sample contamination rate of 5.8% (9 of 156 samples). In the administration areas alone, the rate of preexisting contamination was 78% (61 of 78 samples); with use of the CSTD protocol, the contamination rate was 2.6%. Twenty-six participants rated the CSTD for ease of use, with 100% indicating that they were satisfied or extremely satisfied. A study involving a rigorous protocol and 13 cancer centers across the United States demonstrated that the CSTD reduced surface contamination by cyclophosphamide and fluorouracil during compounding and simulated administration. Participants reported that the CSTD was easy to use. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.
3D printed drug delivery and testing systems - a passing fad or the future?
Lim, Seng Han; Kathuria, Himanshu; Tan, Justin Jia Yao; Kang, Lifeng
2018-05-18
The US Food and Drug Administration approval of the first 3D printed tablet in 2015 has ignited growing interest in 3D printing, or additive manufacturing (AM), for drug delivery and testing systems. Beyond just a novel method for rapid prototyping, AM provides key advantages over traditional manufacturing of drug delivery and testing systems. These includes the ability to fabricate complex geometries to achieve variable drug release kinetics; ease of personalising pharmacotherapy for patient and lowering the cost for fabricating personalised dosages. Furthermore, AM allows fabrication of complex and micron-sized tissue scaffolds and models for drug testing systems that closely resemble in vivo conditions. However, there are several limitations such as regulatory concerns that may impede the progression to market. Here, we provide an overview of the advantages of AM drug delivery and testing, as compared to traditional manufacturing techniques. Also, we discuss the key challenges and future directions for AM enabled pharmaceutical applications. Copyright © 2018 Elsevier B.V. All rights reserved.
Date, Abhijit A.; Long, Julie M.; Nochii, Tomonori; Belshan, Michael; Shibata, Annemarie; Vincent, Heather; Baker, Caroline E.; Thayer, William O.; Kraus, Guenter; Lachaud-Durand, Sophie; Williams, Peter; Destache, Christopher J.; Garcia, J. Victor
2015-01-01
Vaginal HIV transmission accounts for the majority of new infections worldwide. Currently, multiple efforts to prevent HIV transmission are based on pre-exposure prophylaxis with various antiretroviral drugs. Here, we describe two novel nanoformulations of the reverse transcriptase inhibitor rilpivirine for pericoital and coitus-independent HIV prevention. Topically applied rilpivirine, encapsulated in PLGA nanoparticles, was delivered in a thermosensitive gel, which becomes solid at body temperature. PLGA nanoparticles with encapsulated rilpivirine coated the reproductive tract and offered significant protection to BLT humanized mice from a vaginal high-dose HIV-1 challenge. A different nanosuspension of crystalline rilpivirine (RPV LA), administered intramuscularly, protected BLT mice from a single vaginal high-dose HIV-1 challenge one week after drug administration. Using transmitted/founder viruses, which were previously shown to establish de novo infection in humans, we demonstrated that RPV LA offers significant protection from two consecutive high-dose HIV-1 challenges one and four weeks after drug administration. In this experiment, we also showed that, in certain cases, even in the presence of drug, HIV infection could occur without overt or detectable systemic replication until levels of drug were reduced. We also showed that infection in the presence of drug can result in acquisition of multiple viruses after subsequent exposures. These observations have important implications for the implementation of long-acting antiretroviral formulations for HIV prevention. They provide first evidence that occult infections can occur, despite the presence of sustained levels of antiretroviral drugs. Together, our results demonstrate that topically- or systemically administered rilpivirine offers significant coitus-dependent or coitus-independent protection from HIV infection. PMID:26271040
[Drug delivery systems using nano-sized drug carriers].
Nakayama, Masamichi; Okano, Teruo
2005-07-01
Nanotechnology has attracted great attention all over the world in recent several years and has led to the establishment of the novel technical field of "nanomedicine" through collaboration with advanced medical technology. Particularly, site-specific drug targeting using particle drug carrier systems has made substantial progress and been actively developed. This review explains the essential factors (size and chemical character) of drug carriers to allow long circulation in the bloodstream avoiding the reticuloendothelial system, and shows the present status and future perspective of several types of nano-carrier systems (water-soluble polymer, liposome and polymeric micelle). We also introduce the novel concept of multi-targeting system (combination of two or more targeting methodologies) for ideal drug therapies.
Stevens, Jasper; Suidgeest, Ernst; van der Graaf, Piet Hein; Danhof, Meindert; de Lange, Elizabeth C M
2009-08-01
To develop a new minimal-stress model for intranasal administration in freely moving rats and to evaluate in this model the brain distribution of acetaminophen following intranasal versus intravenous administration. Male Wistar rats received one intranasal cannula, an intra-cerebral microdialysis probe, and two blood cannulas for drug administration and serial blood sampling respectively. To evaluate this novel model, the following experiments were conducted. 1) Evans Blue was administered to verify the selectivity of intranasal exposure. 2) During a 1 min infusion 10, 20, or 40 microl saline was administered intranasally or 250 microl intravenously. Corticosterone plasma concentrations over time were compared as biomarkers for stress. 3) 200 microg of the model drug acetaminophen was given in identical setup and plasma, and brain pharmacokinetics were determined. In 96% of the rats, only the targeted nasal cavity was deeply colored. Corticosterone plasma concentrations were not influenced, neither by route nor volume of administration. Pharmacokinetics of acetaminophen were identical after intravenous and intranasal administration, although the Cmax in microdialysates was reached a little earlier following intravenous administration. A new minimal-stress model for intranasal administration in freely moving rats has been successfully developed and allows direct comparison with intravenous administration.
Supersaturating drug delivery systems
DEFF Research Database (Denmark)
Laitinen, Riikka; Löbmann, Korbinian; Grohganz, Holger
2017-01-01
of the bioavailability of poorly water-soluble drugs by increasing the driving force for drug absorption. However, ASDs often require a high weight percentage of carrier (usually a hydrophilic polymer) to ensure molecular mixing of the drug in the carrier and stabilization of the supersaturated state, often leading......Amorphous solid dispersions (ASDs) are probably the most common and important supersaturating drug delivery systems for the formulation of poorly water-soluble compounds. These delivery systems are able to achieve and maintain a sustained drug supersaturation which enables improvement...... strategy for poorly-soluble drugs. While the current research on co-amorphous formulations is focused on preparation and characterization of these systems, more detailed research on their supersaturation and precipitation behavior and the effect of co-formers on nucleation and crystal growth inhibition...
DEFF Research Database (Denmark)
Abrams, J K; Johnson, P L; Hay-Schmidt, Anders
2005-01-01
Serotonergic systems play important roles in modulating behavioral arousal, including behavioral arousal and vigilance associated with anxiety states. To further our understanding of the neural systems associated with increases in anxiety states, we investigated the effects of multiple anxiogenic...... and vigilance behaviors consistent with an increase in anxiety state. In addition, these anxiogenic drugs, excluding yohimbine, had convergent actions on an anatomically-defined subset of serotonergic neurons within the middle and caudal, dorsal subdivision of the DR. High resolution topographical analysis...... nucleus, a forebrain structure important for emotional appraisal and modulation of anxiety-related physiological and behavioral responses. Together these findings support the hypothesis that there is a functional topographical organization in the DR and are consistent with the hypothesis that anxiogenic...
DEFF Research Database (Denmark)
Chu, Brian K.; Deming, Michael; Biritwum, Nana-Kwadwo
2013-01-01
Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached...
2012-02-23
...] Draft Guidance for Industry: Food and Drug Administration Records Access Authority Under the Federal... industry entitled ``FDA Records Access Authority Under Sections 414 and 704 of the Federal Food, Drug...). This updated draft guidance is intended to provide individuals in the human and animal food industries...
Self-Micro Emulsifying Drug Delivery Systems: a Strategy to Improve Oral Bioavailability
Directory of Open Access Journals (Sweden)
Vijay K. Sharma
Full Text Available Aim: Oral route has always been the favorite route of drug administration in many diseases and till today it is the first way investigated in the development of new dosage forms. The major problem in oral drug formulations is low and erratic bioavailability, which mainly results from poor aqueous solubility, thereby pose problems in their formulation. For the therapeutic delivery of lipophilic active moieties (BCS class II drugs, lipid based formulations are inviting increasing attention. Methods: To that aim, from the web sites of PubMed, HCAplus, Thomson, and Registry were used as the main sources to perform the search for the most significant research articles published on the subject. The information was then carefully analyzed, highlighting the most important results in the formulation and development of self-micro emulsifying drug delivery systems as well as its therapeutic activity. Results: Self-emulsifying drug delivery system (SMEDDS has gained more attention due to enhanced oral bio-availability enabling reduction in dose, more consistent temporal profiles of drug absorption, selective targeting of drug(s toward specific absorption window in GIT, and protection of drug(s from the unreceptive environment in gut. Conclusions: This article gives a complete overview of SMEDDS as a promising approach to effectively deal with the problem of poorly soluble molecules.
PRESYNAPTIC DOPAMINE MODULATION BY STIMULANT SELF ADMINISTRATION
España, Rodrigo A.; Jones, Sara R.
2013-01-01
The mesolimbic dopamine system is an essential participant in the initiation and modulation of various forms of goal-directed behavior, including drug reinforcement and addiction processes. Dopamine neurotransmission is increased by acute administration of all drugs of abuse, including the stimulants cocaine and amphetamine. Chronic exposure to these drugs via voluntary self-administration provides a model of stimulant abuse that is useful in evaluating potential behavioral and neurochemical adaptations that occur during addiction. This review describes commonly used methodologies to measure dopamine and baseline parameters of presynaptic dopamine regulation, including exocytotic release and reuptake through the dopamine transporter in the nucleus accumbens core, as well as dramatic adaptations in dopamine neurotransmission and drug sensitivity that occur with acute non-contingent and chronic, contingent self-administration of cocaine and amphetamine. PMID:23277050
Clinical trials for vaccine development in registry of Korea Food and Drug Administration.
Kang, Seog-Youn
2013-01-01
Based on the action plan "Ensuring a stable supply of National Immunization Program vaccines and sovereignty of biopharmaceutical products," Korea Food and Drug Administration (KFDA) has made efforts to develop vaccines in the context of self reliance and to protect public health. Along with the recognized infrastructures for clinical trials, clinical trials for vaccines have also gradually been conducted at multinational sites as well as at local sites. KFDA will support to expand six to eleven kinds of vaccines by 2017. In accordance with integrated regulatory system, KFDA has promoted clinical trials, established national lot release procedure, and strengthened good manufacturing practices inspection and post marketing surveillance. Against this backdrop, KFDA will support the vaccine development and promote excellent public health protection.
Information in the system of state administration
Kalytych, G.; Litosh, G.
2009-01-01
The article analyses the approaches to the notions of "information", "state administration system", "administrative information". The article considers the importance of of information for the whole state administration system and reveals the criteria which provide the information with administrative status. Special attention is paid to making of administrative decisions on the level of the sate which are based on effective information management.
2012-08-27
... obtained. In recognition of the link between drug trafficking and many criminal organizations, the Attorney... to combat firearm-related violent crime. The nexus between drug trafficking and firearm violence is... Involved in Drug Offenses for Administrative Forfeiture (2012R-9P) AGENCY: Department of Justice. ACTION...
Mizokami, Fumihiro; Takahashi, Yoshiko; Hasegawa, Keiko; Hattori, Hideyuki; Nishihara, Keiji; Endo, Hidetoshi; Furuta, Katsunori; Isogai, Zenzo
2016-04-01
Drug-induced akinesia is a potential cause of pressure ulcers. However, pressure ulcers that are caused by drug-induced akinesia are not considered an adverse drug reaction (ADR). We propose that drug-induced pressure ulcers (DIPU) are pressure ulcers that are caused by an external force that is experienced after drug administration, and we considered resolution of these ulcers after drug discontinuation to be a supportive finding. In this report, we reviewed the medical records of pressure ulcer cases from a 300-bed hospital. Among 148 patients, four patients with pressure ulcers met the criterion for DIPU. In these cases, the suspected DIPU were related to treatment with olanzapine, fluvoxamine, valproic acid, clotiazepam, triazolam and rilmazafone. These drugs were administrated to manage the patients' behavioral and psychological symptoms that accompanied dementia. The DIPU in these patients were categorized as stage IV according to the National Pressure Ulcer Advisory Panel criteria. Discontinuation of the causal drugs led to significant improvements or complete healing of the pressure ulcers, and the patients subsequently recovered their mobility. Therefore, we propose that DIPU are potential ADR that have been overlooked in clinical practice. Thus, recognition of DIPU as an ADR may be important in preventing and appropriately managing pressure ulcers among elderly patients. © 2015 Japanese Dermatological Association.
The dopamine motive system: implications for drug and food addiction.
Volkow, Nora D; Wise, Roy A; Baler, Ruben
2017-11-16
Behaviours such as eating, copulating, defending oneself or taking addictive drugs begin with a motivation to initiate the behaviour. Both this motivational drive and the behaviours that follow are influenced by past and present experience with the reinforcing stimuli (such as drugs or energy-rich foods) that increase the likelihood and/or strength of the behavioural response (such as drug taking or overeating). At a cellular and circuit level, motivational drive is dependent on the concentration of extrasynaptic dopamine present in specific brain areas such as the striatum. Cues that predict a reinforcing stimulus also modulate extrasynaptic dopamine concentrations, energizing motivation. Repeated administration of the reinforcer (drugs, energy-rich foods) generates conditioned associations between the reinforcer and the predicting cues, which is accompanied by downregulated dopaminergic response to other incentives and downregulated capacity for top-down self-regulation, facilitating the emergence of impulsive and compulsive responses to food or drug cues. Thus, dopamine contributes to addiction and obesity through its differentiated roles in reinforcement, motivation and self-regulation, referred to here as the 'dopamine motive system', which, if compromised, can result in increased, habitual and inflexible responding. Thus, interventions to rebalance the dopamine motive system might have therapeutic potential for obesity and addiction.
Investigation of the mechanisms of action behind Electromotive Drug Administration (EMDA).
Kos, Bor; Vásquez, Juan Luis; Miklavčič, Damijan; Hermann, Gregers G G; Gehl, Julie
2016-01-01
Bladder cancer is a cause of considerable morbidity worldwide. Electromotive Drug Administration is a method that combines intravesical chemotherapy with local electric field application. Electroporation has been suggested among other mechanisms as having a possible role in the therapy, so the goal of the present study was to investigate the electric fields present in the bladder wall during the treatment to determine which mechanisms might be involved. Electromotive Drug Administration involves applying intravesical mitomycin C with direct current of 20 mA delivered through a catheter electrode for 30 min. For numerical electric field computation we built a 3-D nonhomogeneous patient specific model based on CT images and used finite element method simulations to determine the electric fields in the whole body. Results indicate that highest electric field in the bladder wall was 37.7 V/m. The mean electric field magnitude in the bladder wall was 3.03 V/m. The mean magnitude of the current density in the bladder wall was 0.61 A/m(2). The present study shows that electroporation is not the mechanism of action in EMDA. A more likely explanation of the mechanism of action is iontophoretic forces increasing the mitomycin C concentration in the bladder wall.
2012-08-20
... disability, please contact Cindy Garris, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, rm... that the implant must withstand and perform. Moreover, the optimal preclinical/bench testing paradigm...
Dry powder inhalers for pulmonary drug delivery
Frijlink, H.W.; De Boer, A.H.
2004-01-01
The pulmonary route is an interesting route for drug administration, both for effective local therapy (asthma, chronic obstructive pulmonary disease or cystic fibrosis) and for the systemic administration of drugs (e.g., peptides and proteins). Well-designed dry powder inhalers are highly efficient
2011-12-20
..., electronic record requirements, and investigator initiated research. Topics for discussion include the...] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical... Clinical Research Associates (SoCRA), is announcing a public workshop. The public workshop on FDA's...
2013-02-08
...] Draft Guidance for Industry and Food and Drug Administration Staff; Civil Money Penalties for Tobacco... guidance for industry entitled ``Civil Money Penalties for Tobacco Retailers: Responses to Frequently Asked... civil money penalties for violations of regulations issued under the Federal Food, Drug, and Cosmetic...
2013-12-04
...] Guidance for Industry and Food and Drug Administration Staff; Civil Money Penalties for Tobacco Retailers... the guidance entitled ``Civil Money Penalties for Tobacco Retailers: Responses to Frequently Asked... issuance of civil money penalties for violations of regulations issued under the Federal Food, Drug, and...
Adverse drug reaction and concepts of drug safety in Ayurveda: An overview
Ajanal, Manjunath; Nayak, Shradda; Prasad, Buduru Sreenivasa; Kadam, Avinash
2013-01-01
Drug safety is a very basic and fundamental concept in medical practice. ADRs play an important role in assessing patient safety in any system of medicine. Pharmacovigilance study is thus significant to understand treatment outcomes. Current raised issue with respect to complementary and alternative system medicine (CAM) like Ayurveda is increased in number of safety reports along with report misinterpretation; this generates the negative impact on system. Although, Ayurveda which is holistic system of medicine from India has elaborated the causes and methods of drug-induced consequences along with preventive measures the available data in classical texts is scattered. The compilation and analysis along with modern concept drug safety is need of the hour. Present literature review was conducted from various compendium of Ayurveda and electronic data base with search terms of ‘Vyapad’, ‘Viruddha’, ‘Ahita’, ‘herb–herb interaction’, ‘idiosyncrasy’, ‘Prakritiviruddha’ etc. The reported information was analysed for the possible correlation on concept of ADR and Pharmacovigilance of current science. Overall review demonstrated that drug interaction, iatrogenic, over dose, administration of unsuitable drugs, reprehensive drug administration with respect to disease, complication from five procedural therapies (Panchakarma) and reprehensible preparation of mineral drug are nearer to the modern causes of ADR. Thus, concept of drug safety and ADR is not new to the Ayurveda. The concept “Drug which is not appropriate to be used as medicine”(Abheshaja) of Ayurveda sounds similar as that of modern pharmacovigilance. PMID:24563588
2010-03-25
... requirements, and investigator initiated research. Topics for discussion include the following: (1) What FDA...] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical... Society of Clinical Research Associates, Inc. (SoCRA) is announcing a public workshop entitled ``FDA...
2012-02-15
..., electronic record requirements, and investigator initiated research. Topics for discussion include the...] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical... Research Associates (SoCRA) is announcing a public workshop. The public workshop on FDA's clinical trial...
UNIX and Linux system administration handbook
Nemeth, Evi; Hein, Trent R; Whaley, Ben; Mackin, Dan; Garnett, James; Branca, Fabrizio; Mouat, Adrian
2018-01-01
Now fully updated for today’s Linux distributions and cloud environments, it details best practices for every facet of system administration, including storage management, network design and administration, web hosting and scale-out, automation, configuration management, performance analysis, virtualization, DNS, security, management of IT service organizations, and much more. For modern system and network administrators, this edition contains indispensable new coverage of cloud deployments, continuous delivery, Docker and other containerization solutions, and much more.
López, Cristina; García, Juan José; Sierra, Matilde; Diez, María José; Pérez, Claudia; Sahagún, Ana Maria; Fernández, Nélida
2015-04-09
Mastitis is one of the most important diseases affecting dairy sheep. Antimicrobial drugs are often administered directly through teat to treat or prevent this disease, but data on drug distribution within glandular tissue are scarce and it cannot be estimated from concentrations in milk. Thus, the aim of this study was to investigate systemic and mammary gland distribution of enrofloxacin after intramammary administration. The drug was administered to 6 healthy lactating Assaf sheep with an injector containing an enrofloxacin preparation (1 g drug/5 g ointment). Blood samples were collected at 0, 30, 60, 90, 120, 150 and 180 min. Animals were then sedated and sacrificed, and glandular tissue samples were obtained from treated udders at 2, 4, 6 and 8 cm height. Enrofloxacin concentrations were measured in plasma and tissue samples by UV high-performed liquid chromatography. Mean enrofloxacin plasma concentrations were below 0.5 μg/mL. Mean tissue concentrations decreased in mammary gland with vertical distance from the teat, ranging from 356.6 μg/g at 2 cm to 95.60 μg/g at the base of the udder. Glandular tissue concentrations best fitted to a decreasing monoexponential model, and showed a good correlation with an ex vivo model previously developed. Enrofloxacin concentrations were effective in the entire glandular tissue against the main pathogens causing mastitis in sheep. These results suggest that this drug may be suitable to treat mastitis in sheep by intramammary administration.
Microcontainers for Intestinal Drug Delivery
DEFF Research Database (Denmark)
Tentor, Fabio; Mazzoni, Chiara; Keller, Stephan Sylvest
Among all the drug administration routes, the oral one is the most preferred by the patients being less invasive, faster and easier. Oral drug delivery systems designed to target the intestine are produced by powder technology and capsule formulations. Those systems including micro- and nano...
Gargiulo, Derryn A; Mitchell, Simon J; Sheridan, Janie; Short, Timothy G; Swift, Simon; Torrie, Jane; Webster, Craig S; Merry, Alan F
2016-04-01
The aseptic techniques of anesthesiologists in the preparation and administration of injected medications have not been extensively investigated, but emerging data demonstrate that inadvertent lapses in aseptic technique may be an important contributor to surgical site and other postoperative infections. A prospective, open, microbiological audit of 303 cases in which anesthesiologists were asked to inject all bolus drugs, except propofol and antibiotics, through a 0.2-µm filter was performed. The authors cultured microorganisms, if present, from the 0.2-µm filter unit and from the residual contents of the syringes used for drawing up or administering drugs. Participating anesthesiologists rated ease of use of the filters after each case. Twenty-three anesthesiologists each anesthetized up to 25 adult patients. The authors isolated microorganisms from filter units in 19 (6.3%) of 300 cases (3 cases were excluded), including Staphylococcus capitis, Staphylococcus warneri, Staphylococcus epidermidis, Staphylococcus haemolyticus, Micrococcus luteus/lylae, Corynebacterium, and Bacillus species. The authors collected used syringes at the end of each case and grew microorganisms from residual drug in 55 of these 2,318 (2.4%) syringes including all the aforementioned microorganisms and also Kocuria kristinae, Staphylococcus aureus, and Staphylococcus hominus. Participants' average rating of ease of use of the filter units was 3.5 out of 10 (0 being very easy and 10 being very difficult). Microorganisms with the potential to cause infection are being injected (presumably inadvertently) into some patients during the administration of intravenous drugs by bolus during anesthesia. The relevance of this finding to postoperative infections warrants further investigation.
Ma, Jing; Kim, Jooho; Almanza, Barbara
2017-06-01
The Food and Drug Administration publishes the Food Code to guide restaurant inspections. The most recent version proposes a three-tier system categorizing violations as priority, priority foundation, and core. This study used a scenario-based questionnaire to examine inspector perceptions and preferences for inspection formats. Results suggest that inspectors would be able to maintain consistent evaluations when changing to the three-tier system, although the classifying terms under the three-tier system were confusing. Additionally, inspectors were not very positive about the new system; they were concerned that the new system would not be easy to understand and use, inspections would take a longer time, it would not accurately reflect the amount of risk associated with violations, and it would not be easy for consumers and managers to understand and use. The results suggest the need for additional training for inspectors before adoption, especially on the rationale and benefits of changing to a three-tier system.
2011-04-11
...: Linda C. Ulrich, Office of Orphan Products Development, Food and Drug Administration, 10903 New... projects through the development process, including product identification, prototype design, device...
