Sample records for injectable dosage forms

  1. 21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms. ...

  2. 21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms. ...

  3. 21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms. ...

  4. 21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms. ...

  5. 21 CFR 522.1662 - Oxytetracycline hydrochloride implantation or injectable dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride implantation or injectable dosage forms. 522.1662 Section 522.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1662 Oxytetracycline hydrochloride implantation or injectable...

  6. 21 CFR 522.1660 - Oxytetracycline injectable dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline injectable dosage forms. 522.1660 Section 522.1660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 522.1660 Oxytetracycline injectable dosage forms. ...

  7. 21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

  8. 21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

  9. 21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

  10. 21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

  11. 21 CFR 522.1696 - Penicillin G procaine injectable dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Penicillin G procaine injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1696 Penicillin G procaine injectable dosage forms. ...

  12. 75 FR 9333 - Implantation or Injectable Dosage Form New Animal Drugs; Tilmicosin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-02

    .... FDA-2010-N-0002] Implantation or Injectable Dosage Form New Animal Drugs; Tilmicosin AGENCY: Food and... dose range for use of an injectable solution of tilmicosin phosphate for treatment of respiratory... 300 (tilmicosin injection, USP) Injection, available by veterinary prescription for use in the...

  13. 76 FR 3488 - Implantation or Injectable Dosage Form New Animal Drugs; Oxytetracycline and Flunixin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-20

    .... FDA-2010-N-0002] Implantation or Injectable Dosage Form New Animal Drugs; Oxytetracycline and Flunixin... combination drug injectable solution containing oxytetracycline and flunixin meglumine in cattle. [[Page 3489... veterinary prescription use of HEXASOL (oxytetracycline and flunixin meglumine) Injection for the treatment...

  14. 76 FR 22610 - Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-22

    .... FDA-2011-N-0003] Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin AGENCY: Food... amending the animal drug regulations to reflect approval of a supplemental new animal drug application... INFORMATION: Bayer HealthCare LLC, Animal Health Division, P.O. Box 390, Shawnee Mission, KS 66201, filed a...

  15. 75 FR 13225 - Implantation or Injectable Dosage Form New Animal Drugs; Flunixin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-19

    .... FDA-2010-N-0002] Implantation or Injectable Dosage Form New Animal Drugs; Flunixin AGENCY: Food and... amending the animal drug regulations to reflect approval of an original abbreviated new animal drug... copy of BANAMINE-S, sponsored by Schering-Plough Animal Health Corp. under NADA 101-479. The ANADA is...

  16. 77 FR 4226 - Implantation or Injectable Dosage Form New Animal Drugs; Danofloxacin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-27

    .... FDA-2011-N-0003] Implantation or Injectable Dosage Form New Animal Drugs; Danofloxacin AGENCY: Food... amending the animal drug regulations to reflect approval of a supplemental new animal drug application.... 801-808. List of Subjects in 21 CFR Part 522 Animal drugs. Therefore, under the Federal Food, Drug...

  17. 75 FR 20268 - Implantation or Injectable Dosage Form New Animal Drugs; Change of Sponsor; Propofol

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-19

    ... use in dogs and cats--(1) Amount. The drug is administered by intravenous injection as follows: (i) Dogs. For induction of general anesthesia without the use of preanesthetics the dosage is 5.5 to 7.0 mg...

  18. [Preparing oral dosage form of ketamine in the hospital for simplicity and patient compliance--preparations using agar].

    PubMed

    Kaneuchi, Miki; Kohri, Naonori; Senbongi, Kaname; Sakai, Hideo; Iseki, Ken

    2005-02-01

    Ketamine has been widely used in the operation as intravenous and intramuscular injections, since ketamine has dissociative anesthetic properties. When it is given in sub-anesthetic dose, ketamine is known to have an analgesic effect. The analgesic effect is observed for patients with neuropathic pain when administrated not only by injection but also orally. In Japan, since ketamine is not commercially available except injection forms, patients have to take it as solution of injections for the oral medication. Since the solution of injections has extremely bitter taste, patients intensely desire the development of preparations without the bitterness. In the present study, we prepared oral gel dosage forms of ketamine using agar. It is simple to prepare this dosage form, and most pharmacists can prepare it easily in many hospitals. This gel dosage form met content uniformity requirements and the shape of that was maintained intact during the dissolution test (for 10 hours). The release rate was reduced by additions of additives such as sugar and a flavor in the gel. The reason for the reduction in release could be the suppression of ketamine diffusion depended on the micro-viscosity of solution in the gel. The ketamine contents and the release profile of the gel preparations were unchanged at the room temperature for 12-week storage. The gel preparations in this study would be useful for the oral medication of ketamine, since it is easy for patients to carry them when they go out and the intensely bitter taste could be improved by the addition of a flavor.

  19. Bioavailability of intranasal promethazine dosage forms in dogs

    NASA Technical Reports Server (NTRS)

    Ramanathan, R.; Geary, R. S.; Bourne, D. W.; Putcha, L.

    1998-01-01

    Intramuscular promethazine (PMZ) is used aboard the US Space Shuttle to ameliorate symptoms of space motion sickness. Bioavailability after an oral dose of PMZ during space flight is thought to be impaired because of gastrointestinal disturbances associated with weightlessness and space motion sickness. In an attempt to find an alternative dosage form for use in space, we evaluated two intranasal (i.n.) dosage forms of PMZ in dogs for absorption and bioavailability relative to that of an equivalent intramuscular dose. Promethazine (5 mg kg-1) was administered as two intranasal dosage forms and as an intramuscular (i.m.) dose to three dogs in a randomised cross-over design. Serial blood samples were taken and analysed for PMZ concentrations and the absorption and bioavailability of PMZ were calculated for the three dosage forms. PMZ absorption from the carboxymethyl cellulose microsphere i.n. dosage form was more rapid and complete than from the myverol cubic gel formulation or from an i.m. injection. Bioavailability of the microsphere formulation was also greater than that of the gel formulation (AUC 3009 vs 1727 ng h ml-1). The bioavailability of the two i.n. dosage forms (relative to that of the i.m. injection) were 94% (microsphere) and 54% (gel). The i.n. microsphere formulation of PMZ offers great promise as an effective non-invasive alternative for treating space motion sickness due to its rapid absorption and bioavailability equivalent to the i.m. dose.

  20. Long-acting injectable hormonal dosage forms for contraception.

    PubMed

    Wu, Linfeng; Janagam, Dileep R; Mandrell, Timothy D; Johnson, James R; Lowe, Tao L

    2015-07-01

    Although great efforts have been made to develop long-acting injectable hormonal contraceptives for more than four decades, few long-acting injectable contraceptives have reached the pharmaceutical market or even entered clinical trials. On the other hand, in clinical practice there is an urgent need for injectable long-acting reversible contraceptives which can provide contraceptive protection for more than 3 months after one single injection. Availability of such products will offer great flexibility to women and resolve certain continuation issues currently occurring in clinics. Herein, we reviewed the strategies exploited in the past to develop injectable hormonal contraceptive dosages including drug microcrystal suspensions, drug-loaded microsphere suspensions and in situ forming depot systems for long-term contraception and discussed the potential solutions for remaining issues met in the previous development.

  1. 21 CFR 522.2063 - Pyrilamine maleate injection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522... treating horses in conditions in which antihistaminic therapy may be expected to lead to alleviation of...

  2. 75 FR 54018 - Implantation or Injectable Dosage Form New Animal Drugs; Florfenicol and Flunixin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-03

    ... respiratory disease (BRD) pathogens for which use of an injectable solution containing florfenicol and.... For treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella...

  3. 21 CFR 522.2220 - Sulfadimethoxine injection.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Sulfadimethoxine injection. 522.2220 Section 522.2220 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522...

  4. 21 CFR 522.2615 - Tripelennamine hydrochloride injection.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Tripelennamine hydrochloride injection. 522.2615 Section 522.2615 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS...

  5. 21 CFR 522.2220 - Sulfadimethoxine injection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sulfadimethoxine injection. 522.2220 Section 522.2220 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522...

  6. 21 CFR 522.1081 - Chorionic gonadotropin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    .... Dosage may be repeated in 14 days if the animal's behavior or examination of the ovaries per rectum... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1081...

  7. 21 CFR 522.1081 - Chorionic gonadotropin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... Dosage may be repeated in 14 days if the animal's behavior or examination of the ovaries per rectum... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1081...

  8. 75 FR 62468 - Implantation and Injectable Dosage Form New Animal Drugs; Ceftiofur Crystalline Free Acid

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-12

    ... swine, by intramuscular injection, for the control of swine respiratory disease (SRD) in groups of pigs... treatment of lower respiratory tract infections in horses caused by susceptible strains of Streptococcus...

  9. Determination of dasatinib in the tablet dosage form by ultra high performance liquid chromatography, capillary zone electrophoresis, and sequential injection analysis.

    PubMed

    Gonzalez, Aroa Garcia; Taraba, Lukáš; Hraníček, Jakub; Kozlík, Petr; Coufal, Pavel

    2017-01-01

    Dasatinib is a novel oral prescription drug proposed for treating adult patients with chronic myeloid leukemia. Three analytical methods, namely ultra high performance liquid chromatography, capillary zone electrophoresis, and sequential injection analysis, were developed, validated, and compared for determination of the drug in the tablet dosage form. The total analysis time of optimized ultra high performance liquid chromatography and capillary zone electrophoresis methods was 2.0 and 2.2 min, respectively. Direct ultraviolet detection with detection wavelength of 322 nm was employed in both cases. The optimized sequential injection analysis method was based on spectrophotometric detection of dasatinib after a simple colorimetric reaction with folin ciocalteau reagent forming a blue-colored complex with an absorbance maximum at 745 nm. The total analysis time was 2.5 min. The ultra high performance liquid chromatography method provided the lowest detection and quantitation limits and the most precise and accurate results. All three newly developed methods were demonstrated to be specific, linear, sensitive, precise, and accurate, providing results satisfactorily meeting the requirements of the pharmaceutical industry, and can be employed for the routine determination of the active pharmaceutical ingredient in the tablet dosage form. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. 21 CFR 522.90b - Ampicillin trihydrate powder for injection.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ....90b Section 522.90b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.90b Ampicillin trihydrate powder for injection. (a) Specifications. Each milliliter of...

  11. 75 FR 1274 - Implantation or Injectable Dosage Form New Animal Drugs; Hyaluronate Sodium

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-11

    ... safety warning for use of hyaluronate sodium injectable solution in horses. DATES: This rule is effective... human food safety warning on product labeling. The supplemental NADA is approved as of December 11, 2009...

  12. 77 FR 39390 - Implantation or Injectable Dosage Form New Animal Drugs; Maropitant; Tildipirosin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-03

    ...., Summit, Injectable the treatment NJ 07901. Solution. of bovine respiratory disease (BRD) in beef and non-lactating dairy cattle; and for the control of respiratory disease in beef and non- lactating dairy cattle... subcutaneous injection in the neck. (ii) Indications for use. For the treatment of bovine respiratory disease...

  13. Determination of azathioprine and its related substances by capillary zone electrophoresis and its application to pharmaceutical dosage forms assay.

    PubMed

    Shafaati, A; Clark, B J

    2000-03-01

    The development of a stability-indicating capillary zone electrophoresis (CZE) method for the determination of the drug azathioprine (AZA) and its related substances in bulk and dosage forms is described. Theophylline was used as an internal standard to improve quantitative results. The method was fully validated in terms of repeatability (n = 10, RSD for migration time and peak area ratio were 0.15% and 0.60%, respectively), reproducibility (n = 5, RSD of peak area ratio was 0.84%), linearity at two ranges of the azathioprine concentration, limits of detection (LOD) and quantitation (LOQ), and robustness. The method was applied for determination of the drug in bulk and a commercial tablet dosage form (recovery 98.3-101.3%) and in powder for injection (recovery 98.7-100.6%). The method was fast and reliable for the analysis of AZA and its related substances in bulk and dosage forms.

  14. Semi-solid dosage form of clonazepam for rapid oral mucosal absorption.

    PubMed

    Sakata, Osamu; Machida, Yoshiharu; Onishi, Hiraku

    2011-07-01

    In order to obtain an alternative to the intravenous (i.v.) dosage form of clonazepam (CZ), an oral droplet formulation of CZ was developed previously; however, the droplet was physically unstable. Therefore, in the present study, it was attempted to develop an easily-handled dosage form, which was more physically stable and allowed rapid drug absorption from oral mucosa. A semi-solid dosage form, composed of polyethylene glycol 1500 (PEG), CZ, and oleic acid (OA) at 37/1/2 (w/w) and named PEG/CZ/OA, and a semi-solid dosage form containing PEG and CZ at 39/1 (w/w), called PEG/CZ, were prepared. Their physical stability in air at room temperature and oral mucosal absorption in rats were investigated. The semi-solid dosage forms were much more stable physically than the droplet, that is, no recrystallization of CZ was observed for at least 8 days. The effective concentration for humans and rats (20 ng/mL or more) was achieved within 30 min after buccal administration for both PEG/CZ/OA and PEG/CZ. The plasma concentration increased gradually and less varied at each time point for PEG/CZ/OA. PEG/CZ/OA was found to show more rapid and higher absorption of CZ in buccal administration than in sublingual administration. Buccal administration with the semi-solid dosage PEG/CZ with or without OA was suggested to be a possibly useful novel dosage form as an alternative to i.v. injection.

  15. 21 CFR 522.1155 - Imidocarb powder for injection.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Staff, Veterinary Services, Animal and Plant Health Inspection Service, U.S. Department of Agriculture... 522.1155 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS...

  16. 21 CFR 522.1468 - Naproxen for injection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1468.... Five milligrams per kilogram of body weight intravenously followed by maintenance oral therapy of 10...

  17. 21 CFR 522.311 - Cefovecin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.311 Cefovecin. (a.... A second subcutaneous injection of 3.6 mg/lb (8 mg/kg) may be administered if response to therapy is...

  18. 21 CFR 522.84 - Beta-aminopropionitrile fumarate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 522.84 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.... Do not use in horses with dermal irritation or open skin lesions in the injection area. Do not...

  19. 21 CFR 522.2474 - Tolazoline hydrochloride injection.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Section 522.2474 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS... a general anesthetic. This drug is for use in horses only and not for use in food-producing animals...

  20. 21 CFR 522.2474 - Tolazoline hydrochloride injection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Section 522.2474 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS... a general anesthetic. This drug is for use in horses only and not for use in food-producing animals...

  1. 21 CFR 522.84 - Beta-aminopropionitrile fumarate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 522.84 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.... Do not use in horses with dermal irritation or open skin lesions in the injection area. Do not...

  2. 21 CFR 522.2474 - Tolazoline hydrochloride injection.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Section 522.2474 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS... a general anesthetic. This drug is for use in horses only and not for use in food-producing animals...

  3. 21 CFR 522.84 - Beta-aminopropionitrile fumarate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 522.84 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.... Do not use in horses with dermal irritation or open skin lesions in the injection area. Do not...

  4. 21 CFR 522.2474 - Tolazoline hydrochloride injection.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Section 522.2474 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS... a general anesthetic. This drug is for use in horses only and not for use in food-producing animals...

  5. 21 CFR 522.300 - Carfentanil citrate injection.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522... effect, use 7 milligrams of diprenorphine for each milligram of carefentanil citrate, given intravenously... animals intended for food. Do not use 30 days before or during hunting season. Do not use in animals that...

  6. 76 FR 57905 - Implantation or Injectable Dosage Form New Animal Drugs; Ivermectin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-19

    ... solution for treatment and control of various internal and external parasites in cattle, swine, reindeer...: John K. Harshman, Center for Veterinary Medicine (HFV-170), Food and Drug Administration, 7500 Standish... of BIMECTIN (ivermectin) Injection for Cattle and Swine for treatment and control of various internal...

  7. 75 FR 4692 - Implantation or Injectable Dosage Form New Animal Drugs; Ceftiofur Crystalline Free Acid

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-29

    ... suspension for the treatment of lower respiratory tract infections in horses. DATES: This rule is effective... ceftiofur crystalline free acid injectable suspension for the treatment of lower respiratory tract... of lower respiratory tract infections in horses caused by susceptible strains of Streptococcus equi...

  8. 75 FR 22524 - Implantation or Injectable Dosage Form New Animal Drugs; Butorphanol

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-29

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 [Docket No... application (ANADA) filed by Modern Veterinary Therapeutics, LLC. The ANADA provides for use of an injectable..., 2010. FOR FURTHER INFORMATION CONTACT: John K. Harshman, Center for Veterinary Medicine (HFV-170), Food...

  9. 75 FR 59610 - Implantation and Injectable Dosage Form New Animal Drugs; Firocoxib

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-28

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 [Docket No...) filed by Merial Ltd. The NADA provides for the veterinary prescription use of firocoxib injectable... Veterinary Medicine (HFV-110), Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 240-276...

  10. 21 CFR 522.650 - Dihydrostreptomycin sulfate injection.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS... 055529 in § 510.600(c) of this chapter. (c) National Academy of Sciences/National Research Council (NAS... dihydrostreptomycin resistant organisms. Discontinue use 30 days before slaughter for food. Not for use in animals...

  11. 21 CFR 522.650 - Dihydrostreptomycin sulfate injection.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS... 055529 in § 510.600(c) of this chapter. (c) National Academy of Sciences/National Research Council (NAS... dihydrostreptomycin resistant organisms. Discontinue use 30 days before slaughter for food. Not for use in animals...

  12. 21 CFR 522.480 - Repository corticotropin injection.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS... refrigerated. With prolonged use supplement daily diet with potassium chloride at one gram for small animals and from 5 to 10 grams for large animals. (4) Conditions of use. (i) It is used as an intramuscular or...

  13. 21 CFR 522.480 - Repository corticotropin injection.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS... refrigerated. With prolonged use supplement daily diet with potassium chloride at one gram for small animals and from 5 to 10 grams for large animals. (4) Conditions of use. (i) It is used as an intramuscular or...

  14. 21 CFR 522.300 - Carfentanil citrate injection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... recommend use in pregnant animals. Avoid use during breeding season. Federal law restricts this drug to use...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522... animals intended for food. Do not use 30 days before or during hunting season. Do not use in animals that...

  15. 75 FR 76260 - Implantation or Injectable Dosage Form New Animal Drugs; Flunixin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-08

    ... meglumine solution by intravenous injection in lactating dairy cows for control of pyrexia associated with... cows for control of pyrexia associated with acute bovine mastitis. The supplemental application is... for 36 hours after the last treatment must not be used for food. Do not use in dry dairy cows. A...

  16. Formulation development of allopurinol suppositories and injectables.

    PubMed

    Lee, D K; Wang, D P

    1999-11-01

    Allopurinol was formulated into injectable and suppository dosage forms. The injectable formulation was prepared by dissolving allopurinol in a cosolvent system consisting of dimethyl sulfoxide (DMSO) and propylene glycol (v/v = 50/50). The stability of allopurinol in the cosolvent system was studied under accelerated storage conditions, and results indicate first-order degradation kinetics with an activation energy of 24.3 kcal/mol. The development of suppository dosage forms was performed by formulating allopurinol with polyethylene glycol (PEG) mixtures of different molecular weights. In vitro release profiles of suppositories formulated with different polyethylene bases were obtained in the pH 7.4 buffer solution using the USP 23 paddle method at 100 rpm. Results indicate that the release rate of the suppository formulations containing PEG 1500/PEG 4000 at the ratio (w/w) of 2.5/10 to 10/2.5 appeared to be similar. However, the addition of sodium lauryl sulfate in the suppository decreased the release rate of allopurinol significantly. A future study to establish in vitro/in vivo correlation (iv/ivc) is suggested.

  17. 77 FR 4227 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor Analog...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-27

    ... for Injection, administered as two doses 4 weeks apart to intact male pigs for the reduction of boar... pigs and barrows. Do not use in intact male pigs intended for breeding because of the disruption of.... Pigs should be slaughtered no earlier than 3 weeks and no later than 10 weeks after the second dose...

  18. 76 FR 27888 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor-Diphtheria...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-13

    ... taint in intact male pigs intended for slaughter. DATES: This rule is effective May 13, 2011. FOR... function) and reduction of boar taint in intact male pigs intended for slaughter. The application is... of use in swine--(1) Amount. Administer 0.4 mg per intact male pig (2 mL) by subcutaneous injection...

  19. An injectable hybrid nanoparticle-in-oil-in-water submicron emulsion for improved delivery of poorly soluble drugs

    NASA Astrophysics Data System (ADS)

    Wang, Shuo; Wang, Hua; Liang, Wenquan; Huang, Yongzhuo

    2012-04-01

    Poor drugability problems are commonly seen in a class of chemical entities with poor solubility in water and oil, and moreover, physicochemical instability of these compounds poses extra challenges in design of dosage forms. Such problems contribute a significant high failure rate in new drug development. A hybrid nanoparicle-in-oil-in-water (N/O/W) submicron emulsion was proposed for improved delivery of poorly soluble and unstable drugs (e.g., dihydroartemisinin (DHA)). DHA is known for its potent antimalarial effect and antitumor activity. However, its insolubility and instability impose big challenges for formulations, and so far, no injectable dosage forms are clinically available yet. Therefore, an injectable DHA N/O/W system was developed. Unlike other widely-explored systems (e.g., liposomes, micelles, and emulsions), in which low drug load and only short-term storage are often found, the hybrid submicron emulsion possesses three-fold higher drug-loading capacity than the conventional O/W emulsion. Of note, it can be manufactured into a freeze-drying form and can render its storage up to 6 months even in room temperature. The in vivo studies demonstrated that the PK profiles were significantly improved, and this injectable system was effective in suppressing tumor growth. The strategy provides a useful solution to effective delivery of such a class of drugs.

  20. Factors influencing botulinum toxin dose instability in spasmodic dysphonia patients.

    PubMed

    Rosow, David E; Pechman, Amanda; Saint-Victor, Sandra; Lo, Kaming; Lundy, Donna S; Casiano, Roy R

    2015-05-01

    Many patients with spasmodic dysphonia (SD) see consistent effects from botulinum toxin (BTX) injections of the same dose, whereas others require dosage changes over time. We sought to determine whether demographics (age and gender) or environmental factors (smoking) affect the long-term stability of BTX dosing in these patients. Retrospective review. Charts of all patients undergoing BTX injection for adductor SD were reviewed. Dosage change, defined as whether there was any difference in total dosage used between two beneficial injections, was used as a measure of dosing stability. Beneficial injections were indicated by a voice rating score of at least three of four and any non-zero duration of improved voice. Logistic regression analysis was performed to determine whether age, gender, smoking status, or duration of treatment correlated with odds of having a dosage change. A total of 211 patients were ultimately included. Age, gender, and smoking status were all found to have no correlative effect on dosing stability. The only factor that was predictive of dose stability was the number of previous beneficial injections, as every additional injection led to decreased odds of a change in dosage for the next injection (odds ratio=0.964; 95% confidence interval=0.947-0.981). Dosage of BTX injections for long-term treatment of SD has a significant propensity to remain stable over time. Factors such as age, gender, and smoking status do not appear to influence the dosage stability. These findings should allow for better patient counseling regarding expectations for their long-term treatment. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  1. 21 CFR 522.311 - Cefovecin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.311 Cefovecin. (a... not complete. (ii) Indications for use. For the treatment of skin infections (secondary superficial...

  2. 21 CFR 522.311 - Cefovecin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.311 Cefovecin. (a... not complete. (ii) Indications for use. For the treatment of skin infections (secondary superficial...

  3. 21 CFR 522.311 - Cefovecin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.311 Cefovecin. (a... not complete. (ii) Indications for use. For the treatment of skin infections (secondary superficial...

  4. 21 CFR 522.311 - Cefovecin.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.311 Cefovecin. (a... not complete. (ii) Indications for use. For the treatment of skin infections (secondary superficial...

  5. 21 CFR 522.147 - Atipamezole.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.147... for use. For reversal of the sedative and analgesic effects of dexmedetomidine hydrochloride or...

  6. 21 CFR 522.147 - Atipamezole.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.147... for use. For reversal of the sedative and analgesic effects of dexmedetomidine hydrochloride or...

  7. 21 CFR 522.56 - Amikacin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.56 Amikacin. (a... Escherichia coli and Proteus spp. and skin and soft tissue infections caused by susceptible strains of...

  8. 21 CFR 522.46 - Alfaprostol.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.46 Alfaprostol. (a... the skin and can cause abortion and/or bronchial spasms. Women of childbearing age, asthmatics, and...

  9. 21 CFR 522.56 - Amikacin.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.56 Amikacin. (a... of Escherichia coli and Proteus spp. and skin and soft tissue infections caused by susceptible...

  10. 21 CFR 522.90b - Ampicillin trihydrate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.90b..., gastrointestinal infections, skin infections, soft tissue infections, and postsurgical infections. (iii...

  11. 21 CFR 522.90b - Ampicillin trihydrate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.90b..., gastrointestinal infections, skin infections, soft tissue infections, and postsurgical infections. (iii...

  12. 21 CFR 522.56 - Amikacin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.56 Amikacin. (a... of Escherichia coli and Proteus spp. and skin and soft tissue infections caused by susceptible...

  13. 21 CFR 522.2240 - Sulfaethoxypyridazine.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2240... of respiratory infection (pneumonia, shipping fever), foot rot, calf scours; as adjunctive therapy in...

  14. Basics of Sterile Compounding: Biopharmaceutics of Injectable Dosage Forms.

    PubMed

    Akers, Michael J

    2017-01-01

    Biopharmaceutics studies the relationship between the drug product and what happens after the product is administered. Since the majority of injectables are administered by the intravenous route, thus avoiding the need for drug absorption, not many articles are published compared to other routes of drug administration. However, other routes of administration for drug injection are becoming more frequent because of greater commercial availability of sustained- and controlled-release drug delivery systems. This article reviews basic principles of drug absorption, distribution, metabolism, and elimination of injectable drugs and certain physicochemical and physiological factors affecting injectable drug biopharmaceutics. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

  15. Designing Solvent Exchange-Induced In Situ Forming Gel from Aqueous Insoluble Polymers as Matrix Base for Periodontitis Treatment.