Dominguez Álvarez, Rocío; Calderón Carrasco, Justo; García Colchero, Francisco; Postigo Mota, Salvador; Alburquerque Medina, Eulalia
2015-01-01
To achieve well-being in patients in Palliative Care is required to know which are the most common symptoms, which are the drugs used for relief, which are the routes of administration of drugs that are suitable, how effective the drugs are and what incompatibilities, interactions and adverse effects occur. The aim of this article is to review the relevant issues in the management of the drugs commonly used by nursing in Palliative Care and presenting recommendations to clinical practice. Management interventions drugs for nurses in Palliative Care recommended by the scientific literature after a search of Scopus, CINAHL, Medline, PubMed, UpToDate and Google Scholar are selected. The oral route is the choice for patients in palliative situation and subcutaneous route when the first is not available. The symptoms, complex, intense and moody, should be systematically reevaluated by the nurse, to predict when a possible decompensation of it needing extra dose of medication. Nurses must be able to recognize the imbalance of well-being and act quickly and effectively, to get relief to some unpleasant situations for the patient as the pain symptoms, dyspnea or delirium. For the proper administration of rescue medication, the nurse should know the methods of symptomatic evaluation, pharmacokinetics and pharmacodynamics of drugs, the time intervals to elapse between different rescues and nccocc rocnnnco t thocm
Directory of Open Access Journals (Sweden)
William J Kisoka
Full Text Available BACKGROUND: In most countries of Sub-Saharan Africa, control of lymphatic filariasis (LF is based on annual mass drug administration (MDA with a combination of ivermectin and albendazole. Treatment coverages are however often suboptimal for programmes to reach the goal of transmission interruption within reasonable time. The present study aimed to identify predictors and barriers to individual drug uptake during MDA implementation by the National LF Elimination Programme in Tanzania. METHODS: A questionnaire based cross sectional household survey was carried out in two rural and two urban districts in Lindi and Morogoro regions shortly after the 2011 MDA. 3279 adults (≥15 years were interviewed about personal characteristics, socio-economic status, MDA drug uptake among themselves and their children, reasons for taking/not taking drugs, and participation in previous MDA activities for LF control. FINDINGS: The overall drug uptake rate was 55.1% (range of 44.5-75.6% between districts. There was no overall major difference between children (54.8% and adults (55.2% or between females (54.9% and males (55.8%, but the role of these and other predictors varied to some extent between study sites. Major overall predictors of drug uptake among the interviewed adults were increasing age and history of previous drug uptake. Being absent from home during drug distribution was the main reason for not taking the drugs (50.2% followed by clinical contraindications to treatment (10.8%, missing household visits of drug distributors (10.6%, and households not being informed about the distribution (9.0%. CONCLUSION: Drug uptake relied more on easily modifiable provider-related factors than on individual perceptions and practices in the target population. Limited investments in appropriate timing, dissemination of accurate timing information to recipients and motivation of drug distributors to visit all households (repeatedly when residents are absent are likely
2011-08-17
... requirements, and investigator initiated research. Topics for discussion include the following: (1) What FDA...] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical... Clinical Research Associates (SoCRA) is announcing a public workshop. The public workshop on FDA's clinical...
Green, Dionna J; Liu, Xiaomei I; Hua, Tianyi; Burnham, Janelle M; Schuck, Robert; Pacanowski, Michael; Yao, Lynne; McCune, Susan K; Burckart, Gilbert J; Zineh, Issam
2017-12-08
Clinical trial enrichment involves prospectively incorporating trial design elements that increase the probability of detecting a treatment effect. The use of enrichment strategies in pediatric drug development has not been systematically assessed. We analyzed the use of enrichment strategies in pediatric trials submitted to the US Food and Drug Administration from 2012-2016. In all, 112 efficacy studies associated with 76 drug development programs were assessed and their overall success rates were 78% and 75%, respectively. Eighty-eight trials (76.8%) employed at least one enrichment strategy; of these, 66.3% employed multiple enrichment strategies. The highest trial success rates were achieved when all three enrichment strategies (practical, predictive, and prognostic) were used together within a single trial (87.5%), while the lowest success rate was observed when no enrichment strategy was used (65.4%). The use of enrichment strategies in pediatric trials was found to be associated with trial and program success in our analysis. © 2017 American Society for Clinical Pharmacology and Therapeutics.
Microfluidic Devices for Drug Delivery Systems and Drug Screening
Kompella, Uday B.; Damiati, Safa A.
2018-01-01
Microfluidic devices present unique advantages for the development of efficient drug carrier particles, cell-free protein synthesis systems, and rapid techniques for direct drug screening. Compared to bulk methods, by efficiently controlling the geometries of the fabricated chip and the flow rates of multiphase fluids, microfluidic technology enables the generation of highly stable, uniform, monodispersed particles with higher encapsulation efficiency. Since the existing preclinical models are inefficient drug screens for predicting clinical outcomes, microfluidic platforms might offer a more rapid and cost-effective alternative. Compared to 2D cell culture systems and in vivo animal models, microfluidic 3D platforms mimic the in vivo cell systems in a simple, inexpensive manner, which allows high throughput and multiplexed drug screening at the cell, organ, and whole-body levels. In this review, the generation of appropriate drug or gene carriers including different particle types using different configurations of microfluidic devices is highlighted. Additionally, this paper discusses the emergence of fabricated microfluidic cell-free protein synthesis systems for potential use at point of care as well as cell-, organ-, and human-on-a-chip models as smart, sensitive, and reproducible platforms, allowing the investigation of the effects of drugs under conditions imitating the biological system. PMID:29462948
Popilski, Hen; Stepensky, David
2015-05-01
Solid tumors are characterized by complex morphology. Numerous factors relating to the composition of the cells and tumor stroma, vascularization and drainage of fluids affect the local microenvironment within a specific location inside the tumor. As a result, the intratumoral drug/drug delivery system (DDS) disposition following systemic or local administration is non-homogeneous and its complexity reflects the differences in the local microenvironment. Mathematical models can be used to analyze the intratumoral drug/DDS disposition and pharmacological effects and to assist in choice of optimal anticancer treatment strategies. The mathematical models that have been applied by different research groups to describe the intratumoral disposition of anticancer drugs/DDSs are summarized in this article. The properties of these models and of their suitability for prediction of the drug/DDS intratumoral disposition and pharmacological effects are reviewed. Currently available mathematical models appear to neglect some of the major factors that govern the drug/DDS intratumoral disposition, and apparently possess limited prediction capabilities. More sophisticated and detailed mathematical models and their extensive validation are needed for reliable prediction of different treatment scenarios and for optimization of drug treatment in the individual cancer patients.
Singh, Bhupinder; Bandopadhyay, Shantanu; Kapil, Rishi; Singh, Ramandeep; Katare, O
2009-01-01
Self-emulsifying drug delivery systems (SEDDS) possess unparalleled potential in improving oral bioavailability of poorly water-soluble drugs. Following their oral administration, these systems rapidly disperse in gastrointestinal fluids, yielding micro- or nanoemulsions containing the solubilized drug. Owing to its miniscule globule size, the micro/nanoemulsifed drug can easily be absorbed through lymphatic pathways, bypassing the hepatic first-pass effect. We present an exhaustive and updated account of numerous literature reports and patents on diverse types of self-emulsifying drug formulations, with emphasis on their formulation, characterization, and systematic optimization strategies. Recent advancements in various methodologies employed to characterize their globule size and shape, ability to encapsulate the drug, gastrointestinal and thermodynamic stability, rheological characteristics, and so forth, are discussed comprehensively to guide the formula-tor in preparing an effective and robust SEDDS formulation. Also, this exhaustive review offers an explicit discussion on vital applications of the SEDDS in bioavailability enhancement of various drugs, outlining an overview on myriad in vitro, in situ, and ex vivo techniques to assess the absorption and/ or permeation potential of drugs incorporated in the SEDDS in animal and cell line models, and the subsequent absorption pathways followed by them. In short, the current article furnishes an updated compilation of wide-ranging information on all the requisite vistas of the self-emulsifying formulations, thus paving the way for accelerated progress into the SEDDS application in pharmaceutical research.
Directory of Open Access Journals (Sweden)
Mayank Sharma
2016-01-01
Full Text Available Oral administration is the most convenient route among various routes of drug delivery as it offers high patient compliance. However, the poor aqueous solubility and poor enzymatic/metabolic stability of drugs are major limitations in successful oral drug delivery. There are several approaches to improve problems related to hydrophobic drugs. Among various approaches, nanotechnology based drug delivery system has potential to overcome the challenges associated with the oral route of administration. Novel drug delivery systems are available in many areas of medicine. The application of these systems in the treatment of hypertension continues to broaden. The present review focuses on various nanocarriers available in oral drug administration for improving solubility profile, dissolution, and consequently bioavailability of hydrophobic antihypertensive drugs.
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.
2012-08-09
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001... include an update on the FDA Safety and Innovation Act (Pub. L. 112-144) and an overview of FDA's Network... liaison between FDA Centers and the public on matters that involve medical product safety and also acts as...
Panchagnula, R; Bansal, T; Varma, M V S; Kaul, C L
2005-12-01
P-Glycoprotein (P-gp) mediated efflux is recognized as a significant biochemical barrier affecting oral absorption for a number of drugs. Various conflicting reports have been published regarding the effects of grapefruit juice (GFJ) on P-gp-mediated drug efflux, in which GFJ has been shown both to inhibit and activate it. Hence, the present study adopted a two-way approach, involving both co-treatment and chronic administration. Bi-directional transport of paclitaxel (PCL) was carried out in the absence and presence of GFJ extract, in rat everted ileum sac. Further, the effect of chronic administration of GFJ to rats was characterized by permeability studies with indinavir (INDI). Co-treatment of GFJ extract at 100% concentration reduced the asymmetric transport of PCL (efflux ratio = 20.8) by increasing absorptive (A --> B) transport by 921% and reducing secretory (B --> A) transport by 41%. Further, GFJ showed a concentration dependent effect on PCL permeability. Imipramine, a passive permeability marker with absorptive permeability of 15.33 +/- 4.26 x 10(-6) cm/s showed no asymmetric transport and also no significant (P extract inhibited P-gp-mediated efflux in co-treatment, whereas chronic administration led to increased levels of P-gp expression, thus having a profound effect on intestinal absorption and GFJ-drug interactions in vivo.
Automated drug dispensing system reduces medication errors in an intensive care setting.
Chapuis, Claire; Roustit, Matthieu; Bal, Gaëlle; Schwebel, Carole; Pansu, Pascal; David-Tchouda, Sandra; Foroni, Luc; Calop, Jean; Timsit, Jean-François; Allenet, Benoît; Bosson, Jean-Luc; Bedouch, Pierrick
2010-12-01
We aimed to assess the impact of an automated dispensing system on the incidence of medication errors related to picking, preparation, and administration of drugs in a medical intensive care unit. We also evaluated the clinical significance of such errors and user satisfaction. Preintervention and postintervention study involving a control and an intervention medical intensive care unit. Two medical intensive care units in the same department of a 2,000-bed university hospital. Adult medical intensive care patients. After a 2-month observation period, we implemented an automated dispensing system in one of the units (study unit) chosen randomly, with the other unit being the control. The overall error rate was expressed as a percentage of total opportunities for error. The severity of errors was classified according to National Coordinating Council for Medication Error Reporting and Prevention categories by an expert committee. User satisfaction was assessed through self-administered questionnaires completed by nurses. A total of 1,476 medications for 115 patients were observed. After automated dispensing system implementation, we observed a reduced percentage of total opportunities for error in the study compared to the control unit (13.5% and 18.6%, respectively; perror (20.4% and 13.5%; perror showed a significant impact of the automated dispensing system in reducing preparation errors (perrors caused no harm (National Coordinating Council for Medication Error Reporting and Prevention category C). The automated dispensing system did not reduce errors causing harm. Finally, the mean for working conditions improved from 1.0±0.8 to 2.5±0.8 on the four-point Likert scale. The implementation of an automated dispensing system reduced overall medication errors related to picking, preparation, and administration of drugs in the intensive care unit. Furthermore, most nurses favored the new drug dispensation organization.
Lipid-based formulations for oral administration of poorly water-soluble drugs
DEFF Research Database (Denmark)
Mu, Huiling; Holm, René; Müllertz, Anette
2013-01-01
Lipid-based drug delivery systems have shown great potentials in oral delivery of poorly water-soluble drugs, primarily for lipophilic drugs, with several successfully marketed products. Pre-dissolving drugs in lipids, surfactants, or mixtures of lipids and surfactants omits the dissolving....../dissolution step, which is a potential rate limiting factor for oral absorption of poorly water-soluble drugs. Lipids not only vary in structures and physiochemical properties, but also in their digestibility and absorption pathway; therefore selection of lipid excipients and dosage form has a pronounced effect...
Debian 7 system administration best practices
Pollei, Rich
2013-01-01
A step-by-step, example-based guide to learning how to install and administer the Debian Linux distribution.Debian 7: System Administration Best Practices is for users and administrators who are new to Debian, or for seasoned administrators who are switching to Debian from another Linux distribution. A basic knowledge of Linux or UNIX systems is useful, but not strictly required. Since the book is a high level guide, the reader should be willing to go to the referenced material for further details and practical examples.
Chertok, Beata; David, Allan E; Yang, Victor C
2010-08-01
This study aimed to examine the applicability of polyethyleneimine (PEI)-modified magnetic nanoparticles (GPEI) as a potential vascular drug/gene carrier to brain tumors. In vitro, GPEI exhibited high cell association and low cell toxicity--properties which are highly desirable for intracellular drug/gene delivery. In addition, a high saturation magnetization of 93 emu/g Fe was expected to facilitate magnetic targeting of GPEI to brain tumor lesions. However, following intravenous administration, GPEI could not be magnetically accumulated in tumors of rats harboring orthotopic 9L-gliosarcomas due to its poor pharmacokinetic properties, reflected by a negligibly low plasma AUC of 12 +/- 3 microg Fe/ml min. To improve "passive" GPEI presentation to brain tumor vasculature for subsequent "active" magnetic capture, we examined the intra-carotid route as an alternative for nanoparticle administration. Intra-carotid administration in conjunction with magnetic targeting resulted in 30-fold (p=0.002) increase in tumor entrapment of GPEI compared to that seen with intravenous administration. In addition, magnetic accumulation of cationic GPEI (zeta-potential = + 37.2 mV) in tumor lesions was 5.2-fold higher (p=0.004) than that achieved with slightly anionic G100 (zeta-potential= -12 mV) following intra-carotid administration, while no significant accumulation difference was detected between the two types of nanoparticles in the contra-lateral brain (p=0.187). These promising results warrant further investigation of GPEI as a potential cell-permeable, magnetically-responsive platform for brain tumor delivery of drugs and genes. 2010 Elsevier Ltd. All rights reserved.
System Administrator for LCS Development Sets
Garcia, Aaron
2013-01-01
The Spaceport Command and Control System Project is creating a Checkout and Control System that will eventually launch the next generation of vehicles from Kennedy Space Center. KSC has a large set of Development and Operational equipment already deployed in several facilities, including the Launch Control Center, which requires support. The position of System Administrator will complete tasks across multiple platforms (Linux/Windows), many of them virtual. The Hardware Branch of the Control and Data Systems Division at the Kennedy Space Center uses system administrators for a variety of tasks. The position of system administrator comes with many responsibilities which include maintaining computer systems, repair or set up hardware, install software, create backups and recover drive images are a sample of jobs which one must complete. Other duties may include working with clients in person or over the phone and resolving their computer system needs. Training is a major part of learning how an organization functions and operates. Taking that into consideration, NASA is no exception. Training on how to better protect the NASA computer infrastructure will be a topic to learn, followed by NASA work polices. Attending meetings and discussing progress will be expected. A system administrator will have an account with root access. Root access gives a user full access to a computer system and or network. System admins can remove critical system files and recover files using a tape backup. Problem solving will be an important skill to develop in order to complete the many tasks.
2012-07-03
...] Guidances for Industry and Food and Drug Administration Staff: Computer-Assisted Detection Devices Applied... Clinical Performance Assessment: Considerations for Computer-Assisted Detection Devices Applied to... guidance, entitled ``Computer-Assisted Detection Devices Applied to Radiology Images and Radiology Device...
75 FR 4407 - Science Board to the Food and Drug Administration; Notice of Meeting
2010-01-27
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001... subcommittee reviewing research at the Center for Food Safety and Applied Nutrition. The Science Board will... person on or before Monday, February 15, 2010. Oral presentations from the public will be scheduled...
2013-02-26
... marketing applications, (2) what is meant by ``due diligence'' in obtaining financial disclosures from...: Financial Disclosure by Clinical Investigators; Availability AGENCY: Food and Drug Administration, HHS... guidance entitled ``Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by...
Holm, René; Porter, Christopher J H; Edwards, Glenn A; Müllertz, Anette; Kristensen, Henning G; Charman, William N
2003-09-01
The potential for lipidic self-microemulsifying drug delivery systems (SMEDDS) containing triglycerides with a defined structure, where the different fatty acids on the glycerol backbone exhibit different metabolic fate, to improve the lymphatic transport and the portal absorption of a poorly water-soluble drug, halofantrine, were investigated in fasted lymph cannulated canines. Two different structured triglycerides were incorporated into the SMEDDS; 1,3-dioctanoyl-2-linoleyl-sn-glycerol (C8:0-C18:2-C8:0) (MLM) and 1,3-dilinoyl-2-octanoyl-sn-glycerol (C18:2-C8:0-C18:2) (LML). A previously optimised SMEDDS formulation for halofantrine, comprising of triglyceride, Cremophor EL, Maisine 35-1 and ethanol was selected for bioavailability assessment. The extent of lymphatic transport via the thoracic duct was 17.9% of the dose for the animals dosed with the MLM SMEDDS and 27.4% for LML. Also the plasma availability was affected by the triglyceride incorporated into the multi-component delivery system and availabilities of 56.9% (MLM) and 37.2% (LML) were found. These data indicate that the pharmaceutical scientist can use the structure of the lipid to affect the relative contribution of the two absorption pathways. The MLM formulation produced a total bioavailability of 74.9%, which is higher than the total absorption previously observed after post-prandial administration. This could indicate the utility of disperse lipid-base formulations based on structured triglycerides for the oral delivery of halofantrine, and potentially other lipophilic drugs.
International Nuclear Information System (INIS)
1988-01-01
The FDA Compliance Program Guidance Manual provides a system for issuing and filing program plans and instructions directed to Food and Drug Administration Field operations for project implementation. Section IV provides those chapters of the Compliance Program Guidance Manual which pertain to the areas of medical and radiological devices. Some of the areas of coverage include laser and sunlamp standards inspections, compliance testing of various radiation-emitting products such as television receivers and microwave ovens, emergency response planning and policy, premarket approval and device manufacturers inspections, device problem reporting, sterilization of devices, and consumer education programs on medical and radiological devices
Abdikerimova, Aynur A.
2016-01-01
The purpose of the study is to determine the main contemporary development trends in administrative-legal relations in the field of administrative justice. In order to examine theoretical and practical issues of modern administrative justice, normative legal acts identifying the relations in the system of administrative justice in the Republic in…
Directory of Open Access Journals (Sweden)
Apurv Patel
2016-01-01
Full Text Available The objective of this work was design, characterization, and optimization of controlled drug delivery system containing antibiotic drug/s. Osmotic drug delivery system was chosen as controlled drug delivery system. The porous osmotic pump tablets were designed using Plackett-Burman and Box-Behnken factorial design to find out the best formulation. For screening of three categories of polymers, six independent variables were chosen for Plackett-Burman design. Osmotic agent sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate were chosen as independent variables. Optimization of osmotic tablets was done by Box-Behnken design by selecting three independent variables. Osmotic agent sodium chloride, pore forming agent sodium lauryl sulphate, and coating agent cellulose acetate were chosen as independent variables. The result of Plackett-Burman and Box-Behnken design and ANOVA studies revealed that osmotic agent and pore former had significant effect on the drug release up to 12 hr. The observed independent variables were found to be very close to predicted values of most satisfactory formulation which demonstrates the feasibility of the optimization procedure in successful development of porous osmotic pump tablets containing antibiotic drug/s by using sodium chloride, sodium lauryl sulphate, and cellulose acetate as key excipients.
Drug delivery and formulations.
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.
Bachu, Rinda Devi; Chowdhury, Pallabitha; Al-Saedi, Zahraa H. F.; Karla, Pradeep K.; Boddu, Sai H. S.
2018-01-01
Ocular drug delivery is challenging due to the presence of anatomical and physiological barriers. These barriers can affect drug entry into the eye following multiple routes of administration (e.g., topical, systemic, and injectable). Topical administration in the form of eye drops is preferred for treating anterior segment diseases, as it is convenient and provides local delivery of drugs. Major concerns with topical delivery include poor drug absorption and low bioavailability. To improve the bioavailability of topically administered drugs, novel drug delivery systems are being investigated. Nanocarrier delivery systems demonstrate enhanced drug permeation and prolonged drug release. This review provides an overview of ocular barriers to anterior segment delivery, along with ways to overcome these barriers using nanocarrier systems. The disposition of nanocarriers following topical administration, their safety, toxicity and clinical trials involving nanocarrier systems are also discussed. PMID:29495528
CSR, Inc., Washington, DC.
This handbook is for administrators of programs in higher education settings which deal with alcohol and other drug (AOD) related problems. Chapter 1, "Defining the Problem, Issues, and Trends" examines the problem from various perspectives and presents the latest statistics on the extent of AOD use on campuses, specific problems affecting…
ATLAS TDAQ System Administration:
Lee, Christopher Jon; The ATLAS collaboration; Bogdanchikov, Alexander; Ballestrero, Sergio; Contescu, Alexandru Cristian; Dubrov, Sergei; Fazio, Daniel; Korol, Aleksandr; Scannicchio, Diana; Twomey, Matthew Shaun; Voronkov, Artem
2015-01-01
The ATLAS Trigger and Data Acquisition (TDAQ) system is responsible for the online processing of live data, streaming from the ATLAS experiment at the Large Hadron Collider (LHC) at CERN. The online farm is composed of ̃3000 servers, processing the data readout from ̃100 million detector channels through multiple trigger levels. During the two years of the first Long Shutdown (LS1) there has been a tremendous amount of work done by the ATLAS TDAQ System Administrators, implementing numerous new software applications, upgrading the OS and the hardware, changing some design philosophies and exploiting the High Level Trigger farm with different purposes. During the data taking only critical security updates are applied and broken hardware is replaced to ensure a stable operational environment. The LS1 provided an excellent opportunity to look into new technologies and applications that would help to improve and streamline the daily tasks of not only the System Administrators, but also of the scientists who wil...
2012-08-16
... investigator initiated research. Topics for discussion include the following: (1) What FDA Expects in a...] Food and Drug Administration Clinical Trial Requirements, Compliance, and Good Clinical Practice...-sponsorship with the Society of Clinical Research Associates (SoCRA) is announcing a public workshop. The...
2011-07-01
...-mail: [email protected] . Grants Management Contact Gladys Melendez-Bohler, Office of..., MD 20857, Tele.: 301-827-7175; e-mail: Gladys[email protected] . For more information on...: Gladys Melendez-Bohler, Office of Acquisition and Grant Services (OAGS), Food and Drug Administration...
Ito, Yuta; Noda, Kentaro; Aiba, Keisuke; Yano, Shingo; Fujii, Tsunehiro
A 59-year-old female with diffuse large B-cell lymphoma was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) regimen. In addition, we administered pegfilgrastim for treating chemotherapy-induced febrile neutropenia. She complained of fever and neck and chest pain a few days after pegfilgrastim administration during the third and fourth courses of R-CHOP. Radiological imaging revealed an inflammation of large vessels, which led to the diagnosis of drug-associated vasculitis. We confirmed that vasculitis observed in this case was caused by pegfilgrastim administration because similar symptoms appeared with both injections of pegfilgrastim.
Su, Zu-In; Wenzel, Jennifer; Baird, Rebeccah; Ettenberg, Aaron
2011-04-01
Evidence suggests that responsiveness to a drug-paired cue is predicted by the reinforcing magnitude of the drug during prior self-administration. It remains unclear, however, if this principle holds true when comparisons are made across drug reinforcers. The current study was therefore devised to test the hypothesis that differences in the animals' responsiveness to a cocaine- or heroin-paired cue presented during extinction would reflect differences in the patterns of prior cocaine and heroin runway self-administration. Rats ran a straight alley for single intravenous injections of either heroin (0.1 mg/kg/inj) or cocaine (1.0 mg/kg/inj) each paired with a distinct olfactory cue. Animals experienced 15 trials with each drug reinforcer in a counterbalanced manner. Start latencies, run times, and retreat behaviors (a form of approach-avoidance conflict) provided behavioral indices of the subjects' motivation to seek the reinforcer on each trial. Responsiveness to each drug-paired cue was assessed after 7, 14, or 21 days of non-reinforced extinction trials. Other animals underwent conditioned place preference (CPP) testing to ensure that the two drug reinforcers were capable of producing drug-cue associations. While both drugs produced comparable CPPs, heroin served as a stronger incentive stimulus in the runway as evidenced by faster start and run times and fewer retreats. In contrast, cocaine- but not heroin-paired cues produced increases in drug-seeking behavior during subsequent extinction trials. The subjects' responsiveness to drug-paired cues during extinction was not predicted by differences in the motivation to seek heroin versus cocaine during prior drug self-administration.