    PubMed

    Srichan, Tharatree; Phaechamud, Thawatchai

    2017-01-01

    An in situ forming gel is a dosage form which is promised for site-specific therapy such as periodontal pocket of periodontitis treatment. Ethylcellulose, bleached shellac, and Eudragit RS were applied in this study as a polymeric matrix for in situ forming gel employing N-methyl pyrrolidone (NMP) as solvent. Solutions comprising ethylcellulose, bleached shellac, and Eudragit RS in NMP were evaluated for viscosity, rheology, and rate of water penetration. Ease of administration by injection was determined as the force required to expel polymeric solutions through a needle using texture analyzer. In vitro gel formation and in vitro gel degradation were conducted after injection into phosphate buffer solution pH 6.8. Ethylcellulose, bleached shellac, and Eudragit RS could form the in situ gel, in vitro. Gel viscosity and pH value depended on percentage amount of the polymer, whereas the water diffusion at early period likely relied on types of polymer. Furthermore, the solutions containing higher polymer concentration exhibited the lower degree of degradation. All the preparations were acceptable as injectable dosage forms because the applied force was lower than 50 N. All of them inhibited Staphylococcus aureus, Escherichia coli, Candida albicans, Streptococcus mutans, and Porphyrommonas gingivalis growth owing to antimicrobial activity of NMP which exhibited a potential use for periodontitis treatment. Moreover, the developed systems presented as the solvent exchange induced in situ forming gel and showed capability to be incorporated with the suitable antimicrobial active compounds for periodontitis treatment which should be further studied.

  16. Formulation and delivery strategies of ibuprofen: challenges and opportunities.

    PubMed

    Irvine, Jake; Afrose, Afrina; Islam, Nazrul

    2018-02-01

    Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), is mostly administered orally and topically to relieve acute pain and fever. Due to its mode of action this drug may be useful in the treatment regimens of other, more chronic conditions, like cystic fibrosis. This drug is poorly soluble in aqueous media and thus the rate of dissolution from the currently available solid dosage forms is limited. This leads to poor bioavailability at high doses after oral administration, thereby increasing the risk of unwanted adverse effects. The poor solubility is a problem for developing injectable solution dosage forms. Because of its poor skin permeability, it is difficult to obtain an effective therapeutic concentration from topical preparations. This review aims to give a brief insight into the status of ibuprofen dosage forms and their limitations, particle/crystallization technologies for improving formulation strategies as well as suggesting its incorporation into the pulmonary drug delivery systems for achieving better therapeutic action at low dose.

  17. 21 CFR 522.1081 - Chorionic gonadotropin.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... if the animal's behavior or examination of the ovaries per rectum indicates retreatment. (A) 10,000... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1081...

  18. 21 CFR 522.163 - Betamethasone dipropionate and betamethasone sodium phosphate aqueous suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... sodium phosphate aqueous suspension. 522.163 Section 522.163 Food and Drugs FOOD AND DRUG ADMINISTRATION... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.163 Betamethasone dipropionate and betamethasone sodium phosphate aqueous suspension. (a) Specifications. Betamethasone dipropionate and betamethasone sodium...

  19. 21 CFR 522.535 - Desoxycorticosterone pivalate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522... variable and must be individualized on the basis of the response of the patient to therapy. Initial dose of... as replacement therapy for the mineralocorticoid deficit in dogs with primary adrenocortical...

  20. Dry coating of solid dosage forms: an overview of processes and applications.

    PubMed

    Foppoli, Anastasia Anna; Maroni, Alessandra; Cerea, Matteo; Zema, Lucia; Gazzaniga, Andrea

    2017-12-01

    Dry coating techniques enable manufacturing of coated solid dosage forms with no, or very limited, use of solvents. As a result, major drawbacks associated with both organic solvents and aqueous coating systems can be overcome, such as toxicological, environmental, and safety-related issues on the one hand as well as costly drying phases and impaired product stability on the other. The considerable advantages related to solventless coating has been prompting a strong research interest in this field of pharmaceutics. In the article, processes and applications relevant to techniques intended for dry coating are analyzed and reviewed. Based on the physical state of the coat-forming agents, liquid- and solid-based techniques are distinguished. The former include hot-melt coating and coating by photocuring, while the latter encompass press coating and powder coating. Moreover, solventless techniques, such as injection molding and three-dimensional printing by fused deposition modeling, which are not purposely conceived for coating, are also discussed in that they would open new perspectives in the manufacturing of coated-like dosage forms.

  1. 21 CFR 522.810 - Embutramide, chloroquine, and lidocaine solution.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... euthanasia. (3) Limitations. Not for use in animals intended for food. Federal law restricts this drug to use... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.810 Embutramide, chloroquine, and lidocaine solution. (a) Specifications. Each...

  2. 21 CFR 522.810 - Embutramide, chloroquine, and lidocaine solution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... euthanasia. (3) Limitations. Not for use in animals intended for food. Federal law restricts this drug to use... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.810 Embutramide, chloroquine, and lidocaine solution. (a) Specifications. Each...

  3. 21 CFR 522.810 - Embutramide, chloroquine, and lidocaine solution.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... euthanasia. (3) Limitations. Not for use in animals intended for food. Federal law restricts this drug to use... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.810 Embutramide, chloroquine, and lidocaine solution. (a) Specifications. Each...

  4. 21 CFR 522.810 - Embutramide, chloroquine, and lidocaine solution.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... euthanasia. (3) Limitations. Not for use in animals intended for food. Federal law restricts this drug to use... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.810 Embutramide, chloroquine, and lidocaine solution. (a) Specifications. Each...

  5. 21 CFR 522.1222 - Ketamine.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ketamine. 522.1222 Section 522.1222 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222 Ketamine. (a) Specifications. Each milliliter contains ketamine hydrochloride equivalent to 100 milligrams (mg) ketamine base...

  6. 21 CFR 522.1081 - Chorionic gonadotropin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... repeated in 14 days if the animal's behavior or examination of the ovaries per rectum indicates retreatment... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1081...

  7. 21 CFR 522.1081 - Chorionic gonadotropin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... repeated in 14 days if the animal's behavior or examination of the ovaries per rectum indicates retreatment... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1081...

  8. 75 FR 60307 - Implantation or Injectable Dosage Form New Animal Drugs; Dexmedetomidine

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-30

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 [Docket No... (NADA) filed by Orion Corp. The supplemental NADA provides for veterinary prescription use of... Veterinary Medicine (HFV-110), Food and Drug Administration, 7500 Standish Pl., [[Page 60308

  9. 21 CFR 522.1885 - Prednisolone tertiary butylacetate suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Prednisolone tertiary butylacetate suspension. 522.1885 Section 522.1885 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW...

  10. 21 CFR 522.1890 - Sterile prednisone suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sterile prednisone suspension. 522.1890 Section 522.1890 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS...

  11. 21 CFR 522.1160 - Insulin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Insulin. 522.1160 Section 522.1160 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1160 Insulin. (a) Specifications—(1) Each milliliter (mL) of porcine insulin zinc suspension contains 40 international units (IU...

  12. 21 CFR 522.1160 - Insulin.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Insulin. 522.1160 Section 522.1160 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1160 Insulin. (a) Specifications—(1) Each milliliter (mL) of porcine insulin zinc suspension contains 40 international units (IU...

  13. 21 CFR 522.1160 - Insulin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Insulin. 522.1160 Section 522.1160 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1160 Insulin. (a) Specifications—(1) Each milliliter (mL) of porcine insulin zinc suspension contains 40 international units (IU...

  14. 21 CFR 522.1222a - Ketamine.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ketamine. 522.1222a Section 522.1222a Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222a Ketamine. (a) Specifications. Each milliliter contains ketamine hydrochloride equivalent to 100 milligrams (mg...

  15. 21 CFR 522.1222a - Ketamine.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ketamine. 522.1222a Section 522.1222a Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222a Ketamine. (a) Specifications. Each milliliter contains ketamine hydrochloride equivalent to 100 milligrams (mg...

  16. 21 CFR 522.1222a - Ketamine.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ketamine. 522.1222a Section 522.1222a Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222a Ketamine. (a) Specifications. Each milliliter contains ketamine hydrochloride equivalent to 100 milligrams (mg...

  17. 21 CFR 522.204 - Boldenone.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Boldenone. 522.204 Section 522.204 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.204 Boldenone. (a) Specifications. Each milliliter of solution contains 25 or 50 milligrams (mg) boldenone undecylenate. (b) Sponsor...

  18. 21 CFR 522.204 - Boldenone.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Boldenone. 522.204 Section 522.204 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.204 Boldenone. (a) Specifications. Each milliliter of solution contains 25 or 50 milligrams (mg) boldenone undecylenate. (b) Sponsor...

  19. 21 CFR 522.204 - Boldenone.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Boldenone. 522.204 Section 522.204 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.204 Boldenone. (a) Specifications. Each milliliter of solution contains 25 or 50 milligrams (mg) boldenone undecylenate. (b) Sponsor...

  20. 21 CFR 522.204 - Boldenone.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Boldenone. 522.204 Section 522.204 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.204 Boldenone. (a) Specifications. Each milliliter of solution contains 25 or 50 milligrams (mg) boldenone undecylenate. (b) Sponsor...

  1. 21 CFR 522.204 - Boldenone.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Boldenone. 522.204 Section 522.204 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.204 Boldenone. (a) Specifications. Each milliliter of solution contains 25 or 50 milligrams (mg) boldenone undecylenate. (b) Sponsor...

  2. 21 CFR 522.1222a - Ketamine.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketamine. 522.1222a Section 522.1222a Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222a Ketamine. (a) Specifications. Each milliliter contains ketamine hydrochloride equivalent to 100 milligrams (mg...

  3. 21 CFR 522.1160 - Insulin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Insulin. 522.1160 Section 522.1160 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1160 Insulin. (a) Specifications—(1) Each milliliter (mL) of porcine insulin zinc suspension contains 40 international units (IU...

  4. 21 CFR 522.1160 - Insulin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Insulin. 522.1160 Section 522.1160 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1160 Insulin. (a) Specifications—(1) Each milliliter (mL) of porcine insulin zinc suspension contains 40 international units (IU...

  5. 21 CFR 522.304 - Carprofen.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Carprofen. 522.304 Section 522.304 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.304 Carprofen. (a) Specifications. Each milliliter of solution contains 50 milligrams (mg) carprofen. (b) Sponsor. See No. 000069 in...

  6. 21 CFR 522.304 - Carprofen.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Carprofen. 522.304 Section 522.304 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.304 Carprofen. (a) Specifications. Each milliliter of solution contains 50 milligrams (mg) carprofen. (b) Sponsor. See No. 000069 in...

  7. 21 CFR 522.304 - Carprofen.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Carprofen. 522.304 Section 522.304 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.304 Carprofen. (a) Specifications. Each milliliter of solution contains 50 milligrams (mg) carprofen. (b) Sponsor. See No. 054771 in...

  8. 21 CFR 522.304 - Carprofen.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Carprofen. 522.304 Section 522.304 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.304 Carprofen. (a) Specifications. Each milliliter of solution contains 50 milligrams (mg) carprofen. (b) Sponsor. See No. 000069 in...

  9. 75 FR 38699 - Implantation or Injectable Dosage Form New Animal Drugs; Propofol

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-06

    ...The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a new animal drug application (NADA) filed by Fort Dodge Animal Health, Division of Wyeth. The NADA provides for veterinary prescription use of propofol as an anesthetic in dogs and cats.

  10. 21 CFR 522.46 - Alfaprostol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Alfaprostol. 522.46 Section 522.46 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.46 Alfaprostol. (a...

  11. 21 CFR 522.1680 - Oxytocin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Oxytocin. 522.1680 Section 522.1680 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1680 Oxytocin. (a) Specifications. Each milliliter (mL) of solution contains 20 USP units oxytocin. (b) Sponsors. See Nos. , 000859...

  12. 21 CFR 522.2690 - Zinc gluconate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Zinc gluconate. 522.2690 Section 522.2690 Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2690 Zinc gluconate. (a) Specifications. Each milliliter of solution contains 13.1 milligrams zinc as zinc gluconate...

  13. 21 CFR 522.2690 - Zinc gluconate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Zinc gluconate. 522.2690 Section 522.2690 Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2690 Zinc gluconate. (a) Specifications. Each milliliter of solution contains 13.1 milligrams zinc as zinc gluconate...

  14. 21 CFR 522.304 - Carprofen.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Carprofen. 522.304 Section 522.304 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.304 Carprofen. (a) Specifications. Each milliliter of solution contains 50 milligrams (mg) carprofen. (b) Sponsor. See No. 000069 in...

  15. 21 CFR 522.380 - Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Chloral hydrate, pentobarbital, and magnesium... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.380 Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution. (a) [Reserved] (b)(1) Specifications. Chloral hydrate, pentobarbital, and...

  16. 21 CFR 522.380 - Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Chloral hydrate, pentobarbital, and magnesium... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.380 Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution. (a) [Reserved] (b)(1) Specifications. Chloral hydrate, pentobarbital, and...

  17. 21 CFR 522.380 - Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Chloral hydrate, pentobarbital, and magnesium... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.380 Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution. (a) [Reserved] (b)(1) Specifications. Chloral hydrate, pentobarbital, and...

  18. 21 CFR 522.380 - Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Chloral hydrate, pentobarbital, and magnesium... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.380 Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution. (a) [Reserved] (b)(1) Specifications. Chloral hydrate, pentobarbital, and...

  19. 75 FR 26647 - Implantation or Injectable Dosage Form New Animal Drugs; Ivermectin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-12

    ... solution in cattle and swine for treatment and control of various internal and external parasites. DATES... Veterinary Medicine (HFV-170), Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 240-276... and swine for treatment and control of various internal and external parasites. Sparhawk Laboratories...

  20. 21 CFR 522.88 - Sterile amoxicillin trihydrate for suspension.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.88 Sterile amoxicillin trihydrate for suspension. (a)(1) Specifications. Each vial... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Sterile amoxicillin trihydrate for suspension. 522...

  1. 21 CFR 522.88 - Sterile amoxicillin trihydrate for suspension.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.88 Sterile amoxicillin trihydrate for suspension. (a)(1) Specifications. Each vial... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sterile amoxicillin trihydrate for suspension. 522...

  2. 21 CFR 522.88 - Sterile amoxicillin trihydrate for suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.88 Sterile amoxicillin trihydrate for suspension. (a)(1) Specifications. Each vial... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sterile amoxicillin trihydrate for suspension. 522...

  3. 21 CFR 522.88 - Sterile amoxicillin trihydrate for suspension.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.88 Sterile amoxicillin trihydrate for suspension. (a)(1) Specifications. Each vial... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Sterile amoxicillin trihydrate for suspension. 522...

  4. 21 CFR 522.1155 - Imidocarb dipropionate sterile powder.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Imidocarb dipropionate sterile powder. 522.1155 Section 522.1155 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS...

  5. Development of a Simple RP-HPLC-UV Method for Determination of Azithromycin in Bulk and Pharmaceutical Dosage forms as an Alternative to the USP Method

    PubMed Central

    Ghari, Tayebeh; Kobarfard, Farzad; Mortazavi, Seyed Alireza

    2013-01-01

    The present study was designed to develop a simple, validated liquid chromatographic method for the analysis of azithromycin in bulk and pharmaceutical dosage forms using ultraviolet detector. The best stationary phase was determined as C18 column, 5 μm, 250 mm × 4.6 mm. Mobile phase was optimized to obtain a fast and selective separation of the drug. Flow rate was 1.5 mL/min, Wavelength was set at 210 nm and the volume of each injection was 500 μL. An isocratic methanol/buffer mobile phase at the ratio of 90:10 v/v gave the best separation and resolution. The proposed method was accurate, precise, sensitive, and linear over a wide range of concentration of azithromycin. The developed method has the advantage of using UV detector compared to the USP method in which electrochemical detector has been used. The validated method was successfully applied to the determination of azithromycin in bulk and pharmaceutical dosage forms. PMID:24250672

  6. 21 CFR 522.2690 - Zinc gluconate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Zinc gluconate. 522.2690 Section 522.2690 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2690 Zinc gluconate. (a) Specifications. Each milliliter...

  7. 21 CFR 522.2690 - Zinc gluconate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Zinc gluconate. 522.2690 Section 522.2690 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2690 Zinc gluconate. (a) Specifications. Each milliliter...

  8. 21 CFR 522.2690 - Zinc gluconate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Zinc gluconate. 522.2690 Section 522.2690 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2690 Zinc gluconate. (a) Specifications. Each milliliter...

  9. 75 FR 1274 - Implantation or Injectable Dosage Form New Animal Drugs; Florfenicol and Flunixin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-11

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 [Docket No... AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration... Veterinary Medicine (HFV-130), Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 240-276...

  10. 'Pink eye' or 'zere oogjes' or keratoconjunctivitis infectiosa ovis (KIO). Clinical efficacy of a number of antimicrobial therapies.

    PubMed

    König, C D

    1983-07-01

    In a comparative study the clinical efficacy of five different treatments of keratoconjunctivitis infectiosa ovis (KIO) were tested, namely an intramuscular injection of chloramphenicol base (dosage 15 mg/kg), spiramycin base (Suanovil dosages 10 to 25 mg/kg), oxytetracycline (Engemycine Forte, Terramycin LA, dosages respectively 5 and 10 mg/kg), tiamulin (Dynamutulin, dosage 10 mg/kg) and subcutaneous injection of procaine penicillin G, benzathine penicillin G. and dihydrostreptomycin in the lower eyelid. It appeared from these field trials that spiramycin base, oxytetracycline and tiamulin had a clearly positive effect on the clinical course of 'pink eye', although with tiamulin there was only a temporary effect (high percentage of relapses). In view of the field data the following dosage schemes are, for the time being, advised: spiramycin base (Suanovil), and oxytetracycline (formulation with a good biological availability) both 20 to 30 mg/kg and, if necessary, to be repeated on days 5 and 10 after the first intramuscular injection. The dosage scheme advised for tiamulin is 20-30 mg/kg to be repeated on day 3 and if necessary on days 6 and 9 after the intramuscular injection. In mild cases it is sufficient to rub the eyes with for example oxytetracycline eye-ointment, a few times a day.

  11. Hot Melt Extruded and Injection Moulded Dosage Forms: Recent Research and Patents.

    PubMed

    Major, Ian; McConville, Christopher

    2015-01-01

    Hot Melt Extrusion (HME) and Injection Moulding (IM) are becoming more prevalent in the drug delivery field due to their continuous nature and advantages over current pharmaceutical manufacturing techniques. Hot melt extrusion (HME) is a process that involves the use of at least one reciprocating screw to force a thermoplastic resin along a heated barrel and through a die, while injection moulding is a forming process were molten polymer is forced at high pressure to enter a mould. HME offers a number of advantages over conventional pharmaceutical manufacturing techniques such as increased solubility and bioavailability of poorly water soluble drugs, a solvent free and continuous process, improved content uniformity and flexibility in manufacture. Injection moulding (IM) has been recognised as a rapid and versatile manufacturing technique, which has the advantages of being a continuous process, which is easily scaled up by the use of larger equipment and moulds. However, despite their advantages and the significant number of publications and patents on HME and IM drug delivery devices there are very few marketed formulations. These marketed products range from oral dosage forms which improve bioavailability and reduce pill burden to vaginal rings which provide long-term controlled release thus improving patient compliance. The patenting strategy for IM and HME seems to be focused towards patenting the finished product, more so than patenting the manufacturing process. This is probably due to the fact that the IM and HME processes have already been patented. HME is a process where raw materials (i.e. polymer, plasticizer, drug etc.) are mixed and pumped along by a rotating screw(s) at elevated temperatures through a die to produce a product of uniform shape. IM is similar to HME except that the raw materials are pushed into a mould which is set at lower temperatures. Interest in the use of HME and IM within the pharmaceutical industry is growing with as steady increase in the number of HME patents being issued and with more than 10 products, ranging from oral dosage forms to implantable devices, currently on the market. Therefore, this review of HME and IM is important to the scientific community to further understand and advance these novel and exciting manufacturing techniques.

  12. Prevalence and trends of cellulosics in pharmaceutical dosage forms.

    PubMed

    Mastropietro, David J; Omidian, Hossein

    2013-02-01

    Many studies have shown that cellulose derivatives (cellulosics) can provide various benefits when used in virtually all types of dosage forms. Nevertheless, the popularity of their use in approved drug products is rather unknown. This research reports the current prevalence and trends of use for 15 common cellulosics in prescription drug products. The cellulosics were powdered and microcrystalline cellulose (MCC), ethyl cellulose, hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), hypromellose (HPMC), HPMC phthalate, HPMC acetate succinate, cellulose acetate (CA), CA phthalate, sodium (Na) and calcium (Ca) carboxymethylcellulose (CMC), croscarmellose sodium (XCMCNa), methyl cellulose, and low substituted HPC. The number of brand drug products utilizing each cellulosics was determined using the online drug index Rxlist. A total of 607 brand products were identified having one or more of the cellulosics as an active or inactive ingredient. An array of various dosage forms was identified and revealed HPMC and MCC to be the most utilized cellulosics in all products followed by XCMCNa and HPC. Many products contained two or more cellulosics in the formulation (42% containing two, 23% containing three, and 4% containing 4-5). The largest combination occurrence was HPMC with MCC. The use of certain cellulosics within different dosage form types was found to contain specific trends. All injectables utilized only CMCNa, and the same with all ophthalmic solutions utilizing HPMC, and otic suspensions utilizing HEC. Popularity and trends regarding cellulosics use may occur based on many factors including functionality, safety, availability, stability, and ease of manufacturing.

  13. [Comparative evaluation of clinical and economic efficiency of paliperidone in various dosage forms used in patients with schizophrenia].

    PubMed

    D'yakov, I N; Zyryanov, S K

    To evaluate clinical and economic efficacy of schizophrenia treatment with three forms of paliperidone (peroral form, intramuscular injections once a month and once in three month). Pharmacoeconomic analysis based on the results of earlier foreign randomized clinical studies on paliperidone in treatment of schizophrenia was carried out. Indirect comparison of different medication forms of paliperidone compared to placebo was performed. The analysis of costs was based on a Markov model built for the study. Two categories of costs: costs of pharmacological treatment with paliperidone and costs of disease exacerbation due to the violation of treatment regimen were considered. To assess pharmacoeconomic efficacy of paliperidone, a cost-benefit analysis with calculation of cost utility ratio (CUR) and incremental cost utility ratio (ICUR) was used. In view of the influence on the budget, all forms of paliperidone have similar pharmacoeconomic efficacy with the advantage of prolonged release injectable (depot) forms that increase patient's adherence to treatment. As a result, CUR of injectable forms was lower compared to that of the peroral form by 11,1 and 46,3% of month and 3-month forms, respectively. ICUR for paliperidone used once in 3 month (trevicta) was more effective compared to paliperidone used monthly (xeplion). It has been concluded that paliperidone for prolonged release injections used once in 3 month is most pharmacoeconomically effective.

  14. Gentamicin tissue concentration in various avian species following recommended dosage therapy

    USGS Publications Warehouse

    Bush, M.; Locke, D.; Neal, L.A.; Carpenter, J.W.

    1981-01-01

    Plasma and tissue drug concentrations were compared in eastern bobwhite quail (Colinus virginianus virginianus) and pigeons (Columba livia) given gentamicin by IM administration at the dosage of 10 mg/kg, and in greater sandhill cranes (Grus canadensis tabida) and hybrid rosybill ducks (Netta sp) given the same antibiotic at a dosage of 5 mg/kg. Quail and cranes had significantly higher liver concentrations of gentamicin at 6 hours after injection than did pigeons and ducks. Cranes had significantly higher plasma concentrations than did ducks at 6 hours after injection. Compared with plasma values, gentamicin concentrations were significantly higher in the liver of cranes at 12 hours after injection, and in the kidneys at 18 hours.

  15. A systematic review of the use of dosage form manipulation to obtain required doses to inform use of manipulation in paediatric practice.

    PubMed

    Richey, Roberta H; Hughes, Clare; Craig, Jean V; Shah, Utpal U; Ford, James L; Barker, Catrin E; Peak, Matthew; Nunn, Anthony J; Turner, Mark A

    2017-02-25

    This study sought to determine whether there is an evidence base for drug manipulation to obtain the required dose, a common feature of paediatric clinical practice. A systematic review of the data sources, PubMed, EMBASE, CINAHL, IPA and the Cochrane database of systematic reviews, was used. Studies that considered the dose accuracy of manipulated medicines of any dosage form, evidence of safety or harm, bioavailability, patient experience, tolerability, contamination and comparison of methods of manipulation were included. Case studies and letters were excluded. Fifty studies were eligible for inclusion, 49 of which involved tablets being cut, split, crushed or dispersed. The remaining one study involved the manipulation of suppositories of one drug. No eligible studies concerning manipulation of oral capsules or liquids, rectal enemas, nebuliser solutions, injections or transdermal patches were identified. Twenty four of the tablet studies considered dose accuracy using weight and/or drug content. In studies that considered weight using adapted pharmacopoeial specifications, the percentage of halved tablets meeting these specifications ranged from 30% to 100%. Eighteen studies investigated bioavailability, pharmacokinetics or clinical outcomes following manipulations which included nine delayed or modified release formulations. In each of these nine studies the entirety of the dosage form was administered. Only one of the 18 studies was identified where drugs were manipulated to obtain a proportion of the dosage form, and that proportion administered. The five studies that considered patient perception found that having to manipulate the tablets did not have a negative impact on adherence. Of the 49 studies only two studies reported investigating children. This review yielded limited evidence to support manipulation of medicines for children. The results cannot be extrapolated between dosage forms, methods of manipulation or between different brands of the same drug. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Effect of alcohol on behavioral and autonomic thermoregulation in mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gordon, C.J.; Stead, A.G.

    1986-01-01

    Male, BALB/c mice were injected intraperitoneally with ethyl alcohol (ethanol) in dosages of 0, 0.03, 0.1, 0.3, 1.0, or 3.0 g/kg and then placed in a temperature gradient that permitted the measurement of preferred ambient temperature (Ta). The 3 g/kg dosage of ethanol resulted in a slight lowering of the preferred Ta during the first 30 min of placement in the gradient. However, there was no overall statistically significant effect of alcohol dosage on preferred Ta. In another experiment, BALB/c mice were treated with the aforementioned ethanol dosages while metabolic rate (MR), evaporative water loss (EWL), and colonic temperature weremore » measured 60 min post-injection at Ta's of 20, 30, and 35 C a dosage of 3 g/kg caused a significant decrease in MR, EWL, and colonic temperature. At a Ta of 30 C this same dosage caused significant reduction in colonic temperature, however; at Ta of 35 C ethanol had no effect on these parameters. In spite of the significant decrease in colonic temperature at a Ta of 30 C, which approximates the normal preferred Ta, the behavioral thermal preference was marginally affected. It is not clear whether or not ethanol injection results in a decrease in the set-point body temperature.« less

  17. Creating Drug Solubilization Compartments via Phase Separation in Multicomponent Buccal Patches Prepared by Direct Hot Melt Extrusion-Injection Molding.

    PubMed

    Alhijjaj, Muqdad; Bouman, Jacob; Wellner, Nikolaus; Belton, Peter; Qi, Sheng

    2015-12-07

    Creating in situ phase separation in solid dispersion based formulations to allow enhanced functionality of the dosage form, such as improving dissolution of poorly soluble model drug as well as being mucoadhesive, can significantly maximize the in vitro and in vivo performance of the dosage form. This formulation strategy can benefit a wide range of solid dosage forms for oral and alternative routes of delivery. This study using buccal patches as an example created separated phases in situ of the buccal patches by selecting the excipients with different miscibility with each other and the model drug. The quaternary dispersion based buccal patches containing PEG, PEO, Tween 80, and felodipine were prepared by direct hot melt extrusion-injection molding (HME-IM). The partial miscibility between Tween 80 and semicrystalline PEG-PEO led to the phase separation after extrusion. The Tween phases acted as drug solubilization compartments, and the PEG-PEO phase had the primary function of providing mucoadhesion and carrier controlled dissolution. As felodipine was preferably solubilized in the amorphous regions of PEG-PEO, the high crystallinity of PEG-PEO resulted in an overall low drug solubilizing capacity. Tween 80 was added to improve the solubilization capacity of the system as the model drug showed good solubility in Tween. Increasing the drug loading led to the supersaturation of drug in Tween compartments and crystalline drug dispersed in PEG-PEO phases. The spatial distribution of these phase-separated compartments was mapped using X-ray micro-CT, which revealed that the domain size and heterogeneity of the phase separation increased with increasing the drug loading. The outcome of this study provides new insights into the applicability of in situ formed phase separation as a formulation strategy for the delivery of poorly soluble drugs and demonstrated the basic principle of excipient selection for such technology.

  18. Influence of Dosage Form on the Intravitreal Pharmacokinetics of Diclofenac

    PubMed Central

    Durairaj, Chandrasekar; Kim, Stephen J.; Edelhauser, Henry F.; Shah, Jaymin C.; Kompella, Uday B.

    2009-01-01

    Purpose To prepare a suspension form of diclofenac and compare the influence of the injected form (suspension versus solution) on the intravitreal pharmacokinetics of diclofenac in Dutch belted pigmented rabbits. Methods Diclofenac acid was prepared and characterized in a suspension formulation. Rabbit eyes were injected with either diclofenac sodium solution (0.3 mg) or diclofenac acid suspension (10 mg) prepared in 0.1 mL balanced salt solution. Rabbits were killed at regular time intervals, the eyes enucleated, and drug content quantified in the vitreous humor and retina-choroid tissue by high-performance liquid chromatography. Pharmacokinetic models were developed for both the dosage forms, and simulations were performed for different doses. Results Diclofenac acid with an approximate 5-μm particle size exhibited 3.5-fold lower solubility in vitreous humor, when compared with its sodium salt. The estimated settling velocity of the suspension in the vitreous humor was 3 cm/h. After diclofenac sodium salt solution injection, drug levels declined rapidly with no drug levels detectable after 24 hours in the vitreous humor and 4 hours in the RC. Throughout the assessed time course, drug levels were higher in the vitreous. However, sustained, high drug levels were observed in both the vitreous humor and the retina-choroid even on day 21 after diclofenac acid suspension injection, with retina-choroid drug levels being higher beginning at 0.25 hour. The elimination half-life of diclofenac suspension was 24 and 18 days in vitreous and retina-choroid, respectively, compared to 2.9 and 0.9 hours observed with diclofenac sodium. The pharmacokinetic models developed indicated a slow-release distribution or depot compartment for the diclofenac acid suspension in the posterior segment. Simulations indicated the inability of a 10-mg dose of diclofenac sodium solution to sustain drug levels in the vitreous beyond 11 days. Conclusions By choosing a less soluble form of a drug such as diclofenac acid, vitreous elimination half-life can be prolonged up to 24 days, potentially resulting in therapeutic levels in the posterior segment tissues for a few months. Higher detectable drug levels in the retina-choroid suggest rapid settling and persistent retention of suspension in retina-choroid tissue. PMID:19516015

  19. Intravenous Single Dose Toxicity of Sweet Bee Venom in Sprague-Dawley Rats

    PubMed Central

    Lee, Kwang-Ho; Yu, JunSang; Sun, Seungho; Kwon, KiRok

    2015-01-01

    Objectives: Anaphylactic shock can be fatal to people who become hypersensitive when bee venom pharmacopuncture (BVP) is used. Thus, sweet bee venom (SBV) was developed to reduce these allergic responses. SBV is almost pure melittin, and SBV has been reported to have fewer allergic responses than BVP. BVP has been administered only into acupoints or intramuscularly, but we thought that intravenous injection might be possible if SBV were shown to be a safe medium. The aim of this study is to evaluate the intravenous injection toxicity of SBV through a single-dose test in Sprague-Dawley (SD) rats. Methods: Male and female 6-week-old SD rats were injected intravenously with SBV (high dosage: 1.0 mL/animal; medium dosage: 0.5 mL/animal; low dosage: 0.1 mL/animal). Normal saline was injected into the control group in a similar method. We conducted clinical observations, body weight measurements, and hematology, biochemistry, and histological observations. Results: No death was observed in any of the experimental groups. Hyperemia was observed in the high and the medium dosage groups on the injection day, but from next day, no general symptoms were observed in any of the experimental groups. No significant changes due to intravenous SBV injection were observed in the weights, in the hematology, biochemistry, and histological observations, and in the local tolerance tests. Conclusion: The results of this study confirm that the lethal dose of SBV is over 1.0 mL/animal in SD rats and that the intravenous injection of SBV is safe in SD rats. PMID:26389001

  20. [Clinical outcomes research of use of Shenfu injection based on hospital information system].

    PubMed

    Yang, Jing; Zhao, Ruo-Qi; Xie, Yan-Ming; Yang, Hu; Li, Lin; Zhuang, Yan

    2012-09-01

    To know how Shenfu injection is used in clinical practice and to provide a reference for guiding clinical use of Shenfu injection. Extract Shenfu injection's post-marketing re-evaluation data from the hospital information system (HIS) of 20 national grade III-A General Hospitals, use basic statistical analysis methods to analyze Shenfu injection's indications, usage and dosage, treatment course etc. in clinical practice. In patients using Shenfu injection, the average age was 62. 15, and patients mainly concentrated in cardiovascular medicine. In clinical practice, Shenfu injection was used mainly for treatment of coronary heart disease (diagnosed as chest obstruction in traditional Chinese medicine). The treatment course mainly ranged from 3 to 7 days, and the dosage was within the limits prescribed by the instruction. Shenfu injection was mainly used for elderly patients, and has been used according to instruction in practice almostly.

  1. Controlled delivery of metoclopramide using an injectable semi-solid poly(ortho ester) for veterinary application.

    PubMed

    Schwach-Abdellaoui, Khadija; Moreau, Marinette; Schneider, Marc; Boisramć, Bernard; Gurny, Robert

    2002-11-06

    In animal health care, current therapeutic regimens for gastrointestinal disorders require repeated oral or parenteral dosage forms of anti-emetic agents. However, fluctuations of plasma concentrations produce severe side effects. The aim of this work is to develop a subcutaneous and biodegradable controlled release system containing metoclopramide (MTC). Semi-solid poly(ortho ester)s (POE) prepared by a transesterification reaction between trimethyl orthoacetate and 1,2,6,-hexanetriol were investigated as injectable bioerodible polymers for the controlled release of MTC. MTC is present in the polymeric matrix as a solubilised form and it is released rapidly from the POE by erosion and diffusion because of its acidic character and its high hydrosolubility. If a manual injection is desired, only low molecular weight can be used. However, low molecular weight POEs release the drug rapidly. In order to extend polymer lifetime and decrease drug release rate, a sparingly water-soluble base Mg(OH)(2) was incorporated to the formulation. It was possible to produce low molecular weight POE that can be manually injected and releasing MTC over a period of several days.

  2. Characterizing dense suspensions: two case studies from the pharmaceutical industry

    NASA Astrophysics Data System (ADS)

    Goldfarb, David J.; Khawaja, Nazia; Kazakevich, Irina; Bhattacharjee, Himanshu; Heslinga, Michael; Dalton, Chad

    2015-11-01

    Liquid suspensions of Active Pharmaceutical Ingredient powders are present as pharmaceutical dosage forms in the form of oral suspensions and injectables. We present two case studies, both dense (~ 30-40%) suspensions, in which the physical characterization of the product, specifically, particle size & shape and rheology were key to understanding the key product attributes as pertaining to the manufacturing process and to patient administration. For the one case study, an oral suspension, identifying variations in particle morphology during the wet milling of the product was key to the product understanding necessary to modify the milling process. Rheological measurements were applied as well. For the second case study, an injectable, results from different particle size measurement techniques and rheological measurements indicated the possibility of flocculation in a formulation. Additionally, measurements were obtained to assess the ``injectability'' of the product via rheometer and texture analyzer measurements and Poiseuille flow modeling. As a result, the relevant shear rate regime for this drug product administration was identified.

  3. [Formulation and special investigations of innovative intraoral solid dosage forms.

    PubMed

    Kristo, K; kATONA, B; Piukovics, P; Olah, I; Sipos, B; Sipos, S E; Sovany, T; Hodi, K; Ifi Regdon, G

    During our work, we summarized the types of solid dosage forms which were in the focus of attention in the last years because of their innovative pharmaceutical technology solution and simple use. The biopharmaceutics of solid dosage forms for intraoral use and the advantages of the use of these dosages forms were presented in general. However, these dosage forms cannot always be prepared with conventional pharmaceutical processes, therefore the special pharmaceutical solutions which can be applied for their preparation were presented. In addition to testing the European Pharmacopoeia dosage forms, the special tests which can be applied for the characterization of innovative solid dosage forms were highlighted.

  4. Comparison of injectable molindone and haloperidol followed by oral dosage forms in acutely ill schizophrenics.

    PubMed

    Escobar, J I; Mann, J J; Keller, J; Wilkins, J; Mason, B; Mills, M J

    1985-08-01

    The comparative efficacy of molindone and haloperidol, given by injection for the first 2-3 days of hospitalization and then continued orally for up to 4 weeks, is reported from an ongoing double-blind study. Efficacy and side effects were assessed by the Brief Psychiatric Rating Scale, Clinical Global Impressions, Treatment Emergent Symptom Scale, and Target Symptom Ratings. Analyses based on the first 35 patients who entered the study indicate that both drugs were effective and well tolerated. There were slight advantages for molindone early during the injectable phase of treatment and for haloperidol late during the oral portion of the study, but these differences were not clinically significant. No significant differences in side effects were found between the two drugs.

  5. Formulation and Stability of Solutions.

    PubMed

    Akers, Michael J

    2016-01-01

    Ready-to-use solutions are the most preferable and most common dosage forms for injectable and topical ophthalmic products. Drugs formulated as solution almost always have chemical and physical stability challenges as well as solubility limitations and the need to prevent inadvertent microbial contamination issues. This article, which takes us through a discussion of optimizing the physical stability of solutions, represents the first of a series of articles discussing how these challenges and issues are addressed.

  6. Biopharmaceutical considerations and characterizations in development of colon targeted dosage forms for inflammatory bowel disease.

    PubMed

    Malayandi, Rajkumar; Kondamudi, Phani Krishna; Ruby, P K; Aggarwal, Deepika

    2014-04-01

    Colon targeted dosage forms have been extensively studied for the localized treatment of inflammatory bowel disease. These dosage forms not only improve the therapeutic efficacy but also reduce the incidence of adverse drug reactions and hence improve the patient compliance. However, complex and highly variable gastro intestinal physiology limits the clinical success of these dosage forms. Biopharmaceutical characteristics of these dosage forms play a key role in rapid formulation development and ensure the clinical success. The complexity in product development and clinical success of colon targeted dosage forms are based on the biopharmaceutical characteristics such as physicochemical properties of drug substances, pharmaceutical characteristics of dosage form, physiological conditions and pharmacokinetic properties of drug substances as well as drug products. Various in vitro and in vivo techniques have been employed in past to characterize the biopharmaceutical properties of colon targeted dosage forms. This review focuses on the factors influencing the biopharmaceutical performances of the dosage forms, in vitro characterization techniques and in vivo studies.

  7. Treatment with Myf5-morpholino results in somite patterning and brain formation defects in zebrafish.

    PubMed

    Chen, Yau-Hung; Tsai, Huai-Jen

    2002-10-01

    Myf-5 is a stage-dependent transcription factor associated with somitogenesis. To study its biological functions in zebrafish, we injected the Myf5-morpholinos ZMF-MO (antisense nucleotides 28 to 52) and ZMF-OTHER (antisense nucleotides 3 to 27) into zebrafish embryos to establish a myf-5 gene knockdown. No phenotypic abnormalities were observed following injection with 0.2 ng of ZMF-MO, but defects were displayed in 2 of 118 (1.7%) surviving embryos injected with 1 ng ZMF-MO. Morphological defects became more severe with increased dosages: 105 of 270 (38.9%) surviving embryos injected with 4.5 ng of ZMF-MO displayed such abnormalities as the absence of eyes or brains in addition to the following low-dosage defects in 24 hpf embryos: longitudinal yolk sacs, incomplete epiboly coverage, abnormal and suspended tail buds, diffused somite boundaries, and head shrinkage. Similar results were observed in the 4.5 ng ZMF-OTHER injection group. However, when fish were co-injected with 4.5 ng ZMF-MO and 4.5 ng myf-5 mRNA, abnormality rates decreased from 49.6% to 5.5%. Our results show that the brain krox20 gene was down-regulated at rhombomere 3; the pax2.1 gene was completely down-regulated; myoD was expressed normally; myogenin was substantially down-regulated in whole somites; and desmin was partly inhibited in newly forming somites. Our conclusion is that zebrafish Myf-5 may play important roles in brain formation and in the convergence and extension of shield epiblasts and tail buds during early embryogenesis, in addition to its well-understood role as a muscle regulatory factor in somites.

  8. [Analysis of clinical use of Danhong injection based on hospital information system].

    PubMed

    Chen, Qian; Yi, Danhui; Xie, Yanming; Yang, Wei; Yang, Wei; Zhuang, Yan; Du, Jing

    2011-10-01

    To know how Danhong injection is used in clinical practice and to provide a reference for guiding clinical use of Danhong Injection. Extract Danhong injection's post-marketing re-evaluation data from the Hospital Information System of ten three grade III-A General Hospitals in Beijing, use basic statistical analysis methods to analyze Danhong injection's indications, usage and dosage, days of treatment etc. in clinical practice. In patients using Danhong injection, there were more than 60 percent patients were prescribed based on main-diagnosis, first-visit and other diagnosis, which were also coincided with Danhong injection's instruction. In clinical practice, 95.5 percent of Danhong injection's administration routes conformed to the instruction and more than 90 percent of Danhong injection's dosage were within the limits prescribed by the instruction. Danhong injection was used less than 20 days successively. Danhong injection was used in combination with drugs with the action of removing blood stasis, antianginal drug, antiplatelet drug, drugs for cerebrovascular disease and so on. Danhong injection has been used according to instruction in practice almostly.

  9. Comprehensive review on additives of topical dosage forms for drug delivery.

    PubMed

    Garg, Tarun; Rath, Goutam; Goyal, Amit K

    2015-12-01

    Skin is the largest organ of the human body and plays the most important role in protecting against pathogen and foreign matter. Three important modes such as topical, regional and transdermal are widely used for delivery of various dosage forms. Among these modes, the topical dosage forms are preferred because it provides local therapeutic activity when applied to the skin or mucous membranes. Additives or pharmaceutical excipients (non-drug component of dosage form) are used as inactive ingredients in dosage form or tools for structuring dosage forms. The main use of topical dosage form additives are controling the extent of absorption, maintaining the viscosity, improving the stability as well as organoleptic property and increasing the bulk of the formulation. The overall goal of this article is to provide the clinician with information related to the topical dosage form additives and their current major applications against various diseases.

  10. 21 CFR 522.1720 - Phenylbutazone injection.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... associated with the musculoskeletal system. (2) It is administered intravenously at a dosage level of 10... musculoskeletal system. (2) It is administered intravenously at a dosage level of 1 to 2 grams per 1,000 pounds of...

  11. 21 CFR 522.1720 - Phenylbutazone injection.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... associated with the musculoskeletal system. (2) It is administered intravenously at a dosage level of 10... musculoskeletal system. (2) It is administered intravenously at a dosage level of 1 to 2 grams per 1,000 pounds of...

  12. 21 CFR 522.1720 - Phenylbutazone injection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... associated with the musculoskeletal system. (2) It is administered intravenously at a dosage level of 10... musculoskeletal system. (2) It is administered intravenously at a dosage level of 1 to 2 grams per 1,000 pounds of...

  13. 21 CFR 522.1720 - Phenylbutazone injection.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... associated with the musculoskeletal system. (2) It is administered intravenously at a dosage level of 10... musculoskeletal system. (2) It is administered intravenously at a dosage level of 1 to 2 grams per 1,000 pounds of...

  14. The Effects of Promethazine on Human Performance, Mood States, and Motion Sickness Tolerance

    NASA Technical Reports Server (NTRS)

    Cowings, Patricia S.; Stout, Cynthia; Toscano, William B.; Reynoso, Samuel; DeRoshia, Charles

    1996-01-01

    Intramuscular (IM) injections of promethazine in 25 mg or 50 mg dosages are commonly used to treat space motion sickness in astronauts. The present study examined the effects of IM injections of promethazine on neuropsy-chological performance, mood states, and motion sickness tolerance in humans. Twelve men, mean age 36 plus or minus 3.1 participated in one training (no injections) and three treatment conditions: a 25 mg injection of promethazine, a 50 mg injection of promethazine, and a placebo injection of sterile saline. Each condition, spaced at 7 day intervals, required an 8-10 hr session in which subjects were given four repetitions of 12 performance tasks, and one rotating chair motion sickness test. On the training day subjects were trained on each task to establish stability and proficiency. On treatment days, the order in which the drug or placebo was assigned to subjects was counter-balanced and a double-blind technique was used. Statistically significant decrements in performance were observed on 10 of 12 tasks when subjects were given 25 mg or 50 mg of promethazine as compared to the placebo. Performance decrements were associated with mean blood alcohol dose equivalency levels of 0.085% for 25 mg and 0. 1 37% for 50 mg dosages. The mood scale results showed significant changes in individual subjective experiences with maximum deterioration in the arousal state and fatigue level. When compared to placebo significant increases in motion sickness tolerance were found for both dosages of promethazine. These data suggest that effective dosages of promethazine currently used to counteract motion sickness in astronauts may significantly impair task components of their operational performance.

  15. Optimal Dosing of Botulinum Toxin for Treatment of Chronic Anal Fissure: A Systematic Review and Meta-Analysis.

    PubMed

    Lin, Jin Xin; Krishna, Sanjeev; Su'a, Bruce; Hill, Andrew G

    2016-09-01

    Chronic anal fissures are associated with significant morbidity and reduced quality of life. Studies have investigated the efficacy of botulinum toxin with variable results; thus, there is currently no consensus on botulinum toxin dose or injection sites. This study aimed to systematically analyze trials studying the efficacy of botulinum toxin for treatment of chronic anal fissure to identify an optimum dosage and injection regimen. A comprehensive review of the literature was conducted according to PRISMA guidelines. PubMed/Medline, Embase, Scopus, and the Cochrane Library were searched from inception to June 2015. All clinical trials that investigated the efficacy of botulinum toxin for chronic anal fissure were selected according to specific criteria. The interventions used were various doses of botulinum toxin. Clinical outcomes, dosage, and injection site data were evaluated with weighted pooled results for each dosage and 95% confidence intervals. There were 1158 patients, with 661 in botulinum toxin treatment arms, from 18 clinical trials included in this review. The outcomes of interest were 3-month healing, incontinence, and recurrence rates. Meta-regression analysis demonstrated a small decrease in healing rate (0.34%; 95% CI, 0-0.68; p = 0.048) with each increase in dosage, a small increase in incontinence rate (1.02 times; 95% CI, 1.0002-1.049; p = 0.048) with each increase in dosage and a small increase in recurrence rate (1.037 times; 95% CI, 1.018-1.057; p = 0.0002) with each increase in dosage. The optimum injection site could not be determined. This study was limited by weaknesses in the underlying evidence, such as variable quality, short follow-up, and a limited range of doses represented. Fissure healing with lower doses of botulinum toxin is as effective as with high doses. Lower doses also reduce the risk of incontinence and recurrence in the long term.

  16. Dose Accuracy and Injection Force of Different Insulin Glargine Pens

    PubMed Central

    Friedrichs, Arnd; Bohnet, Janine; Korger, Volker; Adler, Steffen; Schubert-Zsilavecz, Manfred; Abdel-Tawab, Mona

    2013-01-01

    Background Dose accuracy and injection force, representing key parameters of insulin pens, were determined for three pens delivering insulin glargine-based copies, Pen Royale (WR) and DispoPen (WD) for Glaritus® (Wockhardt) and GanLee Pen (GL) for Basalin® (Gan & Lee), compared with pens of the originator, ClikSTAR® (CS) and S o l o S TA R® (SS) for Lantus® (Sanofi) . Methods Using the weighing procedure recommended by DIN EN ISO 11608–1:2000, dose accuracy was evaluated based on nonrandomized delivery of low (5 U), mid (30 U), and high (60 U) dosage levels. Injection force was measured by dispensing the maximum dose of insulin (60 U for the GL, WR, and WD; 80 U for the SS and CS) at dose speeds of 6 and 10 U/s. Results All tested pens delivered comparable average doses within the DIN EN ISO 11608–1:2000 limits at all dosage levels. The GL revealed a higher coefficient of variation (CV) at 5 U, and the WR and WD had higher CVs at all dosage levels compared with the CS and SS. Injection force was higher for the WR, WD, and GL compared with the CS and SS at both dose speeds. In contrast to the CS and SS with an end-of-content feature, doses exceeding the remaining insulin could be dialed with the WR, GL, and WD and, apparently, dispensed with the WD. Conclusions All pens fulfilled the dose accuracy requirements defined by DIN EN ISO 11608–1:2000 standards at all three dosage levels, with the WR, WD, and GL showing higher dosage variability and injection force compared with the SS and CS. Thus, the devices that deliver insulin glargine copies show different performance characteristics compared with the originator. J Diabetes Sci Technol 2013;7(5):1346–1353 PMID:24124963

  17. 21 CFR 524.1662 - Oxytetracycline hydrochloride ophthalmic and topical dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride ophthalmic and topical dosage forms. 524.1662 Section 524.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... DOSAGE FORM NEW ANIMAL DRUGS § 524.1662 Oxytetracycline hydrochloride ophthalmic and topical dosage forms. ...

  18. [Influence of iron nanoparticles on cardiac performance and hemodynamics in rabbits after intravenous administration in acute experiment].

    PubMed

    Doroshenko, A M

    2014-01-01

    Iron nanoparticles are possessed by high potential in the creation of effective and safe antianemic drugs due to the enhanced biological activity of metal nanoparticles. As a step of intravenous dosage form development the study of short-term effects of iron nanoparticles on the cardiovascular system is important. Dose-dependent changes of systemic hemodynamics' parameters were established in acute experiment on rabbits after several intravenous injections of zero-valent iron nanoparticles solution.

  19. Determination of Verapamil HCl in Pharmaceutical Preparations by a Fluorescent Nano Probe Based on CdTe/CdS/ZnS Quantum Dots

    PubMed Central

    Muhammad, Sohail; Xu, Guanhong; Wei, Fangdi; Ma, Yujie; Ma, Yunsu; Song, Yueyue; Shi, Menglan; Xu, Xiaoman; Cen, Yao; Hu, Qin

    2017-01-01

    An analytical technique based on fluorescence quenching of CdTe/CdS/ZnS quantum dots (QDs) was developed to quantify verapamil in commercially available preparations. Various reaction parameters were optimized and the method developed was validated. One way analysis of variance (ANOVA) and post hoc tests at a 5% significance level were performed to justify the significance of the variation in observations. The linear range of the verapamil concentration was 0.25–5 µg/mL while the limit of detection was 20 µg/mL. Recovery and relative standard deviations were not more than ±10% of the actual amount and <5.9%, respectively. Foreign materials, common metal ions and pharmaceutical excipients of dosage forms caused little interference. To verify the application of the analytical method, the quantity of verapamil in commercially available dosage forms was measured. Verapamil content in the tablets and injections was not more than ±10% of the stated amount and it conformed to the specifications of both the British and the United States pharmacopoeias. In the case of statistical analysis, p-value was <0.05 in almost all levels of all parameters except for the optimized level of system. It can be concluded from the results that the designed method is simple, reliable, cost effective, selective, rapid and sensitive enough to be used for quantitative measurement of the verapamil HCl in dosage forms for quality control purposes. PMID:29084166

  20. New Stability-Indicating RP-HPLC Method for Determination of Diclofenac Potassium and Metaxalone from their Combined Dosage Form

    PubMed Central

    Panda, Sagar Suman; Patanaik, Debasis; Ravi Kumar, Bera V. V.

    2012-01-01

    A simple, precise and accurate isocratic RP-HPLC stability-indicating assay method has been developed to determine diclofenac potassium and metaxalone in their combined dosage forms. Isocratic separation was achieved on a Hibar-C18, Lichrosphere-100® (250 mm × 4.6 mm i.d., particle size 5 μm) column at room temperature in isocratic mode, the mobile phase consists of methanol: water (80:20, v/v) at a flow rate of 1.0 ml/min, the injection volume was 20 μl and UV detection was carried out at 280nm. The drug was subjected to acid and alkali hydrolysis, oxidation, photolysis and heat as stress conditions. The method was validated for specificity, linearity, precision, accuracy, robustness and system suitability. The method was linear in the drug concentration range of 2.5–30 μg/ml and 20–240 μg/ml for diclofenac potassium and metaxalone, respectively. The precision (RSD) of six samples was 0.83 and 0.93% for repeatability, and the intermediate precision (RSD) among six-sample preparation was 1.63 and 0.49% for diclofenac potassium and metaxalone, respectively. The mean recoveries were between 100.99–102.58% and 99.97–100.01% for diclofenac potassium and metaxalone, respectively. The proposed method can be used successfully for routine analysis of the drug in bulk and combined pharmaceutical dosage forms. PMID:22396909

  1. 21 CFR 330.3 - Imprinting of solid oral dosage form drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Imprinting of solid oral dosage form drug products... AS SAFE AND EFFECTIVE AND NOT MISBRANDED General Provisions § 330.3 Imprinting of solid oral dosage form drug products. A requirement to imprint an identification code on solid oral dosage form drug...

  2. 21 CFR 330.3 - Imprinting of solid oral dosage form drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Imprinting of solid oral dosage form drug products... AS SAFE AND EFFECTIVE AND NOT MISBRANDED General Provisions § 330.3 Imprinting of solid oral dosage form drug products. A requirement to imprint an identification code on solid oral dosage form drug...