Bashutski, Jill D; Kinney, Janet S; Benavides, Erika; Maitra, Samopriyo; Braun, Thomas M; Giannobile, William V; McCauley, Laurie K; Eber, Robert M
2012-05-01
Teriparatide comprises the first 34 amino acids of parathyroid hormone and is a systemic anabolic agent that is Food and Drug Administration approved for the treatment of osteoporosis but not for periodontitis. To our knowledge, this is the first clinical case report to document the treatment of a patient with severe periodontitis using an open-flap debridement procedure in conjunction with teriparatide. A 45-year-old female patient was diagnosed with severe chronic periodontitis, including the presence of an intrabony defect on tooth #6. She received open-flap debridement surgery in conjunction with daily systemic administration of 20 µg teriparatide, oral vitamin D, and calcium supplements for 6 weeks. Radiographic, clinical, gingival crevicular fluid (pyridinoline cross-linked carboxy-terminal propeptide of type I procollagen, procollagen type 1 N-propeptide, and osteocalcin), and serum parameters (parathyroid hormone, bone alkaline phosphatase, calcium, and 25-hydroxyvitamin D) were assessed. Treatment outcomes were evaluated over 4 years, with successful radiographic and clinical results throughout the follow-up period. Teriparatide administration in conjunction with traditional open-flap debridement surgery offers potential for the treatment of severe intrabony defects resulting from chronic periodontitis.
2013-09-25
... FDA intends to apply its regulatory oversight to only those mobile apps that are medical devices and...] Mobile Medical Applications; Guidance for Industry and Food and Drug Administration Staff; Availability...) is announcing the availability of the guidance entitled ``Mobile Medical Applications.'' The FDA is...
Adverse ocular reactions to drugs.
Spiteri, M. A.; James, D. G.
1983-01-01
Drugs acting on various parts of the body may also affect the eye insidiously. Increased awareness of such drug toxicity by the prescribing doctor should encourage him to consider effects on the cornea, lens, retina, optic nerve and elsewhere when checking the patient's progress. The following review concerns adverse ocular effects of systemic drug administration.
Immediate or deferred adjustment of drug regimens in multidose drug dispensing systems.
Mertens, Bram J; Kwint, Henk-Frans; van Marum, Rob J; Bouvy, Marcel L
2018-05-18
Multidose drug dispensing (MDD) is used to help patients take their medicines appropriately. Little is known about drug regimen changes within these MDD systems and how they are effectuated by the community pharmacist. Manual immediate adjustments of the MDD system could introduce dispensing errors. MDD guidelines therefore recommend to effectuate drug regimen changes at the start of a new MDD system. The aim of this study was to investigate the frequency, type, procedure followed, immediate necessity, and time taken to make MDD adjustments. This was a cross-sectional study in eight community pharmacies in the Netherlands. All adjustments to MDD systems were systematically documented for 3 weeks by the community pharmacist. Overall, 261 MDD adjustments involving 364 drug changes were documented for 250 patients: 127 (35%) drug changes involved the addition of a new drug, 124 (34%) a change in dosage, and 95 (26%) drug discontinuation. Of the MDD adjustments, 135 (52%) were effectuated immediately: 81 (31%) by adjusting the MDD system manually, 49 (19%) by temporarily dispensing the drug separately from the MDD system, and 5 (2%) by ordering a new MDD system. Pharmacists considered that 36 (27%) of the immediate MDD adjustments could have been deferred until the next MDD system was produced. Immediate adjustment took significantly longer than deferred adjustment (p < 0.001). This study shows that in patients using MDD systems, over half of the drug regimen changes are adjusted immediately. The necessity of these immediate changes should be critically evaluated. Copyright © 2018. Published by Elsevier Inc.
Regulatory aspects of teratology: role of the Food and Drug Administration
International Nuclear Information System (INIS)
Kelsey, F.O.
1982-01-01
The Food and Drug Administration is a scientific regulatory agency whose consumer protection activities cover a wide range of products including foods and additives, and pesticide residues on foods; drugs; cosmetics; medical devices; and radiation-emitting electronic products. Amongst its concerns is the possible teratogen effects of regulated products to which the pregnant woman is exposed. The policies and programs of the agency directed toward reducing such risks to the unborn are reviewed. These measures include guidelines for animal reproduction studies and for clinical trials involving women to childbearing potential; labeling of products to disclose known or possible harm to the fetus or embryo; surveillance procedures designed to detect previously unsuspected adverse effects of marketed products; research activities designed to develop better understanding of developmental toxicology and improved techniques for detecting embryocidal and embryotoxic effects; and educational efforts directed both to professionals and the public regarding hazards to the unborn of agency-regulated products
Masuda, Ikuya; Matsuo, Toshihiko; Okamoto, Kazuo; Matsushita, Kyoko; Ohtsuki, Hiroshi
2010-01-01
To report 2 cases of corneal perforation associated with the use of oral nonsteroidal anti-inflammatory drugs (NSAIDs). In a 62-year-old woman and a 79-year-old woman, corneal perforation occurred after 7 days and 5 months of oral NSAIDs administration, respectively. After NSAIDs were discontinued, the cornea epithelialized and the anterior chamber formed within 14 and 10 days, respectively. It is well known that topical NSAIDs cause corneal perforation. Observations in the present cases suggest that the oral administration of NSAIDs may also cause corneal damage, and hence, medical professionals should consider the risk of damage to the cornea when administering these drugs orally.
Jadhav, Pravin R; Neal, Lauren; Florian, Jeff; Chen, Ying; Naeger, Lisa; Robertson, Sarah; Soon, Guoxing; Birnkrant, Debra
2010-09-01
This article presents a prototype for an operational innovation in knowledge management (KM). These operational innovations are geared toward managing knowledge efficiently and accessing all available information by embracing advances in bioinformatics and allied fields. The specific components of the proposed KM system are (1) a database to archive hepatitis C virus (HCV) treatment data in a structured format and retrieve information in a query-capable manner and (2) an automated analysis tool to inform trial design elements for HCV drug development. The proposed framework is intended to benefit drug development by increasing efficiency of dose selection and improving the consistency of advice from US Food and Drug Administration (FDA). It is also hoped that the framework will encourage collaboration among FDA, industry, and academic scientists to guide the HCV drug development process using model-based quantitative analysis techniques.
Krishnan, Jishnu K S; Arun, Peethambaran; Chembukave, Bhadra; Appu, Abhilash P; Vijayakumar, Nivetha; Moffett, John R; Puthillathu, Narayanan; Namboodiri, Aryan M A
2017-07-15
The intranasal route of administration has proven to be an effective method for bypassing the blood brain barrier and avoiding first pass hepatic metabolism when targeting drugs to the brain. Most small molecules gain rapid access to CNS parenchyma when administered intranasally. However, bioavailability is affected by various factors ranging from the molecular weight of the drug to the mode of intranasal delivery. We examined the effects of animal posture, intranasal application method and animal weight and age on the delivery of radiolabeled pralidoxime ( 3 H-2-PAM) to the brain of rats. We found that using upright vs. supine posture did not significantly affect 3 H-2-PAM concentrations in different brain regions. Older animals with higher weights required increased doses to achieve the same drug concentration throughout the brain when compared to young animals with lower body weights. The use of an intranasal aerosol propelled delivery device mainly increased bioavailability in the olfactory bulbs, but did not reliably increase delivery of the drug to various other brain regions, and in some regions of the brain delivered less of the drug than simple pipette administration. In view of the emerging interest in the use of intranasal delivery of drugs to combat cognitive decline in old age, we tested effectiveness in very old rats and found the method to be as effective in the older rats. Copyright © 2017 Elsevier B.V. All rights reserved.
Muhič, Neža; Mrhar, Ales; Brvar, Miran
2017-07-01
Drug-drug interaction (DDI) screening systems report potential DDIs. This study aimed to find the prevalence of probable DDI-related adverse drug reactions (ADRs) and compare the clinical usefulness of different DDI screening systems to prevent or warn against these ADRs. A prospective cohort study was conducted in patients urgently admitted to medical departments. Potential DDIs were checked using Complete Drug Interaction®, Lexicomp® Online™, and Drug Interaction Checker®. The study team identified the patients with probable clinically relevant DDI-related ADRs on admission, the causality of which was assessed using the Drug Interaction Probability Scale (DIPS). Sensitivity, specificity, and positive and negative predictive values of screening systems to prevent or warn against probable DDI-related ADRs were evaluated. Overall, 50 probable clinically relevant DDI-related ADRs were found in 37 out of 795 included patients taking at least two drugs, most common of them were bleeding, hyperkalemia, digitalis toxicity, and hypotension. Complete Drug Interaction showed the best sensitivity (0.76) for actual DDI-related ADRs, followed by Lexicomp Online (0.50), and Drug Interaction Checker (0.40). Complete Drug Interaction and Drug Interaction Checker had positive predictive values of 0.07; Lexicomp Online had 0.04. We found no difference in specificity and negative predictive values among these systems. DDI screening systems differ significantly in their ability to detect probable clinically relevant DDI-related ADRs in terms of sensitivity and positive predictive value.
Peer influences on drug self-administration: an econometric analysis in socially housed rats.
Peitz, Geoffrey W; Strickland, Justin C; Pitts, Elizabeth G; Foley, Mark; Tonidandel, Scott; Smith, Mark A
2013-04-01
Social-learning theories of substance use propose that members of peer groups influence the drug use of other members by selectively modeling, reinforcing, and punishing either abstinence-related or drug-related behaviors. The objective of the present study was to examine the social influences on cocaine self-administration in isolated and socially housed rats, under conditions where the socially housed rats were tested simultaneously with their partner in the same chamber. To this end, male rats were obtained at weaning and housed in isolated or pair-housed conditions for 6 weeks. Rats were then implanted with intravenous catheters and cocaine self-administration was examined in custom-built operant conditioning chambers that allowed two rats to be tested simultaneously. For some socially housed subjects, both rats had simultaneous access to cocaine; for others, only one rat of the pair had access to cocaine. An econometric analysis was applied to the data, and the reinforcing strength of cocaine was measured by examining consumption (i.e. quantity demanded) and elasticity of demand as a function of price, which was manipulated by varying the dose and ratio requirements on a fixed ratio schedule of reinforcement. Cocaine consumption decreased as a function of price in all groups. Elasticity of demand did not vary across groups, but consumption was significantly lower in socially housed rats paired with a rat without access to cocaine. These data suggest that the presence of an abstaining peer decreases the reinforcing strength of cocaine, thus supporting the development of social interventions in drug abuse prevention and treatment programs.
CONTRACT ADMINISTRATIVE TRACKING SYSTEM (CATS)
The Contract Administrative Tracking System (CATS) was developed in response to an ORD NHEERL, Mid-Continent Ecology Division (MED)-recognized need for an automated tracking and retrieval system for Cost Reimbursable Level of Effort (CR/LOE) Contracts. CATS is an Oracle-based app...
Distributed Administrative Management Information System (DAMIS).
Juckiewicz, Robert; Kroculick, Joseph
Columbia University's major program to distribute its central administrative data processing to its various schools and departments is described. The Distributed Administrative Management Information System (DAMIS) will link every department and school within the university via micrcomputers, terminals, and/or minicomputers to the central…
Bioadhesive polymeric platforms for transmucosal drug delivery ...
African Journals Online (AJOL)
Bioadhesive polymeric platforms for transmucosal drug delivery systems – a review. ... administration of certain classes of drugs, especially peptides and proteins. ... characteristics of desired bioadhesive polymers, this article then proceeds to ...
The Research Progress of Targeted Drug Delivery Systems
Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie
2017-06-01
Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.
Drug resistance in leishmaniasis: current drug-delivery systems and future perspectives.
Yasinzai, Masoom; Khan, Momin; Nadhman, Akhtar; Shahnaz, Gul
2013-10-01
Leishmaniasis is a complex of diseases with numerous clinical manifestations for instance harshness from skin lesions to severe disfigurement and chronic systemic infection in the liver and spleen. So far, the most classical leishmaniasis therapy, despite its documented toxicities, remains pentavalent antimonial compounds. The arvailable therapeutic modalities for leishmaniasis are overwhelmed with resistance to leishmaniasis therapy. Mechanisms of classical drug resistance are often related with the lower drug uptake, increased efflux, the faster drug metabolism, drug target modifications and over-expression of drug transporters. The high prevalence of leishmaniasis and the appearance of resistance to classical drugs reveal the demand to develop and explore novel, less toxic, low cost and more promising therapeutic modalities. The review describes the mechanisms of classical drug resistance and potential drug targets in Leishmania infection. Moreover, current drug-delivery systems and future perspectives towards Leishmaniasis treatment are also covered.
Directory of Open Access Journals (Sweden)
O.K. Botvin’ev
2009-01-01
Full Text Available The microbial inflammatory diseases of urinary system in children can be often accompanied with fever and pain. The article presents an experience of ibuprofen (Nurofen for Children administration for the purpose of stopping fever and pain in 420 children in age 3 months — 3 years old with microbial inflammatory diseases of urinary system. The observation showed high effectiveness of short treatment with ibuprofen course (2–5 days. As clinical and laboratory observation showed, the short-termed administration of the drug was well-tolerated and did not cause significant adverse effects, excluding single cases of allergic rash and light dyspeptic disorders.Key words: children, microbial inflammatory diseases of urinary system, ibuprofen, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(5:84-87
A stochastic model for the probability of malaria extinction by mass drug administration.
Pemberton-Ross, Peter; Chitnis, Nakul; Pothin, Emilie; Smith, Thomas A
2017-09-18
Mass drug administration (MDA) has been proposed as an intervention to achieve local extinction of malaria. Although its effect on the reproduction number is short lived, extinction may subsequently occur in a small population due to stochastic fluctuations. This paper examines how the probability of stochastic extinction depends on population size, MDA coverage and the reproduction number under control, R c . A simple compartmental model is developed which is used to compute the probability of extinction using probability generating functions. The expected time to extinction in small populations after MDA for various scenarios in this model is calculated analytically. The results indicate that mass drug administration (Firstly, R c must be sustained at R c 95% to have a non-negligible probability of successful elimination. Stochastic fluctuations only significantly affect the probability of extinction in populations of about 1000 individuals or less. The expected time to extinction via stochastic fluctuation is less than 10 years only in populations less than about 150 individuals. Clustering of secondary infections and of MDA distribution both contribute positively to the potential probability of success, indicating that MDA would most effectively be administered at the household level. There are very limited circumstances in which MDA will lead to local malaria elimination with a substantial probability.
Formulation of Bioadhesive Carbomer Gel Incorporating Drug ...
African Journals Online (AJOL)
incorporated into carbomer gel and evaluated for drug release. Results: ... localized delivery system for the treatment inflammation and infection in periodontal pockets. ..... loaded with diclofenac sodium for intra- articular administration. J Drug ...
Smart Drug Delivery Systems in Cancer Therapy.
Unsoy, Gozde; Gunduz, Ufuk
2018-02-08
Smart nanocarriers have been designed for tissue-specific targeted drug delivery, sustained or triggered drug release and co-delivery of synergistic drug combinations to develop safer and more efficient therapeutics. Advances in drug delivery systems provide reduced side effects, longer circulation half-life and improved pharmacokinetics. Smart drug delivery systems have been achieved successfully in the case of cancer. These nanocarriers can serve as an intelligent system by considering the differences of tumor microenvironment from healthy tissue, such as low pH, low oxygen level, or high enzymatic activity of matrix metalloproteinases. The performance of anti-cancer agents used in cancer diagnosis and therapy is improved by enhanced cellular internalization of smart nanocarriers and controlled drug release. Here, we review targeting, cellular internalization; controlled drug release and toxicity of smart drug delivery systems. We are also emphasizing the stimulus responsive controlled drug release from smart nanocarriers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
2013-12-19
... 866-561-8558 (toll free). Food and beverages will be available for purchase by participants during the... accessible at http://www.regulations.gov . It may be viewed at the Division of Dockets Management, Food and... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001...
Vaginal drug delivery systems: A Review of Current Status | Dobaria ...
African Journals Online (AJOL)
Among the various routes of drug delivery, the vaginal route offers many advantages due to its large permeation area, rich vascularization, avoidance of first pass metabolism and relatively low enzymatic activity. Several studies have shown that the vaginal cavity is an effective route for drug administration intended mainly ...
A simple, rapid, and sensitive system for the evaluation of anti-viral drugs in rats
Energy Technology Data Exchange (ETDEWEB)
Li, Xiaoguang [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Department of Medical Microbiology, Harbin Medical University, Harbin 150086 (China); Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811 (Japan); Qian, Hua [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811 (Japan); Miyamoto, Fusako [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Naito, Takeshi [Laboratory of Virus Control, Institute for Virus Research, Kyoto University, 53 Kawaramachi, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Kawaji, Kumi [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Kajiwara, Kazumi [Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501 (Japan); JST Innovation Plaza Kyoto, Japan Science and Technology Agency, Nishigyo-ku, Kyoto 615-8245 (Japan); Hattori, Toshio [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Matsuoka, Masao [Laboratory of Virus Control, Institute for Virus Research, Kyoto University, 53 Kawaramachi, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Watanabe, Kentaro; Oishi, Shinya; Fujii, Nobutaka [Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501 (Japan); and others
2012-07-27
Highlights: Black-Right-Pointing-Pointer We established a novel, simple and rapid in vivo system for evaluation of anti-HIV-1 drugs with rats. Black-Right-Pointing-Pointer The system may be applicable for other antiviral drugs, and/or useful for initial screening in vivo. Black-Right-Pointing-Pointer In this system, TRI-1144 displayed the most potent anti-HIV-1 activity in vivo. -- Abstract: The lack of small animal models for the evaluation of anti-human immunodeficiency virus type 1 (HIV-1) agents hampers drug development. Here, we describe the establishment of a simple and rapid evaluation system in a rat model without animal infection facilities. After intraperitoneal administration of test drugs to rats, antiviral activity in the sera was examined by the MAGI assay. Recently developed inhibitors for HIV-1 entry, two CXCR4 antagonists, TF14016 and FC131, and four fusion inhibitors, T-20, T-20EK, SC29EK, and TRI-1144, were evaluated using HIV-1{sub IIIB} and HIV-1{sub BaL} as representative CXCR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1{sub IIIB} activity, whereas fusion inhibitors showed both anti-HIV-1{sub IIIB} and anti-HIV-1{sub BaL} activities in rat sera. These results indicate that test drugs were successfully processed into the rat sera and could be detected by the MAGI assay. In this system, TRI-1144 showed the most potent and sustained antiviral activity. Sera from animals not administered drugs showed substantial anti-HIV-1 activity, indicating that relatively high dose or activity of the test drugs might be needed. In conclusion, the novel rat system established here, 'phenotypic drug evaluation', may be applicable for the evaluation of various antiviral drugs in vivo.
A simple, rapid, and sensitive system for the evaluation of anti-viral drugs in rats
International Nuclear Information System (INIS)
Li, Xiaoguang; Qian, Hua; Miyamoto, Fusako; Naito, Takeshi; Kawaji, Kumi; Kajiwara, Kazumi; Hattori, Toshio; Matsuoka, Masao; Watanabe, Kentaro; Oishi, Shinya; Fujii, Nobutaka
2012-01-01
Highlights: ► We established a novel, simple and rapid in vivo system for evaluation of anti-HIV-1 drugs with rats. ► The system may be applicable for other antiviral drugs, and/or useful for initial screening in vivo. ► In this system, TRI-1144 displayed the most potent anti-HIV-1 activity in vivo. -- Abstract: The lack of small animal models for the evaluation of anti-human immunodeficiency virus type 1 (HIV-1) agents hampers drug development. Here, we describe the establishment of a simple and rapid evaluation system in a rat model without animal infection facilities. After intraperitoneal administration of test drugs to rats, antiviral activity in the sera was examined by the MAGI assay. Recently developed inhibitors for HIV-1 entry, two CXCR4 antagonists, TF14016 and FC131, and four fusion inhibitors, T-20, T-20EK, SC29EK, and TRI-1144, were evaluated using HIV-1 IIIB and HIV-1 BaL as representative CXCR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1 IIIB activity, whereas fusion inhibitors showed both anti-HIV-1 IIIB and anti-HIV-1 BaL activities in rat sera. These results indicate that test drugs were successfully processed into the rat sera and could be detected by the MAGI assay. In this system, TRI-1144 showed the most potent and sustained antiviral activity. Sera from animals not administered drugs showed substantial anti-HIV-1 activity, indicating that relatively high dose or activity of the test drugs might be needed. In conclusion, the novel rat system established here, “phenotypic drug evaluation”, may be applicable for the evaluation of various antiviral drugs in vivo.
2012-09-13
...] Food and Drug Administration/American Glaucoma Society Workshop on the Validity, Reliability, and... entitled ``FDA/American Glaucoma Society (AGS) Workshop on the Validity, Reliability, and Usability of... research. The purpose of this public workshop is to provide a forum for discussing the validity...
Fox, Helen C; Sinha, Rajita
2009-01-01
Extensive research indicates that chronic substance abuse disrupts stress and reward systems of the brain. Gender variation within these stress-system alterations, including the impact of sex hormones on these changes, may influence sex-specific differences in both the development of, and recovery from, dependency. As such, gender variations in stress-system function may also provide a viable explanation for why women are markedly more vulnerable than men to the negative consequences of drug use. This article therefore initially reviews studies that have examined gender differences in emotional and biophysiological changes to the stress and reward system following the acute administration of drugs, including cocaine, alcohol, and nicotine. The article then reviews studies that have examined gender differences in response to various types of stress in both healthy and drug-abusing populations. Studies examining the impact of sex hormones on these gender-related responses are also reported. The implications of these sex-specific variations in stress and reward system function are discussed in terms of both comorbid psychopathology and treatment outcome.
Macpherson, Eleanor E; Adams, Emily R; Bockarie, Moses J; Hollingsworth, T Deirdre; Kelly-Hope, Louise A; Lehane, Mike; Kovacic, Vanja; Harrison, Robert A; Paine, Mark Ji; Reimer, Lisa J; Torr, Stephen J
2015-01-01
Achieving the 2020 goals for Neglected Tropical Diseases (NTDs) requires scale-up of Mass Drug Administration (MDA) which will require long-term commitment of national and global financing partners, strengthening national capacity and, at the community level, systems to monitor and evaluate activities and impact. For some settings and diseases, MDA is not appropriate and alternative interventions are required. Operational research is necessary to identify how existing MDA networks can deliver this more complex range of interventions equitably. The final stages of the different global programmes to eliminate NTDs require eliminating foci of transmission which are likely to persist in complex and remote rural settings. Operational research is required to identify how current tools and practices might be adapted to locate and eliminate these hard-to-reach foci. Chronic disabilities caused by NTDs will persist after transmission of pathogens ceases. Development and delivery of sustainable services to reduce the NTD-related disability is an urgent public health priority. LSTM and its partners are world leaders in developing and delivering interventions to control vector-borne NTDs and malaria, particularly in hard-to-reach settings in Africa. Our experience, partnerships and research capacity allows us to serve as a hub for developing, supporting, monitoring and evaluating global programmes to eliminate NTDs.
Systems Pharmacology in Small Molecular Drug Discovery
Directory of Open Access Journals (Sweden)
Wei Zhou
2016-02-01
Full Text Available Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity, target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level.
Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery.
Szunerits, Sabine; Boukherroub, Rabah
2018-01-01
Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs), which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum , the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section "Frontiers in Bioengineering and Biotechnology," the advances in this field and the handful of
Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery
Directory of Open Access Journals (Sweden)
Priya Bawa
2011-12-01
Full Text Available Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments.
Bilayered buccal films as child-appropriate dosage form for systemic administration of propranolol.
Abruzzo, Angela; Nicoletta, Fiore Pasquale; Dalena, Francesco; Cerchiara, Teresa; Luppi, Barbara; Bigucci, Federica
2017-10-05
Buccal mucosa has emerged as an attractive site for systemic administration of drug in paediatric patients. This route is simple and non-invasive, even if the saliva wash-out effect and the relative permeability of the mucosa can reduce drug absorption. Mucoadhesive polymers represent a common employed strategy to increase the contact time of the formulation at the application site and to improve drug absorption. Among the different mucoadhesive dosage forms, buccal films are particularly addressed for paediatric population since they are thin, adaptable to the mucosal surface and able to offer an exact and flexible dose. The objective of the present study was to develop bilayered buccal films for the release of propranolol hydrochloride. A primary polymeric layer was prepared by casting and drying of solutions of film-forming polymers, such as polyvinylpyrrolidone (PVP) or polyvinylalcohol (PVA), added with different weight ratios of gelatin (GEL) or chitosan (CH). In order to achieve unidirectional drug delivery towards buccal mucosa, a secondary ethylcellulose layer was applied onto the primary layer. Bilayered films were characterized for their physico-chemical (morphology, thickness, drug content and solid state) and functional (water uptake, mucoadhesion, drug release and permeation) properties. The inclusion of CH into PVP and PVA primary layer provided the best mucoadhesion ability. Films containing CH provided a lower drug release with respect to films containing GEL and increased the amount of permeated drug through buccal mucosa, thanks to its ability of interfering with the lipid organization. The secondary ethylcellulose layer did not interfere with drug permeation, but it could limit drug release in the buccal cavity. Copyright © 2017 Elsevier B.V. All rights reserved.