  3. Crystallization processes in pharmaceutical technology and drug delivery design

    NASA Astrophysics Data System (ADS)

    Shekunov, B. Yu; York, P.

    2000-04-01

    Crystallization is a major technological process for particle formation in pharmaceutical industry and, in addition, plays an important role in defining the stability and drug release properties of the final dosage forms. Industrial and regulatory aspects of crystallization are briefly reviewed with reference to solid-state properties of pharmaceuticals. Crystallization, incorporating wider definition to include precipitation and solid-state transitions, is considered in terms of preparation of materials for direct compression, formation of amorphous, solvated and polymorphic forms, chiral separation of drugs, production of materials for inhalation drug delivery and injections. Finally, recent developments in supercritical fluid particle technology is considered in relationship to the areas discussed.

  4. Injection Molding and its application to drug delivery.

    PubMed

    Zema, Lucia; Loreti, Giulia; Melocchi, Alice; Maroni, Alessandra; Gazzaniga, Andrea

    2012-05-10

    Injection Molding (IM) consists in the injection, under high pressure conditions, of heat-induced softened materials into a mold cavity where they are shaped. The advantages the technique may offer in the development of drug products concern both production costs (no need for water or other solvents, continuous manufacturing, scalability, patentability) and technological/biopharmaceutical characteristics of the molded items (versatility of the design and composition, possibility of obtaining solid molecular dispersions/solutions of the active ingredient). In this article, process steps and formulation aspects relevant to IM are discussed, with emphasis on the issues and advantages connected with the transfer of this technique from the plastics industry to the production of conventional and controlled-release dosage forms. Moreover, its pharmaceutical applications thus far proposed in the primary literature, intended as either alternative manufacturing strategies for existing products or innovative systems with improved design and performance characteristics, are critically reviewed. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Comparison of essential drug list in a rural secondary care hospital in south India with Indian & World Health Organization list 2011.

    PubMed

    Rao, Seetharama G; Thomas, Dixon; Zachariah, Seeba; Kannan, M S; Alvarez-Uria, Gerardo

    2012-01-01

    Fixed drug combinations are a major marketing strategy in India but it can compromise the rational use of medicines. In this study we compared the fixed drug combinations and dosage forms in the hospital pharmacy before and after introducing the essential drug list. We also compared the Hospital Essential Drug List (HEDL) 2011 with the World Health Organization (WHO) Essential Drug List (EDL) 2011 and the National Essential Drug List of India (NEDL) 2011. The study was done in a secondary level care charity hospital at Anantapur, AP with a bed size of 315 and an average OP per day of 1200-1700 visits. We compared the three essential drug lists (HEDL, WHOEDL and NEDL) and the hospital drug list before introducing EDL. Drugs which were present in NEDL and not present in the HEDL were also screened. Microsoft excel was used to tabulate the results and for graphs. The number of medicines used in the hospital before and after the introduction of the HEDL was 1627 and 424 respectively. On comparison, WHOEDL 2011 have 350 and NEDL of India have 348 medicines. While preparing the HEDL, 46 double drug combinations decreased to 15 and 9 triple drug combinations decreased to 1. In the case of injections, 20 double drug combinations decreased to 6 and 1 triple drug combination increased to 2. The number of tablets, capsules, injections, syrups, powders and inhalers was reduced to almost half. The great reductions were in 51 ointments to 9, 69 drops to 5, 11 paste to 0, 21 solutions to 3 and 14 creams to 1. The dosage forms removed included elixirs, insulin pens, gums, paste, paints, gargles and mouthwashes. There was drastic reduction in the number of medicines and dosage forms when the HEDL was implemented. Many of the fixed drug combinations were also removed for improving the rational use of medicines. The WHO essential drug list 2011, national essential drug list of India 2011 and the hospital essential drug list 2011 were comparable with few exceptions.

  6. Microbiological assay for the determination of meropenem in pharmaceutical dosage form.

    PubMed

    Mendez, Andreas S L; Weisheimer, Vanessa; Oppe, Tércio P; Steppe, Martin; Schapoval, Elfrides E S

    2005-04-01

    Meropenem is a highly active carbapenem antibiotic used in the treatment of a wide range of serious infections. The present work reports a microbiological assay, applying the cylinder-plate method, for the determination of meropenem in powder for injection. The validation method yielded good results and included linearity, precision, accuracy and specificity. The assay is based on the inhibitory effect of meropenem upon the strain of Micrococcus luteus ATCC 9341 used as the test microorganism. The results of assay were treated statistically by analysis of variance (ANOVA) and were found to be linear (r=0.9999) in the range of 1.5-6.0 microg ml(-1), precise (intra-assay: R.S.D.=0.29; inter-assay: R.S.D.=0.94) and accurate. A preliminary stability study of meropenem was performed to show that the microbiological assay is specific for the determination of meropenem in the presence of its degradation products. The degraded samples were also analysed by the HPLC method. The proposed method allows the quantitation of meropenem in pharmaceutical dosage form and can be used for the drug analysis in routine quality control.

  7. Validation of HPLC and UV spectrophotometric methods for the determination of meropenem in pharmaceutical dosage form.

    PubMed

    Mendez, Andreas S L; Steppe, Martin; Schapoval, Elfrides E S

    2003-12-04

    A high-performance liquid chromatographic method and a UV spectrophotometric method for the quantitative determination of meropenem, a highly active carbapenem antibiotic, in powder for injection were developed in present work. The parameters linearity, precision, accuracy, specificity, robustness, limit of detection and limit of quantitation were studied according to International Conference on Harmonization guidelines. Chromatography was carried out by reversed-phase technique on an RP-18 column with a mobile phase composed of 30 mM monobasic phosphate buffer and acetonitrile (90:10; v/v), adjusted to pH 3.0 with orthophosphoric acid. The UV spectrophotometric method was performed at 298 nm. The samples were prepared in water and the stability of meropenem in aqueous solution at 4 and 25 degrees C was studied. The results were satisfactory with good stability after 24 h at 4 degrees C. Statistical analysis by Student's t-test showed no significant difference between the results obtained by the two methods. The proposed methods are highly sensitive, precise and accurate and can be used for the reliable quantitation of meropenem in pharmaceutical dosage form.

  8. Simultaneous in vivo visualization and localization of solid oral dosage forms in the rat gastrointestinal tract by magnetic resonance imaging (MRI).

    PubMed

    Christmann, V; Rosenberg, J; Seega, J; Lehr, C M

    1997-08-01

    Bioavailability of orally administered drugs is much influenced by the behavior, performance and fate of the dosage form within the gastrointestinal (GI) tract. Therefore, MRI in vivo methods that allow for the simultaneous visualization of solid oral dosage forms and anatomical structures of the GI tract have been investigated. Oral contrast agents containing Gd-DTPA were used to depict the lumen of the digestive organs. Solid oral dosage forms were visualized in a rat model by a 1H-MRI double contrast technique (magnetite-labelled microtablets) and a combination of 1H- and 19F-MRI (fluorine-labelled minicapsules). Simultaneous visualization of solid oral dosage forms and the GI environment in the rat was possible using MRI. Microtablets could reproducibly be monitored in the rat stomach and in the intestines using a 1H-MRI double contrast technique. Fluorine-labelled minicapsules were detectable in the rat stomach by a combination of 1H- and 19F-MRI in vivo. The in vivo 1H-MRI double contrast technique described allows solid oral dosage forms in the rat GI tract to be depicted. Solid dosage forms can easily be labelled by incorporating trace amounts of non-toxic iron oxide (magnetite) particles. 1H-MRI is a promising tool for observing such pharmaceutical dosage forms in humans. Combined 1H- and 19F-MRI offer a means of unambiguously localizing solid oral dosage forms in more distal parts of the GI tract. Studies correlating MRI examinations with drug plasma levels could provide valuable information for the development of pharmaceutical dosage forms.

  9. Onabotulinum toxin A dosage trends over time for adductor spasmodic dysphonia: A 15-year experience.

    PubMed

    Tang, Christopher G; Novakovic, Daniel; Mor, Niv; Blitzer, Andrew

    2016-03-01

    Although onabotulinum neurotoxin A (BoNTA) has been used for over three decades for the treatment of adductor spasmodic dysphonia, no study has been performed to look at the trend of BoNTA dosages across time. The goal of this study is to evaluate the dosage trends to determine if the dosage necessary for voice improvement in patients increases over time. Charts were reviewed for patients with 15 years or more of experience. Linear regression analysis was performed to determine correlation coefficients and trends. Fifty-five patients receiving BoNTA injections by the senior author (a.b.) for over 15 years were evaluated. Thirty-nine patients (82% female) met inclusion criteria. Patients received injections over an average of 18.6 years ± 1.36 years, with the longest follow-up of 21.5 years. Of 39 patients, 16 (41%) had a negative correlation coefficient (Pearson's r) suggesting a decrease over time, whereas 23 (59%) had a positive correlation coefficient suggesting an increase over time. The mean correlation coefficient was 0.139 ± 0.534 and P < 0.05 in 19 patients and P > 0.05 in 20 patients. R(2) for all patients were less than 0.75. Onabotulinum neurotoxin A injection dosage trends vary depending on the individual over time. Overall, the dose range appears to be stable in the majority of patients, suggesting that tolerance does not play a significant part in dose variation over time. 4. Laryngoscope, 126:678-681, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  10. Magnetic marker monitoring: high resolution real-time tracking of oral solid dosage forms in the gastrointestinal tract.

    PubMed

    Weitschies, Werner; Blume, Henning; Mönnikes, Hubert

    2010-01-01

    Knowledge about the performance of dosage forms in the gastrointestinal tract is essential for the development of new oral delivery systems, as well as for the choice of the optimal formulation technology. Magnetic Marker Monitoring (MMM) is an imaging technology for the investigation of the behaviour of solid oral dosage forms within the gastrointestinal tract, which is based on the labelling of solid dosage forms as a magnetic dipole and determination of the location, orientation and strength of the dipole after oral administration using measurement equipment and localization methods that are established in biomagnetism. MMM enables the investigation of the performance of solid dosage forms in the gastrointestinal tract with a temporal resolution in the range of a few milliseconds and a spatial resolution in 3D in the range of some millimetres. Thereby, MMM provides real-time tracking of dosage forms in the gastrointestinal tract. MMM is also suitable for the determination of dosage form disintegration and for quantitative measurement of in vivo drug release in case of appropriate extended release dosage forms like hydrogel-forming matrix tablets. The combination of MMM with pharmacokinetic measurements (pharmacomagnetography) enables the determination of in vitro-in vivo correlations (IVIC) and the delineation of absorption sites in the gastrointestinal tract. Copyright 2009 Elsevier B.V. All rights reserved.

  11. Alternative antiretroviral therapy formulations for patients unable to swallow solid oral dosage forms.

    PubMed

    Duggan, Joan M; Akpanudo, Barbara; Shukla, Vipul; Gutterson, Glen; Eitniear, Lindsey; Sahloff, Eric G

    2015-09-15

    Evidence-based guidance is presented to assist clinicians in selecting alternative formulations of antiretroviral (ARV) agents for patients with human immunodeficiency virus (HIV) infection who are unable to swallow tablets or capsules. The inability to take medications in standard oral dosage forms can be associated with nonadherence or the use of alternative administration strategies such as capsule or tablet breaking, crushing, or chewing. Patients with HIV infection require long-term ARV therapy to maintain viral suppression; ARV agents are predominately available as tablets and capsules that may pose swallowing difficulties for some patients. Using a variety of sources (the primary literature, pharmaceutical package inserts, and requests for unpublished data from drug manufacturers), available evidence on the bioavailability of ARV medications after disruption of the capsule or tablet matrix was reviewed; information on alternative formulations of ARV agents was also assessed. With several ARV agents, disruption of the solid oral dosage form by crushing, chewing, or breaking tablets or opening capsules prior to ingestion has been shown to result in altered bioavailability or pharmacokinetics and thus the potential for incomplete virological suppression, increased adverse effects, and suboptimal health outcomes. Of the 33 single-agent ARV medications and combination ARV products in five classes available at the time of review, approximately half exist as powders, liquids, injectables, or chewable or dissolvable tablets. If alternative ARV formulations or administration methods are used, close monitoring for achievement of virological and immunologic success and potential toxicities is recommended. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  12. Formulation and Stability of Solutions.

    PubMed

    Akers, Michael J

    2016-01-01

    Ready-to-use solutions are the most preferable and most common dosage forms for injectable and topical ophthalmic products. Drugs formulated as solution almost always have chemical and physical stability challenges as well as solubility limitations and the need to prevent inadvertent microbial contamination issues. The first in this series of articles took us through a discussion of optimizing the physical stability of solutions. This article concludes this series of articles with a discussion on foreign particles, protein aggregation, and immunogenicity; optimizing microbiological activity; and osmolality (tonicity) agents, and discusses how these challenges and issues are addressed.

  13. Supercritical fluid extraction of 13-cis retinoic acid and its photoisomers from selected pharmaceutical dosage forms.

    PubMed

    Simmons, B R; Chukwumerije, O; Stewart, J T

    1997-11-01

    13-Cis retinoic acid (Accutane) was extracted from a cream, gel, capsule and beadlet dosage from using supercritical carbon dioxide modified with 5% methanol as the mobile phase. The pump pressure and the extraction chamber and restrictor temperature were experimentally optimized at 325 atm and 45 degrees C, respectively. A 2.5-min static and 5-min dynamic extraction time were used. The supercritical fluid extraction (SFE) eluent was trapped in methanol, injected into the high-performance liquid chromatographic (HPLC) system, and quantitated by ultraviolet detection at 360 nm. Application of the SFE method to spiked placebo dosage forms gave 13-cis retinoic acid recoveries of 98.8, 98.9, 98.8 and 100% for the cream, gel, capsule and beadlet, respectively, with R.S.D.s in the range 0.6-0.9% (n = 4). Inter-day percent error and precision of the extraction were 1.1-2.0 and 0.2-2.4% (n = 3), respectively, and intra-day percent error and precision were 1.0-3.0 and 0.3-2.1% (n = 8), respectively. Percent error and precision data for spiked celite samples in the 0.05-1.0 microgram ml-1 range were 0.59-4.75 and 1.8-2.1% (n = 3), respectively. The extraction method was applied to commercial 13-cis retinoic acid dosage forms and the results compared to unextracted samples. Linear regression analysis of concentration versus peak height gave a correlation coefficient of 0.9991 with a slope of 7.468 and a y-intercept of 0.1923. The percent error and precision data were 1.3-5.3 and 0.2-1.5% (n = 4), respectively. The photoisomers of 13-cis retinoic acid were also extracted with the method and recoveries of 90.4-92.4% with R.S.D.s of 1.5-3.4% were obtained (n = 4).

  14. 21 CFR 520.905 - Fenbendazole oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Fenbendazole oral dosage forms. 520.905 Section 520.905 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Fenbendazole oral dosage forms. ...

  15. 21 CFR 526.1696 - Penicillin intramammary dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Penicillin intramammary dosage forms. ...

  16. 21 CFR 526.1696 - Penicillin intramammary dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Penicillin intramammary dosage forms. ...

  17. 21 CFR 526.1696 - Penicillin intramammary dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Penicillin intramammary dosage forms. ...

  18. 21 CFR 526.1696 - Penicillin intramammary dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Penicillin intramammary dosage forms. ...

  19. [Pharmacodynamic experiment of the antivirus effect of Houttuynia cordata injection on influenza virus in mice].

    PubMed

    Liu, Fang-zhou; Shi, Han; Shi, Yu-jing; Liu, Ying; Jin, Ya-hong; Gao, Ying-jie; Guo, Shan-shan; Cui, Xiao-lan

    2010-03-01

    It is to investigate the effect of two kinds of Houttuynia Cordata Injection on preventing and treating H1N1 influenza virus infection in mice. Pneumonia model was set up by intranasal infection of the normal and immunocompromised mice with influenza virus FM1 and PR8. The two injections were administered before and after the administration of virus, separately, and the lung index was observed. The results showed that the two preparations have obvious therapeutic effect on normal mice infected with influenza virus FM1 and PR8. And to FM1, the new injection's effect is better at small dosage. The results also showed that the two preparations have obvious prophylactic effect on immunodepressed mice infected with influenza virus FM1 and PR8. And to PR8, the old injection's effect is better at small dosage. Houttuynia Cordata Injection can improve the mice pneumonia caused by influenza virus H1N1 and decrease the lung index markedly. It has a remarkable preventive and therapeutic effect on H1N1 influenza virus in mice.

  20. In-vitro Drug Dissolution Studies in Medicinal Compounds.

    PubMed

    Bozal-Palabiyik, Burcin; Uslu, Bengi; Ozkan, Yalcin; Ozkan, Sibel A

    2018-03-22

    After oral administration, drug absorption from solid dosage forms depend on the release of the drug active compounds from the dosage form, the dissolution or solubilization of the drug under physiological conditions, and the permeability across the gastrointestinal tract. Dissolution testing is an essential part of designing more effective solid dosage forms in pharmaceutical industry. Moreover dissolution testing contributes to the selection of appropriate formulation excipients for improving the dosage form efficiency. This study aims to analyze in-vitro drug dissolution testing in solid dosage forms since 2010 in order to present a comprehensive outlook of recent trends. In doing that the previous studies in the literature are summarized in the form of a table to demonstrate the apparatuses used for dissolution testing, the media in which the solid dosage form is dissolved, the method preferred for analysis from dissolution media, the conditions of analyses and the results obtained. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Manufacturing Solid Dosage Forms from Bulk Liquids Using the Fluid-bed Drying Technology.

    PubMed

    Qi, Jianping; Lu, Y I; Wu, Wei

    2015-01-01

    Solid dosage forms are better than liquid dosage forms in many ways, such as improved physical and chemical stability, ease of storage and transportation, improved handling properties, and patient compliance. Therefore, it is required to transform dosage forms of liquid origins into solid dosage forms. The functional approaches are to absorb the liquids by solid excipients or through drying. The conventional drying technologies for this purpose include drying by heating, vacuum-, freeze- and spray-drying, etc. Among these drying technologies, fluidbed drying emerges as a new technology that possesses unique advantages. Fluid-bed drying or coating is highly efficient in solvent removal, can be performed at relatively low temperatures, and is a one-step process to manufacture formulations in pellet forms. In this article, the status of the art of manufacturing solid dosage forms from bulk liquids by fluid-bed drying technology was reviewed emphasizing on its application in solid dispersion, inclusion complexes, self-microemulsifying systems, and various nanoscale drug delivery systems.

  2. A benefit/risk approach towards selecting appropriate pharmaceutical dosage forms - an application for paediatric dosage form selection.

    PubMed

    Sam, Tom; Ernest, Terry B; Walsh, Jennifer; Williams, Julie L

    2012-10-05

    The design and selection of new pharmaceutical dosage forms involves the careful consideration and balancing of a quality target product profile against technical challenges and development feasibility. Paediatric dosage forms present particular complexity due to the diverse patient population, patient compliance challenges and safety considerations of this vulnerable population. This paper presents a structured framework for assessing the comparative benefits and risks of different pharmaceutical design options against pre-determined criteria relating to (1) efficacy, (2) safety and (3) patient access. This benefit/risk framework has then been applied to three hypothetical, but realistic, scenarios for paediatric dosage forms in order to explore its utility in guiding dosage form design and formulation selection. The approach allows a rigorous, systematic and qualitative assessment of the merits and disadvantages of each dosage form option and helps identify mitigating strategies to modify risk. The application of a weighting and scoring system to the criteria depending on the specific case could further refine the analysis and aid decision-making. In this paper, one case study is scored for illustrative purposes. However, it is acknowledged that in real development scenarios, the generation of actual data considering the very specific situation for the patient/product/developer would come into play to drive decisions on the most appropriate dosage form strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. 21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... sulfate oral dosage forms. ...

  4. 21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... sulfate oral dosage forms. ...

  5. 21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... sulfate oral dosage forms. ...

  6. 21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... sulfate oral dosage forms. ...

  7. [Pharmaceutical advice concerning different pharmaceutical dosage forms].

    PubMed

    Szakonyi, Gergely; Zelkó, Romána

    2010-01-01

    The present paper summarizes the commonly applied types of drug uptake and the pharmacists' advice concerning a certain dosage form. The manuscript also deals with the modified release dosage forms and their abbreviations in the name of the marketing authorized products.

  8. The evaluation of physical properties of injection molded systems based on poly(ethylene oxide) (PEO).

    PubMed

    Pajander, Jari; Rensonnet, Alexia; Hietala, Sami; Rantanen, Jukka; Baldursdottir, Stefania

    2017-02-25

    The effect of product design parameters on the formation and properties of an injection molded solid dosage form consisting of poly(ethylene oxide)s (PEO) and two different active pharmaceutical ingredients (APIs) was studied. The product design parameters explored were melting temperature and the duration of melting, API loading degree and the molecular weight (M w ) of PEO. The solid form composition of the model APIs, theophylline and carbamazepine, was of specific interest, and its possible impact on the in vitro drug release behavior. M w of PEO had the greatest impact on the release rate of both APIs. High M w resulted in slower API release rate. Process temperature had two-fold effect with PEO 300,000g/mol. Firstly, higher process temperature transformed the crystalline part of the polymer into metastable folded form (more folded crystalline regions) and less into the more stable extended form (more extended crystalline regions), which lead to enhanced theophylline release rate. Secondly, the higher process temperature seemed to induce carbamazepine polymorphic transformation from p-monoclinic form III (carbamazepine (M)) into trigonal form II (carbamazepine (T)). The results indicated that the actual content of carbamazepine (T) affected drug release behavior more than the magnitude of transformation. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Alteration of Skin Mechanical Properties in Patients Undergoing Botulinum Toxin Type A Injections of Forehead Rhytides.

    PubMed

    Min, Peiru; Zhang, Zheng; Grassetti, Luca; Perdanasari, Aurelia Trisliana; Torresetti, Matteo; Pu, Zheming; Zhang, Yan; Han, Sheng; Marsili, Riccardo; Zhang, Yi Xin; di Benedetto, Giovanni; Lazzeri, Davide

    2016-06-01

    Although application of botulinum toxin type A (BTX-A) for the treatment of forehead rhytides has become very popular, the effects of its intramuscular injections on the skin mechanical properties remain unclear. We prospectively investigated the alterations in the mechanical properties of the skin of patients who received intramuscular injections of botulinum toxin A (BTX-A) for forehead rhytides and compared two injection doses. Of the 42 enrolled patients, one randomly assigned half received intramuscular injections of two units (group I), and the other half received four units (group II) of BTX-A in each injection point. The baseline and post-treatment skin mechanical parameters, including gross elasticity (R2), net elasticity (R5), viscoelastic ratio (R6) and biological elasticity (R7), were measured using the Cutometer(®) and compared. Treatment with BTX-A resulted in significant overall alterations in the mechanical properties of skin at the injection sites of both treatment groups during the 16-week period, and no significant differences were observed between groups. Significant decreases in biological elasticity, net elasticity and viscoelasticity properties were observed at 2 weeks follow-up and began to recover at that time. All of the skin mechanical properties recovered to baseline levels by 16 weeks of follow-up in both dosage groups, which indicates that the higher dosage (4 units) did not delay relapse compared to the two-unit dosage. We concluded that intramuscular injections of BTX-A significantly regulated the gross elasticity, net elasticity, functional elasticity and viscoelastic elasticity at the injection point over a radius of 1.5 cm at 2, 4 and 8 weeks follow-up. The alteration in the skin measurements had completely diminished by the 16-week follow-up. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  10. Melt-processed polymeric cellular dosage forms for immediate drug release.

    PubMed

    Blaesi, Aron H; Saka, Nannaji

    2015-12-28

    The present immediate-release solid dosage forms, such as the oral tablets and capsules, comprise granular matrices. While effective in releasing the drug rapidly, they are fraught with difficulties inherent in processing particulate matter. By contrast, liquid-based processes would be far more predictable; but the standard cast microstructures are unsuited for immediate-release because they resist fluid percolation and penetration. In this article, we introduce cellular dosage forms that can be readily prepared from polymeric melts by incorporating the nucleation, growth, and coalescence of microscopic gas bubbles in a molding process. We show that the cell topology and formulation of such cellular structures can be engineered to reduce the length-scale of the mass-transfer step, which determines the time of drug release, from as large as the dosage form itself to as small as the thickness of the cell wall. This allows the cellular dosage forms to achieve drug release rates over an order of magnitude faster compared with those of cast matrices, spanning the entire spectrum of immediate-release and beyond. The melt-processed polymeric cellular dosage forms enable predictive design of immediate-release solid dosage forms by tailoring microstructures, and could be manufactured efficiently in a single step.

  11. Soft gelatin capsules (softgels).

    PubMed

    Gullapalli, Rampurna Prasad

    2010-10-01

    It is estimated that more than 40% of new chemical entities (NCEs) coming out of the current drug discovery process have poor biopharmaceutical properties, such as low aqueous solubility and/or permeability. These suboptimal properties pose significant challenges for the oral absorption of the compounds and for the development of orally bioavailable dosage forms. Development of soft gelatin capsule (softgel) dosage form is of growing interest for the oral delivery of poorly water soluble compounds (BCS class II or class IV). The softgel dosage form offers several advantages over other oral dosage forms, such as delivering a liquid matrix designed to solubilize and improve the oral bioavailability of a poorly soluble compound as a unit dose solid dosage form, delivering low and ultra-low doses of a compound, delivering a low melting compound, and minimizing potential generation of dust during manufacturing and thereby improving the safety of production personnel. However, due to the very dynamic nature of the softgel dosage form, its development and stability during its shelf-life are fraught with several challenges. The goal of the current review is to provide an in-depth discussion on the softgel dosage form to formulation scientists who are considering developing softgels for therapeutic compounds.

  12. Controlled release liquid dosage formulation

    DOEpatents

    Benton, Ben F.; Gardner, David L.

    1989-01-01

    A liquid dual coated dosage formulation sustained release pharmaceutic having substantial shelf life prior to ingestion is disclosed. A dual coating is applied over controlled release cores to form dosage forms and the coatings comprise fats melting at less than approximately 101.degree. F. overcoated with cellulose acetate phthalate or zein. The dual coated dosage forms are dispersed in a sugar based acidic liquid carrier such as high fructose corn syrup and display a shelf life of up to approximately at least 45 days while still retaining their release profiles following ingestion. Cellulose acetate phthalate coated dosage form cores can in addition be dispersed in aqueous liquids of pH <5.