2010-11-30
... the program expansion including the availability of appropriate staff and sufficient funding. 4. The...] Supplemental Funding Under the Food and Drug Administration's Convener of Active Medical Product Surveillance... expansion of its Conference Cooperative Agreement Program (U13), awarded to the Engelberg Center for Health...
Influence of mianserin on the activity of some hypotensive drugs in spontaneously hypertensive rats.
Górska, Dorota; Andrzejczak, Dariusz
2003-01-01
Mianserin might be an alternative drug in patients with depression accompanied by hypertension because of its effectiveness and lack of side effects in the circulatory system. However, a few studies reported in literature show influence of the drug on blood pressure. We investigate interactions between mianserin and commonly used hypotensive drugs (propranolol, enalapril and prazosin) in spontaneously hypertensive rats (SHR). The experiments were performed in two experimental designs: a single administration of both mianserin and a hypotensive drug, and repeated administration of mianserin with a single administration of a hypotensive drug. Arterial blood pressure was measured by bloodless method with manometer made by LETICA. A single administration of mianserin caused a statistically significant decrease in systolic, diastolic and mean blood pressure in the 60th minute of observation and intensified hypotensive effect of prazosin. However, long-term administration of mianserin in SHR rats had no significant influence on arterial blood pressure. Chronic and single administration of mianserin with propranolol or enalapril did not influence the circulatory system. A long-term administration of mianserin intensified the hypotensive effect of prazosin. This interaction might suggest possibility of dangerous complications in the treatment of humans with this drug combination.
Parker, Melissa; Allen, Tim
2013-07-01
This article documents understandings and responses to mass drug administration (MDA) for the treatment and prevention of lymphatic filariasis among adults and children in northern coastal Tanzania from 2004 to 2011. Assessment of village-level distribution registers, combined with self-reported drug uptake surveys of adults, participant observation and interviews, revealed that at study sites in Pangani and Muheza districts the uptake of drugs was persistently low. The majority of people living at these highly endemic locations either did not receive or actively rejected free treatment. A combination of social, economic and political reasons explain the low uptake of drugs. These include a fear of treatment (attributable, in part, to a lack of trust in international aid and a questioning of the motives behind the distribution); divergence between biomedical and local understandings of lymphatic filariasis; and limited and ineffective communication about the rationale for mass treatment. Other contributory factors are the reliance upon volunteers for distribution within villages and, in some locations, strained relationships between different groups of people within villages as well as between local leaders and government officials. The article also highlights a disjuncture between self-reported uptake of drugs by adults at a village level and the higher uptake of drugs recorded in official reports. The latter informs claims that elimination will be a possibility by 2020. This gives voice to a broader problem: there is considerable pressure for those implementing MDA to report positive results. The very real challenges of making MDA work are pushed to one side - adding to a rhetoric of success at the expense of engaging with local realities. It is vital to address the kind of issues raised in this article if current attempts to eliminate lymphatic filariasis in mainland coastal Tanzania are to achieve their goal.
VETSTAT - the Danish system for surveillance of the veterinary use of drugs for production animals
DEFF Research Database (Denmark)
Stege, H.; Bager, Flemming; Jacobsen, Erik
2003-01-01
The Danish Ministry of Food, Agriculture and Fisheries funds a monitoring system based on drug usage information collected at the herd level: VETSTAT. VETSTAT is constructed as a relational database and data originates from three sources: pharmacies, veterinarians and feed mills. All administration...... of drugs for use in animal production is reported on a monthly basis. Pharmacies provided 95% of the total weight antimicrobial compounds used in Denmark in 2001. More than 80% of the antimicrobial compounds reported by pharmacies were sold on prescription to end-users (owners) and included information...
Nasa-wide Standard Administrative Systems
Schneck, P.
1984-01-01
Factors to be considered in developing agency-wide standard administrative systems for NASA include uniformity of hardware and software; centralization vs. decentralization; risk exposure; and models for software development.
Hwang, Thomas J; Avorn, Jerry; Carpenter, Daniel; Kesselheim, Aaron S
2014-02-01
The Food and Drug Administration (FDA) frequently uses its rulemaking process to establish or modify the way it regulates drugs, medical devices, and other medical products. The federal agency's rulemaking is controversial because of its perceived complexity, lack of transparency, and lengthy duration. To shed light on the FDA's rulemaking process, we examined the evolution of significant rules that the agency published during 2000-12 for drugs, devices, and other medical products. We found that the rules' median time to finalization was 7.3 years, with the pre-rule phase and postreview deliberation within the FDA accounting for the majority of that time. Rules that involved mandatory cost-benefit analyses were associated with an additional delay of approximately two years. We also found that longer review times were significantly associated with a reduction in the stringency of final rules, compared to the originally proposed versions. We recommend improving FDA's rulemaking by allocating additional resources to increase efficiency and by embarking on initiatives to promote transparency by the FDA and other parts of the executive branch.
Microcontainers - an oral drug delivery system for poorly soluble drugs
DEFF Research Database (Denmark)
Nielsen, Line Hagner; Petersen, Ritika Singh; Marizza, Paolo
In oral delivery, it can sometimes be necessary to employ drug delivery systems to achieve targeted delivery to the intestine. Microcontainers are polymeric, cylindrical devices in the micrometer size range (Figure 1), and are suggested as a promising oral drug delivery system [1],[2]. The purpose...... of these studies was to fabricate microcontainers in either SU-8 or biodegradable poly-L-lactic acid (PLLA), and fill the microcontainers with poorly soluble drugs. Furthermore, the application of the microcontainers as an oral drug delivery system was investigated in terms of release, in situ intestinal perfusion...... medium at pH 6.5 was observed. In situ intestinal perfusions were performed in rats of the Eudragit-coated ASSF-filled microcontainers and compared to a furosemide solution. At the end of the study, the small intestine was harvested from the rat and imaged under a light microscope. The absorption rate...
Python for Unix and Linux system administration
Gift, Noah
2007-01-01
Python is an ideal language for solving problems, especially in Linux and Unix networks. With this pragmatic book, administrators can review various tasks that often occur in the management of these systems, and learn how Python can provide a more efficient and less painful way to handle them. Each chapter in Python for Unix and Linux System Administration presents a particular administrative issue, such as concurrency or data backup, and presents Python solutions through hands-on examples. Once you finish this book, you'll be able to develop your own set of command-line utilities with Pytho
Blundell, M; Dargan, P; Wood, D
2018-01-01
There is limited published scientific data on vaping recreational drugs other than cannabis. A recent review suggested that 15% of people vaping cannabis have also vaped a synthetic cannabinoid receptor agonist (SCRA) and identified over 300 Internet reports of e-liquid manufacture of recreational drugs and/or new psychoactive substances (NPS). To determine the prevalence of use of electronic vaping devices for recreational drug and NPS delivery in the UK. A voluntary online survey using a convenience sample of UK adult participants (aged 16 years old and over) identified by a market research company. Data was collected regarding demographics, smoking history, electronic vaping device history and recreational drug/NPS use and route of administration. There were 2501 respondents. The mean (±SD) age was 46.2 ± 16.8 years old. The commonest lifetime recreational drug used was Cannabis (818, 32.7%). The majority of respondents had smoked (1545, 61.8%) with 731 (29.2%) being current smokers. The most commonly used SCRA product was 'Spice Gold' (173, 6.9%) and SCRA compound was ADB-CHMICA (48, 1.9%). 861 (34.4%) had used an electronic vaping device; 340 (13.6%) having used them for recreational drug administration; 236 (9.4%) reporting current use. The commonest lifetime recreational drug to be vaped was cannabis (155, 65.7%), with electronic cigarettes (230, 48.2%) being the commonest reported route of SCRA compound administration. 9.4% of respondents currently use electronic vaping devices for recreational drug administration with 6.2% reporting lifetime cannabis vaping use. Further larger scale studies are required to help inform the appropriate treatment and primary prevention strategies. © The Author 2017. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com
Expert Systems in Government Administration
Weintraub, Joseph
1989-01-01
Artificial Intelligence is solving more and more real world problems, but penetration into the complexities of government administration has been minimal. The author suggests that combining expert system technology with conventional procedural computer systems can lead to substantial efficiencies. Business rules can be removed from business-oriented computer systems and stored in a separate but integrated knowledge base, where maintenance will be centralized. Fourteen specific practical appli...
Integrated system for error prevention in process of drugs used in oncology
International Nuclear Information System (INIS)
Soriano Garcia, Jorge L; Lima Perez, Mayte; Gonzalez Gonzalez, Joaquin; Batista Albuerne, Noyde; Rodriguez Lopez, Roberto; Garcia Dieguez, Robin; Gonzalez Duennas, Marta; Ugando, Elizabeth
2007-01-01
Medication mistakes in case of chemotherapy or adjuvant treatment used in any stage of drug application process: prescription, transcription, preparation, dispense or administration, are a frequent cause of side effects of antineoplastic drugs. (Author)
Preparation of Simvastatin Hydrogel through Arginine Addition for Drug Delivery System
Directory of Open Access Journals (Sweden)
Rosyida Niswati Fathmah
2018-01-01
Full Text Available Simvastatin is a lipid lowering agent which has been used recently as drug delivery system for stimulating bone regeneration. Because of low therapeutic efficacy and bioavailability, it is necessary to deliver simvastatin by local administration e.g. by hydrogel system. However, simvastatin has very poor solubility which restricts to prepare hydrogel formulation. The aim of this study is to improve solubility of simvastatin with arginine as co-solvent for developing a controlled released drug delivery system by loading simvastatin into gelatin hydrogel. The solubility study was performed by addition of an excess mass of simvastatin into the specified molar solutions of the arginine. All conical flasks were placed in a mechanical water bath shaker at the temperature of 25, 40, and 50 °C and shaken for a maximum period of 72 hours. The drug concentration was analyzed by UV/Visible spectroscopy at 238 nm. The hydrogel was prepared by a dehydrothermal method. The results showed that simvastatin solubility increases with increasing arginine concentrations and temperature. Characterizations showed a successful preparation of simvastatin-loaded gelatin hydrogel. The arginine simvastatin hydrogel and the gelatin hydrogel (as a blank exhibited a comparable swelling index (ca. 6.5. Furthermore, microparticles of the material show a narrow particle size distribution in the range between 150-250 μm.
75 FR 32482 - Investigational New Drug Applications; Co-development of Investigational Drugs
2010-06-08
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0247] Investigational New Drug Applications; Co-development of Investigational Drugs AGENCY: Food and Drug Administration, HHS. ACTION: Notice; establishment of docket; request for comments. SUMMARY: The Food and Drug...
2013-06-07
... adhesive label to assist the office in processing your requests. The guidance may also be obtained by mail... and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. FOR FURTHER INFORMATION... June 2013. FDA is providing this final guidance document to assist industry in developing technical and...
Yung-Yi Cheng; Chen-Hsi Hsieh; Tung-Hu Tsai
2018-01-01
With an increasing number of cancer patients seeking an improved quality of life, complementary and alternative therapies are becoming more common ways to achieve such improvements. The potential risks of concurrent administration are serious and must be addressed. However, comprehensive evidence for the risks and benefits of combining anticancer drugs with traditional herbs is rare. Pharmacokinetic investigations are an efficient way to understand the influence of concomitant remedies. There...
Formulation and development of a self-nanoemulsifying drug delivery system of irbesartan
Directory of Open Access Journals (Sweden)
Jaydeep Patel
2011-01-01
Full Text Available Irbesartan (IRB is an angiotensin II receptor blocker antihypertensive agent. The aim of the present investigation was to develop a self-nanoemulsifying drug delivery system (SNEDDS to enhance the oral bioavailability of poorly water-soluble IRB. The solubility of IRB in various oils was determined to identify the oil phase of SNEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify the selected oil. Pseudoternary phase diagrams were constructed to identify the efficient self-emulsifying region. The optimized SNEDDS formulation contained IRB (75 mg, Cremophor® EL (43.33%, Carbitol® (21.67% and Capryol® 90 (32%. SNEDDS was further evaluated for its percentage transmittance, emulsification time, drug content, phase separation, dilution, droplet size and zeta potential. The optimized formulation of IRB-loaded SNEDDS exhibited complete in vitro drug release in 15 min as compared with the plain drug, which had a limited dissolution rate. It was also compared with the pure drug solution by oral administration in male Wister rats. The in vivo study exhibited a 7.5-fold increase in the oral bioavailability of IRB from SNEDDS compared with the pure drug solution. These results suggest the potential use of SNEDDS to improve dissolution and oral bioavailability of poorly water-soluble IRB.
A REVIEW ON OSMOTIC DRUG DELIVERY SYSTEM
Harnish Patel; Upendra Patel; Hiren Kadikar; Bhavin Bhimani; Dhiren Daslaniya; Ghanshyam Patel
2012-01-01
Conventional oral drug delivery systems supply an instantaneous release of drug, which cannot control the release of the drug and effective concentration at the target site. This kind of dosing pattern may result in constantly changing, unpredictable plasma concentrations. Drugs can be delivered in a controlled pattern over a long period of time by the process of osmosis. Osmotic devices are the most promising strategy based systems for controlled drug delivery. They are the most reliable con...
Tsujimura, Takanori; Sakai, Shogo; Suzuki, Taku; Ujihara, Izumi; Tsuji, Kojun; Magara, Jin; Canning, Brendan J; Inoue, Makoto
2017-05-01
Dysphagia is caused not only by neurological and/or structural damage but also by medication. We hypothesized memantine, dextromethorphan, diazepam, and baclofen, all commonly used drugs with central sites of action, may regulate swallowing function. Swallows were evoked by upper airway (UA)/pharyngeal distension, punctate mechanical stimulation using a von Frey filament, capsaicin or distilled water (DW) applied topically to the vocal folds, and electrical stimulation of a superior laryngeal nerve (SLN) in anesthetized rats and were documented by recording electromyographic activation of the suprahyoid and thyrohyoid muscles and by visualizing laryngeal elevation. The effects of intraperitoneal or topical administration of each drug on swallowing function were studied. Systemic administration of diazepam and baclofen, but not memantine or dextromethorphan, inhibited swallowing evoked by mechanical, chemical, and electrical stimulation. Both benzodiazepines and GABA A receptor antagonists diminished the inhibitory effects of diazepam, whereas a GABA B receptor antagonist diminished the effects of baclofen. Topically applied diazepam or baclofen had no effect on swallowing. These data indicate that diazepam and baclofen act centrally to inhibit swallowing in anesthetized rats. NEW & NOTEWORTHY Systemic administration of diazepam and baclofen, but not memantine or dextromethorphan, inhibited swallowing evoked by mechanical, chemical, and electrical stimulation. Both benzodiazepines and GABA A receptor antagonists diminished the inhibitory effects of diazepam, whereas a GABA B receptor antagonist diminished the effects of baclofen. Topical applied diazepam or baclofen was without effect on swallowing. Diazepam and baclofen act centrally to inhibit swallowing in anesthetized rats. Copyright © 2017 the American Physiological Society.
Directory of Open Access Journals (Sweden)
Wei Xu
2013-01-01
Full Text Available Oral administration is the most commonly used and readily accepted form of drug delivery; however, it is find that many drugs are difficult to attain enough bioavailability when administered via this route. Polymeric micelles (PMs can overcome some limitations of the oral delivery acting as carriers able to enhance drug absorption, by providing (1 protection of the loaded drug from the harsh environment of the GI tract, (2 release of the drug in a controlled manner at target sites, (3 prolongation of the residence time in the gut by mucoadhesion, and (4 inhibition of efflux pumps to improve the drug accumulation. To explain the mechanisms for enhancement of oral bioavailability, we discussed the special stability of PMs, the controlled release properties of pH-sensitive PMs, the prolongation of residence time with mucoadhesive PMs, and the P-gp inhibitors commonly used in PMs, respectively. The primary purpose of this paper is to illustrate the potential of PMs for delivery of poorly water-soluble drugs with bioavailability being well maintained.
Lammers, Laureen A; Achterbergh, Roos; van Schaik, Ron H N; Romijn, Johannes A; Mathôt, Ron A A
2017-10-01
Short-term fasting can alter drug exposure but it is unknown whether this is an effect of altered oral bioavailability and/or systemic clearance. Therefore, the aim of our study was to assess the effect of short-term fasting on oral bioavailability and systemic clearance of different drugs. In a randomized, controlled, crossover trial, 12 healthy subjects received a single administration of a cytochrome P450 (CYP) probe cocktail, consisting of caffeine (CYP1A2), metoprolol (CYP2D6), midazolam (CYP3A4), omeprazole (CYP2C19) and warfarin (CYP2C9), on four occasions: an oral (1) and intravenous (2) administration after an overnight fast (control) and an oral (3) and intravenous (4) administration after 36 h of fasting. Pharmacokinetic parameters of the probe drugs were analyzed using the nonlinear mixed-effects modeling software NONMEM. Short-term fasting increased systemic caffeine clearance by 17% (p = 0.04) and metoprolol clearance by 13% (p < 0.01), whereas S-warfarin clearance decreased by 19% (p < 0.01). Fasting did not affect bioavailability. The study demonstrates that short-term fasting alters CYP-mediated drug metabolism in a non-uniform pattern without affecting oral bioavailability.
Hertel, Moritz; Schmidt-Westhausen, Andrea Maria; Strietzel, Frank-Peter
2016-09-01
In order to identify oral candidiasis patients being at risk of carrying potentially drug-resistant Candida, the aim of the study was to detect local, systemic, demographic, and health-related factors influencing (I) yeast spectrum composition and (II) antifungal administration frequency. Additionally, the aim was to investigate (III) species shift occurrence. Data from 798 patients (496 females, 302 males; mean age 59.7) with oral candidiasis diagnosed based on positive clinical and microbial findings (species identification and CFU count) between 2006 and 2011 were retrospectively analyzed using Pearson's chi(2) test and regression analysis. Among 958 isolates, Candida albicans was the most frequently detected (76.8 %). Also, species intrinsically resistant to azoles were frequently isolated (15.8 and 17.7 % of isolates and patients). (I) Infections only caused by C. albicans were significantly associated with the use of inhalation steroids (p = 0.001) and antibiotics (p = 0.04), super-infection of lichen planus (p = 0.002), and the absence of removable dentures (p oral candidiasis remains C. albicans. Nevertheless, therapeutic problems may be caused by the frequent presence of species intrinsically resistant to azoles, especially in patients wearing dentures.
Changes in the equine fecal microbiota associated with the use of systemic antimicrobial drugs.
Costa, Marcio C; Stämpfli, Henry R; Arroyo, Luis G; Allen-Vercoe, Emma; Gomes, Roberta G; Weese, J Scott
2015-02-03
The intestinal tract is a rich and complex environment and its microbiota has been shown to have an important role in health and disease in the host. Several factors can cause disruption of the normal intestinal microbiota, including antimicrobial therapy, which is an important cause of diarrhea in horses. This study aimed to characterize changes in the fecal bacterial populations of healthy horses associated with the administration of frequently used antimicrobial drugs. Twenty-four adult mares were assigned to receive procaine penicillin intramuscularly (IM), ceftiofur sodium IM, trimethoprim sulfadiazine (TMS) orally or to a control group. Treatment was given for 5 consecutive days and fecal samples were collected before drug administration (Day 1), at the end of treatment (Days 5), and on Days 14 and 30 of the trial. High throughput sequencing of the V4 region of the 16S rRNA gene was performed using an Illumina MiSeq sequencer. Significant changes of population structure and community membership were observed after the use of all drugs. TMS caused the most marked changes on fecal microbiota even at higher taxonomic levels including a significant decrease of richness and diversity. Those changes were mainly due to a drastic decrease of Verrucomicrobia, specifically the "5 genus incertae sedis". Changes in structure and membership caused by antimicrobial administration were specific for each drug and may be predictable. Twenty-five days after the end of treatment, bacterial profiles were more similar to pre-treatment patterns indicating a recovery from changes caused by antimicrobial administration, but differences were still evident, especially regarding community membership. The use of systemic antimicrobials leads to changes in the intestinal microbiota, with different and specific responses to different antimicrobials. All antimicrobials tested here had some impact on the microbiota, but TMS significantly reduced bacterial species richness and diversity and
Elastin-Like Recombinamers As Smart Drug Delivery Systems.
Arias, F Javier; Santos, Mercedes; Ibanez-Fonseca, Arturo; Pina, Maria Jesus; Serrano, Sofía
2018-02-19
Drug delivery systems that are able to control the release of bioactive molecules and designed to carry drugs to target sites are of particular interest for tissue therapy. Moreover, systems comprising materials that can respond to environmental stimuli and promote self-assembly and higher order supramolecular organization are especially useful in the biomedical field. Objetive: This review focuses on biomaterials suitable for this purpose and that include elastin-like recombinamers (ELRs), a class of proteinaceous polymers bioinspired by natural elastin, designed using recombinant technologies. The self-assembly and thermoresponsive behaviour of these systems, along with their biodegradability, biocompatibility and well-defined composition as a result of their tailormade design, make them particularly attractive for controlled drug delivery. ELR-based delivery systems that allow targeted delivery are reviewed, especially ELR-drug recombinant fusion constructs, ELR-drug systems chemically bioconjugated in their monomeric and soluble forms, and drug encapsulation by nanoparticle-forming ELRs. Subsequently, the review focuses on those drug carriers in which smart release is triggered by pH or temperature with a particular focus on cancer treatments. Systems for controlled drug release based on depots and hydrogels that act as both a support and reservoir in which drugs can be stored will be described, and their applications in drug delivery discussed. Finally, smart drug-delivery systems not based on ELRs, including those comprising proteins, synthetic polymers and non-polymeric systems, will also be briefly discussed. Several different constructions based on ELRs are potential candidates for controlled drug delivery to be applied in advanced biomedical treatments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
A review on target drug delivery: magnetic microspheres
Amit Chandna; Deepa Batra; Satinder Kakar; Ramandeep Singh
2013-01-01
Novel drug delivery system aims to deliver the drug at a rate directed by the needs of the body during the period of treatment, and target the active entity to the site of action. A number of novel drug delivery systems have emerged encompassing various routes of administration, to achieve controlled and targeted drug delivery, magnetic micro carriers being one of them. Magnetic microsphere is newer approach in pharmaceutical field. Magnetic microspheres as an alternative to traditional ra...
Directory of Open Access Journals (Sweden)
Linardi Renata Lehn
2006-01-01
Full Text Available (MDR1 gene expressed in tumor cells and also in several normal tissues, such as intestine, liver, kidney, blood-brain barrier, spinal cord, and placenta. P-gp has been identified in mice, rat, bovine, monkey, rodents, and human beings and has been receiving a particular clinical relevance because this protein expression limits brain access and intestinal absorption of many drugs. This protein plays a role as a protective barrier against a wide variety of substrates, avoiding drug entry into the central nervous system. P-glycoprotein also interferes with drug bioavailability and disposition, including absorption, distribution, metabolization, and excretion, influencing pharmacokinetic and pharmacodynamic of drugs. Modulation of P-gp may help the efficacy of treatment of several diseases and can explain some adverse central nervous system effects induced by drugs after intravenous administration and the poor response of oral administration in patients. Alteration in P-gp expression or function has been associated with several diseases susceptibility in humans and animals. Furthermore, additional studies relating MDR1 and P-gp expression has an important clinical implication also in terms of treatment efficacy.
Radiopharmaceutical drug review process
International Nuclear Information System (INIS)
Frankel, R.
1985-01-01
To ensure proper radioactive drug use (such as quality, diagnostic improvement, and minimal radioactive exposure), the Food and Drug Administration evaluates new drugs with respect to safety, effectiveness, and accuracy and adequacy of the labeling. The IND or NDA process is used for this purpose. A brief description of the process, including the Chemical Classification System and the therapeutic potential classification, is presented as it applies to radiopharmaceuticals. Also, the status of the IND or NDA review of radiopharmaceuticals is given
Improved oral bioavailability of glyburide by a self-nanoemulsifying drug delivery system.