  13. Botulinum toxin therapy in Frey's syndrome: a retrospective study of 440 treatments in 100 patients.

    PubMed

    Jansen, S; Jerowski, M; Ludwig, L; Fischer-Krall, E; Beutner, D; Grosheva, M

    2017-04-01

    Frey's syndrome is characterised as sweating, redness and warmth of the parotideal area and is often treated with botulinum toxin A. The objective of this retrospective study was to prove whether the toxin dosage and time-to-treatment intervals change after repeated botulinum toxin injections. The charts of patients, who were treated for Frey's syndrome during the last 16 years, were assessed. Three brands of botulinum toxin A were available for therapy. The Minor test was used to confirm the sweating before each treatment and to determine the toxin dosage. Constant amount of botulinum toxin was injected per cm 2 of the affected area. Patients consulted our department for the next treatment as soon as they felt disturbed by recurring sweating and when the sweating was objectively evident in the Minor test. Time intervals between treatments and injected toxin dosages were assessed. In total, 100 patients received 440 treatments in 16 years. Repeated injections, median 4.0, were carried out in 70.5% of patients. Median time interval to the first injection was 2.8 years. Median time interval between treatments was 12.0 months and showed to be steady (anova, P = .49, F = 1.01). Duration of effect of botulinum toxin on Frey's syndrome was long-lasting and stable with no significantly different time intervals between treatments. The extent of the sweating area did not vary significantly after repeated treatments and required a constant dose of botulinum toxin A. © 2016 John Wiley & Sons Ltd.

  14. The impact of space travel on dosage form design and use.

    PubMed

    Aronsohn, A; Brazeau, G; Hughes, J

    1999-07-01

    The author speculates on potential factors that may influence the utilization of dosage forms in space. A key assumption is that most of the arguments will be based on current understanding of how dosage forms work on earth. Factors discussed include dosage form stability; and administration of drugs, particularly inhalation and aerosols. A sample experiment used a tissue culture model of drug transfer for passively absorbed drugs to address how alterations in hydrostatic pressure would change paracellular transport.

  15. Physicochemical interactions in solid dosage forms.

    PubMed

    Narang, Ajit S; Desai, Divyakant; Badawy, Sherif

    2012-10-01

    Complete characterization and mechanistic understanding of physicochemical interactions in solid dosage forms are not only important for consistent manufacturability, stability, and bioavailability of the drug product, but are also expected under the quality-by-design paradigm of drug development. Lack of this understanding can impact successful and timely development, scale-up, and commercial manufacture of dosage forms. This article highlights the stability and bioavailability implications of physicochemical interactions in dosage forms citing a couple of examples where such interactions necessitated the recall of commercial drug products.

  16. Over-the-counter pharmaceuticals: exploratory research of consumer preference toward solid oral dosage forms.

    PubMed

    Reisenwitz, T H; Wimbish, G J

    1996-01-01

    The capsule dosage form in nonprescription pharmaceuticals persists as being one of the most vulnerable to product tampering. This study examines consumer preference toward three solid oral dosage forms (capsules, caplets, and tablets) in nonprescription products. Thirteen independent variables representing dosage form attributes are measured on semantic differential scales. The data are analyzed using analysis of variance (ANOVA) and factor analysis. Implications for the pharmaceutical marketer are noted. Future directions for research are also outlined.

  17. Pharmacokinetics of the prototype and hydrolyzed carboxylic forms of ginkgolides A, B, and K administered as a ginkgo diterpene lactones meglumine injection in beagle dogs.

    PubMed

    Wang, Shu-Yao; A, Ji-Ye; Fei, Fei; Geng, Jian-Liang; Peng, Ying; Ouyang, Bing-Chen; Wang, Pei; Jin, Xiao-Liang; Zhao, Yu-Qing; Wang, Jian-Kun; Geng, Ting; Li, Yan-Jing; Huang, Wen-Zhe; Wang, Zhen-Zhong; Xiao, Wei; Wang, Guang-Ji

    2017-10-01

    Ginkgo diterpene lactones meglumine injection (GDLI) is a commercially available product used for neuroprotection. However, the pharmacokinetic properties of the prototypes and hydrolyzed carboxylic forms of the primary components in GDLI, i.e., ginkgolide A (GA), ginkgolide B (GB), and ginkgolide K (GK), have never been fully evaluated in beagle dogs. In this work, a simple, sensitive, and reliable method based on ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was developed, and the prototypes and total amounts of GA, GB, and GK were determined in beagle dog plasma. The plasma concentrations of the hydrolyzed carboxylic forms were calculated by subtracting the prototype concentrations from the total lactone concentrations. For the first time, the pharmacokinetics of GA, GB, and GK were fully assessed in three forms, i.e., the prototypes, the hydrolyzed carboxylic forms, and the total amounts, after intravenous administration of GDLI in beagle dogs. It was shown that ginkgolides primarily existed in the hydrolyzed form in plasma, and the ratio of hydrolysates to prototype forms of GA and GB decreased gradually to a homeostatic ratio. All of the three forms of the three ginkgolides showed linear exposure of AUC to the dosages. GA, GB, and GK showed a constant half-life approximately 2.7, 3.4, and 1.2 h, respectively, which were consistent for the forms at three dose levels (0.3, 1.0, and 3.0 mg·kg -1 ) and after a consecutive injection of GDLI for 7 days (1.0 mg·kg -1 ). Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  18. In vitro cytotoxic effects of benzalkonium chloride in corticosteroid injection suspension.

    PubMed

    Davis, Daniel; Cyriac, Mathew; Ge, Dongxia; You, Zongbing; Savoie, Felix H

    2010-01-01

    Some deleterious effects on cartilage and even severe arthropathy have been reported after intra-articular corticosteroid injections. The objective of the present in vitro study was to determine if an injectable corticosteroid suspension is toxic to articular chondrocytes and synovial cells. Human and bovine articular chondrocytes, bovine synovial cells, mouse C3H10T1/2 cells, and human osteosarcoma MG-63 cells were treated for thirty minutes in monolayer or suspension culture with an injectable corticosteroid suspension or its chemical components, including betamethasone sodium phosphate, betamethasone acetate, and benzalkonium chloride (as preservative). Cell viability was determined by means of microscopy or flow cytometry analysis. In monolayer culture, the betamethasone corticosteroids per se did not cause cell death, whereas benzalkonium chloride caused death of articular chondrocytes. In suspension culture, betamethasone sodium phosphate at dosages of as high as 6 mg/mL did not cause significant death of human or bovine articular chondrocytes (p > 0.05). In contrast, benzalkonium chloride caused a death rate of 10.6% in human articular chondrocytes at a dosage of 10 microg/mL (p < 0.01), 21.0% at a dosage of 13.3 microg/mL (p < 0.01), and 99.3% and 99.4% at dosages of 20 and 200 microg/mL, respectively (p < 0.001 for both). Similarly, benzalkonium chloride caused death of bovine articular chondrocytes, bovine synovial cells, C3H10T1/2 cells, and MG-63 cells in a dose-dependent manner. When treated with a combination of betamethasone sodium phosphate and 200 microg/mL benzalkonium chloride, >99% of human or bovine articular chondrocytes were dead (p < 0.001). The injectable corticosteroid suspension caused death in in vitro culture of human and bovine articular chondrocytes as well as bovine synovial cells because of its preservative benzalkonium chloride. The betamethasone corticosteroids per se did not cause significant chondrocyte death under the conditions tested.

  19. Chemical and pharmacological comparison of modern and traditional dosage forms of Joshanda.

    PubMed

    Parveen, Sajida; Irfan Bukhari, Nadeem; Shehzadi, Naureen; Qamar, Shaista; Ali, Ejaz; Naheed, Surriya; Latif, Abida; Yuchi, Alamgeer; Hussain, Khalid

    2017-12-11

    Recently, a traditional remedy (Joshanda) has been replaced largely by modern ready-to-use dosage forms, which have not been compared to the original remedy. Therefore, the present study aimed to compare a number of modern dosage forms with traditional remedy. Seven brands, 3 batches each, were compared with a Lab-made formulation with reference to analytical (proximate analyses, spectroscopic and chromatographic metabolomes) and pharmacological profiles (anti-inflammatory and antibacterial activities). Chemical and pharmacological differences were found between Lab-made Joshanda and modern dosage forms. Such variations were also found within the brands and batches of modern formulations (p < 0.05). The Lab-made Joshanda showed significantly higher pharmacological activities as compared to modern brands (p ). The results of the present study indicate that modern dosage forms are unstandardised and less effective than the traditional remedy. Characteristic profiles obtained from Lab-made Joshanda may be used as reference to produce comparable dosage forms.

  20. [Consideration of drug absorption in customizing drug therapy].

    PubMed

    Walter-Sack, I; Haefeli, W E

    2000-09-01

    The rate and extent of drug absorption from the small intestine are related to the release of the active ingredient from a dosage form, its solubility in the liquid phase of gastrointestinal contents, and the transport of the dissolved compound or the intact dosage form from the stomach into the duodenum. With pharmaceutical preparations releasing the active compound within the stomach, and enteric-coated "micro"-formulations (micropellets), gastric emptying is possible during the interdigestive and the digestive period. Potential differences of drug absorption between fasting administration and intake during the digestive period are unpredictable, because they are related to the release characteristics of the dosage form. However, larger enteric-coated preparations like tablets can leave the stomach only with a phase 3 contraction of fasting motility; intake during the digestive period will result in gastric retention of this type of dosage form until all food has left the stomach and fasting motility is restored. Consequently the onset of drug absorption is delayed. This interaction between food and large enteric-coated dosage forms is predictable from pyloric function in relation to the gastric motility. As it occurs regularly, it can be taken into account when prescribing enteric-coated dosage forms. If concomitant intake of food and enteric-coated drugs is unavoidable, but a rapid onset of drug absorption is necessary, micropellets are the dosage form of choice. When the therapeutic effect is insufficient, drug dosage form and timing of drug administration should be checked before prescribing a different active compound.

  1. The transit of dosage forms through the small intestine.

    PubMed

    Yuen, Kah-Hay

    2010-08-16

    The human small intestine, with its enormous absorptive surface area, is invariably the principal site of drug absorption. Hence, the residence time of a dosage form in this part of the gut can have a great influence on the absorption of the contained drug. Various methods have been employed to monitor the gastrointestinal transit of pharmaceutical dosage forms, but the use of gamma-scintigraphy has superceded all the other methods. However, careful consideration of the time interval for image acquisition and proper analysis of the scintigraphic data are important for obtaining reliable results. Most studies reported the mean small intestinal transit time of various dosage forms to be about 3-4h, being closely similar to that of food and water. The value does not appear to be influenced by their physical state nor the presence of food, but the timing of food intake following administration of the dosage forms can influence the small intestinal transit time. While the mean small intestinal transit time is quite consistent among dosage forms and studies, individual values can vary widely. There are differing opinions regarding the effect of density and size of dosage forms on their small intestinal transit properties. Some common excipients employed in pharmaceutical formulations can affect the small intestinal transit and drug absorption. There is currently a lack of studies regarding the effects of excipients, as well as the timing of food intake on the small intestinal transit of dosage forms and drug absorption. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  2. 3D-micro-patterned fibrous dosage forms for immediate drug release.

    PubMed

    Blaesi, Aron H; Saka, Nannaji

    2018-03-01

    At present, the most prevalent pharmaceutical dosage forms, the orally-delivered immediate-release tablets and capsules, are porous, granular solids. They disintegrate into their constituent particulates upon ingestion to release drug rapidly. The design, development, and manufacture of such granular solids, however, is inefficient due to difficulties associated with the unpredictable inter-particle interactions. Therefore, to achieve more predictable dosage form properties and processing, we have recently introduced melt-processed polymeric cellular dosage forms. The cellular forms disintegrated and released drug rapidly if the cells were predominantly interconnected. Preparation of interconnected cells, however, relies on the coalescence of gas bubbles in the melt, which is unpredictable. In the present work, therefore, new melt-processed fibrous dosage forms with contiguous void space are presented. The dosage forms are prepared by melt extrusion of the drug-excipient mixture followed by patterning the fibrous extrudate on a moving surface. It is demonstrated that the resulting fibrous structures are fully predictable by the extruder nozzle diameter and the motion of the surface. Furthermore, drug release experiments show that the disintegration time of the fibrous forms prepared in this work is of the order of that of the corresponding single fibers. The thin fibers of polyethylene glycol (excipient) and acetaminophen (drug) in turn disintegrate in a time proportional to the fiber radius and well within immediate-release specification. Finally, models of dosage form disintegration and drug release by single fibers and fibrous dosage forms are developed. It is found that drug release from fibrous forms is predictable by the physico-chemical properties of the excipient and such microstructural parameters as the fiber radius, the inter-fiber spacing, and the volume fraction of water-soluble excipient in the fibers. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Layer chicken embryo survival to hatch when administered an in ovo vaccination of strain F Mycoplasma gallisepticum and locations of bacteria prevalence in the newly hatched chick.

    PubMed

    Elliott, K E C; Branton, S L; Evans, J D; Gerard, P D; Peebles, E D

    2017-09-01

    Mycoplasma gallisepticum (MG) is a bacterial pathogen that causes production losses in layer chickens. To combat MG, multiage layer facilities vaccinate pullets by either spray or eye-drop vaccination. The objective in this study was to evaluate the use of in ovo vaccination as a potential alternative for MG vaccination. Layer embryos at 18 d of incubation were either not-injected (control), or were hand-injected with either commercial Marek's disease vaccine diluent alone or with a high, medium, low, or very low dosage of a live attenuated strain F (FMG) vaccine suspended in the commercial diluent. Hatch success and residual egg embryonic mortality were determined after 23 d of incubation. Six hatched chicks per treatment were swabbed for the detection of FMG at 4 different sites (trachea, mouth and esophagus, yolk sac membrane, and the lumen of the duodenal loop) via real-time PCR. Embryos were found to be administered 106 CFU per dose in the high treatment, 104 CFU/dose in the medium treatment, 102 CFU/dose in the low treatment, and between 5.06 and 5.93 CFU/dose in the very low treatment. Hatch of embryonated eggs was decreased by the medium and high doses (P = 0.02). These embryos died while pipping. No FMG was detected in the control and diluent-injected chicks. In the FMG treatments, FMG was found in all sites and dosages, with a greater number of positive chicks found in the higher FMG dosage treatments. These findings indicate the potential practicality of vaccinating layer embryos with FMG by in ovo injection based on the observed hatch success at lower dosages. Also, once injected into the amnion, the bacteria are present in the upper respiratory and gastrointestinal tracts as well the yolk sac membrane and the small intestine of hatchlings. Future research will need to ascertain the effects of FMG administered by in ovo injection on posthatch immunity and mortality. © 2017 Poultry Science Association Inc.

  4. Excipients and their role in approved injectable products: current usage and future directions.

    PubMed

    Nema, Sandeep; Brendel, Ronald J

    2011-01-01

    This review article is a current survey of excipients used in approved injectable products. Information provided includes concentration ranges, function, frequency of use, and role in dosage form. This article is an update of a paper published more than a decade ago (reference 11). Since then many new products have been approved. Safety concerning excipients has evolved as the scientific community continues to learn about their usage. New excipients are being used in early phases of clinical trials to support novel therapeutic entities like RNAi, aptamers, anti-sense, fusion proteins, monoclonal antibodies, and variant scaffolds. Because these excipients are not inert, various pharmacopoeias are responding with monographs or informational chapters addressing excipient functionality. The final sections of this article discuss new excipients, serving specific needs that traditional excipients are unable to provide and for which safety studies are necessary to support a novel excipient for marketing applications. Excipients are added to parenteral dosage forms to serve a variety of functions including stabilization and as vehicles. This review article is a survey of excipients used in approved injectable products. Information provided includes excipient concentrations, functional roles, and frequency of use. This article is an update of an article originally published over a decade ago. Since then new products have been approved and safety concerns have evolved as the scientific community has learned about the usage of excipients. In addition, new excipients are being used in early phases of clinical trials to support novel therapeutic entities such as RNAi, aptamers, anti-sense, fusion proteins, monoclonal antibodies, and variant scaffolds. Because these excipients are not inert, various pharmacopoeias are responding with monographs or informational chapters addressing excipient functionality. The final sections of this article discuss new excipients, serving specific needs that traditional excipients are unable to provide and for which safety studies are necessary to support a novel excipient for marketing applications.

  5. 21 CFR 520.1802 - Piperazine-carbon disulfide complex oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Piperazine-carbon disulfide complex oral dosage forms. 520.1802 Section 520.1802 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.1802 Piperazine-carbon disulfide complex oral dosage forms. ...

  6. 21 CFR 524.1484 - Neomycin sulfate ophthalmic and topical dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Neomycin sulfate ophthalmic and topical dosage forms. 524.1484 Section 524.1484 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1484 Neomycin sulfate ophthalmic and topical dosage forms. ...

  7. 21 CFR 524.1044 - Gentamicin sulfate ophthalmic and topical dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate ophthalmic and topical dosage forms. 524.1044 Section 524.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1044 Gentamicin sulfate ophthalmic and topical dosage forms. ...

  8. 21 CFR 524.1484 - Neomycin sulfate ophthalmic and topical dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Neomycin sulfate ophthalmic and topical dosage forms. 524.1484 Section 524.1484 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1484 Neomycin sulfate ophthalmic and topical dosage forms. ...

  9. 21 CFR 529.1044 - Gentamicin sulfate in certain other dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate in certain other dosage forms. 529.1044 Section 529.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 529.1044 Gentamicin sulfate in certain other dosage forms. ...

  10. 21 CFR 529.1044 - Gentamicin sulfate in certain other dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate in certain other dosage forms. 529.1044 Section 529.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 529.1044 Gentamicin sulfate in certain other dosage forms. ...

  11. 21 CFR 524.1484 - Neomycin sulfate ophthalmic and topical dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Neomycin sulfate ophthalmic and topical dosage forms. 524.1484 Section 524.1484 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1484 Neomycin sulfate ophthalmic and topical dosage forms. ...

  12. 21 CFR 529.1044 - Gentamicin sulfate in certain other dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate in certain other dosage forms. 529.1044 Section 529.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 529.1044 Gentamicin sulfate in certain other dosage forms. ...

  13. 21 CFR 524.1044 - Gentamicin sulfate ophthalmic and topical dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate ophthalmic and topical dosage forms. 524.1044 Section 524.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1044 Gentamicin sulfate ophthalmic and topical dosage forms. ...

  14. 21 CFR 524.1044 - Gentamicin sulfate ophthalmic and topical dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate ophthalmic and topical dosage forms. 524.1044 Section 524.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1044 Gentamicin sulfate ophthalmic and topical dosage forms. ...

  15. 21 CFR 524.1044 - Gentamicin sulfate ophthalmic and topical dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate ophthalmic and topical dosage forms. 524.1044 Section 524.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1044 Gentamicin sulfate ophthalmic and topical dosage forms. ...

  16. 21 CFR 529.1044 - Gentamicin sulfate in certain other dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate in certain other dosage forms. 529.1044 Section 529.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 529.1044 Gentamicin sulfate in certain other dosage forms. ...

  17. 21 CFR 524.1484 - Neomycin sulfate ophthalmic and topical dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Neomycin sulfate ophthalmic and topical dosage forms. 524.1484 Section 524.1484 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1484 Neomycin sulfate ophthalmic and topical dosage forms. ...

  18. 21 CFR 520.390 - Chloramphenicol oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Chloramphenicol oral dosage forms. 520.390 Section 520.390 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.390...

  19. 21 CFR 520.445 - Chlortetracycline oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Chlortetracycline oral dosage forms. 520.445 Section 520.445 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.445...

  20. 21 CFR 520.540 - Dexamethasone oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.540...

  1. 21 CFR 520.540 - Dexamethasone oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.540...

  2. 21 CFR 520.300 - Cambendazole oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Cambendazole oral dosage forms. 520.300 Section 520.300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.300...

  3. 21 CFR 520.300 - Cambendazole oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Cambendazole oral dosage forms. 520.300 Section 520.300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.300...

  4. 21 CFR 520.540 - Dexamethasone oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.540...

  5. 21 CFR 520.390 - Chloramphenicol oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Chloramphenicol oral dosage forms. 520.390 Section 520.390 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.390...

  6. 21 CFR 520.540 - Dexamethasone oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.540...

  7. 21 CFR 520.620 - Diethylcarbamazine oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Diethylcarbamazine oral dosage forms. 520.620 Section 520.620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.620...

  8. 21 CFR 520.390 - Chloramphenicol oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Chloramphenicol oral dosage forms. 520.390 Section 520.390 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.390...

  9. 21 CFR 520.540 - Dexamethasone oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.540...

  10. 21 CFR 520.620 - Diethylcarbamazine oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Diethylcarbamazine oral dosage forms. 520.620 Section 520.620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.620...

  11. 21 CFR 520.620 - Diethylcarbamazine oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Diethylcarbamazine oral dosage forms. 520.620 Section 520.620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.620...

  12. 21 CFR 520.390 - Chloramphenicol oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Chloramphenicol oral dosage forms. 520.390 Section 520.390 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.390...

  13. 21 CFR 520.620 - Diethylcarbamazine oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Diethylcarbamazine oral dosage forms. 520.620 Section 520.620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.620...

  14. 21 CFR 520.445 - Chlortetracycline oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Chlortetracycline oral dosage forms. 520.445 Section 520.445 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.445...

  15. 21 CFR 520.300 - Cambendazole oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Cambendazole oral dosage forms. 520.300 Section 520.300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.300...

  16. 21 CFR 520.620 - Diethylcarbamazine oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Diethylcarbamazine oral dosage forms. 520.620 Section 520.620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.620...

  17. 21 CFR 520.300 - Cambendazole oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Cambendazole oral dosage forms. 520.300 Section 520.300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.300...

  18. 21 CFR 520.905 - Fenbendazole oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Fenbendazole oral dosage forms. 520.905 Section 520.905 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.905...

  19. 21 CFR 526.1696 - Penicillin intramammary dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS INTRAMAMMARY DOSAGE FORMS § 526.1696 Penicillin...

  20. Oral Medicines for Children in the European Paediatric Investigation Plans

    PubMed Central

    van Riet – Nales, Diana A.; Römkens, Erwin G. A. W.; Saint-Raymond, Agnes; Kozarewicz, Piotr; Schobben, Alfred F. A. M.; Egberts, Toine C. G.; Rademaker, Carin M. A.

    2014-01-01

    Introduction Pharmaceutical industry is no longer allowed to develop new medicines for use in adults only, as the 2007 Paediatric Regulation requires children to be considered also. The plans for such paediatric development called Paediatric Investigation Plans (PIPs) are subject to agreement by the European Medicines Agency (EMA) and its Paediatric Committee (PDCO). The aim of this study was to evaluate the key characteristics of oral paediatric medicines in the PIPs and the changes implemented as a result of the EMA/PDCO review. Methods All PIPs agreed by 31 December 2011 were identified through a proprietary EMA-database. PIPs were included if they contained an agreed proposal to develop an oral medicine for children 0 to 11 years. Information on the therapeutic area (EMA classification system); target age range (as defined by industry) and pharmaceutical characteristics (active substance, dosage form(s) as listed in the PIP, strength of each dosage form, excipients in each strength of each dosage form) was extracted from the EMA website or the EMA/PDCO assessment reports. Results A hundred and fifty PIPs were included corresponding to 16 therapeutic areas and 220 oral dosage forms in 431 strengths/compositions. Eighty-two PIPs (37%) included tablets, 44 (20%) liquids and 35 (16%) dosage forms with a specific composition/strength that were stored as a solid but swallowed as a liquid e.g. dispersible tablets. The EMA/PDCO review resulted in an increase of 13 (207 to 220) oral paediatric dosage forms and 44 (387 to 431) dosage forms with a specific composition/strength. For many PIPs, the target age range was widened and the excipient composition and usability aspects modified. Conclusion The EMA/PDCO review realized an increase in the number of requirements for the development of oral dosage forms and a larger increase in the number of dosage forms with a specific composition/strength, both targeting younger children. Changes to their pharmaceutical design were less profound. PMID:24897509

  1. Oral medicines for children in the European paediatric investigation plans.

    PubMed

    van Riet-Nales, Diana A; Römkens, Erwin G A W; Saint-Raymond, Agnes; Kozarewicz, Piotr; Schobben, Alfred F A M; Egberts, Toine C G; Rademaker, Carin M A

    2014-01-01

    Pharmaceutical industry is no longer allowed to develop new medicines for use in adults only, as the 2007 Paediatric Regulation requires children to be considered also. The plans for such paediatric development called Paediatric Investigation Plans (PIPs) are subject to agreement by the European Medicines Agency (EMA) and its Paediatric Committee (PDCO). The aim of this study was to evaluate the key characteristics of oral paediatric medicines in the PIPs and the changes implemented as a result of the EMA/PDCO review. All PIPs agreed by 31 December 2011 were identified through a proprietary EMA-database. PIPs were included if they contained an agreed proposal to develop an oral medicine for children 0 to 11 years. Information on the therapeutic area (EMA classification system); target age range (as defined by industry) and pharmaceutical characteristics (active substance, dosage form(s) as listed in the PIP, strength of each dosage form, excipients in each strength of each dosage form) was extracted from the EMA website or the EMA/PDCO assessment reports. A hundred and fifty PIPs were included corresponding to 16 therapeutic areas and 220 oral dosage forms in 431 strengths/compositions. Eighty-two PIPs (37%) included tablets, 44 (20%) liquids and 35 (16%) dosage forms with a specific composition/strength that were stored as a solid but swallowed as a liquid e.g. dispersible tablets. The EMA/PDCO review resulted in an increase of 13 (207 to 220) oral paediatric dosage forms and 44 (387 to 431) dosage forms with a specific composition/strength. For many PIPs, the target age range was widened and the excipient composition and usability aspects modified. The EMA/PDCO review realized an increase in the number of requirements for the development of oral dosage forms and a larger increase in the number of dosage forms with a specific composition/strength, both targeting younger children. Changes to their pharmaceutical design were less profound.

  2. A novel stability-indicating UPLC method development and validation for the determination of seven impurities in various diclofenac pharmaceutical dosage forms.