Liu, Hongzhuo; Shang, Kuimao; Liu, Weina; Leng, Donglei; Li, Ran; Kong, Ying; Zhang, Tianhong
2014-01-01
The present study aimed at the development and characterisation of self-nanoemulsifying drug delivery system (SNEDDS) to improve the oral bioavailability of poorly soluble glyburide. The solubility of glyburide was determined in various oils, surfactants and co-surfactants which were grouped into two different combinations to construct ternary phase diagrams. The formulations were evaluated for emulsification time, droplet size, zeta-potential, electrical conductivity and stability of nanoemulsions. The optimised SNEDDS loading with 5 mg/g glyburide comprised 55% Cremophor® RH 40, 15% propanediol and 30% Miglyol® 812, which rapidly formed fine oil-in-water nanoemulsions with 46 ± 4 nm particle size. Compared with the commercial micronised tablets (Glynase®PresTab®), enhanced in vitro release profiles of SNEDDS were observed, resulting in the 1.5-fold increase of AUC following oral administration of SNEDDS in fasting beagle dogs. These results indicated that SNEDDS is a promising drug delivery system for increasing the oral bioavailability of glyburide.
Evaluation of anti-GERD activity of gastro retentive drug delivery system of itopride hydrochloride.
Satapathy, Trilochan; Panda, Prasana K; Goyal, Amit K; Rath, Goutam
2010-08-01
The present work describes the formulation and evaluation of the gastroretentive system of Itopride hydrochloride. In this research, we have formulated floating hydrogel-based microspheres employing calcium carbonate (CaCO(3)) as a gas forming agent dispersed in alginate matrix. In vitro characterizations such as drug content, particle size, and drug release were carried out. GI motility was determined by administration of charcoal meal to rats. Results demonstrated that prepared microspheres were spherical in shape with smooth surface, good loading efficiency, and excellent buoyancy. The gastro retentive dosage form of itiopride demonstrated significant antacid, anti-ulcer, and anti-GERD activity after 12 hours in comparison with the conventional dosage form.
Biopharmaceutical aspects of oral drug delivery
Faassen, Werenfriedus Adrianus
2004-01-01
Most drugs display their therapeutic activity on specific places in the human body and should reach the systemic circulation in order to be transported towards the site of action. Irrespective of the route of administration the same sequence of steps are of relevance for the exposure to a drug:
Accelerated approval of oncology products: the food and drug administration experience.
Johnson, John R; Ning, Yang-Min; Farrell, Ann; Justice, Robert; Keegan, Patricia; Pazdur, Richard
2011-04-20
We reviewed the regulatory history of the accelerated approval process and the US Food and Drug Administration (FDA) experience with accelerated approval of oncology products from its initiation in December 11, 1992, to July 1, 2010. The accelerated approval regulations allowed accelerated approval of products to treat serious or life-threatening diseases based on surrogate endpoints that are reasonably likely to predict clinical benefit. Failure to complete postapproval trials to confirm clinical benefit with due diligence could result in removal of the accelerated approval indication from the market. From December 11, 1992, to July 1, 2010, the FDA granted accelerated approval to 35 oncology products for 47 new indications. Clinical benefit was confirmed in postapproval trials for 26 of the 47 new indications, resulting in conversion to regular approval. The median time between accelerated approval and regular approval of oncology products was 3.9 years (range = 0.8-12.6 years) and the mean time was 4.7 years, representing a substantial time savings in terms of earlier availability of drugs to cancer patients. Three new indications did not show clinical benefit when confirmatory postapproval trials were completed and were subsequently removed from the market or had restricted distribution plans implemented. Confirmatory trials were not completed for 14 new indications. The five longest intervals from receipt of accelerated approval to July 1, 2010, without completion of trials to confirm clinical benefit were 10.5, 6.4, 5.5, 5.5, and 4.7 years. The five longest intervals between accelerated approval and successful conversion to regular approval were 12.6, 9.7, 8.1, 7.5, and 7.4 years. Trials to confirm clinical benefit should be part of the drug development plan and should be in progress at the time of an application seeking accelerated approval to prevent an ineffective drug from remaining on the market for an unacceptable time.
Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery
Directory of Open Access Journals (Sweden)
Sabine Szunerits
2018-02-01
Full Text Available Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs, which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum, the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section “Frontiers in Bioengineering and Biotechnology,” the advances in this field
Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery
Szunerits, Sabine; Boukherroub, Rabah
2018-01-01
Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs), which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum, the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section “Frontiers in Bioengineering and Biotechnology,” the advances in this field and the handful of
Nanomedicine: Drug Delivery Systems and Nanoparticle Targeting
International Nuclear Information System (INIS)
Youn, Hye Won; Kang, Keon Wook; Chung, Jun Key; Lee, Dong Soo
2008-01-01
Applications of nanotechnology in the medical field have provided the fundamentals of tremendous improvement in precise diagnosis and customized therapy. Recent advances in nanomedicine have led to establish a new concept of theragnosis, which utilizes nanomedicines as a therapeutic and diagnostic tool at the same time. The development of high affinity nanoparticles with large surface area and functional groups multiplies diagnostic and therapeutic capacities. Considering the specific conditions related to the disease of individual patient, customized therapy requires the identification of disease target at the cellular and molecular level for reducing side effects and enhancing therapeutic efficiency. Well-designed nanoparticles can minimize unnecessary exposure of cytotoxic drugs and maximize targeted localization of administrated drugs. This review will focus on major pharmaceutical nanomaterials and nanoparticles as key components of designing and surface engineering for targeted theragnostic drug development
Hydrogel nanoparticles and nanocomposites for nasal drug/vaccine delivery.
Salatin, Sara; Barar, Jaleh; Barzegar-Jalali, Mohammad; Adibkia, Khosro; Milani, Mitra Alami; Jelvehgari, Mitra
2016-09-01
Over the past few years, nasal drug delivery has attracted more and more attentions, and been recognized as the most promising alternative route for the systemic medication of drugs limited to intravenous administration. Many experiments in animal models have shown that nanoscale carriers have the ability to enhance the nasal delivery of peptide/protein drugs and vaccines compared to the conventional drug solution formulations. However, the rapid mucociliary clearance of the drug-loaded nanoparticles can cause a reduction in bioavailability percentage after intranasal administration. Thus, research efforts have considerably been directed towards the development of hydrogel nanosystems which have mucoadhesive properties in order to maximize the residence time, and hence increase the period of contact with the nasal mucosa and enhance the drug absorption. It is most certain that the high viscosity of hydrogel-based nanosystems can efficiently offer this mucoadhesive property. This update review discusses the possible benefits of using hydrogel polymer-based nanoparticles and hydrogel nanocomposites for drug/vaccine delivery through the intranasal administration.
Directory of Open Access Journals (Sweden)
Ladislav Hess
2012-01-01
Full Text Available The aim of this work was to study the effect of site of intramuscular administration of anaesthetic drugs on the course of immobilisation in macaque monkeys (Macaca mulatta. Twenty macaque monkeys were given medetomidine (25 µg·kg-1 and ketamine (3 mg·kg-1 intramuscularly to the deltoid (n = 10 animals or gluteus (n = 10 animals muscles. Behavioural changes, loss of aggressiveness, immobilisation time and cardiorespiratory changes were recorded. The effect of drugs was reversed after 20 min by i.m. administration of atipamezole at the dose of 250 µg·kg-1. Highly significant differences (P < 0.001 were found between groups with gluteal or deltoid administration of drugs on the onset of immobilisation effect (71.3 s and 108.3 s, respectively, and immobilisation time (152.7 s and 254.4 s, respectively. In the gluteus muscle group, the grasp reflex was still present at the beginning of immobilisation and slowly wore off in 15–45 s. The same was valid for muscle tone. There were no differences in cardiorespiratory parameters in any of the groups. Animals of both groups recovered in 3–6 min after atipamezole administration. Administration of drugs to the deltoid muscle resulted in a more rapid onset and increased effect of immobilisation than administration to the gluteus muscle. Both in veterinary and human medicine, injection to the deltoid muscle may be more convenient in all cases, when rapid and more prominent effect is desirable as in premedication before surgery or in emergency medicine. The study is the first to compare the effect of administering drugs to different muscles and the results may improve the practice of intramuscular injections in animals and in humans.
A wireless actuating drug delivery system
International Nuclear Information System (INIS)
Jo, Won-Jun; Baek, Seung-Ki; Park, Jung-Hwan
2015-01-01
A wireless actuating drug delivery system was devised. The system is based on induction heating for drug delivery. In this study, thermally generated nitrogen gas produced by induction heating of azobisisobutyronitrile (AIBN) was utilized for pressure-driven release of the drug. The delivery device consists of an actuator chamber, a drug reservoir, and a microchannel. A semicircular copper disc (5 and 6 mm in diameter and 100 µm thick), and thermal conductive tape were integrated as the heating element in the actuator chamber. The final device was 2.7 mm thick. 28 µl of drug solution were placed in the reservoir and the device released the drug quickly at the rate of 6 µl s −1 by induction heating at 160 µT of magnetic intensity. The entire drug solution was released and dispersed after subcutaneous implantation under identical experimental condition. This study demonstrates that the device was simply prepared and drug delivery could be achieved by wireless actuation of a thin, pressure-driven actuator. (paper)
Fonseca-Santos, Bruno; Dos Santos, Aline Martins; Rodero, Camila Fernanda; Gremião, Maria Palmira Daflon; Chorilli, Marlus
From previous studies, it has been found that curcumin exhibits an anti-inflammatory activity and is being used for the treatment of skin disorders; however, it is hydrophobic and has weak penetrating ability, resulting in poor drug transport through the stratum corneum. The aim of this study was to develop liquid crystalline systems for topical administration of curcumin for the treatment of inflammation. These liquid crystalline systems were developed from oleic acid, polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol, and water as the surfactant, oil phase, and aqueous phase, respectively. These systems were characterized, and polarized light microscopy showed anisotropy with lamellar mesophases (Formulation 1) and hexagonal mesophases (Formulations 2 and 3), which were confirmed by the peak ratio measured using small-angle X-ray scattering. In addition, rheological tests revealed that the formulations exhibited gel-like behavior (G'>G″), as evidenced by the increased G' values that indicate structured systems. Texture profile analysis showed that hexagonal mesophases have high values of hardness, adhesiveness, and compressibility, which indicate structured systems. In vitro studies on bioadhesion revealed that the hexagonal mesophases increased the bioadhesiveness of the systems to the skin of the pig ear. An in vivo inflammation experiment showed that the curcumin-loaded hexagonal mesophase exhibited an anti-inflammatory activity as compared to the positive control (dexamethasone). The results suggest that this system has a potential to be used as a bioadhesive vehicle for the topical administration of curcumin. Therefore, it is possible to conclude that these systems can be used for the optimization of drug delivery systems to the skin.
Saddoris, Michael P; Wang, Xuefei; Sugam, Jonathan A; Carelli, Regina M
2016-01-06
Chronic exposure to drugs of abuse is linked to long-lasting alterations in the function of limbic system structures, including the nucleus accumbens (NAc). Although cocaine acts via dopaminergic mechanisms within the NAc, less is known about whether phasic dopamine (DA) signaling in the NAc is altered in animals with cocaine self-administration experience or if these animals learn and interact normally with stimuli in their environment. Here, separate groups of rats self-administered either intravenous cocaine or water to a receptacle (controls), followed by 30 d of enforced abstinence. Next, all rats learned an appetitive Pavlovian discrimination and voltammetric recordings of real-time DA release were taken in either the NAc core or shell of cocaine and control subjects. Cocaine experience differentially impaired DA signaling in the core and shell relative to controls. Although phasic DA signals in the shell were essentially abolished for all stimuli, in the core, DA did not distinguish between cues and was abnormally biased toward reward delivery. Further, cocaine rats were unable to learn higher-order associations and even altered simple conditioned approach behaviors, displaying enhanced preoccupation with cue-associated stimuli (sign-tracking; ST) but diminished time at the food cup awaiting reward delivery (goal-tracking). Critically, whereas control DA signaling correlated with ST behaviors, cocaine experience abolished this relationship. These findings show that cocaine has persistent, differential, and pathological effects on both DA signaling and DA-dependent behaviors and suggest that psychostimulant experience may remodel the very circuits that bias organisms toward repeated relapse. Relapsing to drug abuse despite periods of abstinence and sincere attempts to quit is one of the most pernicious facets of addiction. Unfortunately, little is known about how the dopamine (DA) system functions after periods of drug abstinence, particularly its role in
Wang, Xuefei; Sugam, Jonathan A.; Carelli, Regina M.
2016-01-01
Chronic exposure to drugs of abuse is linked to long-lasting alterations in the function of limbic system structures, including the nucleus accumbens (NAc). Although cocaine acts via dopaminergic mechanisms within the NAc, less is known about whether phasic dopamine (DA) signaling in the NAc is altered in animals with cocaine self-administration experience or if these animals learn and interact normally with stimuli in their environment. Here, separate groups of rats self-administered either intravenous cocaine or water to a receptacle (controls), followed by 30 d of enforced abstinence. Next, all rats learned an appetitive Pavlovian discrimination and voltammetric recordings of real-time DA release were taken in either the NAc core or shell of cocaine and control subjects. Cocaine experience differentially impaired DA signaling in the core and shell relative to controls. Although phasic DA signals in the shell were essentially abolished for all stimuli, in the core, DA did not distinguish between cues and was abnormally biased toward reward delivery. Further, cocaine rats were unable to learn higher-order associations and even altered simple conditioned approach behaviors, displaying enhanced preoccupation with cue-associated stimuli (sign-tracking; ST) but diminished time at the food cup awaiting reward delivery (goal-tracking). Critically, whereas control DA signaling correlated with ST behaviors, cocaine experience abolished this relationship. These findings show that cocaine has persistent, differential, and pathological effects on both DA signaling and DA-dependent behaviors and suggest that psychostimulant experience may remodel the very circuits that bias organisms toward repeated relapse. SIGNIFICANCE STATEMENT Relapsing to drug abuse despite periods of abstinence and sincere attempts to quit is one of the most pernicious facets of addiction. Unfortunately, little is known about how the dopamine (DA) system functions after periods of drug abstinence
Venturinil, C G; Bruinsmann, A; Oliveira, C P; Contri, R V; Pohlmann, A R; Guterres, S S
2016-02-01
An innovative nanocapsule formulation for parenteral administration using selected vegetable oils (mango, jojoba, pequi, oat, annatto, calendula, and chamomile) was developed that has the potential to encapsulate various drugs. The vegetable oil-loaded nanocapsules were prepared by interfacial deposition and compared with capric/caprylic triglyceride-loaded lipid core nanocapsules. The major objective was to investigate the effect of vegetable oils on particle size distribution and physical stability and to determine the hemolytic potential of the nanocapsules, considering their applicability for intravenous administration. Taking into account the importance of accurately determining particle size for the selected route of administration, different size characterization techniques were employed, such as Laser Diffraction, Dynamic Light Scattering, Multiple Light Scattering, Nanoparticle Tracking Analysis, and Transmission Electronic Microscopy. Laser diffraction studies indicated that the mean particle size of all nanocapsules was below 300 nm. For smaller particles, the laser diffraction and multiple light scattering data were in agreement (D[3,2]-130 nm). Dynamic light scattering and nanoparticle tracking analysis, two powerful techniques that complement each other, exhibited size values between 180 and 259 nm for all nanoparticles. Stability studies demonstrated a tendency of particle creaming for jojoba-nanocapsules and sedimentation for the other nanoparticles; however, no size variation occurred over 30 days. The hemolysis test proved the hemocompatibility of all nanosystems, irrespective of the type of oil. Although all developed nanocapsules presented the potential for parenteral administration, jojoba oil-loaded nanocapsules were selected as the most promising nanoformulation due to their low average size and high particle size homogeneity.
Permeation enhancer strategies in transdermal drug delivery.
Marwah, Harneet; Garg, Tarun; Goyal, Amit K; Rath, Goutam
2016-01-01
Today, ∼74% of drugs are taken orally and are not found to be as effective as desired. To improve such characteristics, transdermal drug delivery was brought to existence. This delivery system is capable of transporting the drug or macromolecules painlessly through skin into the blood circulation at fixed rate. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive techniques of drug delivery. Several important advantages of transdermal drug delivery are prevention from hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug. Human skin surface, as a site of drug application for both local and systemic effects, is the most eligible candidate available. New controlled transdermal drug delivery systems (TDDS) technologies (electrically-based, structure-based and velocity-based) have been developed and commercialized for the transdermal delivery of troublesome drugs. This review article covers most of the new active transport technologies involved in enhancing the transdermal permeation via effective drug delivery system.
Shah, Utpal U; Roberts, Matthew; Orlu Gul, Mine; Tuleu, Catherine; Beresford, Michael W
2011-09-15
Parenteral routes of drug administration have poor acceptability and tolerability in children. Advances in transdermal drug delivery provide a potential alternative for improving drug administration in this patient group. Issues with parenteral delivery in children are highlighted and thus illustrate the scope for the application of needle-free and microneedle technologies. This mini-review discusses the opportunities and challenges for providing disease-modifying antirheumatic drugs (DMARDs) currently prescribed to paediatric rheumatology patients using such technologies. The aim is to raise further awareness of the need for age-appropriate formulations and drug delivery systems and stimulate exploration of these options for DMARDs, and in particular, rapidly emerging biologics on the market. The ability of needle-free and microneedle technologies to deliver monoclonal antibodies and fusion proteins still remains largely untested. Such an understanding is crucial for future drug design opportunities. The bioavailability, safety and tolerance of delivering biologics into the viable epidermis also need to be studied. Copyright © 2011 Elsevier B.V. All rights reserved.
Park, Sang-In; Oh, Jaeseong; Jang, Kyungho; Yoon, Jangsoo; Moon, Seol Ju; Park, Jong Sun; Lee, Jae Ho; Song, Junghan; Jang, In-Jin; Yu, Kyung-Sang; Chung, Jae-Yong
2015-08-01
Therapeutic drug monitoring (TDM) of second-line antituberculosis drugs would allow for optimal individualized dosage adjustments and improve drug safety and therapeutic outcomes. To evaluate the pharmacokinetic (PK) characteristics of clinically relevant, multidrug treatment regimens and to improve the feasibility of TDM, we conducted an open-label, multiple-dosing study with 16 healthy subjects who were divided into two groups. Cycloserine (250 mg), p-aminosalicylic acid (PAS) (5.28 g), and prothionamide (250 mg) twice daily and pyrazinamide (1,500 mg) once daily were administered to both groups. Additionally, levofloxacin (750 mg) and streptomycin (1 g) once daily were administered to group 1 and moxifloxacin (400 mg) and kanamycin (1 g) once daily were administered to group 2. Blood samples for PK analysis were collected up to 24 h following the 5 days of drug administration. The PK parameters, including the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve during a dosing interval at steady state (AUCτ), were evaluated. The correlations between the PK parameters and the concentrations at each time point were analyzed. The mean Cmax and AUCτ, respectively, for each drug were as follows: cycloserine, 24.9 mg/liter and 242.3 mg · h/liter; PAS, 65.9 mg/liter and 326.5 mg · h/liter; prothionamide, 5.3 mg/liter and 22.1 mg · h/liter; levofloxacin, 6.6 mg/liter and 64.4 mg · h/liter; moxifloxacin, 4.7 mg/liter and 54.2 mg · h/liter; streptomycin, 42.0 mg/liter and 196.7 mg · h/liter; kanamycin, 34.5 mg/liter and 153.5 mg · h/liter. The results indicated that sampling at 1, 2.5, and 6 h postdosing is needed for TDM when all seven drugs are administered concomitantly. This study indicates that PK characteristics must be considered when prescribing optimal treatments for patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT02128308.). Copyright © 2015, American Society for
Buccal bioadhesive drug delivery--a promising option for orally less efficient drugs.
Sudhakar, Yajaman; Kuotsu, Ketousetuo; Bandyopadhyay, A K
2006-08-10
Rapid developments in the field of molecular biology and gene technology resulted in generation of many macromolecular drugs including peptides, proteins, polysaccharides and nucleic acids in great number possessing superior pharmacological efficacy with site specificity and devoid of untoward and toxic effects. However, the main impediment for the oral delivery of these drugs as potential therapeutic agents is their extensive presystemic metabolism, instability in acidic environment resulting into inadequate and erratic oral absorption. Parenteral route of administration is the only established route that overcomes all these drawbacks associated with these orally less/inefficient drugs. But, these formulations are costly, have least patient compliance, require repeated administration, in addition to the other hazardous effects associated with this route. Over the last few decades' pharmaceutical scientists throughout the world are trying to explore transdermal and transmucosal routes as an alternative to injections. Among the various transmucosal sites available, mucosa of the buccal cavity was found to be the most convenient and easily accessible site for the delivery of therapeutic agents for both local and systemic delivery as retentive dosage forms, because it has expanse of smooth muscle which is relatively immobile, abundant vascularization, rapid recovery time after exposure to stress and the near absence of langerhans cells. Direct access to the systemic circulation through the internal jugular vein bypasses drugs from the hepatic first pass metabolism leading to high bioavailability. Further, these dosage forms are self-administrable, cheap and have superior patient compliance. Developing a dosage form with the optimum pharmacokinetics is a promising area for continued research as it is enormously important and intellectually challenging. With the right dosage form design, local environment of the mucosa can be controlled and manipulated in order to
Govender, Thiresen; Choonara, Yahya E; Kumar, Pradeep; Bijukumar, Divya; du Toit, Lisa C; Modi, Girish; Naidoo, Dinesh; Pillay, Viness
2017-06-01
The complexity of the brain and the membranous blood-brain barrier (BBB) has proved to be a significant limitation to the systemic delivery of pharmaceuticals to the brain rendering them sub-therapeutic and ineffective in the treatment of neurological diseases. Apart from this, lack of innovation in product development to counteract the problem is also a major contributing factor to a poor therapeutic outcome. Various innovative strategies show potential in treating some of the neurological disorders; however, drug delivery remains the most popular. To attain therapeutic drug levels in the central nervous system, large, intolerable systemic doses are generally administered. The major factors responsible for the success maintenance therapy of neurological diseases included controlled and sustained release of neurotherapeutics, reduced frequency of administration, higher bioavailability, and patient compliances. Conventional oral or injectable formulations cannot satisfy all the requirements in many circumstances. This article reviews the therapeutic implantable polymeric and transdermal devices employed in an attempt to effectively achieve therapeutic quantities of drug across the BBB over a prolonged period, to improve patient disease prognosis.
Mueller, Claudia; Dietel, Elke; Heynen, Severin R; Nalenz, Heiko; Goldbach, Pierre; Mahler, Hanns-Christian; Schmidt, Johannes; Grauschopf, Ulla; Schoenhamnmer, Karin
2015-01-01
MabThera is an essential component of the standard-of-care regimens in the treatment of non-Hodgkin lymphoma and Chronic Lymphatic Leukemia. MabThera for subcutaneous injection is a novel line extension that has been approved by the European Medicines Agency for the treatment of patients with follicular lymphoma and diffuse large B-cell lymphoma. This study aimed to evaluate in-use stability data of MabThera subcutaneous drug-product solution in single-use syringes for subcutaneous administration according to the European Medicines Agency guideline. The drug-product solution was exposed to material contact surfaces of five different administration setups commonly used in subcutaneous drug delivery. MabThera subcutaneous was transferred under aseptic conditions into polypropylene and polycarbonate syringes and stored for 1, 2, and 4 weeks at 2°C to 8°C followed by 24 hours at 30°C. After storage, subcutaneous administration was simulated and MabThera subcutaneous drug-product solution quality attributes were evaluated by using compendial physico-chemical tests, as well as suitable and validated molecule- and formulation-specific analytical methods. MabThera subcutaneous vials were treated and analyzed in parallel. The physico-chemical results of MabThera subcutaneous in the different setups were comparable to the control for all timepoints. No change in drug-product quality after storage and simulated administration was found compared to the control. However, since single-dose products do not contain preservatives, microbial contamination and growth needs to be avoided and product sterility needs to be ensured. The results showed that MabThera subcutaneous remains compatible and stable, from a physico-chemical perspective, for up to 4 weeks at 2°C to 8°C followed by 24 hours at 30°C with the contact materials tested in this study. In order to avoid and minimize microbial growth, MabThera subcutaneous should be used immediately after removal from the original
Modeling the modified drug release from curved shape drug delivery systems - Dome Matrix®.
Caccavo, D; Barba, A A; d'Amore, M; De Piano, R; Lamberti, G; Rossi, A; Colombo, P
2017-12-01
The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated). In these simulations, the erosion rate was used asa fitting parameter, and its dependence upon the surface area/volume ratio and upon the local fluid dynamics was discussed. The model parameters were determined by comparison with the drug release profile from a cylindrical tablet, then the model was successfully used for the prediction of the drug release from a Dome Matrix® system, for simple module configuration and for module assembled (void and piled) configurations. It was also demonstrated that, given the same initial S/V ratio, the drug release is independent upon the shape of the tablets but it is only influenced by the S/V evolution. The model reveals itself able to describe the observed phenomena, and thus it can be of use for the design of oral drug delivery systems, even if complex shaped. Copyright © 2017 Elsevier B.V. All rights reserved.
21 CFR 1316.13 - Frequency of administrative inspections.
2010-04-01
... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Frequency of administrative inspections. 1316.13 Section 1316.13 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE ADMINISTRATIVE... as circumstances may require, based in part on the registrant's history of compliance with the...
Basch, Ethan; Geoghegan, Cindy; Coons, Stephen Joel; Gnanasakthy, Ari; Slagle, Ashley F; Papadopoulos, Elektra J; Kluetz, Paul G
2015-06-01
Data reported directly by patients about how they feel and function are rarely included in oncology drug labeling in the United States, in contrast to Europe and to nononcology labeling in the United States, where this practice is more common. Multiple barriers exist, including challenges unique to oncology trials, and industry's concerns regarding cost, logistical complexities, and the Food and Drug Administration's (FDA's) rigorous application of its 2009 guidance on the use of patient-reported outcome (PRO) measures. A panel consisting of representatives of industry, FDA, the PRO Consortium, clinicians, and patients was assembled at a 2014 workshop cosponsored by FDA to identify practical recommendations for overcoming these barriers. Key recommendations included increasing proactive encouragement by FDA to clinical trial sponsors for including PROs in drug development programs; provision of comprehensive PRO plans by sponsors to FDA early in drug development; promotion of an oncology-specific PRO research agenda; development of an approach to existing ("legacy") PRO measures, when appropriate (focused initially on symptoms and functional status); and increased FDA and industry training in PRO methodology. FDA has begun implementing several of these recommendations.
21 CFR 862.3360 - Drug metabolizing enzyme genotyping system.
2010-04-01
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Drug metabolizing enzyme genotyping system. 862... Test Systems § 862.3360 Drug metabolizing enzyme genotyping system. (a) Identification. A drug metabolizing enzyme genotyping system is a device intended for use in testing deoxyribonucleic acid (DNA...
2012-07-27
...] Draft Guidance for Industry and Food and Drug Administration Staff; Safety Considerations for 510(k... serious and sometimes fatal consequences to patients. This guidance provides recommendations to 510(k... unintended connections between enteral and nonenteral devices. This draft guidance is not final nor is it in...
2011-01-31
... of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville... harmful constituents, including smoke constituents, to health in each tobacco product by brand and by quantity in each brand and subbrand.'' The guidance discusses the meaning of the term ``harmful and...
2011-04-25
...] Guidance for Food and Drug Administration Staff and Tobacco Retailers on Civil Money Penalties and No... entitled ``Civil Money Penalties and No- Tobacco-Sale Orders for Tobacco Retailers.'' This guidance document describes FDA's current policies with respect to civil money penalties and no-tobacco-sale orders...
2010-08-31
...] Draft Guidance for Food and Drug Administration Staff and Tobacco Retailers on Civil Money Penalties and... guidance entitled ``Civil Money Penalties and No-Tobacco-Sale Orders for Tobacco Retailers.'' This guidance document is intended to describe FDA's current policies with respect to civil money penalties and no...
International Nuclear Information System (INIS)
Takasu, T.
1980-01-01
A drug given to an animal becomes widely distributed throughout the body, acting on the living mechanisms or structures, and is gradually excreted. Some drugs can remain in some parts of the body for a long period. For example, 14 C-chloramphenical was found to remain preferentially in the salivary gland, liver and bone marrow of mice 24 hours after its oral administration. If such a drug is given repeatedly, it could possibly accumulate gradually in these organs. Thus, when its accumulation in a particular part of the body exceeds a certain level, the living mechanism or structure may possibly be injured. The harmful effects of a drug in repeated administration are called its chronic toxicity. The author discusses whether it is possible to predict the toxicity of a drug by studying its distribution in relation to time, and, if possible, the points in time. This problem is studied especially in relation to the nervous system. (Auth.)
Formulation and evaluation of in situ gelling systems for intranasal administration of gastrodin.
Cai, Zheng; Song, Xiangrong; Sun, Feng; Yang, Zhaoxiang; Hou, Shixiang; Liu, Zhongqiu
2011-12-01
Gastrodin is the major bioactive constituent of the traditional Chinese drug "Tianma." It is used in the treatment of some nervous system diseases and can be transported to the brain via intranasal administration. In the current paper, the development of a novel ion-activated in situ gelling system for the nasal delivery of gastrodin is discussed. An in situ perfusion model was used to determine the absorption-rate constant of gastrodin through rat nasal mucosa. The optimal formulation was determined by measuring the critical cation concentration, anti-dilution capacity, gel expansion coefficient, water-holding capacity, and adhesive capacity. The best formulation consisted of 10% gastrodin, 0.5% deacetylated gellan gum as the gelatinizer, and 0.03% ethylparaben as the preservative. The rheological properties of gastrodin nasal in situ gels were also investigated. The viscosity and elasticity sharply increased at temperatures below 25°C. When physiological concentrations of cations were added into the preparation, the mixture gelled into a semi-solid. The results of an accelerated stability test show that gastrodin nasal in situ gels can be stable for more than 2 years. Mucociliary toxicity was evaluated using the in situ toad palate model and the rat nasal mucociliary method; both models demonstrated no measurable ciliotoxicity. Pharmacodynamic studies suggest that similar acesodyne and sedative effects were induced following intranasal administration of 50 mg/kg gastrodin nasal in situ gels or oral administration of 100 mg/kg gastrodin solution. The in situ gel preparation is a safe and effective nasal delivery system for gastrodin.
Directory of Open Access Journals (Sweden)
Hao Chang
2017-01-01
Full Text Available Noise-induced hearing loss (NIHL is a global health problem affecting over 5% of the population worldwide. We have shown previously that acute noise-induced cochlear injury can be ameliorated by administration of drugs acting on adenosine receptors in the inner ear, and a selective A1 adenosine receptor agonist adenosine amine congener (ADAC has emerged as a potentially effective treatment for cochlear injury and resulting hearing loss. This study investigated pharmacokinetic properties of ADAC in rat perilymph after systemic (intravenous administration using a newly developed liquid chromatography-tandem mass spectrometry detection method. The method was developed and validated in accordance with the USA FDA guidelines including accuracy, precision, specificity, and linearity. Perilymph was sampled from the apical turn of the cochlea to prevent contamination with the cerebrospinal fluid. ADAC was detected in cochlear perilymph within two minutes following intravenous administration and remained in perilymph above its minimal effective concentration for at least two hours. The pharmacokinetic pattern of ADAC was significantly altered by exposure to noise, suggesting transient changes in permeability of the blood-labyrinth barrier and/or cochlear blood flow. This study supports ADAC development as a potential clinical otological treatment for acute sensorineural hearing loss caused by exposure to traumatic noise.
Nuclear methods for food analysis at the U.S. Food and Drug Administration
International Nuclear Information System (INIS)
Anderson, D.L.; Cunningham, W.C.; Capar, S.G.; Baratta, E.J.; Mackill, P.
2001-01-01
An overview radioanalytical techniques used in support of research, monitoring programs, and field assignments directed by the U.S. Food and Drug Administration's Center for Food Safety and Applied Nutrition (CFSAN) is presented. The Winchester Engineering and Analytical Center annually determines radionuclide concentrations in 260 Total Diet Study foods, approximately 80 imported foods, and a selection of domestic foods collected near U.S. nuclear power plants. Radioanalytical techniques used at CFSAN's neutron analysis laboratory at the National Institute of Standards and Technology are discussed along with applications for research, quality control, and special projects. (author)
Some Recent Advances in Transdermal Drug Delivery Systems ...
African Journals Online (AJOL)
Some Recent Advances in Transdermal Drug Delivery Systems. ... Advances in Transdermal Drug Delivery Systems. EC Ibezim, B Kabele-Toge, CO Anie, C Njoku. Abstract. Transdermal delivery systems are forms of drug delivery involving the dermis, as distinct from topical, oral or other forms of parenteral dosage forms.
Mass drug administration for trachoma: how long is not long enough?
Directory of Open Access Journals (Sweden)
Violeta Jimenez
2015-03-01
Full Text Available Blinding trachoma is targeted for elimination by 2020 using the SAFE strategy (Surgery, Antibiotics, Facial cleanliness, and Environmental improvements. Annual mass drug administration (MDA with azithromycin is a cornerstone of this strategy. If baseline prevalence of clinical signs of trachomatous inflammation - follicular among 1-9 year-olds (TF1-9 is ≥ 10% but 30%, 7 or more annual MDAs may be required to achieve the target. There are five years left before the 2020 deadline to eliminate blinding trachoma. Low endemic settings are poised to succeed in their elimination goals. However, newly-identified high prevalence districts warrant immediate inclusion in the global program. Intensified application of the SAFE strategy is needed in order to guarantee blinding trachoma elimination by 2020.
Ophthalmic Drug Dosage Forms: Characterisation and Research Methods
Baranowski, Przemysław; Karolewicz, Bożena; Gajda, Maciej; Pluta, Janusz
2014-01-01
This paper describes hitherto developed drug forms for topical ocular administration, that is, eye drops, ointments, in situ gels, inserts, multicompartment drug delivery systems, and ophthalmic drug forms with bioadhesive properties. Heretofore, many studies have demonstrated that new and more complex ophthalmic drug forms exhibit advantage over traditional ones and are able to increase the bioavailability of the active substance by, among others, reducing the susceptibility of drug forms to...
2013-08-06
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2004-N-0451... should review the supplementary information sheet for the standard to understand fully the extent to... incorporating medical devices--Part 2-2: Guidance 2012-07 for the disclosure and communication of medical device...
Directory of Open Access Journals (Sweden)
Hetal Thakkar
2011-01-01
Full Text Available Background : Raloxifene, a second-generation selective estrogen receptor modulator (SERM used to prevent osteoporosis in postmenopausal women is administered orally in the form of a tablet. The absolute bioavailability of the drug is only 2% because of extensive hepatic first-pass metabolism. Lipid-based formulations are reported to reduce the first-pass metabolism by promoting its lymphatic uptake. Materials and Methods : In the present investigation, microemulsion and Self-Microemulsifying Drug Delivery System (SMEDDS formulations of Raloxifene were prepared. The prepared formulations were characterized for drug loading, size, transparency, zeta potential, Transmission Electron Microscopy (TEM and in vitro intestinal permeability. Results : The results indicated that high drug loading, optimum size and desired zeta potential and transparency could be achieved with both SMEDDS and microemulsion. The TEM studies indicated the absence of aggregation with both the systems. The in vitro intestinal permeability results showed that the permeation of the drug from the microemulsion and SMEDDs was significantly higher than that obtained from the drug dispersion and marketed formulation. Conclusion : Lipid based formulations such as microemulsion and Self Microemulsifying drug delivery systems are expected to increase the oral bioavailability as evidenced by the increased intestinal permeation.
Thakkar, Hetal; Nangesh, Jitesh; Parmar, Mayur; Patel, Divyakant
2011-01-01
Background: Raloxifene, a second-generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women is administered orally in the form of a tablet. The absolute bioavailability of the drug is only 2% because of extensive hepatic first-pass metabolism. Lipid-based formulations are reported to reduce the first-pass metabolism by promoting its lymphatic uptake. Materials and Methods: In the present investigation, microemulsion and Self-Microemulsifying Drug Delivery System (SMEDDS) formulations of Raloxifene were prepared. The prepared formulations were characterized for drug loading, size, transparency, zeta potential, Transmission Electron Microscopy (TEM) and in vitro intestinal permeability. Results: The results indicated that high drug loading, optimum size and desired zeta potential and transparency could be achieved with both SMEDDS and microemulsion. The TEM studies indicated the absence of aggregation with both the systems. The in vitro intestinal permeability results showed that the permeation of the drug from the microemulsion and SMEDDs was significantly higher than that obtained from the drug dispersion and marketed formulation. Conclusion: Lipid based formulations such as microemulsion and Self Microemulsifying drug delivery systems are expected to increase the oral bioavailability as evidenced by the increased intestinal permeation. PMID:21966167
Microemulsion Drug Delivery Systems for Radiopharmacy Studies
Directory of Open Access Journals (Sweden)
Emre Ozgenc
2016-11-01
Full Text Available Microemulsions have been used increasingly for last year’s because of ideal properties like favorable drug delivery, ease of preparation and physical stability. They have been improved the solubility and efficacy of the drug and reduce the side effects. Use of radiolabeled microemulsions plays an alternative role in drug delivery systems by investigating the formation, stability and application of microemulsions in radiopharmacy. Gama scintigraphic method is well recognized for developing and detecting the biodistribution of newly developed drugs or formulation. This review will focus on how radionuclides are able to play role with characterization studies of microemulsion drug delivery systems.
Federal Emergency Management Information System (FEMIS) system administration guide. Version 1.3
Energy Technology Data Exchange (ETDEWEB)
Burford, M.J.; Burnett, R.A.; Downing, T.R. [and others
1996-12-01
The Federal Emergency Management Information System (FEMIS) is an emergency management planning and analysis tool that was developed by the (Pacific Northwest National Laboratory) (PNNL) under the direction of the U.S. Army Chemical Biological Defense Command. The FEMIS System Administration Guide defines FEMIS hardware and software requirements and gives instructions for installing the FEMIS software package. 91 This document also contains information on the following: software installation for the FEMIS data servers, communication server, mail server, and the emergency management workstations; distribution media loading and FEMIS installation validation and troubleshooting; and system management of FEMIS users, login, privileges, and usage. The system administration utilities (tools), available in the FEMIS client software, are described for user accounts and site profile. This document also describes the installation and use of system and database administration utilities that will assist in keeping the FEMIS system running in an operational environment.
Neurobiology of dysregulated motivational systems in drug addiction
Edwards, Scott; Koob, George F
2010-01-01
The progression from recreational drug use to drug addiction impacts multiple neurobiological processes and can be conceptualized as a transition from positive to negative reinforcement mechanisms driving both drug-taking and drug-seeking behaviors. Neurobiological mechanisms for negative reinforcement, defined as drug taking that alleviates a negative emotional state, involve changes in the brain reward system and recruitment of brain stress (or antireward) systems within forebrain structures, including the extended amygdala. These systems are hypothesized to be dysregulated by excessive drug intake and to contribute to allostatic changes in reinforcement mechanisms associated with addiction. Points of intersection between positive and negative motivational circuitry may further drive the compulsivity of drug addiction but also provide a rich neurobiological substrate for therapeutic intervention. PMID:20563312
Luschmann, Christoph; Tessmar, Joerg; Schoeberl, Simon; Strauss, Olaf; Framme, Carsten; Luschmann, Karl; Goepferich, Achim
2013-11-20
With about 50-60 million cases in the US alone, dry eye disease represents a severe health care problem. Cyclosporin A (CsA) would be a potent candidate for a causal therapy. However, CsA is not sufficiently water soluble to be administrated via simple eye drops. We developed an in situ nanosuspension (INS) as a novel approach towards the administration of CsA to the cornea. It precipitates upon contact with the tear fluid and creates CsA nanoparticles that enter the cornea and release the drug by dissolution. We selected two liquid poly(ethylene glycols) (PEG) that dissolve CsA and create nanoparticles by precipitation of CsA upon water contact. Aqueous solutions of PEG and Solutol, a non-ionic surfactant, were well tolerated by primary human epithelial cells in vitro. To determine the critical water content needed for a precipitation, the solubility of CsA was investigated in quaternary systems of drug, solvent, surfactant and water. The best INS formulation showed a particle size of 505 ± 5 nm, a polydispersity index (PdI) of 0.23 ± 0.03 and a neutral zeta potential of -0.07 ± 0.05 mV. After single administration to porcine eyes in vitro, 3165 ± 597 ng(CsA)/g(cornea) were detected in corneal tissue, while the levels of Restasis a commercial formulation were, with 545 ± 137 ng(CsA)/g(cornea), significantly lower (P<0.01). These results demonstrate that an INS is a promising, novel approach towards the causal treatment of inflammatory diseases at the anterior eye. Copyright © 2013 Elsevier B.V. All rights reserved.
In situ gel systems as 'smart' carriers for sustained ocular drug delivery.
Agrawal, Ashish Kumar; Das, Manasmita; Jain, Sanyog
2012-04-01
In situ gel systems refer to a class of novel delivery vehicles, composed of natural, semisynthetic or synthetic polymers, which present the unique property of sol-gel conversion on receipt of biological stimulus. The present review summarizes the latest developments in in situ gel technology, with regard to ophthalmic drug delivery. Starting with the mechanism of ocular absorption, the review expands on the fabrication of various polymeric in situ gel systems, made up of two or more polymers presenting multi-stimuli sensitivity, coupled with other interesting features, such as bio-adhesion, enhanced penetration or sustained release. Various key issues and challenges in this area have been addressed and critically analyzed. The advent of in situ gel systems has inaugurated a new transom for 'smart' ocular delivery. By virtue of possessing stimuli-responsive phase transition properties, these systems can easily be administered into the eye, similar to normal eye drops. Their unique gelling properties endow them with special features, such as prolonged retention at the site of administration, followed by sustained drug release. Despite the superiority of these systems as compared with conventional ophthalmic formulations, further investigations are necessary to address the toxicity issues, so as to minimize regulatory hurdles during commercialization.
Drug accumulation by means of noninvasive magnetic drug delivery system
International Nuclear Information System (INIS)
Chuzawa, M.; Mishima, F.; Akiyama, Y.; Nishijima, S.
2011-01-01
The medication is one of the most general treatment methods, but drugs diffuse in the normal tissues other than the target part by the blood circulation. Therefore, side effect in the medication, particularly for a drug with strong effect such as anti-cancer drug, are a serious issue. Drug Delivery System (DDS) which accumulates the drug locally in the human body is one of the techniques to solve the side-effects. Magnetic Drug Delivery System (MDDS) is one of the active DDSs, which uses the magnetic force. The objective of this study is to accumulate the ferromagnetic drugs noninvasively in the deep part of the body by using MDDS. It is necessary to generate high magnetic field and magnetic gradient at the target part to reduce the side-effects to the tissues with no diseases. The biomimetic model was composed, which consists of multiple model organs connected with diverged blood vessel model. The arrangement of magnetic field was examined to accumulate ferromagnetic drug particles in the target model organ by using a superconducting bulk magnet which can generate high magnetic fields. The arrangement of magnet was designed to generate high and stable magnetic field at the target model organ. The accumulation experiment of ferromagnetic particles has been conducted. In this study, rotating HTS bulk magnet around the axis of blood vessels by centering on the target part was suggested, and the model experiment for magnet rotation was conducted. As a result, the accumulation of the ferromagnetic particles to the target model organ in the deep part was confirmed.
Development Considerations for Nanocrystal Drug Products.
Chen, Mei-Ling; John, Mathew; Lee, Sau L; Tyner, Katherine M
2017-05-01
Nanocrystal technology has emerged as a valuable tool for facilitating the delivery of poorly water-soluble active pharmaceutical ingredients (APIs) and enhancing API bioavailability. To date, the US Food and Drug Administration (FDA) has received over 80 applications for drug products containing nanocrystals. These products can be delivered by different routes of administration and are used in a variety of therapeutic areas. To aid in identifying key developmental considerations for these products, a retrospective analysis was performed on the submissions received by the FDA to date. Over 60% of the submissions were for the oral route of administration. Based on the Biopharmaceutics Classification System (BCS), most nanocrystal drugs submitted to the FDA are class II compounds that possess low aqueous solubility and high intestinal permeability. Impact of food on drug bioavailability was reduced for most nanocrystal formulations as compared with their micronized counterparts. For all routes of administration, dose proportionality was observed for some, but not all, nanocrystal products. Particular emphasis in the development of nanocrystal products was placed on the in-process tests and controls at critical manufacturing steps (such as milling process), mitigation and control of process-related impurities, and the stability of APIs or polymorphic form (s) during manufacturing and upon storage. This emphasis resulted in identifying challenges to the development of these products including accurate determination of particle size (distribution) of drug substance and/or nanocrystal colloidal dispersion, identification of polymorphic form (s), and establishment of drug substance/product specifications.
Nanoparticle-Mediated Pulmonary Drug Delivery: A Review
Directory of Open Access Journals (Sweden)
Mukta Paranjpe
2014-04-01
Full Text Available Colloidal drug delivery systems have been extensively investigated as drug carriers for the application of different drugs via different routes of administration. Systems, such as solid lipid nanoparticles, polymeric nanoparticles and liposomes, have been investigated for a long time for the treatment of various lung diseases. The pulmonary route, owing to a noninvasive method of drug administration, for both local and systemic delivery of an active pharmaceutical ingredient (API forms an ideal environment for APIs acting on pulmonary diseases and disorders. Additionally, this route offers many advantages, such as a high surface area with rapid absorption due to high vascularization and circumvention of the first pass effect. Aerosolization or inhalation of colloidal systems is currently being extensively studied and has huge potential for targeted drug delivery in the treatment of various diseases. Furthermore, the surfactant-associated proteins present at the interface enhance the effect of these formulations by decreasing the surface tension and allowing the maximum effect. The most challenging part of developing a colloidal system for nebulization is to maintain the critical physicochemical parameters for successful inhalation. The following review focuses on the current status of different colloidal systems available for the treatment of various lung disorders along with their characterization. Additionally, different in vitro, ex vivo and in vivo cell models developed for the testing of these systems with studies involving cell culture analysis are also discussed.
Microemulsions based transdermal drug delivery systems.
Vadlamudi, Harini C; Narendran, Hyndavi; Nagaswaram, Tejeswari; Yaga, Gowri; Thanniru, Jyotsna; Yalavarthi, Prasanna R
2014-01-01
Since the discovery of microemulsions by Jack H Schulman, there has been huge progress made in applying microemulsion systems in plethora of research and industrial process. Microemulsions are optically isotropic systems consisting of water, oil and amphiphile. These systems are beneficial due to their thermodynamic stability, optical clarity, ease of preparation, higher diffusion and absorption rates. Moreover, it has been reported that the ingredients of microemulsion can effectively overcome the diffusion barrier and penetrate through the stratum corneum of the skin. Hence it becomes promising for both transdermal and dermal drug delivery. However, low viscosity of microemulsion restrains its applicability in pharmaceutical industry. To overcome the above drawback, the low viscous microemulsions were added to viscous gel bases to potentiate its applications as topical drug delivery systems so that various drug related toxic effects and erratic drug absorption can be avoided. The present review deals with the microemulsions, various techniques involved in the development of organic nanoparticles. The review emphasized on microemulsion based systems such as hydrogels and organogels. The physicochemical characteristics, mechanical properties, rheological and stability principles involved in microemulsion based viscous gels were also explored.
1999-05-14
The Food and Drug Administration (FDA) is announcing the availability of a new compliance policy guide (CPG) entitled "Year 2000 (Y2K) Computer Compliance" (section 160-800). This guidance document represents the agency's current thinking on the manufacturing and distribution of domestic and imported products regulated by FDA using computer systems that may not perform properly before, or during, the transition to the year 2000 (Y2K). The text of the CPG is included in this notice. This compliance guidance document is an update to the Compliance Policy Guides Manual (August 1996 edition). It is a new CPG, and it will be included in the next printing of the Compliance Policy Guides Manual. This CPG is intended for FDA personnel, and it is available electronically to the public.
School Search and Seizure Law: A Guideline for K-12 Administrators
Frandsen, Scott
2010-01-01
In an effort to safeguard the learning environment, school administrators generally rely on district or local school guidelines and professional judgment. With new technology, the proliferation of drug use, and increased school violence, schools have become a complex environment to manage for both system and local leadership. Administrators are…
Energy Technology Data Exchange (ETDEWEB)
Bower, John C.(BATTELLE (PACIFIC NW LAB)); Burnett, Robert A.(BATTELLE (PACIFIC NW LAB)); Carter, Richard J.(BATTELLE (PACIFIC NW LAB)); Downing, Timothy R.(BATTELLE (PACIFIC NW LAB)); Homer, Brian J.(BATTELLE (PACIFIC NW LAB)); Holter, Nancy A.(BATTELLE (PACIFIC NW LAB)); Johnson, Daniel M.(BATTELLE (PACIFIC NW LAB)); Johnson, Ranata L.(BATTELLE (PACIFIC NW LAB)); Johnson, Sharon M.(BATTELLE (PACIFIC NW LAB)); Loveall, Robert M.(BATTELLE (PACIFIC NW LAB)); Ramos Jr., Juan (BATTELLE (PACIFIC NW LAB)); Schulze, Stacy A.(BATTELLE (PACIFIC NW LAB)); Sivaraman, Chitra (BATTELLE (PACIFIC NW LAB)); Stephan, Alex J.(BATTELLE (PACIFIC NW LAB)); Stoops, Lamar R.(BATTELLE (PACIFIC NW LAB)); Wood, Blanche M.(BATTELLE (PACIFIC NW LAB))
2001-12-01
The Federal Emergency Management System (FEMIS) is an emergency management planning and response tool. The FEMIS System Administration Guide provides information on FEMIS System Administrator activities as well as the utilities that are included with FEMIS.