    PubMed

    Azougagh, M; Elkarbane, M; Bakhous, K; Issmaili, S; Skalli, A; Iben Moussad, S; Benaji, B

    2016-09-01

    An innovative simple, fast, precise and accurate ultra-high performance liquid chromatography (UPLC) method was developed for the determination of diclofenac (Dic) along with its impurities including the new dimer impurity in various pharmaceutical dosage forms. An Acquity HSS T3 (C18, 100×2.1mm, 1.8μm) column in gradient mode was used with mobile phase comprising of phosphoric acid, which has a pH value of 2.3 and methanol. The flow rate and the injection volume were set at 0.35ml·min(-1) and 1μl, respectively, and the UV detection was carried out at 254nm by using photodiode array detector. Dic was subjected to stress conditions from acid, base, hydrolytic, thermal, oxidative and photolytic degradation. The new developed method was successfully validated in accordance to the International Conference on Harmonization (ICH) guidelines with respect to specificity, limit of detection, limit of quantitation, precision, linearity, accuracy and robustness. The degradation products were well resolved from main peak and its seven impurities, proving the specificity power of the method. The method showed good linearity with consistent recoveries for Dic content and its impurities. The relative percentage of standard deviation obtained for the repeatability and intermediate precision experiments was less than 3% and LOQ was less than 0.5μg·ml(-1) for all compounds. The new proposed method was found to be accurate, precise, specific, linear and robust. In addition, the method was successfully applied for the assay determination of Dic and its impurities in the several pharmaceutical dosage forms. Copyright © 2016 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

  3. Practical considerations in clinical strategy to support the development of injectable drug-device combination products for biologics.

    PubMed

    Li, Zhaoyang; Easton, Rachael

    2018-01-01

    The development of an injectable drug-device combination (DDC) product for biologics is an intricate and evolving process that requires substantial investments of time and money. Consequently, the commercial dosage form(s) or presentation(s) are often not ready when pivotal trials commence, and it is common to have drug product changes (manufacturing process or presentation) during clinical development. A scientifically sound and robust bridging strategy is required in order to introduce these changes into the clinic safely. There is currently no single developmental paradigm, but a risk-based hierarchical approach has been well accepted. The rigor required of a bridging package depends on the level of risk associated with the changes. Clinical pharmacokinetic/pharmacodynamic comparability or outcome studies are only required when important changes occur at a late stage. Moreover, an injectable DDC needs to be user-centric, and usability assessment in real-world clinical settings may be required to support the approval of a DDC. In this review, we discuss the common issues during the manufacturing process and presentation development of an injectable DDC and practical considerations in establishing a clinical strategy to address these issues, including key elements of clinical studies. We also analyze the current practice in the industry and review relevant and status of regulatory guidance in the DDC field.

  4. Practical considerations in clinical strategy to support the development of injectable drug-device combination products for biologics

    PubMed Central

    Easton, Rachael

    2018-01-01

    ABSTRACT The development of an injectable drug-device combination (DDC) product for biologics is an intricate and evolving process that requires substantial investments of time and money. Consequently, the commercial dosage form(s) or presentation(s) are often not ready when pivotal trials commence, and it is common to have drug product changes (manufacturing process or presentation) during clinical development. A scientifically sound and robust bridging strategy is required in order to introduce these changes into the clinic safely. There is currently no single developmental paradigm, but a risk-based hierarchical approach has been well accepted. The rigor required of a bridging package depends on the level of risk associated with the changes. Clinical pharmacokinetic/pharmacodynamic comparability or outcome studies are only required when important changes occur at a late stage. Moreover, an injectable DDC needs to be user-centric, and usability assessment in real-world clinical settings may be required to support the approval of a DDC. In this review, we discuss the common issues during the manufacturing process and presentation development of an injectable DDC and practical considerations in establishing a clinical strategy to address these issues, including key elements of clinical studies. We also analyze the current practice in the industry and review relevant and status of regulatory guidance in the DDC field. PMID:29035675

  5. Poly(2-ethyl-2-oxazoline) as matrix excipient for drug formulation by hot melt extrusion and injection molding.

    PubMed

    Claeys, Bart; Vervaeck, Anouk; Vervaet, Chris; Remon, Jean Paul; Hoogenboom, Richard; De Geest, Bruno G

    2012-10-15

    Here we evaluate poly(2-ethyl-2-oxazoline)s (PEtOx) as a matrix excipient for the production of oral solid dosage forms by hot melt extrusion (HME) followed by injection molding (IM). Using metoprolol tartrate as a good water-soluble model drug we demonstrate that drug release can be delayed by HME/IM, with the release rate controlled by the molecular weight of the PEtOx. Using fenofibrate as a lipophilic model drug we demonstrate that relative to the pure drug the dissolution rate is strongly enhanced by formulation in HME/IM tablets. For both drug molecules we find that solid solutions, i.e. molecularly dissolved drug in a polymeric matrix, are obtained by HME/IM. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. 21 CFR 522.1920 - Prochlorperazine, isopropamide for injection.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... prochlorperazine edisylate (equivalent to 4 milligrams prochlorperazine), and 0.38 milligrams of isopropamide... subcutaneous injection twice daily as follows: Weight of animal in pounds Dosage in Milliliters Up to 4 0.25 5 to 14 0.5-1 15 to 30 2-3 30 to 45 3-4 45 to 60 4-5 Over 60 6 Following the last injection, administer...

  7. 21 CFR 500.26 - Timed-release dosage form drugs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 201(v) of the Federal Food, Drug, and Cosmetic Act. (b) Timed-release dosage form animal drugs that... using procedures and controls to ensure release of the total dosage at a safe and effective rate. Data...

  8. 21 CFR 500.26 - Timed-release dosage form drugs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 201(v) of the Federal Food, Drug, and Cosmetic Act. (b) Timed-release dosage form animal drugs that... using procedures and controls to ensure release of the total dosage at a safe and effective rate. Data...

  9. 21 CFR 500.26 - Timed-release dosage form drugs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 201(v) of the Federal Food, Drug, and Cosmetic Act. (b) Timed-release dosage form animal drugs that... using procedures and controls to ensure release of the total dosage at a safe and effective rate. Data...

  10. 21 CFR 500.26 - Timed-release dosage form drugs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 201(v) of the Federal Food, Drug, and Cosmetic Act. (b) Timed-release dosage form animal drugs that... using procedures and controls to ensure release of the total dosage at a safe and effective rate. Data...

  11. 21 CFR 500.26 - Timed-release dosage form drugs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 201(v) of the Federal Food, Drug, and Cosmetic Act. (b) Timed-release dosage form animal drugs that... using procedures and controls to ensure release of the total dosage at a safe and effective rate. Data...

  12. 21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Diethylcarbamazine citrate oral dosage forms. 520.622 Section 520.622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.622...

  13. 21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Diethylcarbamazine citrate oral dosage forms. 520.622 Section 520.622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.622...

  14. 21 CFR 520.88 - Amoxicillin oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Amoxicillin oral dosage forms. 520.88 Section 520.88 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.88 Amoxicillin oral...

  15. 21 CFR 520.90 - Ampicillin oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ampicillin oral dosage forms. 520.90 Section 520.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.90 Ampicillin oral...

  16. 21 CFR 520.154 - Bacitracin oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Bacitracin oral dosage forms. 520.154 Section 520.154 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.154 Bacitracin oral...

  17. 21 CFR 520.45 - Albendazole oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Albendazole oral dosage forms. 520.45 Section 520.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.45 Albendazole oral...

  18. 21 CFR 520.88 - Amoxicillin oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Amoxicillin oral dosage forms. 520.88 Section 520.88 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.88 Amoxicillin oral...

  19. 21 CFR 520.763 - Dithiazanine iodide oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Dithiazanine iodide oral dosage forms. 520.763 Section 520.763 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.763...

  20. 21 CFR 520.82 - Aminopropazine fumarate oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Aminopropazine fumarate oral dosage forms. 520.82 Section 520.82 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.82...

  1. 21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Diethylcarbamazine citrate oral dosage forms. 520.622 Section 520.622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.622...

  2. 21 CFR 520.45 - Albendazole oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Albendazole oral dosage forms. 520.45 Section 520.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.45 Albendazole oral...

  3. 21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1044 Gentamicin...

  4. 21 CFR 520.763 - Dithiazanine iodide oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Dithiazanine iodide oral dosage forms. 520.763 Section 520.763 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.763...

  5. 21 CFR 520.45 - Albendazole oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Albendazole oral dosage forms. 520.45 Section 520.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.45 Albendazole oral...

  6. 21 CFR 520.90 - Ampicillin oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ampicillin oral dosage forms. 520.90 Section 520.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.90 Ampicillin oral...

  7. 21 CFR 520.82 - Aminopropazine fumarate oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Aminopropazine fumarate oral dosage forms. 520.82 Section 520.82 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.82...

  8. 21 CFR 520.1120 - Haloxon oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Haloxon oral dosage forms. 520.1120 Section 520.1120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1120 Haloxon oral...

  9. 21 CFR 520.763 - Dithiazanine iodide oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Dithiazanine iodide oral dosage forms. 520.763 Section 520.763 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.763...

  10. 21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Diethylcarbamazine citrate oral dosage forms. 520.622 Section 520.622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.622...

  11. 21 CFR 520.82 - Aminopropazine fumarate oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Aminopropazine fumarate oral dosage forms. 520.82 Section 520.82 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.82...

  12. 21 CFR 520.763 - Dithiazanine iodide oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Dithiazanine iodide oral dosage forms. 520.763 Section 520.763 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.763...

  13. 21 CFR 520.763 - Dithiazanine iodide oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Dithiazanine iodide oral dosage forms. 520.763 Section 520.763 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.763...

  14. 21 CFR 520.90 - Ampicillin oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ampicillin oral dosage forms. 520.90 Section 520.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.90 Ampicillin oral...

  15. 21 CFR 520.903 - Febantel oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Febantel oral dosage forms. 520.903 Section 520.903 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.903 Febantel oral...

  16. 21 CFR 520.88 - Amoxicillin oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Amoxicillin oral dosage forms. 520.88 Section 520.88 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.88 Amoxicillin oral...

  17. 21 CFR 520.38 - Albendazole oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Albendazole oral dosage forms. 520.38 Section 520.38 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.38 Albendazole oral...

  18. 21 CFR 520.90 - Ampicillin oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ampicillin oral dosage forms. 520.90 Section 520.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.90 Ampicillin oral...

  19. 21 CFR 520.154 - Bacitracin oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Bacitracin oral dosage forms. 520.154 Section 520.154 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.154 Bacitracin oral...

  20. 21 CFR 520.1242 - Levamisole hydrochloride oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Levamisole hydrochloride oral dosage forms. 520.1242 Section 520.1242 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1242...

  1. 21 CFR 520.154 - Bacitracin oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Bacitracin oral dosage forms. 520.154 Section 520.154 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.154 Bacitracin oral...

  2. 21 CFR 520.622 - Diethylcarbamazine citrate oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Diethylcarbamazine citrate oral dosage forms. 520.622 Section 520.622 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.622...

  3. 21 CFR 520.154 - Bacitracin oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Bacitracin oral dosage forms. 520.154 Section 520.154 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.154 Bacitracin oral...

  4. 21 CFR 520.82 - Aminopropazine fumarate oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Aminopropazine fumarate oral dosage forms. 520.82 Section 520.82 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.82...

  5. 21 CFR 520.88 - Amoxicillin oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Amoxicillin oral dosage forms. 520.88 Section 520.88 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.88 Amoxicillin oral...

  6. 21 CFR 520.1696 - Penicillin oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Penicillin oral dosage forms. 520.1696 Section 520.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696 Penicillin oral...

  7. 21 CFR 520.1696 - Penicillin oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Penicillin oral dosage forms. 520.1696 Section 520.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696 Penicillin oral...

  8. 21 CFR 520.1696 - Penicillin oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin oral dosage forms. 520.1696 Section 520.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696 Penicillin oral...

  9. Determination of the mechanical properties of solid and cellular polymeric dosage forms by diametral compression.

    PubMed

    Blaesi, Aron H; Saka, Nannaji

    2016-07-25

    At present, the immediate-release solid dosage forms, such as the oral tablets and capsules, are granular solids. They release drug rapidly and have adequate mechanical properties, but their manufacture is fraught with difficulties inherent in processing particulate matter. Such difficulties, however, could be overcome by liquid-based processing. Therefore, we have recently introduced polymeric cellular (i.e., highly porous) dosage forms prepared from a melt process. Experiments have shown that upon immersion in a dissolution medium, the cellular dosage forms with polyethylene glycol (PEG) as excipient and with predominantly open-cell topology disintegrate by exfoliation, thus enabling rapid drug release. If the volume fraction of voids of the open-cell structures is too large, however, their mechanical strength is adversely affected. At present, the common method for determining the tensile strength of brittle, solid dosage forms (such as select granular forms) is the diametral compression test. In this study, the theory of diametral compression is first refined to demonstrate that the relevant mechanical properties of ductile and cellular solids (i.e., the elastic modulus and the yield strength) can also be extracted from this test. Diametral compression experiments are then conducted on PEG-based solid and cellular dosage forms. It is found that the elastic modulus and yield strength of the open-cell structures are about an order of magnitude smaller than those of the non-porous solids, but still are substantially greater than the stiffness and strength requirements for handling the dosage forms manually. This work thus demonstrates that melt-processed polymeric cellular dosage forms that release drug rapidly can be designed and manufactured to have adequate mechanical properties. Copyright © 2016. Published by Elsevier B.V.

  10. Buccal Dosage Forms: General Considerations for Pediatric Patients.

    PubMed

    Montero-Padilla, Soledad; Velaga, Sitaram; Morales, Javier O

    2017-02-01

    The development of an appropriate dosage form for pediatric patients needs to take into account several aspects, since adult drug biodistribution differs from that of pediatrics. In recent years, buccal administration has become an attractive route, having different dosage forms under development including tablets, lozenges, films, and solutions among others. Furthermore, the buccal epithelium can allow quick access to systemic circulation, which could be used for a rapid onset of action. For pediatric patients, dosage forms to be placed in the oral cavity have higher requirements for palatability to increase acceptance and therapy compliance. Therefore, an understanding of the excipients required and their functions and properties needs to be particularly addressed. This review is focused on the differences and requirements relevant to buccal administration for pediatric patients (compared to adults) and how novel dosage forms can be less invasive and more acceptable alternatives.

  11. Oral drug delivery in personalized medicine: unmet needs and novel approaches.

    PubMed

    Wening, Klaus; Breitkreutz, Jörg

    2011-02-14

    Increasing knowledge into personalized medicine has demonstrated the need for individual dosing. Drug dosage forms are urgently needed enabling an individual therapy, especially for oral drug delivery. This review is focusing on approaches for solid and liquid oral dosage forms for individual dosing. The proposed dosage forms and devices may be distinguished into assembling and partition concepts and have been categorized regarding their applicability, costs, dose flexibility and potential benefits. Opportunities, challenges and further unmet needs are elaborated and critically discussed. Liquid dosage forms can be accurately dosed by novel dropping tubes or oral syringes, but less precisely by dosing spoons and cups. Breaking scored tablets into fragments show major risks such as inaccurate dosing, formation of potent dust and stability issues of the residual segments. Novel approaches are proposed for solid dosage forms enabling a flexible and appropriate therapy such as various dispensers for multiparticulate drug formulations. However, most of the proposals still have to prove their applicability in practice. Promising concepts are the solid dosage pen and drug-loaded oral films which can be cut in individual sections enabling freely selectable doses. Further research and development are required for novel dosage forms and medical devices appropriate for individualized therapy. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Applications of Natural Polymeric Materials in Solid Oral Modified-Release Dosage Forms.

    PubMed

    Li, Liang; Zhang, Xin; Gu, Xiangqin; Mao, Shirui

    2015-01-01

    Solid oral modified-release dosage forms provide numerous advantages for drug delivery compared to dosage forms where the drugs are released and absorbed rapidly following ingestion. Natural polymers are of particular interest as drug carriers due to their good safety profile, biocompatibility, biodegradability, and rich sources. This review described the current applications of important natural polymers, such as chitosan, alginate, pectin, guar gum, and xanthan gum, in solid oral modified-release dosage forms. It was shown that natural polymers have been widely used to fabricate solid oral modified-release dosage forms such as matrix tablets, pellets and beads, and especially oral drug delivery systems such as gastroretentive and colon drug delivery systems. Moreover, chemical modifications could overcome the shortcomings associated with the use of natural polymers, and the combination of two or more polymers presented further advantages compared with that of single polymer. In conclusion, natural polymers and modified natural polymers have promising applications in solid oral modified-release dosage forms. However, commercial products based on them are still limited. To accelerate the application of natural polymers in commercial products, in vivo behavior of natural polymers-based solid oral modified-release dosage forms should be deeply investigated, and meanwhile quality of the natural polymers should be controlled strictly, and the influence of formulation and process parameters need to be understood intensively.

  13. A step toward development of printable dosage forms for poorly soluble drugs.

    PubMed

    Raijada, Dhara; Genina, Natalja; Fors, Daniela; Wisaeus, Erik; Peltonen, Jouko; Rantanen, Jukka; Sandler, Niklas

    2013-10-01

    The purpose of this study was to formulate printable dosage forms for a poorly soluble drug (piroxicam; PRX) and to gain understanding of critical parameters to be considered during development of such dosage forms. Liquid formulations of PRX were printed on edible paper using piezoelectric inkjet printing (PIJ) and impression printing (flexography). The printed dosage forms were characterized using scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX) and the amount of drug was determined using high-performance liquid chromatography. Solutions of PRX in polyethylene glycol 400 (PEG-400):ethanol (40:60) and in PEG-400 were found to be optimal formulations for PIJ and flexography, respectively. SEM-EDX analysis revealed no visible solid particles on the printed dosage forms indicating the drug most likely remained in solution after printing. More accurate drug deposition was obtained by PIJ as compared with flexography. More than 90% drug release was achieved within 5 min regardless of printing method used. The solubility of drug in solvents/cosolvents, rheological properties of formulations, properties of substrate, feasibility and accuracy of the printing methods, and detection limit of analytical techniques for characterization of printed dosage forms are some of the concerns that need to be addressed for development of printable dosage forms of poorly soluble drugs. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  14. 21 CFR 522.1920 - Prochlorperazine, isopropamide for injection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Prochlorperazine, isopropamide for injection. 522.1920 Section 522.1920 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... which gastrointestinal disturbances are associated with emotional stress. (2) Dosage is administered by...

  15. Anaesthetic induction with alfaxalone in the ball python (Python regius): dose response and effect of injection site.

    PubMed

    James, Lauren E; Williams, Catherine Ja; Bertelsen, Mads F; Wang, Tobias

    2018-05-01

    To characterise the minimum dose of intramuscular alfaxalone required to facilitate intubation for mechanical ventilation, and to investigate the impact of cranial versus caudal injection on anaesthetic depth. Randomised crossover study. Six healthy juvenile ball pythons (Python regius). Three dosages (10, 20 and 30 mg kg -1 ) of alfaxalone were administered to each python in a caudal location with a minimum 2 weeks washout. Induction and recovery were monitored by assessing muscle tone, righting reflex, response to a noxious stimulus and the ability to intubate. A subsequent experiment assessed the influence of injection site by comparing administration of 20 mg kg -1 alfaxalone in a cranial location (1 cm cranial to the heart) with the caudal site. Respiration rate was monitored throughout, and when intubation was possible, snakes were mechanically ventilated. Regardless of dose and injection site, maximum effect was reached within 10.0 ± 2.7 minutes. When administered at the caudal injection site, intubation was only successful after a dosage of 30 mg kg- 1 , which is higher than in previous reports for other reptiles. However, intubation was possible in all cases after 7.2 ± 1.6 minutes upon cranial administration of 20 mg kg -1 , and anaesthetic duration was significantly lengthened (p < 0.001). Both 30 mg kg -1 at the caudal site and 20 mg kg -1 at the cranial site led to apnoea approximately 10 minutes post-injection, at which time the snakes were intubated and mechanically ventilated. Alfaxalone provided rapid, smooth induction when administered intramuscularly to pythons, and may serve as a useful induction agent prior to provision of volatile anaesthetics. The same dosage injected in the cranial site led to deeper anaesthesia than when injected caudally, suggesting that shunting to the liver and first-pass metabolism of alfaxalone occur when injected caudally, via the renal portal system. Copyright © 2018 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

  16. Advances in solid dosage form manufacturing technology.

    PubMed

    Andrews, Gavin P

    2007-12-15

    Currently, the pharmaceutical and healthcare industries are moving through a period of unparalleled change. Major multinational pharmaceutical companies are restructuring, consolidating, merging and more importantly critically assessing their competitiveness to ensure constant growth in an ever-more demanding market where the cost of developing novel products is continuously increasing. The pharmaceutical manufacturing processes currently in existence for the production of solid oral dosage forms are associated with significant disadvantages and in many instances provide many processing problems. Therefore, it is well accepted that there is an increasing need for alternative processes to dramatically improve powder processing, and more importantly to ensure that acceptable, reproducible solid dosage forms can be manufactured. Consequently, pharmaceutical companies are beginning to invest in innovative processes capable of producing solid dosage forms that better meet the needs of the patient while providing efficient manufacturing operations. This article discusses two emerging solid dosage form manufacturing technologies, namely hot-melt extrusion and fluidized hot-melt granulation.

  17. Automatic identification and normalization of dosage forms in drug monographs

    PubMed Central

    2012-01-01

    Background Each day, millions of health consumers seek drug-related information on the Web. Despite some efforts in linking related resources, drug information is largely scattered in a wide variety of websites of different quality and credibility. Methods As a step toward providing users with integrated access to multiple trustworthy drug resources, we aim to develop a method capable of identifying drug's dosage form information in addition to drug name recognition. We developed rules and patterns for identifying dosage forms from different sections of full-text drug monographs, and subsequently normalized them to standardized RxNorm dosage forms. Results Our method represents a significant improvement compared with a baseline lookup approach, achieving overall macro-averaged Precision of 80%, Recall of 98%, and F-Measure of 85%. Conclusions We successfully developed an automatic approach for drug dosage form identification, which is critical for building links between different drug-related resources. PMID:22336431

  18. Transit of pharmaceutical dosage forms through the small intestine.

    PubMed Central

    Davis, S S; Hardy, J G; Fara, J W

    1986-01-01

    The gastrointestinal transit of pharmaceutical dosage forms has been measured in 201 studies in normal subjects using gamma scintigraphy. Solutions, small pellets, and single units (matrix tablets and osmotic pumps) were administered with different amounts of food in the stomach, ranging from fasted state to heavy breakfast. Gastric emptying was affected by the nature of the dosage form and the presence of food in the stomach. Solutions and pellets were emptied even when the stomach was in the digestive mode, while single units were retained for long periods of time, depending on the size of the meal. In contrast, measured intestinal transit times were independent of the dosage form and fed state. The small intestinal transit time of about three hours (mean +/- 1 h SEM) has implications for the design of dosage forms for the sustained release of drugs in specific positions in the gastrointestinal tract. PMID:3732895

  19. THE EFFECT OF X-RAY IRRADIATION ON THE GROWTH, AND THE MICROSCOPIC AND SUB- MICROSCOPIC STRUCTURE OF BONE SARCOMAS INDUCED BY RADIOACTIVE STRONTIUM (in Russian)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Khomutovskii, O.A.

    1963-01-01

    Bone sarcomas were induced in rats by the intraperitoneal injection of two doses of Sr/sup 90/ at monthly intervals using a dosage of 0.32 mu C of Sr/ sup 90/ per gram of body weight. The sarcomas appeared in 15 out of 60 rats on the 170th to 200th day after injection of the injection of the Sr/sup 90/. Induced sarcom as were given a local x-ray dose of 9 kr and 18 kr. With an irradiation dose of 18 kr, growth of the sarcoma is retarded, and the parts of the tumor where formation of osteoid material occurs aremore » almost completely destroyed. With a dose of 9 kr, the tumor continues to grow, and the destruction is less marked. Cancer cells from the irradiated sarcoma can be transplanted. However, in the transplanted tumor, the cells lose their ability to metastasize to other sites, to lyse osseous tissue, and to form osteoid materiai. Changes in the size and form of the mitochrondria snd the shell nucleus of the cells were observed after x-ray irradiation of the bone sarcoma. (TTT)« less

  20. 21 CFR 520.1802 - Piperazine-carbon disulfide complex oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Piperazine-carbon disulfide complex oral dosage forms. 520.1802 Section 520.1802 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1802 Piperazine-carbon disulfide comple...

  1. An integrated system for dissolution studies and magnetic resonance imaging of controlled release, polymer-based dosage forms-a tool for quantitative assessment of hydrogel formation processes.

    PubMed

    Kulinowski, Piotr; Dorozyński, Przemysław; Jachowicz, Renata; Weglarz, Władysław P

    2008-11-04

    Controlled release (CR) dosage forms are often based on polymeric matrices, e.g., sustained-release tablets and capsules. It is crucial to visualise and quantify processes of the hydrogel formation during the standard dissolution study. A method for imaging of CR, polymer-based dosage forms during dissolution study in vitro is presented. Imaging was performed in a non-invasive way by means of the magnetic resonance imaging (MRI). This study was designed to simulate in vivo conditions regarding temperature, volume, state and composition of dissolution media. Two formulations of hydrodynamically balanced systems (HBS) were chosen as model CR dosage forms. HBS release active substance in stomach while floating on the surface of the gastric content. Time evolutions of the diffusion region, hydrogel formation region and "dry core" region were obtained during a dissolution study of L-dopa as a model drug in two simulated gastric fluids (i.e. in fed and fasted state). This method seems to be a very promising tool for examining properties of new formulations of CR, polymer-based dosage forms or for comparison of generic and originator dosage forms before carrying out bioequivalence studies.

  2. Novel delivery device for monolithical solid oral dosage forms for personalized medicine.

    PubMed

    Wening, Klaus; Breitkreutz, Jörg

    2010-08-16

    There is an evident need for solid oral dosage forms allowing patients' tailor-made dosing due to variations in metabolization or small therapeutic indexes of drug substances. The objective of this work is the development of a device equipped with a novel solid dosage form, containing carvedilol as model drug, for the delivery of monolithical drug carriers in individual doses. The device was developed and constructed enabling an exact feed rate and dose adjustment by a cutting mechanism. A twin-screw extruder was used for producing cylindrical solid dosage forms. Divided doses were characterized by mass variation, cutting behavior and drug dissolution in order to investigate their applicability for practical use. Different formulations could be extruded obtaining straight cylindrical rods, which are divisible in exact slices by using the novel device. Forces below 20 N were needed to divide doses which comply with pharmacopoeial specification "conformity of mass". The developed formulations exhibit a sustained release of carvedilol within a range from 7 up to 16 h. A novel system consisting of a device and a cylindrical dosage form was developed. Patients' individual doses can be applied as monolithical solid dosage forms for oral use.