75 FR 79383 - Unapproved Animal Drugs
2010-12-20
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0528] Unapproved Animal Drugs AGENCY: Food and Drug Administration, HHS. ACTION: Notice; request for comments. SUMMARY: The Food and Drug Administration (FDA, the Agency) is soliciting comments from stakeholders on...
Norman, Jessica L; Fixen, Danielle R; Saseen, Joseph J; Saba, Laura M; Linnebur, Sunny A
2017-01-01
Background: Women have higher morning serum zolpidem concentrations than men after taking an evening dose, potentially leading to increased risk of harm. On 19 April 2013, the United States Food and Drug Administration required labeling changes for zolpidem, recommending an initial dose of no greater than 5 mg (immediate release) or 6.25 mg (controlled release) per night in women. Objectives: The primary objective of this study was to compare prescribing practices before and after the 2013 zo...
Directory of Open Access Journals (Sweden)
Steven G Morgan
2010-12-01
Full Text Available Increasing attention is being paid to variations in the use of prescription drugs because their role in health care has grown to the point where their use can be considered a proxy for health system performance. Studies have shown that prescription drug use varies across regions in the US, UK, and Canada by more than would be predicted based on age and health status alone. In this paper, we explore the determinants of variations in the use of prescription drugs, drawing on health services theories of access to care.We conducted a cross-sectional analysis using population-based administrative health care data for British Columbia (BC, Canada. We used logistic and hierarchical regressions to analyze the effects of individual- and area-level determinants of use of prescriptions overall and rates of purchase of prescriptions from five therapeutic categories representing a range of indications: antihypertensives, statins, acid reducing drugs, opioid drugs, and antidepressants. To indicate the relative scale of regional variations and the importance of individual- and area-level variables in explaining them, we computed standardized rates of utilization for 49 local health areas in BC.We found that characteristics of individuals and the areas in which they live affect likelihood of prescription drug purchase. Individual-level factors influenced prescription drug purchases in ways generally consistent with behavioral models of health services use. Contextual variables exerted influences that differed by type of drug studied. Population health, education levels, and ethnic composition of local areas were associated with significant differences in the likelihood of purchasing medications. Relatively modest regional variations remained after both individual-level and area-level determinants were taken into account.The results of this study suggest that individual- and area-level factors should be considered when studying variations in the use of
Morgan, Steven G; Cunningham, Colleen M; Hanley, Gillian E
2010-12-29
Increasing attention is being paid to variations in the use of prescription drugs because their role in health care has grown to the point where their use can be considered a proxy for health system performance. Studies have shown that prescription drug use varies across regions in the US, UK, and Canada by more than would be predicted based on age and health status alone. In this paper, we explore the determinants of variations in the use of prescription drugs, drawing on health services theories of access to care. We conducted a cross-sectional analysis using population-based administrative health care data for British Columbia (BC), Canada. We used logistic and hierarchical regressions to analyze the effects of individual- and area-level determinants of use of prescriptions overall and rates of purchase of prescriptions from five therapeutic categories representing a range of indications: antihypertensives, statins, acid reducing drugs, opioid drugs, and antidepressants. To indicate the relative scale of regional variations and the importance of individual- and area-level variables in explaining them, we computed standardized rates of utilization for 49 local health areas in BC. We found that characteristics of individuals and the areas in which they live affect likelihood of prescription drug purchase. Individual-level factors influenced prescription drug purchases in ways generally consistent with behavioral models of health services use. Contextual variables exerted influences that differed by type of drug studied. Population health, education levels, and ethnic composition of local areas were associated with significant differences in the likelihood of purchasing medications. Relatively modest regional variations remained after both individual-level and area-level determinants were taken into account. The results of this study suggest that individual- and area-level factors should be considered when studying variations in the use of prescription drugs. Some
Pharmacokinetics of a self-microemulsifying drug delivery system of tacrolimus.
von Suesskind-Schwendi, Marietta; Gruber, Michael; Touraud, Didier; Kunz, Werner; Schmid, Christof; Hirt, Stephan W; Lehle, Karla
2013-07-01
This study evaluated the pharmacokinetics of tacrolimus (Tac) in a novel self-microemulsifying drug delivery system (SMEDDS) for improved oral administration. SMEDDS Tac consisted of ethyl oleate as the oily phase, Solutol HS 15 as the surfactant and glycofurol as the co-surfactant and contained 0.5mg/mL tacrolimus. Blood and tissue concentrations of tacrolimus from two study groups (oral application of SMEDDS Tac and Prograf®) were determined using ELISA technique following tacrolimus administration in rats. There was no difference between area under the whole blood concentration-time curve in the SEDDM Tac group and the Prograf® group. Maximum concentrations of the drug were three times higher (P<0.05) in the SEDDM Tac group accompanied by a 3-fold earlier peak time. Elimination half-life was significantly lower in the SEDDM Tac group. Application of SMEDDS Tac increased tissue accumulation. Already after 15 min, Tac levels of small intestine, liver, kidney, spleen, heart and bone marrow were significantly higher in the SMEDDS Tac group than in the Prograf® group (P<0.05). However, the Tac concentration in the kidney was significantly lower in the SMEDDS Tac group. Formulation of SMEDDS did not affect blood-brain barrier function. The SMEDDS is a potentially useful method for a local delivery of Tac to target organs. The selection of the optimum SMEDDS Tac composition might have advantage as an alternative oral dosage form for Tac. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
2012-02-14
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0081] Draft Guidance on Investigational New Drug Applications for Positron Emission Tomography Drugs; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...
21 CFR 880.5440 - Intravascular administration set.
2010-04-01
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Intravascular administration set. 880.5440 Section 880.5440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL HOSPITAL AND PERSONAL USE DEVICES General Hospital and Personal Use...
International Nuclear Information System (INIS)
1986-01-01
The FDA Compliance Program Guidance Manual provides a system for issuing and filing program plans and instructions directed to Food and Drug Administration Field operations for project implementation. Section IV provides those chapters of the Compliance Program Guidance Manual which pertain to the areas of medical and radiological devices. Some of the areas of coverage include laser and sunlamp standards inspections, compliance testing of various radiation-emitting products such as television receivers and microwave ovens, emergency response planning and policy, premarket approval and device manufacturers inspections, device problem reporting, sterilization of devices, and consumer education programs on medical and radiological devices
Biomimetics in drug delivery systems: A critical review.
Sheikhpour, Mojgan; Barani, Leila; Kasaeian, Alibakhsh
2017-05-10
Today, the advanced drug delivery systems have been focused on targeted drug delivery fields. The novel drug delivery is involved with the improvement of the capacity of drug loading in drug carriers, cellular uptake of drug carriers, and the sustained release of drugs within target cells. In this review, six groups of therapeutic drug carriers including biomimetic hydrogels, biomimetic micelles, biomimetic liposomes, biomimetic dendrimers, biomimetic polymeric carriers and biomimetic nanostructures, are studied. The subject takes advantage of the biomimetic methods of productions or the biomimetic techniques for the surface modifications, similar to what accrues in natural cells. Moreover, the effects of these biomimetic approaches for promoting the drug efficiency in targeted drug delivery are visible. The study demonstrates that the fabrication of biomimetic nanocomposite drug carriers could noticeably promote the efficiency of drugs in targeted drug delivery systems. Copyright © 2017 Elsevier B.V. All rights reserved.
International Nuclear Information System (INIS)
Connor, Michael J.; Marshall, Deborah C.; Moiseenko, Vitali; Moore, Kevin; Cervino, Laura; Atwood, Todd; Sanghvi, Parag; Mundt, Arno J.; Pawlicki, Todd; Recht, Abram; Hattangadi-Gluth, Jona A.
2017-01-01
Purpose: Radiation oncology relies on rapidly evolving technology and highly complex processes. The US Food and Drug Administration collects reports of adverse events related to medical devices. We sought to characterize all events involving radiation oncology devices (RODs) from the US Food and Drug Administration's postmarket surveillance Manufacturer and User Facility Device Experience (MAUDE) database, comparing these with non–radiation oncology devices. Methods and Materials: MAUDE data on RODs from 1991 to 2015 were sorted into 4 product categories (external beam, brachytherapy, planning systems, and simulation systems) and 5 device problem categories (software, mechanical, electrical, user error, and dose delivery impact). Outcomes included whether the device was evaluated by the manufacturer, adverse event type, remedial action, problem code, device age, and time since 510(k) approval. Descriptive statistics were performed with linear regression of time-series data. Results for RODs were compared with those for other devices by the Pearson χ"2 test for categorical data and 2-sample Kolmogorov-Smirnov test for distributions. Results: There were 4234 ROD and 4,985,698 other device adverse event reports. Adverse event reports increased over time, and events involving RODs peaked in 2011. Most ROD reports involved external beam therapy (50.8%), followed by brachytherapy (24.9%) and treatment planning systems (21.6%). The top problem types were software (30.4%), mechanical (20.9%), and user error (20.4%). RODs differed significantly from other devices in each outcome (P<.001). RODs were more likely to be evaluated by the manufacturer after an event (46.9% vs 33.0%) but less likely to be recalled (10.5% vs 37.9%) (P<.001). Device age and time since 510(k) approval were shorter among RODs (P<.001). Conclusions: Compared with other devices, RODs may experience adverse events sooner after manufacture and market approval. Close postmarket surveillance, improved
Energy Technology Data Exchange (ETDEWEB)
Connor, Michael J. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Department of Radiation Oncology, University of California Irvine School of Medicine, Irvine, California (United States); Marshall, Deborah C.; Moiseenko, Vitali; Moore, Kevin; Cervino, Laura; Atwood, Todd; Sanghvi, Parag; Mundt, Arno J.; Pawlicki, Todd [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Recht, Abram [Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (United States); Hattangadi-Gluth, Jona A., E-mail: jhattangadi@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)
2017-01-01
Purpose: Radiation oncology relies on rapidly evolving technology and highly complex processes. The US Food and Drug Administration collects reports of adverse events related to medical devices. We sought to characterize all events involving radiation oncology devices (RODs) from the US Food and Drug Administration's postmarket surveillance Manufacturer and User Facility Device Experience (MAUDE) database, comparing these with non–radiation oncology devices. Methods and Materials: MAUDE data on RODs from 1991 to 2015 were sorted into 4 product categories (external beam, brachytherapy, planning systems, and simulation systems) and 5 device problem categories (software, mechanical, electrical, user error, and dose delivery impact). Outcomes included whether the device was evaluated by the manufacturer, adverse event type, remedial action, problem code, device age, and time since 510(k) approval. Descriptive statistics were performed with linear regression of time-series data. Results for RODs were compared with those for other devices by the Pearson χ{sup 2} test for categorical data and 2-sample Kolmogorov-Smirnov test for distributions. Results: There were 4234 ROD and 4,985,698 other device adverse event reports. Adverse event reports increased over time, and events involving RODs peaked in 2011. Most ROD reports involved external beam therapy (50.8%), followed by brachytherapy (24.9%) and treatment planning systems (21.6%). The top problem types were software (30.4%), mechanical (20.9%), and user error (20.4%). RODs differed significantly from other devices in each outcome (P<.001). RODs were more likely to be evaluated by the manufacturer after an event (46.9% vs 33.0%) but less likely to be recalled (10.5% vs 37.9%) (P<.001). Device age and time since 510(k) approval were shorter among RODs (P<.001). Conclusions: Compared with other devices, RODs may experience adverse events sooner after manufacture and market approval. Close postmarket surveillance
Clinical Pharmacokinetics of Systemically Administered Antileishmanial Drugs
Kip, Anke E; Schellens, Jan H M; Beijnen, Jos H; Dorlo, Thomas P C
This review describes the pharmacokinetic properties of the systemically administered antileishmanial drugs pentavalent antimony, paromomycin, pentamidine, miltefosine and amphotericin B (AMB), including their absorption, distribution, metabolism and excretion and potential drug-drug interactions.
Adverse event management in mass drug administration for neglected tropical diseases.
Caplan, Arthur; Zink, Amanda
2014-03-01
The ethical challenges of reporting and managing adverse events (AEs) and serious AEs (SAEs) in the context of mass drug administration (MDA) for the treatment of neglected tropical diseases (NTDs) require reassessment of domestic and international policies on a global scale. Although the World Health Organization has set forth AE/SAE guidelines specifically for NTD MDA that incorporate suspected causality, and recommends that only SAEs get reported in this setting, most regulatory agencies continue to require the reporting of all SAEs exhibiting even a merely temporal relationship to activities associated with an MDA program. This greatly increases the potential for excess "noise" and undue risk aversion and is not only impractical but arguably unethical where huge proportions of populations are being treated for devastating diseases, and no good baseline exists against which to compare possible AE/SAE reports. Other population-specific variables that might change the way drug safety ought to be assessed include differing efficacy rates of a drug, background morbidity/mortality rates of the target disease in question, the growth rate of the incidence of disease, the availability of rescue or salvage therapies, and the willingness of local populations to take risks that other populations might not. The fact that NTDs are controllable and potentially eradicable with well-tolerated, effective, existing drugs might further alter our assessment of MDA safety and AE/SAE tolerability. At the same time, diffuseness of population, communication barriers, lack of resources, and other difficult surveillance challenges may present in NTD-affected settings. These limitations could impair the ability to monitor an MDA program's success, as well as hinder efforts to obtain informed consent or provide rescue therapy. Denying beneficial research interventions and MDA programs intended to benefit millions requires sound ethical justification based on more than the identification of
Targeted electrohydrodynamic printing for micro-reservoir drug delivery systems
International Nuclear Information System (INIS)
Hwang, Tae Heon; Kim, Jin Bum; Yang, Da Som; Ryu, WonHyoung; Park, Yong-il
2013-01-01
Microfluidic drug delivery systems consisting of a drug reservoir and microfluidic channels have shown the possibility of simple and robust modulation of drug release rate. However, the difficulty of loading a small quantity of drug into drug reservoirs at a micro-scale limited further development of such systems. Electrohydrodynamic (EHD) printing was employed to fill micro-reservoirs with controlled amount of drugs in the range of a few hundreds of picograms to tens of micrograms with spatial resolution of as small as 20 µm. Unlike most EHD systems, this system was configured in combination with an inverted microscope that allows in situ targeting of drug loading at micrometer scale accuracy. Methylene blue and rhodamine B were used as model drugs in distilled water, isopropanol and a polymer solution of a biodegradable polymer and dimethyl sulfoxide (DMSO). Also tetracycline-HCl/DI water was used as actual drug ink. The optimal parameters of EHD printing to load an extremely small quantity of drug into microscale drug reservoirs were investigated by changing pumping rates, the strength of an electric field and drug concentration. This targeted EHD technique was used to load drugs into the microreservoirs of PDMS microfluidic drug delivery devices and their drug release performance was demonstrated in vitro. (paper)
NELIS-an illicit drug detection system
International Nuclear Information System (INIS)
Dokhale, P.A.; Csikai, J.; Womble, P.C.; Vourvopoulos, G.
2001-01-01
NELIS (Neutron Elemental Inspection System) is currently being developed to inspect pallets laden with various commodities for contraband (drugs, etc.). NELIS analyzes the characteristic gamma rays from the elements in drugs such as C, O, H, Cl, N, etc. that are produced by nuclear reactions from fast and thermal neutrons (Pulsed Fast/Thermal Neutron Analysis). Hidden drugs are identified through the measurement of the elemental content of the object, and the comparison of expected and measured elemental ratios. NELIS can be coupled with conventional X-ray imaging system to optimize the inspection capabilities at ports of entry
Méthot, Julie; Brisson, Diane; Gaudet, Daniel
2012-04-01
Investigators and research teams participating in clinical trials have to deal with complex investigational products, study designs, and research environments. The emergence of new drug delivery systems and investigational products combining more than one drug and the development of biodrugs such as monoclonal antibodies, peptides, siRNA, and gene therapy to treat orphan or common diseases constitute a new challenge for investigators and clinical sites. We describe the requirements and challenges of drug management in conformity with Good Clinical Practices (GCPs) for investigators and sites participating in clinical trials. Review At all sites participating in clinical trials, standard operating procedures (SOPs) covering the critical path of drug and drug delivery systems management are required. All steps should be auditable, including reception, validation, storage, access, preparation, distribution, techniques of administration, use, return, and destruction of research products. Biodrugs require traceability and specific SOPs on the management of potential immune reactions. Investigational products must be stored under standard auditable conditions. The traceability of storage conditions (including temperature) requires these conditions to be monitored on a continuous basis. A dedicated space with restricted access limited to authorized qualified personnel facilitates the monitoring. The development of standardized, auditable settings and the application of dedicated, site-specific SOPs for the management of investigational products and drug delivery systems contribute to guarantee the compliance to GCP requirements.
Silumbwe, Adam; Zulu, Joseph Mumba; Halwindi, Hikabasa; Jacobs, Choolwe; Zgambo, Jessy; Dambe, Rosalia; Chola, Mumbi; Chongwe, Gershom; Michelo, Charles
2017-05-22
Understanding factors surrounding the implementation process of mass drug administration for lymphatic filariasis (MDA for LF) elimination programmes is critical for successful implementation of similar interventions. The sub-Saharan Africa (SSA) region records the second highest prevalence of the disease and subsequently several countries have initiated and implemented MDA for LF. Systematic reviews have largely focused on factors that affect coverage and compliance, with less attention on the implementation of MDA for LF activities. This review therefore seeks to document facilitators and barriers to implementation of MDA for LF in sub-Saharan Africa. A systematic search of databases PubMed, Science Direct and Google Scholar was conducted. English peer-reviewed publications focusing on implementation of MDA for LF from 2000 to 2016 were considered for analysis. Using thematic analysis, we synthesized the final 18 articles to identify key facilitators and barriers to MDA for LF programme implementation. The main factors facilitating implementation of MDA for LF programmes were awareness creation through innovative community health education programmes, creation of partnerships and collaborations, integration with existing programmes, creation of morbidity management programmes, motivation of community drug distributors (CDDs) through incentives and training, and management of adverse effects. Barriers to implementation included the lack of geographical demarcations and unregistered migrations into rapidly urbanizing areas, major disease outbreaks like the Ebola virus disease in West Africa, delayed drug deliveries at both country and community levels, inappropriate drug delivery strategies, limited number of drug distributors and the large number of households allocated for drug distribution. Mass drug administration for lymphatic filariasis elimination programmes should design their implementation strategies differently based on specific contextual factors to
Directory of Open Access Journals (Sweden)
Adam Silumbwe
2017-05-01
Full Text Available Abstract Background Understanding factors surrounding the implementation process of mass drug administration for lymphatic filariasis (MDA for LF elimination programmes is critical for successful implementation of similar interventions. The sub-Saharan Africa (SSA region records the second highest prevalence of the disease and subsequently several countries have initiated and implemented MDA for LF. Systematic reviews have largely focused on factors that affect coverage and compliance, with less attention on the implementation of MDA for LF activities. This review therefore seeks to document facilitators and barriers to implementation of MDA for LF in sub-Saharan Africa. Methods A systematic search of databases PubMed, Science Direct and Google Scholar was conducted. English peer-reviewed publications focusing on implementation of MDA for LF from 2000 to 2016 were considered for analysis. Using thematic analysis, we synthesized the final 18 articles to identify key facilitators and barriers to MDA for LF programme implementation. Results The main factors facilitating implementation of MDA for LF programmes were awareness creation through innovative community health education programmes, creation of partnerships and collaborations, integration with existing programmes, creation of morbidity management programmes, motivation of community drug distributors (CDDs through incentives and training, and management of adverse effects. Barriers to implementation included the lack of geographical demarcations and unregistered migrations into rapidly urbanizing areas, major disease outbreaks like the Ebola virus disease in West Africa, delayed drug deliveries at both country and community levels, inappropriate drug delivery strategies, limited number of drug distributors and the large number of households allocated for drug distribution. Conclusion Mass drug administration for lymphatic filariasis elimination programmes should design their implementation
Directory of Open Access Journals (Sweden)
Yung-Yi Cheng
2018-04-01
Full Text Available With an increasing number of cancer patients seeking an improved quality of life, complementary and alternative therapies are becoming more common ways to achieve such improvements. The potential risks of concurrent administration are serious and must be addressed. However, comprehensive evidence for the risks and benefits of combining anticancer drugs with traditional herbs is rare. Pharmacokinetic investigations are an efficient way to understand the influence of concomitant remedies. Therefore, this study aimed to collect the results of pharmacokinetic studies relating to the concurrent use of cancer chemotherapy and complementary and alternative therapies. According to the National Health Insurance (NHI database in Taiwan and several publications, the three most commonly prescribed formulations for cancer patients are Xiang-Sha-Liu-Jun-Zi-Tang, Jia-Wei-Xiao-Yao-San and Bu-Zhong-Yi-Qi-Tang. The three most commonly prescribed single herbs for cancer patients are Hedyotis diffusa, Scutellaria barbata, and Astragalus membranaceus. Few studies have discussed herb–drug interactions involving these herbs from a pharmacokinetics perspective. Here, we reviewed Jia-Wei-Xiao-Yao-San, Long-Dan-Xie-Gan-Tang, Curcuma longa and milk thistle to provide information based on pharmacokinetic evidence for healthcare professionals to use in educating patients about the risks of the concomitant use of various remedies. Keywords: Traditional Chinese medicine, Chemotherapy drug, Pharmacokinetics, Herb–drug interaction
STRATEGIES AND PROSPECTS OF NASAL DRUG DELIVERY SYSTEMS
Gannu Praveen Kumar
2012-01-01
The recent advancement of nasal drug delivery systems has increased enormously and is gaining significant importance. Intranasal therapy has been an accepted form of treatment in the Ayurvedic system of Indian Medicine. The non-invasive delivery of nasal drug delivery systems made to exploit for the development of successful treatment. The advantages, disadvantages, mechanism of action and application of nasal drug delivery system in local delivery, systematic delivery, nasal vaccines and CNS...
75 FR 81455 - New Animal Drugs; Deslorelin
2010-12-28
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510 and 522 [Docket No. FDA-2010-N-0002] New Animal Drugs; Deslorelin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...
75 FR 1275 - New Animal Drugs; Ractopamine
2010-01-11
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 558 [Docket No. FDA-2009-N-0665] New Animal Drugs; Ractopamine AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to...
System Administrator | IDRC - International Development Research ...
International Development Research Centre (IDRC) Digital Library (Canada)
Administers an effective patch management program to mitigate risks by applying ... technologies which can be used to protect the information systems and ... information on IT administration and troubleshooting techniques and skills to IMTD ...
Drug delivery system and radiation therapy
International Nuclear Information System (INIS)
Shibata, Tokushi
2005-01-01
This paper describes the review of radiation therapy, neutron capture therapy (NCT) and drug delivery system for the latter. In cancer radiation therapy, there are problems of body movement like breathing, needless irradiation of normal tissues, difficulty to decide the correct irradiation position and tumor morphology. NCT has advantages to overcome these, and since boron has a big cross section for thermal neutron, NPT uses the reaction 10 B(n, α) 7 Li in the target cancer which previously incorporated the boron-containing drug. During the period 1966-1996, 246 patients were treated with this in Japan and the treatment has been continued thereafter. The tasks for NCT are developments of drug delivery system efficient to deliver the drug into the tumor and of convenient neutron source like the accelerator. (S.I.)
REVERSIBLE VENTILATION SYSTEM FOR ADMINISTRATIVE BUILDINGS
Directory of Open Access Journals (Sweden)
Valery Yu. Kravchuk
2017-01-01
Full Text Available Abstract. Objectives To consider the possibility of applying the principle of reversing air flows for a centralised ventilation system; to develop a specific scheme for air exchange reversible ventilation, which will take into account the peculiarities of the microclimate of administrative buildings; to select the type of filling of the air-permeable element and justify this choice; to determine the conditions for changing the direction of air movement in the ventilation system and the area of its application; to form a list of equipment necessary for the operation of such a system; to consider the influence of supply and exhaust devices on the heat and humidity regime of claddings. Methods To achieve this goal, the published thematic material was reviewed and a patent search carried out using Russian and European databases. Data on mathematical modelling of filtration in porous media and experimental results were used. A method for ventilating rooms in administrative building using the reversal of movement of supply and exhaust air streams along the same channels was applied. Results Schemas for reversible ventilation systems are presented and their modes of operation considered. It is established that the idea of reversing ventilation flows has not yet been applied in the development of centralised ventilation systems. Based on these published materials, it was concluded that the proposed design of supply and exhaust devices can be used in practice. An original air exchange scheme for the ventilation of administrative buildings and design of supply and exhaust devices for this system are proposed. The conditions for changing the operating modes of the system and the scope of its application are determined. Conclusion The use of the proposed ventilation system allows normative air exchange to be provided without using a supply unit during the cold season. This application of airflow reversal allows the potential of natural forces to be used
2010-10-01
... Science and Innovation, (2) Strengthen the Safety and Integrity of the Global Supply Chain, (3) Strengthen... comments to the Division of Dockets Management (HFA- 305), Food and Drug Administration, 5630 Fishers Lane... strengthen the strategic management structure currently in place. For comparison purposes, the current FDA...
Frakt, Austin B; Pizer, Steven D; Hendricks, Ann M
2008-12-01
Medicare and the Veterans Health Administration (VA) both finance large outpatient prescription drug programs, though in very different ways. In the ongoing debate on how to control Medicare spending, some suggest that Medicare should negotiate directly with drug manufacturers, as the VA does. In this article we relate the role of interest groups to policy differences between Medicare and the VA and, in doing so, explain why such a large change to the Medicare drug program is unlikely. We argue that key policy differences are attributable to stable differences in interest group involvement. While this stability makes major changes in Medicare unlikely, it suggests the possibility of leveraging VA drug purchasing to achieve savings in Medicare. This could be done through a VA-administered drug-only benefit for Medicare-enrolled veterans. Such a partnership could incorporate key elements of both programs: capacity to accept large numbers of enrollees (like Medicare) and leverage to negotiate prescription drug prices (like the VA). Moreover, it could be implemented at no cost to the VA while achieving savings for Medicare and beneficiaries.
Fautrel, Bruno; Balsa, Alejandro; Van Riel, Piet; Casillas, Marta; Capron, Jean-Philippe; Cueille, Carine; de la Torre, Inmaculada
2017-07-01
A comprehensive review was performed to investigate the effect of route of administration on medication adherence and persistence in rheumatoid arthritis (RA) and to compare adherence/persistence with oral medications between RA and a non-painful disease (dyslipidemia). Comprehensive database searches were performed to identify studies investigating medication adherence and/or persistence in adults with RA receiving conventional synthetic or biologic agents. Similar searches were performed for studies of patients with dyslipidemia receiving statins. Studies had to be published after 1998 in English and involve ≥6 months' follow up. Adherence and persistence were compared between the different routes of drug administration in RA, and between the two diseases for oral medications. A total of 35 and 28 papers underwent data extraction for RA and dyslipidemia, respectively. Within the constraints of the analysis, adherence and persistence rates appeared broadly similar for the different routes of drug administration in RA. Adherence to oral medications was also broadly similar across the two diseases, but persistence was lower in dyslipidemia. Poor adherence has clinical consequences in both diseases: greater disease activity and risk of flare in RA, and increased serum cholesterol levels and risk of heart and cerebrovascular disease in dyslipidemia. Over 1-3 years, poor adherence to biologic RA medications led to increased resource use and medical costs but lower total direct costs due to reduced biologic drug costs. Conversely, poor adherence to dyslipidemia medications resulted in increased total direct costs. In both diseases, adherence improved with patient education/support. The route of drug administration and the symptomatic (pain) nature of the disease do not appear to be dominant factors for drug adherence or persistence in RA. The wide range of adherence and persistence values and definitions across studies made comparisons between drug formulations and
76 FR 6326 - New Animal Drugs; Masitinib
2011-02-04
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510 and 516 [Docket No. FDA-2011-N-0003] New Animal Drugs; Masitinib AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to...
75 FR 79295 - New Animal Drugs; Mupirocin
2010-12-20
... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510 and 524 [Docket No. FDA-2010-N-0002] New Animal Drugs; Mupirocin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to...
Mucoadhesive drug delivery systems
Directory of Open Access Journals (Sweden)
Rahamatullah Shaikh
2011-01-01
Full Text Available Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal.
Anti-Obesity Agents and the US Food and Drug Administration.
Casey, Martin F; Mechanick, Jeffrey I
2014-09-01
Despite the growing market for obesity care, the US Food and Drug Administration (FDA) has approved only two new pharmaceutical agents-lorcaserin and combination phentermine/topiramate-for weight reduction since 2000, while removing three agents from the market in the same time period. This article explores the FDA's history and role in the approval of anti-obesity medications within the context of a public health model of obesity. Through the review of obesity literature and FDA approval documents, we identified two major barriers preventing fair evaluation of anti-obesity agents including: (1) methodological pitfalls in clinical trials and (2) misaligned values in the assessment of anti-obesity agents. Specific recommendations include the use of adaptive (Bayesian) design protocols, value-based analyses of risks and benefits, and regulatory guidance based on a comprehensive, multi-platform obesity disease model. Positively addressing barriers in the FDA approval process of anti-obesity agents may have many beneficial effects within an obesity disease model.
NOVEL APROACHES ON BUCCAL MUCOADHESIVE DRUG DELIVERY SYSTEM
Dibyalochan Mohanty* , C. Gurulatha, Dr.Vasudha Bakshi, B. Mavya
2018-01-01
Among novel drug delivery system ,Buccal mucoadhesive systems have attracted great attention in recent years due to their ability to adhere and remain on the oral mucosa and to release their drug content gradually ,bioadhesion refers to any bond formed between two biological surface or a bond between a biological and a systemic surface. Buccal mucosa is preferred for both systemic and local drug action. The mucosa has a rich blood supply and it relatively permeable. Buccal mucoadhesive films ...
A Touch-Communication Framework for Drug Delivery Based on a Transient Microbot System.
Yifan Chen; Kosmas, Panagiotis; Anwar, Putri Santi; Limin Huang
2015-06-01
Recent progress in bioresorbable radio frequency electronics and engineered bacteria has promised the prospect of realizing a transient microbot (TM) system for therapeutic applications. The inorganic or organic miniature robots will dissolve into the human body after completing the required tasks and cause no side-effect. In this paper, we propose a potential architecture of a TM system for transporting pharmaceutical compounds inside the body, and analyze the system using a micro-to-macro cross-scale communication model. The remote controllability and tangibility of a TM essentially lead to a touch-communication (TouchCom) paradigm. Externally maneuverable and trackable TMs are responsible for the delivery of drug particles (information molecules in the TouchCom context). The loading/injection and unloading of the drug correspond to the transmitting and receiving processes in the TouchCom framework. Subsequently, we investigate simulation tools for the propagation and transient characteristics of TMs in the blood vessels. We also define the propagation delay, path loss, as well as angular and delay spectra of targeting intensity, which are parallel to their counterpart concepts in the conventional wireless channel. Finally, our approach is illustrated with comprehensive simulation studies of targeted drug delivery by using the proposed analytical framework integrating robotics and communications at crossover length scales. The proposed methodology may find important applications in the design and analysis of TM-assisted administration of pharmaceutical compounds.
Information System for Educational Policy and Administration.
Clayton, J. C., Jr.
Educational Information System (EIS) is a proposed computer-based data processing system to help schools solve current educational problems more efficiently. The system would allow for more effective administrative operations in student scheduling, financial accounting, and long range planning. It would also assist school trustees and others in…
ICT enabled land administration systems for sustainable development
DEFF Research Database (Denmark)
Enemark, Stig
2006-01-01
This paper analyses the current Land Administration System (LAS) in Denmark with a focus on institutional arrangements, land policies, land information infrastructure, and the four land administration functions: land tenure, land value, land-use, and land development. The analysis, this way, builds...
Microfluidic cell culture systems for drug research.
Wu, Min-Hsien; Huang, Song-Bin; Lee, Gwo-Bin
2010-04-21
In pharmaceutical research, an adequate cell-based assay scheme to efficiently screen and to validate potential drug candidates in the initial stage of drug discovery is crucial. In order to better predict the clinical response to drug compounds, a cell culture model that is faithful to in vivo behavior is required. With the recent advances in microfluidic technology, the utilization of a microfluidic-based cell culture has several advantages, making it a promising alternative to the conventional cell culture methods. This review starts with a comprehensive discussion on the general process for drug discovery and development, the role of cell culture in drug research, and the characteristics of the cell culture formats commonly used in current microfluidic-based, cell-culture practices. Due to the significant differences in several physical phenomena between microscale and macroscale devices, microfluidic technology provides unique functionality, which is not previously possible by using traditional techniques. In a subsequent section, the niches for using microfluidic-based cell culture systems for drug research are discussed. Moreover, some critical issues such as cell immobilization, medium pumping or gradient generation in microfluidic-based, cell-culture systems are also reviewed. Finally, some practical applications of microfluidic-based, cell-culture systems in drug research particularly those pertaining to drug toxicity testing and those with a high-throughput capability are highlighted.
Design and Efficacy of Nanogels Formulations for Intranasal Administration
Directory of Open Access Journals (Sweden)
Blessing A. Aderibigbe
2018-05-01
Full Text Available Nanogels are drug delivery systems that can bypass the blood-brain barrier and deliver drugs to the desired site when administered intranasally. They have been used as a drug delivery platform for the management of brain diseases such as Alzheimer disease, migraine, schizophrenia and depression. nanogels have also been developed as vaccine carriers for the protection of bacterial infections such as influenza, meningitis, pneumonia and as veterinary vaccine carriers for the protection of animals from encephalomyelitis and mouth to foot disease. It has been developed as vaccine carriers for the prevention of lifestyle disease such as obesity. Intranasal administration of therapeutics using nanogels for the management of brain diseases revealed that the drug transportation was via the olfactory nerve pathway resulting in rapid drug delivery to the brain with excellent neuroprotective effect. The application of nanogels as vaccine carriers also induced significant responses associated with protective immunity against selected bacterial and viral infections. This review provides a detailed information on the enhanced therapeutic effects, mechanisms and biological efficacy of nanogels for intranasal administration.
FDA's requirements for radiation dosimetry of radiopharmaceutical drug products
International Nuclear Information System (INIS)
Abel, N.M.
1986-01-01
The primary concern of the Office of Drug Research and Review of the Food and Drug Administration in the field of radiation dosimetry is to ensure that radiopharmaceutical drug products are safe when used as investigational drugs (INDs) and are both safe and effective when a new drug application (NDA) is approved. In order to accomplish this, the sponsor of either an IND or applicant in the case of NDA must provide information that clearly describes the radiation dose that a patient will receive from the administration of the drug. The submitted numerical estimates of the radiation dose should be based on an absorbed fraction method of radiation dose calculation, such as the system set forth by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine or the system set forth by the International Commission on Radiological Protection (ICRP). This presentation will describe in detail the data that a sponsor of an IND needs to submit to satisfy the regulatory requirements. Examples will be given of common mistakes and omissions by sponsors in their presentation of data
Guo, Feng; Zhong, Haijun; He, Jing; Xie, Baogang; Liu, Fen; Xu, Helin; Liu, Minmin; Xu, Chunlian
2011-07-01
Dipyridamole shows poor and variable bioavailability after oral administration due to pHdependent solubility, low biomembrane permeability as well as being a substrate of P-glycoprotein. In order to improve the oral absorption of dipyridamole, a self-microemulsifying drug delivery system (SMEDDS) for dipyridamole was prepared and evaluated in vitro and in vivo. The optimum formulation was 18% oleic acid, 12% Labrafac lipophile WL 1349, 42% Solutol HS 15 and 28% isopropyl alcohol. It was found that the performance of self-microemulsification with the combination of oleic acid and Labrafac lipophile WL 1349 increased compared with just one oil. The results obtained from an in vitro dissolution assay indicated that dipyridamole in SMEDDS dissolved rapidly and completely in pH 6.8 aqueous media, while the commercial drug tablet was less soluble. An oral bioavailability study in rats showed that dipyridamole in the SMEDDS formulation had a 2.06-fold increased absorption compared with the simple drug suspension. It was evident that SMEDDS may be an effective approach to improve the oral absorption for drugs having pH-dependent solubility.
A new prize system for drug innovation.
Gandjour, Afschin; Chernyak, Nadja
2011-10-01
We propose a new prize (reward) system for drug innovation which pays a price based on the value of health benefits accrued over time. Willingness to pay for a unit of health benefit is determined based on the cost-effectiveness ratio of palliative/nursing care. We solve the problem of limited information on the value of health benefits by mathematically relating reward size to the uncertainty of information including information on potential drug overuse. The proposed prize system offers optimal incentives to invest in research and development because it rewards the innovator for the social value of drug innovation. The proposal is envisaged as a non-voluntary alternative to the current patent system and reduces excessive marketing of innovators and generic drug producers. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Comparison of scientific and administrative database management systems
Stoltzfus, J. C.
1983-01-01
Some characteristics found to be different for scientific and administrative data bases are identified and some of the corresponding generic requirements for data base management systems (DBMS) are discussed. The requirements discussed are especially stringent for either the scientific or administrative data bases. For some, no commercial DBMS is fully satisfactory, and the data base designer must invent a suitable approach. For others, commercial systems are available with elegant solutions, and a wrong choice would mean an expensive work-around to provide the missing features. It is concluded that selection of a DBMS must be based on the requirements for the information system. There is no unique distinction between scientific and administrative data bases or DBMS. The distinction comes from the logical structure of the data, and understanding the data and their relationships is the key to defining the requirements and selecting an appropriate DBMS for a given set of applications.
Inhalation of nanoparticle-based drug for lung cancer treatment: Advantages and challenges
Directory of Open Access Journals (Sweden)
Wing-Hin Lee
2015-12-01
Full Text Available Ever since the success of developing inhalable insulin, drug delivery via pulmonary administration has become an attractive route to treat chronic diseases. Pulmonary delivery system for nanotechnology is a relatively new concept especially when applicable to lung cancer therapy. Nano-based systems such as liposome, polymeric nanoparticles or micelles are strategically designed to enhance the therapeutic index of anti-cancer drugs through improvement of their bioavailability, stability and residency at targeted lung regions. Along with these benefits, nano-based systems also provide additional diagnostic advantages during lung cancer treatment, including imaging, screening and drug tracking. Nevertheless, delivery of nano-based drugs via pulmonary administration for lung cancer therapy is still in its infancy and numerous challenges are expected. Pharmacology, immunology, toxicology and large-scale manufacturing (stability and activity of drugs are some aspects in nanotechnology that should be taken into consideration for the development of inhalable nano-based chemotherapeutic drugs. This review will focus on the current inhalable nano-based drugs for lung cancer treatment.
Microneedle-based drug delivery systems for transdermal route.
Pierre, Maria Bernadete Riemma; Rossetti, Fabia Cristina
2014-03-01
Transdermal delivery offers an attractive, noninvasive administration route but it is limited by the skin's barrier to penetration. Minimally invasive techniques, such as the use of microneedles (MNs), bypass the stratum corneum (SC) barrier to permit the drug's direct access to the viable epidermis. These novel micro devices have been developed to puncture the skin for the transdermal delivery of hydrophilic drugs and macromolecules, including peptides, DNA and other molecules, that would otherwise have difficulty passing the outermost layer of the skin, the SC. Using the tools of the microelectronics industry, MNs have been fabricated with a range of sizes, shapes and materials. MNs have been shown to be robust enough to penetrate the skin and dramatically increase the skin permeability of several drugs. Moreover, MNs have reduced needle insertion pain and tissue trauma and provided controlled delivery across the skin. This review focuses on the current state of the art in the transdermal delivery of drugs using various types of MNs and developments in the field of microscale devices, as well as examples of their uses and clinical safety.
A case-mix classification system for explaining healthcare costs using administrative data in Italy.
Corti, Maria Chiara; Avossa, Francesco; Schievano, Elena; Gallina, Pietro; Ferroni, Eliana; Alba, Natalia; Dotto, Matilde; Basso, Cristina; Netti, Silvia Tiozzo; Fedeli, Ugo; Mantoan, Domenico
2018-03-04
The Italian National Health Service (NHS) provides universal coverage to all citizens, granting primary and hospital care with a copayment system for outpatient and drug services. Financing of Local Health Trusts (LHTs) is based on a capitation system adjusted only for age, gender and area of residence. We applied a risk-adjustment system (Johns Hopkins Adjusted Clinical Groups System, ACG® System) in order to explain health care costs using routinely collected administrative data in the Veneto Region (North-eastern Italy). All residents in the Veneto Region were included in the study. The ACG system was applied to classify the regional population based on the following information sources for the year 2015: Hospital Discharges, Emergency Room visits, Chronic disease registry for copayment exemptions, ambulatory visits, medications, the Home care database, and drug prescriptions. Simple linear regressions were used to contrast an age-gender model to models incorporating more comprehensive risk measures aimed at predicting health care costs. A simple age-gender model explained only 8% of the variance of 2015 total costs. Adding diagnoses-related variables provided a 23% increase, while pharmacy based variables provided an additional 17% increase in explained variance. The adjusted R-squared of the comprehensive model was 6 times that of the simple age-gender model. ACG System provides substantial improvement in predicting health care costs when compared to simple age-gender adjustments. Aging itself is not the main determinant of the increase of health care costs, which is better explained by the accumulation of chronic conditions and the resulting multimorbidity. Copyright © 2018. Published by Elsevier B.V.
A study on nanodiamond-based drug delivery system
International Nuclear Information System (INIS)
Li Jing; Zhang Xiaoyong; Zhu Ying; Li Wenxin; Huang Qing
2010-01-01
A multifunctional drug delivery system based on nanodiamonds (NDs) has been developed. FITC, HCPT and TF were absorbed on NDs successively to form the multifunctional complex. The NDs and ND complex samples were characterized by TEM, FR-IR and UV-V. The results indicated that this drug delivery system is a high loading system. Efficacy of the drug delivery system on Hela cell was evaluated with MTT assays and fluorescence microscopy. The results show that multifunction of the NDs complex include fluorescence, targeting and high efficacy. (authors)
Recent trends in drug delivery system using protein nanoparticles.
Sripriyalakshmi, S; Jose, Pinkybel; Ravindran, Aswathy; Anjali, C H
2014-09-01
Engineered nanoparticles that can facilitate drug formulation and passively target tumours have been under extensive research in recent years. These successes have driven a new wave of significant innovation in the generation of advanced particles. The fate and transport of diagnostic nanoparticles would significantly depend on nonselective drug delivery, and hence the use of high drug dosage is implemented. In this perspective, nanocarrier-based drug targeting strategies can be used which improve the selective delivery of drugs to the site of action, i.e. drug targeting. Pharmaceutical industries majorly focus on reducing the toxicity and side effects of drugs but only recently it has been realised that carrier systems themselves may pose risks to the patient. Proteins are compatible with biological systems and they are biodegradable. They offer a multitude of moieties for modifications to tailor drug binding, imaging or targeting entities. Thus, protein nanoparticles provide outstanding contributions as a carrier for drug delivery systems. This review summarises recent progress in particle-based therapeutic delivery and discusses important concepts in particle design and biological barriers for developing the next generation of particles drug delivery systems.
Photoprocesses of photosensitizing drugs within cyclodextrin cavities.
Monti, Sandra; Sortino, Salvatore
2002-09-01
Recently some interest has been focused on the photobehavior of CD-drug inclusion complexes in relation to the problem of the biological photosensitization by drugs. This review is dedicated to the illustration of the mechanistic aspects of the photoprocesses occurring in some non-steroidal anti-inflammatory drugs (NSAIDs), with photosensitising side effects, within CD cavities. It is shown how the photobehavior of the CD-drug associates can help to model the photoreactivity of the drugs in biological sites. The limitations for the use of CDs as protective systems for the clinical administration of photosensitising drugs is also evidenced.
Stimuli-sensitive hydrogels: A novel ophthalmic drug delivery system
Directory of Open Access Journals (Sweden)
Singh Vinod
2010-01-01
Full Text Available Background: Stimuli-sensitive hydrogels are three-dimensional, hydrophilic, polymeric networks capable of imbibing large amounts of water or biological fluids on stimulation, such as pH, temperature and ionic change. Aim: To develop hydrogels that are sensitive to stimuli, i.e. pH, in the cul-de-sac of the eye for providing a prolonged effect and increased bioavailability with reduction in frequency of administration. Materials and Methods: Hydrogels were formulated by using timolol maleate as the model drug, polyacrylic acid as the gelling agents, hydroxyl ethyl cellulose as the viscolizer and sodium chloride as the isotonic agent. Stirring of ingredients in pH 4 phosphate buffer at high speed was carried out. The dynamic dialysis technique was used for drug release studies. In vivo study for reduction in intraocular pressure was carried out by using albino rabbits. Statistical Analysis: Drug release studies data were used for statistical analysis in first-order plots, Higuchi plots and Peppas exponential plots. Student t-test was performed for in vivo study. Results: Viscosity of the hydrogel increases from 3.84 cps to 9.54 cps due to change in pH 4 to pH 7.4. The slope value of the Peppas equation was found to be 0.3081, 0.3743 and 0.2964. Up to 80% of drug was released in an 8 h drug release study. Sterile hydrogels with no ocular irritation were obtained. Conclusions: Hydrogels show increase in viscosity due to change in pH. Hydrogels were therapeutically effacious, stable, non-irritant and showed Fickian diffusion. In vivo results clearly show a prolonged reduction in intraocular pressure, which was helpful for reduction in the frequency of administration.
Drugs and drug delivery systems targeting amyloid-β in Alzheimer's disease
Directory of Open Access Journals (Sweden)
Morgan Robinson
2015-07-01
Full Text Available Alzheimer's disease (AD is a devastating neurodegenerative disorder with no cure and limited treatment solutions that are unable to target any of the suspected causes. Increasing evidence suggests that one of the causes of neurodegeneration is the overproduction of amyloid beta (Aβ and the inability of Aβ peptides to be cleared from the brain, resulting in self-aggregation to form toxic oligomers, fibrils and plaques. One of the potential treatment options is to target Aβ and prevent self-aggregation to allow for a natural clearing of the brain. In this paper, we review the drugs and drug delivery systems that target Aβ in relation to Alzheimer's disease. Many attempts have been made to use anti-Aβ targeting molecules capable of targeting Aβ (with much success in vitro and in vivo animal models, but the major obstacle to this technique is the challenge posed by the blood brain barrier (BBB. This highly selective barrier protects the brain from toxic molecules and pathogens and prevents the delivery of most drugs. Therefore novel Aβ aggregation inhibitor drugs will require well thought-out drug delivery systems to deliver sufficient concentrations to the brain.
Kalam, Mohd Abul; Raish, Mohammad; Ahmed, Ajaz; Alkharfy, Khalid M; Mohsin, Kazi; Alshamsan, Aws; Al-Jenoobi, Fahad I; Al-Mohizea, Abdullah M; Shakeel, Faiyaz
2017-07-01
Thymoquinone (TQ) is a poorly water soluble bioactive compound which shows poor oral bioavailability upon oral administration. Due to poor aqueous solubility and bioavailability of TQ, various self-nanoemulsifying drug delivery systems (SNEDDS) of TQ were developed and evaluated for enhancement of its hepatoprotective effects and oral bioavailability. Hepatoprotective and pharmacokinetic studies of TQ suspension and TQ-SNEDDS were carried out in rat models. Different SNEDDS formulations of TQ were developed and thermodynamically stable TQ-SNEDDS were characterized for physicochemical parameters and evaluated for drug release studies via dialysis membrane. Optimized SNEDDS formulation of TQ was selected for further evaluation of in vivo evaluation. In vivo hepatoprotective investigations showed significant hepatoprotective effects for optimized TQ-SNEDDS in comparison with TQ suspension. The oral administration of optimized SNEDDS showed significant improvement in in vivo absorption of TQ in comparison with TQ suspension. The relatively bioavailability of TQ was enhanced 3.87-fold by optimized SNEDDS in comparison with TQ suspension. The results of this research work indicated the potential of SNEDDS in enhancing relative bioavailability and therapeutic effects of natural bioactive compounds such as TQ. Copyright © 2017 Elsevier B.V. All rights reserved.