  3. Pharmaceutical approaches to preparing pelletized dosage forms using the extrusion-spheronization process.

    PubMed

    Trivedi, Namrata R; Rajan, Maria Gerald; Johnson, James R; Shukla, Atul J

    2007-01-01

    Pelletized dosage forms date back to the 1950s, when the first product was introduced to the market. Since then, these dosage forms have gained considerable popularity because of their distinct advantages, such as ease of capsule filling because of better flow properties of the spherical pellets; enhancement of drug dissolution; ease of coating; sustained, controlled, or site-specific delivery of the drug from coated pellets; uniform packing; even distribution in the GI tract; and less GI irritation. Pelletized dosage forms can be prepared by a number of techniques, including drug layering on nonpareil sugar or microcrystalline cellulose beads, spray drying, spray congealing, rotogranulation, hot-melt extrusion, and spheronization of low melting materials or extrusion-spheronization of a wet mass. This review discusses recent developments in the pharmaceutical approaches that have been used to prepare pelletized dosage forms using the extrusion-spheronization process over the last decade. The review is divided into three parts: the first part discusses the extrusion-spheronization process, the second part discusses the effect of varying formulation and process parameters on the properties of the pellets, and the last part discusses the different approaches that have been used to prepare pelletized dosage forms using the extrusion-spheronization process.

  4. The Efficacy of Cyclic Injection of Bone Morphogenetic Protein-2 in Large-Scale Calvarial Bone Defects.

    PubMed

    Choi, Jin Mi; Jeong, Woo Shik; Park, Eun Jung; Choi, Jong Woo

    2017-03-01

    Bone morphogenetic protein-2 (BMP-2) appears to be one of the most potent growth factors thus far studied. However, recent publications on the clinical application of BMP-2 revealed that its correct control is the paramount issue in clinical practice. For improving BMP-2 delivery, the cyclic administration might be an alternative. Accordingly, the authors cyclically injected BMP-2 in a cyclic injection model of large cranial defects to maintain the proper dosage during the bone healing process. A 10-mm diameter calvarial bone defect was produced using a round drill in 8-week-old Sprague-Dawley rats. Silk-hydroxyapatite scaffolds soaked in the appropriate concentration of BMP-2 were implanted into the defect. The animals were split into 4 single-injection groups and 3 multiple-injection groups; the latter groups received weekly subcutaneous injections of BMP-2 solution (1, 5, and 10 μg/mL) for 4 weeks, whereas the former groups received a single injection of BMP-2 at these concentrations. Each rat underwent computed tomography at 8 weeks. In terms of total volumes of the new bone, the 5 μg/mL multiple-injection BMP-2 group had significantly greater increases in bone volume than the single-injection groups. In terms of bone thickness, the multiple-injection groups had better outcomes than the single-injection groups. Thus, the cyclic injection protocol restored the original thickness without overgrowth. Cyclic injection of BMP-2 permits more accurate dosage control than single injection and improves thickness and dense bone regeneration. Therefore, it may represent a promising approach for future clinical trials. Further investigation using a greater number of animals is required.

  5. Cost implication of irrational prescribing of chloroquine in Lagos State general hospitals.

    PubMed

    Aina, Bolajoko A; Tayo, Fola; Taylor, Ogori

    2008-02-01

    A major share of the hospital budget is spent on drugs. Irrational use of these drugs is a waste of financial and human resources that could have been deployed for another use within the hospital setting especially in cases where such drugs are provided free to patients. Also there is increased morbidity and progression of severity with irrational use. The objective of this study was to determine the irrational use of chloroquine and the subsequent cost implications in Lagos State general hospitals. A retrospective study period of one year (January to December, 2000) was selected. A total of 18,781 prescription forms of "Free Eko Malaria" were sampled for children and adults from all the Lagos State general hospitals. Drug costs in each prescription form were identified. Cost effectiveness analysis of chloroquine tablet and intramuscular injection was undertaken. The average cost of medicine per prescription was 132.071 ($1.03) which should have been 94.22 ($0.73) if prescribed rationally. The total cost of prescriptions for malaria under study was 2,480,425.00 ($19,348.09). About 68% {(1,679,444.00) ($13,100.19)} of the total cost was lost to irrational prescribing. This is a waste of scarce resources. When the prescriptions were differentiated into the different dosage forms prescribed, the prescriptions containing intramuscular injections only had over 90% of the cost lost to irrational prescribing. Cost effectiveness analysis showed that chloroquine tablet was 17 times more cost effective than chloroquine injection (intramuscular) from a health care system perspective while it was 14 times more cost effective from a patient perspective. There is waste of scarce resources with irrational dispensing of drugs and these resources could have been deployed to other uses or areas within the hospitals. The tablet chloroquine was more cost effective than injection chloroquine (intramuscular). Increasing the cost of tablets, decreasing effectiveness of tablets, decreasing the cost of injections and increasing the effectiveness of injections did not change the cost effectiveness conclusion.

  6. Antitumor and synergistic effect of Chinese medicine “Bushen huayu jiedu recipe” and chemotherapy on transplanted animal hepatocarcinoma

    PubMed Central

    Cao, Yong; Xia, Qing-Hua; Meng, Hua; Zhong, An-Pu

    2005-01-01

    AIM: To investigate the antitumor and synergistic effect of Chinese medicine “Bushen huayu jiedu recipe” (recipe for invigorating the kidney, removing blood stasis and toxic substances) and chemotherapy on mice hepatocarcinoma. METHODS: Bushen huayu jiedu recipe (BSHYJDR) consisting of Chinese Cassia Bark, Psoralea, Zedoary, Rhubarb, etc. is equal to 1.5 g/mL liquid of originated herbs after being decocted, filtered, and concentrated. Kunming mice, weighing 18-22 g, were injected with 0.2 mL ascitic hepatocarcinoma H22 containing 1×107 cells/mL into armpit of the right forelimb of mice. After 24 h, the mice were weighed and randomly divided into tumor-bearing model control group, cisplatin (DDP) group, BSHYJDR high dosage group, low dosage BSHYJDR group, DDP combined with high and low dosage BSHYJDR group, 10 mice in each group. DDP group received injection intraperitoneally (ip) at the dosage of 1 mg/kg (equal to 1/10 LD50), once a day for 4 d. High and low dosage BSHYJDR groups received intragastric BSHYJDR at the dosages of 26.6 and 13.3 g/kg (20 and 10 times each of clinical adult dosage) respectively, while tumor-bearing model group received the equal volume of distilled water once a day for 10 d. On the 11th d, the mice were weighed and killed, then the tumor was dissected and weighed, the repression rate (RR) was calculated according to the mean weight of tumor (MWT). RESULTS: Compared to the model group (MWT: 1.30±0.73), DDP group (MWT: 0.41±0.09, RR: 68.46%) had a significant difference in the inhibition of hepatocarcinoma H22 (P<0.01). High dosage BSHYJDR group (MWT: 0.69±0.29, RR: 46.92%) also had a significant difference in inhibition (P<0.05), while no difference was found in low dosage BSHYJDR group (MWT: 0.85±0.34, RR: 34.62%) (P>0.05). When DDP was combined with high dosage BSHYJDR (MWT: 0.29±0.17, RR: 77.69%) and low dosage BSHYJDR (MWT: 0.38±0.21, RR: 70.77%) respectively, we could see improvement of the inhibition effect of DDP on transplanted hepatocarcinoma H22. DDP combined with high dosage BSHYJDR had a significant difference (P<0.001) compared to DDP, while DDP combined with low dosage BSHYJDR only had a little improvement that is not remarkable. CONCLUSION: Chinese medicine BSHYJDR in combination with chemotherapy can inhibit transplanted hepatocarcinoma in mice. PMID:16127756

  7. Injection molding as a one-step process for the direct production of pharmaceutical dosage forms from primary powders.

    PubMed

    Eggenreich, K; Windhab, S; Schrank, S; Treffer, D; Juster, H; Steinbichler, G; Laske, S; Koscher, G; Roblegg, E; Khinast, J G

    2016-05-30

    The objective of the present study was to develop a one-step process for the production of tablets directly from primary powder by means of injection molding (IM), to create solid-dispersion based tablets. Fenofibrate was used as the model API, a polyvinyl caprolactame-polyvinyl acetate-polyethylene glycol graft co-polymer served as a matrix system. Formulations were injection-molded into tablets using state-of-the-art IM equipment. The resulting tablets were physico-chemically characterized and the drug release kinetics and mechanism were determined. Comparison tablets were produced, either directly from powder or from pre-processed pellets prepared via hot melt extrusion (HME). The content of the model drug in the formulations was 10% (w/w), 20% (w/w) and 30% (w/w), respectively. After 120min, both powder-based and pellet-based injection-molded tablets exhibited a drug release of 60% independent of the processing route. Content uniformity analysis demonstrated that the model drug was homogeneously distributed. Moreover, analysis of single dose uniformity also revealed geometric drug homogeneity between tablets of one shot. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. 76 FR 63304 - Guidance for Industry on Incorporation of Physical-Chemical Identifiers Into Solid Oral Dosage...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-12

    ...] Guidance for Industry on Incorporation of Physical-Chemical Identifiers Into Solid Oral Dosage Form Drug... entitled ``Incorporation of Physical-Chemical Identifiers Into Solid Oral Dosage Form Drug Products for Anticounterfeiting.'' This guidance provides recommendations on design considerations for incorporating physical...

  9. Dosage and Distribution in Morphosyntax Intervention: Current Evidence and Future Needs

    ERIC Educational Resources Information Center

    Proctor-Williams, Kerry

    2009-01-01

    This article reviews the effectiveness of dose forms and the efficacy of dosage and distribution in morphosyntax intervention for children. Dose forms include the commonly used techniques, procedures, and intervention contexts that constitute teaching episodes; dosage includes the quantitative measures of dose, dose frequency, total intervention…

  10. Microbicide dosage forms.

    PubMed

    Rohan, L C; Devlin, B; Yang, H

    2014-01-01

    Microbicides are topically applied, user controlled dosage forms that are being developed to prevent the transmission of HIV during coitus. Early candidates focused on coitally dependent dosage forms such as gels and creams. More recent development has focused on broadening the coitally dependent options through the introduction of films and fast dissolving tablets. Additionally, it has become important to have longer acting products to minimize the burden of user compliance and thus vaginal rings have been developed providing sustained delivery of antiretroviral drugs. This chapter discusses the history of microbicides along with a detailed description of coitally dependent products, gels, films, tablets diaphragms, as well as coitally independent dosage forms such as vaginal rings and the introduction of a new technology, electrospun fibers.

  11. 21 CFR 522.1820 - Pituitary luteinizing hormone for injection.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) Conditions of use. (1) The drug is an aid in the treatment of breeding disorders related to pituitary hypofunction in cattle, horses, swine, sheep, and dogs. (2) Preferably given by intravenous injection, it may be administered subcutaneously; dosage is as follows: Cattle and horses, 25 mg; swine, 5 mg; sheep, 2...

  12. 21 CFR 522.1820 - Pituitary luteinizing hormone for injection.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) Conditions of use. (1) The drug is an aid in the treatment of breeding disorders related to pituitary hypofunction in cattle, horses, swine, sheep, and dogs. (2) Preferably given by intravenous injection, it may be administered subcutaneously; dosage is as follows: Cattle and horses, 25 mg; swine, 5 mg; sheep, 2...

  13. Injectable controlled release depots for large molecules

    PubMed Central

    Schwendeman, Steven P.; Shah, Ronak B.; Bailey, Brittany A.; Schwendeman, Anna S.

    2014-01-01

    Biodegradable, injectable depot formulations for long-term controlled drug release have improved therapy for a number of drug molecules and led to over a dozen highly successful pharmaceutical products. Until now, success has been limited to several small molecules and peptides, although remarkable improvements have been accomplished in some of these cases. For example, twice-a-year depot injections with leuprolide are available compared to the once-a-day injection of the solution dosage form. Injectable depots are typically prepared by encapsulation of the drug in poly(lactic-co-glycolic acid) (PLGA), a polymer that is used in children every day as a resorbable suture material, and therefore, highly biocompatible. PLGAs remain today as one of the few “real world” biodegradable synthetic biomaterials used in US FDA-approved parenteral long-acting-release (LAR) products. Despite their success, there remain critical barriers to the more widespread use of PLGA LAR products, particularly for delivery of more peptides and other large molecular drugs, namely proteins. In this review, we describe key concepts in the development of injectable PLGA controlled-release depots for peptides and proteins, and then use this information to identify key issues impeding greater widespread use of PLGA depots for this class of drugs. Finally, we examine important approaches, particularly those developed in our research laboratory, toward overcoming these barriers to advance commercial LAR development. PMID:24929039

  14. Biorelevant in vitro performance testing of orally administered dosage forms-workshop report.

    PubMed

    Reppas, Christos; Friedel, Horst-Dieter; Barker, Amy R; Buhse, Lucinda F; Cecil, Todd L; Keitel, Susanne; Kraemer, Johannes; Morris, J Michael; Shah, Vinod P; Stickelmeyer, Mary P; Yomota, Chikako; Brown, Cynthia K

    2014-07-01

    Biorelevant in vitro performance testing of orally administered dosage forms has become an important tool for the assessment of drug product in vivo behavior. An in vitro performance test which mimics the intraluminal performance of an oral dosage form is termed biorelevant. Biorelevant tests have been utilized to decrease the number of in vivo studies required during the drug development process and to mitigate the risk related to in vivo bioequivalence studies. This report reviews the ability of current in vitro performance tests to predict in vivo performance and generate successful in vitro and in vivo correlations for oral dosage forms. It also summarizes efforts to improve the predictability of biorelevant tests. The report is based on the presentations at the 2013 workshop, Biorelevant In Vitro Performance Testing of Orally Administered Dosage Forms, in Washington, DC, sponsored by the FIP Dissolution/Drug Release Focus Group in partnership with the American Association of Pharmaceutical Scientists (AAPS) and a symposium at the AAPS 2012 Annual meeting on the same topic.

  15. Evaluation of use of tiletamine/zolazepam for anesthesia of bullfrogs and leopard frogs.

    PubMed

    Letcher, J; Durante, R

    1995-07-01

    Use of tiletamine hydrochloride and zolazepam hydrochloride (1:1 fixed ratio combination) as an anesthetic agent in 2 anuran species was studied. A dosage of 5 mg/kg of body weight, administered IM, resulted in variable weak tranquilization. Intramuscular administration at dosages of 10 and 20 mg/kg induced variable states of tranquilization or anesthesia in leopard frogs (Rana pipiens) and bullfrogs (R catesbeiana). The dosages of 50 mg/kg induced anesthesia with greater consistency than lower dosages in bullfrogs, but resulted in mortalities. The same dosage was uniformly fatal in leopard frogs. Neither gross nor histologic lesions were identified in the frogs that died. Depth and duration of anesthesia was dosage related. At the 20 and 50 mg/kg dosages, leopard frogs attained a greater depth of anesthesia and remained anesthetized for a significantly greater duration than did bullfrogs; however, at the 5 and 10 mg/kg dosages, bullfrogs developed greater tranquilization for longer periods than did leopard frogs. Results of this study revealed profound intraspecies variation in depth and duration of effect of tiletamine/zolazepam; therefore, the drug does not appear to be a suitable injectable anesthetic in anurans.

  16. Photodynamic therapy with PhotoPoint photosensitiser MV6401, indium chloride methyl pyropheophorbide, achieves selective closure of rat corneal neovascularisation and rabbit choriocapillaris

    PubMed Central

    Ciulla, T A; Criswell, M H; Snyder, W J; Small, W

    2005-01-01

    Aim: The new photosensitiser PhotoPoint MV6401, indium chloride methyl pyropheophorbide, was assessed as a possible ocular photodynamic therapy agent in a rat model of experimentally induced corneal neovascularisation and in choriocapillaris closure in the rabbit. Optimal drug and light activation parameters were determined. Methods: MV6401 (Miravant Pharmaceuticals, Inc, Santa Barbara, CA, USA) was activated at 664 nm using a DD3-0665 (Miravant Systems Inc) 0.5 W diode laser. Corneal neovascularisation in rats was induced using an N-heptanol technique. The evaluated drug dosages, light dosages, and post-injection activation times ranged from 0.01–0.1 μmol/kg, 5–25 J/cm2, and 10–60 minutes, respectively. The efficacy of MV6401 on normal choriocapillaris and choroidal vessels was evaluated in rabbits with indirect ophthalmoscopy, fundus photography, fluorescein angiography, and histology. In rabbits, the evaluated drug dosages, light dosages, and post-injection activation times ranged from 0.025–0.25 μmol/kg, 3.3–20 J/cm2, and 10 minutes, respectively. Results: In the rat corneal neovascularisation model, an optimal intravenous drug dosage of 0.075 μmol/kg was activated by a 20 J/cm2 light dose at 10 minutes after drug administration, the results of which demonstrated early evidence of efficacy in ocular neovascularisation. In rabbits, closure of the normal choriocapillaris was selectively achieved at a drug dosage of 0.15 μmol/kg using light doses from 3.3 to 20 J/cm2. Conclusion: PhotoPoint MV6401 is a potent photosensitiser that demonstrates both efficacy and selectivity in experimental ocular models. PMID:15615758

  17. Photodynamic therapy with PhotoPoint photosensitiser MV6401, indium chloride methyl pyropheophorbide, achieves selective closure of rat corneal neovascularisation and rabbit choriocapillaris.

    PubMed

    Ciulla, T A; Criswell, M H; Snyder, W J; Small, W

    2005-01-01

    The new photosensitiser PhotoPoint MV6401, indium chloride methyl pyropheophorbide, was assessed as a possible ocular photodynamic therapy agent in a rat model of experimentally induced corneal neovascularisation and in choriocapillaris closure in the rabbit. Optimal drug and light activation parameters were determined. MV6401 (Miravant Pharmaceuticals, Inc, Santa Barbara, CA, USA) was activated at 664 nm using a DD3-0665 (Miravant Systems Inc) 0.5 W diode laser. Corneal neovascularisation in rats was induced using an N-heptanol technique. The evaluated drug dosages, light dosages, and post-injection activation times ranged from 0.01-0.1 micromol/kg, 5-25 J/cm(2), and 10-60 minutes, respectively. The efficacy of MV6401 on normal choriocapillaris and choroidal vessels was evaluated in rabbits with indirect ophthalmoscopy, fundus photography, fluorescein angiography, and histology. In rabbits, the evaluated drug dosages, light dosages, and post-injection activation times ranged from 0.025-0.25 micromol/kg, 3.3-20 J/cm(2), and 10 minutes, respectively. In the rat corneal neovascularisation model, an optimal intravenous drug dosage of 0.075 micromol/kg was activated by a 20 J/cm(2) light dose at 10 minutes after drug administration, the results of which demonstrated early evidence of efficacy in ocular neovascularisation. In rabbits, closure of the normal choriocapillaris was selectively achieved at a drug dosage of 0.15 micromol/kg using light doses from 3.3 to 20 J/cm(2). PhotoPoint MV6401 is a potent photosensitiser that demonstrates both efficacy and selectivity in experimental ocular models.

  18. Fibrous dosage forms by wet 3D-micro-patterning: process design, manufacture, and drug release rate.

    PubMed

    Blaesi, Aron H; Saka, Nannaji

    2018-06-19

    Recently, we have introduced fibrous dosage forms prepared by 3D-micro-patterning of drug-laden viscous melts. Such dosage forms enable predictable microstructures and increased drug release rates, and they can be manufactured continuously. However, melt processing is not applicable if the melting temperature of the formulation is greater than the degradation temperature of the drug or of the excipient. In this work, therefore, a continuous wet micro-patterning process that operates at ambient temperature is presented. The excipient is plasticized by a solvent and the patterned dosage form is solidified by air drying. Process models show that the micro-patterning time is the ratio of the fiber length in the dosage form and the velocity of the fiber stream. It was 1.3 minutes in the experiments, but can be reduced further. The drying time is limited by the diffusive flux of solvent through the fibers: it was about 3 minutes for the experimental conditions. Furthermore, models are developed to illustrate the effects of fiber radius, inter-fiber spacing, viscosity of the drug-excipient-solvent mixture, and drying conditions on the microstructure of the dosage form. Models and experimental results show that for a viscosity of the wet fibers of the order 10 3 Pa·s, both the patterned microstructure is well preserved and the crossed fibers are well bonded. Finally, the drug release rate by the dosage forms is experimentally determined and theoretically modeled. The results of the experiments validate the models fairly. Copyright © 2018. Published by Elsevier B.V.

  19. Delayed release film coating applications on oral solid dosage forms of proton pump inhibitors: case studies.

    PubMed

    Missaghi, Shahrzad; Young, Cara; Fegely, Kurt; Rajabi-Siahboomi, Ali R

    2010-02-01

    Formulation of proton pump inhibitors (PPIs) into oral solid dosage forms is challenging because the drug molecules are acid-labile. The aim of this study is to evaluate different formulation strategies (monolithic and multiparticulates) for three PPI drugs, that is, rabeprazole sodium, lansoprazole, and esomeprazole magnesium, using delayed release film coating applications. The core tablets of rabeprazole sodium were prepared using organic wet granulation method. Multiparticulates of lansoprazole and esomeprazole magnesium were prepared through drug layering of sugar spheres, using powder layering and suspension layering methods, respectively. Tablets and drug-layered multiparticulates were seal-coated, followed by delayed release film coating application, using Acryl-EZE(R), aqueous acrylic enteric system. Multiparticulates were then filled into capsules. The final dosage forms were evaluated for physical properties, as well as in vitro dissolution testing in both compendial acid phase, 0.1N HCl (pH 1.2), and intermediate pH, acetate buffer (pH 4.5), followed by phosphate buffer, pH 6.8. The stability of the delayed release dosage forms was evaluated upon storage in accelerated conditions [40 degrees C/75% relative humidity] for 3 months. All dosage forms demonstrated excellent enteric protection in the acid phase, followed by rapid release in their respective buffer media. Moreover, the delayed release dosage forms remained stable under accelerated stability conditions for 3 months. Results showed that Acryl-EZE enteric coating systems provide excellent performance in both media (0.1N HCl and acetate buffer pH 4.5) for monolithic and multiparticulate dosage forms.

  20. Electropolymerized fluorinated aniline-based fiber for headspace solid-phase microextraction and gas chromatographic determination of benzaldehyde in injectable pharmaceutical formulations.

    PubMed

    Mohammadi, Ali; Mohammadi, Somayeh; Bayandori Moghaddam, Abdolmajid; Masoumi, Vahideh; Walker, Roderick B

    2014-10-01

    In this study, a simple method was developed and validated to detect trace levels of benzaldehyde in injectable pharmaceutical formulations by solid-phase microextraction coupled with gas chromatography-flame ionization detector. Polyaniline was electrodeposited on a platinum wire in trifluoroacetic acid solvent by cyclic voltammetry technique. This fiber shows high thermal and mechanical stability and high performance in extraction of benzaldehyde. Extraction and desorption time and temperature, salt effect and gas chromatography parameters were optimized as key parameters. At the optimum conditions, the fiber shows good linearity between peak area ratio of benzaldehyde/3-chlorobenzaldehyde and benzaldehyde concentration in the range of 50-800 ng/mL with percent relative standard deviation values ranging from 0.75 to 8.64% (n = 3). The limits of quantitation and detection were 50 and 16 ng/mL, respectively. The method has the requisite selectivity, sensitivity, accuracy and precision to assay benzaldehyde in injectable pharmaceutical dosage forms. © The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. MRI as a tool for evaluation of oral controlled release dosage forms.

    PubMed

    Dorożyński, Przemysław P; Kulinowski, Piotr; Młynarczyk, Anna; Stanisz, Greg J

    2012-02-01

    The magnetic resonance imaging (MRI) studies of controlled-release (CR) dosage forms can be roughly divided into two groups. The first comprises studies performed in static conditions (small solvent volumes and ambient temperature). Such studies have provided insight into molecular phenomena in hydrating polymeric matrices. The second group covers research performed in dynamic conditions (medium flow or stirring) related to drug dissolution. An important issue is supplementation of the MRI results with data obtained by complementary techniques, such as X-ray microtomography (μCT). As we discuss here, an understanding of the mechanism underlying the release of the drug from the dosage form will lead to the development of detailed, molecularly defined, CR dosage forms. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Efficacy of a DNA vaccine carrying Eimeria maxima Gam56 antigen gene against coccidiosis in chickens.

    PubMed

    Xu, Jinjun; Zhang, Yan; Tao, Jianping

    2013-04-01

    To control coccidiosis without using prophylactic medications, a DNA vaccine targeting the gametophyte antigen Gam56 from Eimeria maxima in chickens was constructed, and the immunogenicity and protective effects were evaluated. The ORF of Gam56 gene was cloned into an eukaryotic expression vector pcDNA3.1(zeo)+. Expression of Gam56 protein in COS-7 cells transfected with recombinant plasmid pcDNA-Gam56 was confirmed by indirect immunofluorescence assay. The DNA vaccine was injected intramuscularly to yellow feathered broilers of 1-week old at 3 dosages (25, 50, and 100 µg/chick). Injection was repeated once 1 week later. One week after the second injection, birds were challenged orally with 5×10(4) sporulated oocysts of E. maxima, then weighed and killed at day 8 post challenge. Blood samples were collected and examined for specific peripheral blood lymphocyte proliferation activity and serum antibody levels. Compared with control groups, the administration of pcDNA-Gam56 vaccine markedly increased the lymphocyte proliferation activity (P<0.05) at day 7 and 14 after the first immunization. The level of lymphocyte proliferation started to decrease on day 21 after the first immunization. A similar trend was seen in specific antibody levels. Among the 3 pcDNA-Gam56 immunized groups, the median dosage group displayed the highest lymphocyte proliferation and antibody levels (P<0.05). The median dosage group had the greatest relative body weight gain (89.7%), and the greatest oocyst shedding reduction (53.7%). These results indicate that median dosage of DNA vaccine had good immunogenicity and immune protection effects, and may be used in field applications for coccidiosis control.

  3. Efficacy of a DNA Vaccine Carrying Eimeria maxima Gam56 Antigen Gene against Coccidiosis in Chickens

    PubMed Central

    Xu, Jinjun; Zhang, Yan

    2013-01-01

    To control coccidiosis without using prophylactic medications, a DNA vaccine targeting the gametophyte antigen Gam56 from Eimeria maxima in chickens was constructed, and the immunogenicity and protective effects were evaluated. The ORF of Gam56 gene was cloned into an eukaryotic expression vector pcDNA3.1(zeo)+. Expression of Gam56 protein in COS-7 cells transfected with recombinant plasmid pcDNA-Gam56 was confirmed by indirect immunofluorescence assay. The DNA vaccine was injected intramuscularly to yellow feathered broilers of 1-week old at 3 dosages (25, 50, and 100 µg/chick). Injection was repeated once 1 week later. One week after the second injection, birds were challenged orally with 5×104 sporulated oocysts of E. maxima, then weighed and killed at day 8 post challenge. Blood samples were collected and examined for specific peripheral blood lymphocyte proliferation activity and serum antibody levels. Compared with control groups, the administration of pcDNA-Gam56 vaccine markedly increased the lymphocyte proliferation activity (P<0.05) at day 7 and 14 after the first immunization. The level of lymphocyte proliferation started to decrease on day 21 after the first immunization. A similar trend was seen in specific antibody levels. Among the 3 pcDNA-Gam56 immunized groups, the median dosage group displayed the highest lymphocyte proliferation and antibody levels (P<0.05). The median dosage group had the greatest relative body weight gain (89.7%), and the greatest oocyst shedding reduction (53.7%). These results indicate that median dosage of DNA vaccine had good immunogenicity and immune protection effects, and may be used in field applications for coccidiosis control. PMID:23710081

  4. 21 CFR 522.468 - Colistimethate sodium powder for injection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....600(c) of this chapter. (c) [Reserved] (d) Conditions of use. (1) 1- to 3-day-old chickens. (i) Dosage. 0.2 milligram colistin activity per chicken. (ii) Indications for use. Control of early mortality... injection in the neck of 1- to 3-day-old chickens. Not for use in laying hens producing eggs for human...

  5. 21 CFR 500.55 - Exemption from certain drug-labeling requirements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... the stated maximum per dosage unit: Atropine sulfate. As an injectable for cattle, goats, horses, pigs..., pigs, and sheep (except as provided in § 500.65). Morphine sulfate. As an injectable for dogs, not in... cats, dogs, cattle, goats, horses, pigs, and sheep. Thyroid. For oral use in dogs, not in excess of 60...

  6. 21 CFR 500.55 - Exemption from certain drug-labeling requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... the stated maximum per dosage unit: Atropine sulfate. As an injectable for cattle, goats, horses, pigs..., pigs, and sheep (except as provided in § 500.65). Morphine sulfate. As an injectable for dogs, not in... cats, dogs, cattle, goats, horses, pigs, and sheep. Thyroid. For oral use in dogs, not in excess of 60...

  7. 21 CFR 500.55 - Exemption from certain drug-labeling requirements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... the stated maximum per dosage unit: Atropine sulfate. As an injectable for cattle, goats, horses, pigs..., pigs, and sheep (except as provided in § 500.65). Morphine sulfate. As an injectable for dogs, not in... cats, dogs, cattle, goats, horses, pigs, and sheep. Thyroid. For oral use in dogs, not in excess of 60...

  8. 21 CFR 500.55 - Exemption from certain drug-labeling requirements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... the stated maximum per dosage unit: Atropine sulfate. As an injectable for cattle, goats, horses, pigs..., pigs, and sheep (except as provided in § 500.65). Morphine sulfate. As an injectable for dogs, not in... cats, dogs, cattle, goats, horses, pigs, and sheep. Thyroid. For oral use in dogs, not in excess of 60...

  9. 21 CFR 500.55 - Exemption from certain drug-labeling requirements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... the stated maximum per dosage unit: Atropine sulfate. As an injectable for cattle, goats, horses, pigs..., pigs, and sheep (except as provided in § 500.65). Morphine sulfate. As an injectable for dogs, not in... cats, dogs, cattle, goats, horses, pigs, and sheep. Thyroid. For oral use in dogs, not in excess of 60...

  10. On the exfoliating polymeric cellular dosage forms for immediate drug release.

    PubMed

    Blaesi, Aron H; Saka, Nannaji

    2016-06-01

    The most prevalent pharmaceutical dosage forms at present-the oral immediate-release tablets and capsules-are granular solids. Though effective in releasing drug rapidly, development and manufacture of such dosage forms are fraught with difficulties inherent to particulate processing. Predictable dosage form manufacture could be achieved by liquid-based processing, but cast solid dosage forms are not suitable for immediate drug release due to their resistance to fluid percolation. To overcome this limitation, we have recently introduced cellular dosage forms that can be readily prepared from polymeric melts. It has been shown that open-cell structures comprising polyethylene glycol 8000 (PEG 8k) excipient and a drug exfoliate upon immersion in a dissolution medium. The drug is then released rapidly due to the large specific surface area of the exfoliations. In this work, we vary the molecular weight of the PEG excipient and investigate its effect on the drug release kinetics of structures with predominantly open-cell topology. We demonstrate that the exfoliation rate decreases substantially if the excipient molecular weight is increased from 12 to 100kg/mol, which causes the drug dissolution time to increase by more than a factor of ten. A model is then developed to elucidate the exfoliation behavior of cellular structures. Diverse transport processes are considered: percolation due to capillarity, diffusion of dissolution medium through the cell walls, and viscous flow of the saturated excipient. It is found that the lower exfoliation rate and the longer dissolution time of the dosage forms with higher excipient molecular weight are primarily due to the greater viscosity of the cell walls after fluid penetration. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. [Oral controlled release dosage forms].

    PubMed

    Mehuys, Els; Vervaet, Chris

    2010-06-01

    Several technologies to control drug release from oral dosage forms have been developed. Drug release can be regulated in several ways: sustained release, whereby the drug is released slowly over a prolonged period of time, postponed release, whereby drug release is delayed until passage from the stomach into the intestine (via enteric coating), and targeted release, whereby the drug is targeted to a specific location of the gastrointestinal tract. This article reviews the various oral controlled release dosage forms on the market.

  12. Effects of pharmaceutical processing on pepsin activity during the formulation of solid dosage forms.

    PubMed

    Kristó, Katalin; Pintye-Hódi, Klára

    2013-02-01

    The main aim of this study was to investigate the effects of pharmaceutical technological methods on pepsin activity during the formulation of solid dosage forms. The circumstances of direct compression and wet granulation were modeled. During direct compression, the heat and the compression force must be taken into consideration. The effects of these parameters were investigated in three materials (pure pepsin, and 1:1 (w/w) pepsin-tartaric acid and 1:1 (w/w) pepsin-citric acid powder mixtures). It was concluded that direct compression is appropriate for the formulation of solid dosage forms containing pepsin through application without acids or with acids at low compression force. The effects of wet granulation were investigated with a factorial design for the same three materials. The factors were time, temperature and moisture content. There was no significant effect of the factors when acids were not applied. Temperature was a significant factor when acids were applied. The negative effect was significantly higher for citric acid than for tartaric acid. It was found that wet granulation can be utilized for the processing of pepsin into solid dosage forms under well-controlled circumstances. The application of citric acid is not recommended during the formulation of solid dosage forms through wet granulation. A mathematically based optimization may be necessary for preformulation studies of the preparation of dosage forms containing sensitive enzymes.

  13. A survey of caregivers of Nigerian children less than 6 years of age to determine the experience and perception of acceptability of oral solid dosage forms.

    PubMed

    Orubu, Samuel; Okwelogu, Chinyere; Opanuga, Olabisi; Tuleu, Catherine

    2018-02-05

    The World Health Organization (WHO) recommends flexible solid oral dosage forms such as dispersible tablet as the preferred formulation for (young) children, especially in developing/low- and middle-income countries, LMIC. The aim of this study was to assess experience, perceptions of acceptability, and formulation preferences, among 10 oral dosage forms for young children in a sample of end-users in Nigeria as an exemplar LMIC. Using a semi-structured and validated questionnaire, 148 caregivers were surveyed. Acceptability was assessed by level of liking using a 3-point Likert scale and ease of administration. Preference was assessed from participants' dosage form of choice. Oral dosage forms assessed were those mentioned in the British National Formulary for children, 2013. The formulation perceived as the most acceptable was the chewable/suckable tablet. However, preference was for liquids. Specifically with the dispersible tablet, whilst 89% (n=111) of caregivers of young children found it easy-to-administer, only 50% of children liked it. There is a gap between the proposal of dispersible tablet as the preferred dosage form for young children and caregivers' perceptions of acceptability and preference. Educational strategies to increase acceptability of dispersible tablets as the preferred formulation for young children would be required. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. An introduction to fast dissolving oral thin film drug delivery systems: a review.

    PubMed

    Kathpalia, Harsha; Gupte, Aasavari

    2013-12-01

    Many pharmaceutical companies are switching their products from tablets to fast dissolving oral thin films (OTFs). Films have all the advantages of tablets (precise dosage, easy administration) and those of liquid dosage forms (easy swallowing, rapid bioavailability). Statistics have shown that four out of five patients prefer orally disintegrating dosage forms over conventional solid oral dosages forms. Pediatric, geriatric, bedridden, emetic patients and those with Central Nervous System disorders, have difficulty in swallowing or chewing solid dosage forms. Many of these patients are non-compliant in administering solid dosage forms due to fear of choking. OTFs when placed on the tip or the floor of the tongue are instantly wet by saliva. As a result, OTFs rapidly hydrate and then disintegrate and/or dissolve to release the medication for local and/or systemic absorption. This technology provides a good platform for patent non- infringing product development and for increasing the patent life-cycle of the existing products. The application of fast dissolving oral thin films is not only limited to buccal fast dissolving system, but also expands to other applications like gastroretentive, sublingual delivery systems. This review highlights the composition including the details of various types of polymers both natural and synthetic, the different types of manufacturing techniques, packaging materials and evaluation tests for the OTFs.

  15. Biorelevant in-vitro performance testing of orally administered dosage forms.

    PubMed

    Reppas, Christos; Vertzoni, Maria

    2012-07-01

    This review focuses on the evolution and current status of biorelevant media and hydrodynamics, and discusses the usefulness of biorelevant performance testing in the evaluation of specific dosage form related lumenal processes. During the last 15 years our knowledge of the gastrointestinal environment (including the lower gut) has improved dramatically and biorelevant media composition and, to a lesser extent, biorelevant hydrodynamics, have been refined. Biorelevant dissolution/release testing is useful for the evaluation of formulation and food effects on plasma levels after administration of immediate release dosage forms containing low solubility compounds and after administration of extended release products. Lumenal disintegration times of immediate release dosage forms and the bile acid sequestering activity of resins in the lumen can also be successfully forecasted with biorelevant in vitro testing. Biorelevant in-vitro performance testing is an important tool for evaluating intralumenal dosage form performance. Since the formulation of new active pharmaceutical ingredients for oral delivery is more challenging than ever before, efforts to improve the predictability of biorelevant tests are expected to continue. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  16. Nasal Drug Delivery in Traditional Persian Medicine

    PubMed Central

    Zarshenas, Mohammad Mehdi; Zargaran, Arman; Müller, Johannes; Mohagheghzadeh, Abdolali

    2013-01-01

    Background Over one hundred different pharmaceutical dosage forms have been recorded in literatures of Traditional Persian Medicine among which nasal forms are considerable. Objectives This study designed to derive the most often applied nasal dosage forms together with those brief clinical administrations. Materials and Methods In the current study remaining pharmaceutical manuscripts of Persia during 9th to 18th century AD have been studied and different dosage forms related to nasal application of herbal medicines and their therapeutic effects were derived. Results By searching through pharmaceutical manuscripts of medieval Persia, different nasal dosage forms involving eleven types related to three main groups are found. These types could be derived from powder, solution or liquid and gaseous forms. Gaseous form were classified into fumigation (Bakhoor), vapor bath (Enkebab), inhalation (Lakhlakheh), aroma agents (Ghalieh) and olfaction or smell (Shomoom). Nasal solutions were as drops (Ghatoor), nasal snuffing drops (Saoot) and liquid snuff formulations (Noshoogh). Powders were as nasal insufflation or snorting agents (Nofookh) and errhine or sternutator medicine (Otoos). Nasal forms were not applied only for local purposes. Rather systemic disorders and specially CNS complications were said to be a target for these dosage forms. Discussion While this novel type of drug delivery is known as a suitable substitute for oral and parenteral administration, it was well accepted and extensively mentioned in Persian medical and pharmaceutical manuscripts and other traditional systems of medicine as well. Accordingly, medieval pharmaceutical standpoints on nasal dosage forms could still be an interesting subject of study. Therefore, the current work can briefly show the pharmaceutical knowledge on nasal formulations in medieval Persia and clarify a part of history of traditional Persian pharmacy. PMID:24624204

  17. Effect of Calcium Ions on the Disintegration of Enteric-Coated Solid Dosage Forms.

    PubMed

    Al-Gousous, Jozef; Langguth, Peter

    2016-02-01

    To investigate the effect of calcium ions on the disintegration of enteric-coated dosage forms, disintegration testing was performed on enteric-coated aspirin tablets in the presence and absence of calcium in the test media. The results show that the presence of calcium ions retards the disintegration of enteric-coated dosage forms. This finding, which has not been reported in scientific literature, sheds light on the importance of conducting well-designed detailed investigations into the potential of calcium from dietary sources, calcium supplements, antacids, and/or phosphate binders affecting the absorption of drugs formulated into enteric-coated dosage forms. Moreover, it shows the necessity to investigate the potential of the occurrence of additional nutrient-excipient interactions. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

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

    PubMed

    Shen, Jie; Burgess, Diane J

    2012-07-01

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

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

    PubMed Central

    Shen, Jie; Burgess, Diane J.

    2012-01-01

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

  20. Tiletamine-zolazepam, ketamine, and xylazine anesthesia of captive cheetah (Acinonyx jubatus).

    PubMed

    Lewandowski, Albert H; Bonar, Christopher J; Evans, Sara E

    2002-12-01

    Thirty-two anesthetic episodes used a combination of tiletamine-zolezepam (50 mg/ml each), ketamine (80 mg/ml), and xylazine (20 mg/ml) at various dosages for routine diagnostic and minor surgical procedures in 13 captive cheetahs (Acinonyx jubatus). The mean dosage (0.023 +/- 0.003 ml/kg) provided rapid induction with a single i.m. injection along with safe predictable working time, good muscle relaxation, and analgesia. Yohimbine administration subsequently accelerated smooth and rapid recovery.

  1. An Accelerated Release Study to Evaluate Long-Acting Contraceptive Levonorgestrel-Containing in Situ Forming Depot Systems

    PubMed Central

    Janagam, Dileep R.; Wang, Lizhu; Ananthula, Suryatheja; Johnson, James R.; Lowe, Tao L.

    2016-01-01

    Biodegradable polymer-based injectable in situ forming depot (ISD) systems that solidify in the body to form a solid or semisolid reservoir are becoming increasingly attractive as an injectable dosage form for sustained (months to years) parenteral drug delivery. Evaluation of long-term drug release from the ISD systems during the formulation development is laborious and costly. An accelerated release method that can effectively correlate the months to years of long-term release in a short time such as days or weeks is economically needed. However, no such accelerated ISD system release method has been reported in the literature to date. The objective of the current study was to develop a short-term accelerated in vitro release method for contraceptive levonorgestrel (LNG)-containing ISD systems to screen formulations for more than 3-month contraception after a single subcutaneous injection. The LNG-containing ISD formulations were prepared by using biodegradable poly(lactide-co-glycolide) and polylactic acid polymer and solvent mixtures containing N-methyl-2-pyrrolidone and benzyl benzoate or triethyl citrate. Drug release studies were performed under real-time (long-term) conditions (PBS, pH 7.4, 37 °C) and four accelerated (short-term) conditions: (A) PBS, pH 7.4, 50 °C; (B) 25% ethanol in PBS, pH 7.4, 50 °C; (C) 25% ethanol in PBS, 2% Tween 20, pH 7.4, 50 °C; and (D) 25% ethanol in PBS, 2% Tween 20, pH 9, 50 °C. The LNG release profile, including the release mechanism under the accelerated condition D within two weeks, correlated (r2 ≥ 0.98) well with that under real-time conditions at four months. PMID:27598191

  2. Evaluation of a quali embryo model for the detection of botulism toxin type A activity

    USDA-ARS?s Scientific Manuscript database

    The Japanese quail embryo (Coturnix japonica) was evaluated for use as a bioassay to detect biologically active botulinum toxin serotype A (BoNT/A). Day 15 of incubation embryos were injected with decreasing dosages of BoNT/A from 250 to 0.5 ng of toxin. At 1 day post-injection, embryos receiving ...

  3. Muscle Injury After Intramuscular Administration of Diclofenac: A Case Report Supported by Magnetic Resonance Imaging.

    PubMed

    Probst, Mareike; Kühn, Jens-Peter; Modeß, Christiane; Scheuch, Eberhard; Seidlitz, Anne; Hosten, Norbert; Siegmund, Werner; Weitschies, Werner

    2017-12-01

    Intramuscular injection of diclofenac is still frequently practiced, although there is ample evidence that the risk of local tissue intolerability is highly underestimated. The aim of this study was to evaluate local toxicity in a patient using magnetic resonance imaging. A patient who gave written informed consent received a medically indicated intramuscular administration of diclofenac 75 mg/2 mL. Simultaneously with magnetic resonance imaging of the depot, a clinical-chemical evaluation and quantification of diclofenac in plasma was performed. A manifold enhancement of the T2-weighted magnetic resonance signal was observed in a muscle area of approximately 60 mL volume, with maximum signal intensity 30 min after injection, the time of maximum diclofenac plasma exposure. Plasma creatine kinase activity was elevated approximately sixfold within 8 h and normalized within 1 week, whereas the magnetic resonance enhancement disappeared within 5 weeks. Interestingly, the patient did not complain about any clinical symptoms at the injection site. Asymptomatic tissue injury after intramuscular injection of diclofenac, caused by intramuscular dosing, can be reliably evaluated by magnetic resonance imaging and should be applied early during the development of parenteral dosage forms. Clinical Trials Registration Number: BB130/16 (Ethics Committee of the University Medicine Greifswald).

  4. [Rational estimation of drug dosage through pharmacometric modeling: The case of a long-acting depot antipsychotic].

    PubMed

    Simon, N; Azorin, J-M

    2015-04-01

    Drug manufacturer seeking authorization to bring a newly medicinal compound to the market (Market Authorization Application) have to undertake various studies, each of them providing a specific report. It is however essential to know how to pool results in order to understand the behavior of the drug in all the situations likely to be encountered in clinical practice. The exploitation of these data is now carried out through pharmacometric analyzes which aim at quantifying the exposure and the response of a drug over time. These methods (named "population approach") are based on non-linear mixed effects model and therefore, on the identification of a mathematical model. A first step is to model the variations in concentrations over time by integrating the physio-pathological characteristics of the patients. At this stage, the Bayesian analysis is essential to identify and select the factors of interindividual variability. This pharmacokinetic (PK) modeling allows us to obtain the prescribed dose for each patient, but also their exposure. The second step consists in defining the relationship between exposure and effect: pharmacodynamic (PD) modeling. In psychiatry, the response can be the receptors' occupancy rate or the evolution of a clinical score (BPRS, PANSS…) over time. The final PK-PD model defines the target exposure, that is to say, the concentration values required to achieve maximum effect on the score studied without risking over-exposure. Ultimately, a Monte Carlo simulation will be conducted which will test the expected response for different doses and will facilitate a rational choice in dosage. Assessing the process behind the transition from an oral to a long-acting injectable form of an active ingredient such as aripiprazole can be done by following the same protocol. A 10- to 30-mg per day therapeutic range has thus been identified. The model incorporates all the identified factors of variability of aripiprazole (drug interactions and genetic polymorphism of the P450 2D6 cytochrome) and showed that with an injectable sustained release form, a monthly dose of 400mg would allow 90% of patients to gain exposure in the therapeutic range. In case of a drug inhibition and/or of a slow metabolizing profile, dosage adjustment is necessary. Copyright © 2015 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

  5. Prescribing Errors Involving Medication Dosage Forms

    PubMed Central

    Lesar, Timothy S

    2002-01-01

    CONTEXT Prescribing errors involving medication dose formulations have been reported to occur frequently in hospitals. No systematic evaluations of the characteristics of errors related to medication dosage formulation have been performed. OBJECTIVE To quantify the characteristics, frequency, and potential adverse patient effects of prescribing errors involving medication dosage forms . DESIGN Evaluation of all detected medication prescribing errors involving or related to medication dosage forms in a 631-bed tertiary care teaching hospital. MAIN OUTCOME MEASURES Type, frequency, and potential for adverse effects of prescribing errors involving or related to medication dosage forms. RESULTS A total of 1,115 clinically significant prescribing errors involving medication dosage forms were detected during the 60-month study period. The annual number of detected errors increased throughout the study period. Detailed analysis of the 402 errors detected during the last 16 months of the study demonstrated the most common errors to be: failure to specify controlled release formulation (total of 280 cases; 69.7%) both when prescribing using the brand name (148 cases; 36.8%) and when prescribing using the generic name (132 cases; 32.8%); and prescribing controlled delivery formulations to be administered per tube (48 cases; 11.9%). The potential for adverse patient outcome was rated as potentially “fatal or severe” in 3 cases (0.7%), and “serious” in 49 cases (12.2%). Errors most commonly involved cardiovascular agents (208 cases; 51.7%). CONCLUSIONS Hospitalized patients are at risk for adverse outcomes due to prescribing errors related to inappropriate use of medication dosage forms. This information should be considered in the development of strategies to prevent adverse patient outcomes resulting from such errors. PMID:12213138

  6. [Cluster-immunotherapy in seasonal allergic rhinitis: safety aspects of induction therapy with depot allergoids (Purethal)].

    PubMed

    Hansen, I; Hörmann, K; Stuck, B A; Schneider-Gêne, S; Mösges, R; Klimek, L

    2003-08-01

    Specific immunotherapy (SIT) represents the only specific treatment that can be offered to allergic patients apart from allergen avoidance. SIT has been widely used in pollen allergic rhinitis. Clinical efficacy has been demonstrated in several controlled clinical trials and depends on the specific allergen the individual patient is sensitive to, the quality and total amount of allergen applied, and the SIT schedule. In classic SIT, gradually increasing dosages of the allergen extract are injected subcutaneously. Several dosage schedules for subcutaneous SIT can be applied. In Cluster-SIT, 2 - 3 injections per day of treatment are given once a week during induction treatment. In this study, we investigated 64 patients (33 female, 31 male) from 18 to 54 years (26.9 +/- 5.1 years) in terms of side-effects of Cluster-SIT during induction treatment. The total amount of enlarged local reactions (> grade 1) was n = 77 or 15.2 % of all injections. Of these, 68 (88 %) were classified as immediate reactions, 8 (11 %) were late phase reactions and 1 (1 %) was immediate as well as late phase reaction. Of all enlarged local reactions, 48 (62 %) were grade 1 reactions, 13 (17 %) were grade 2 reactions, 13 (17 %) were grade 3 reactions and 1 (1 %) was a grade 4 reaction. The total amount of systemic reactions was n = 22 or 4.3 % of all injections. Of these, 19 (86 %) were classified as immediate reactions, 3 (14 %) were delayed reactions. Of all systemic reactions, 18 (82 %) were grade 1 reactions and 4 (18 %) grade 2 reactions. Grade 3 or grade 4 reactions did not occur. There were no differences in gender or age regarding the occurrence of side effects (all p > 0.05). Frequency and severity of adverse side effects in Cluster-SIT correspond to those in other dosage schedules. On behalf of security aspects, Cluster-SIT could become an interesting alternative dosage schedule for dose increase during SIT. Furthermore, in Cluster-SIT with allergoids, induction treatment can be carried out in two treatment days of approximately 2.5 hours each.

  7. Dissolution behavior of Cu, Fe and Zn from gold sulfide concentrate during pre-oxidation using ozone in neutral media

    NASA Astrophysics Data System (ADS)

    Kurniawan, Mubarok, M. Zaki

    2018-04-01

    The aim of this work was to observe the dissolution behaviour of Cu, Fe and Zn from gold sulfide concentrate during preoxidation with ozone as the oxidant and distillation water as the media. The preoxidation experiments were carried out in five-necked reactor with variations of retention time, percent solid, particle size and oxygen dosage injected to ozone generator. The retention time was varied at 6 hours, 8 hours, 12 hours and 24 hours. The percent solid was varied at 10%, 20% and 30% while the particle size was varied at P80 -75 mesh dan P80 -20 mesh. The dosage of oxygen injection to ozone generator was varried at 1 liter per minute and 2 liter per minute. The ozone gas was produced by using ozone generator type OZ-03 and injected to the slurry by using Mazzei injector. The soluble Cu, Fe and Zn were measured by using Atomic Absorption Spectrophotometry (AAS). The concentrates were characterized by X-Ray Diffraction (XRD), mineragraphy, fire assay and Inductively Coupled Plasma (ICP). Fire assay, ICP and XRD were used to analyse the residues and froth. The solubilition of metals (Cu, Fe and Zn) was obtained through the formation of sulphate ion and H+ which decreased the pH, released a number of heat and then was continued by the formation of elemental sulphur (S°). The interaction of particles and gas yielded the formation of froth. The highest dissolution percentage of Cu, Fe and Zn was achieved through 24 hours oxidation at 20% (w/w), P80 -20 mesh and one liter per minute of oxygen injection dosage by 83.016%, 24.7303% and 91.6808%, respectively.

  8. High Serum FSH is Associated with Brown Oocyte Formation and a Lower Pregnacy Rate in Human IVF Parctice.

    PubMed

    Xu, Hongyi; Deng, Kai; Luo, Qingbing; Chen, Juan; Zhang, Xin; Wang, Xiaoyan; Diao, Honglu; Zhang, Changjun

    2016-01-01

    To investigate whether brown zona pellucida (ZP) of oocytes affects the outcome of fertilization, embryo quality and pregnancy rate in in vitro fertilization-embryo transfer (IVF-ET). Based on the ZP color of their oocytes, a total number of 703 patients dated from 2012 to 2014 were divided into a normal egg group (group A) and a brown oocyte group (group B), with 629 and 74 cases, respectively. Clinical characteristics, gonadotropin (Gn) days, Gn dosage, serum hormone levels on the day of human chorionic gonadotropin (HCG) injection, ZP thickness (ZPT) of the eggs, fertilization rate, rescue intracytoplasmic sperm injection (rICSI) rate, good-quality embryo rate and pregnancy rate were compared between the two groups. No significant differences were found in the duration and the causes of infertility, and their basal level of endocrine hormone before IVF-ET between normal egg group and brown egg group. The level of serum hormone including estradiol, progesterone and luteinizing hormone on the day of HCG injection were again similar. Moreover, there were no differences in number of mature oocytes, oocyte fertilization rates and rICSI rates after IVF between the two groups. However, we observed that the ZPT of brown oocytes (group B) was higher than that of normal oocytes (group A). Moreover, the Gn dosage and FSH levels on the day of HCG injection were significantly higher in group B than in group A and the good-quality embryo rate and pregnancy rate in group B were lower than those in group A. Compared with normal eggs, oocytes with a brown ZP were found to have a higher ZPT, lower embryo quality and lower pregnancy rate, which might be due to a high Gn dosage injection and high serum FSH levels during IVT-ET cycles. © 2016 The Author(s) Published by S. Karger AG, Basel.

  9. Effects of agkistrodon in different dosage forms on collagen-induced arthritis in rats.

    PubMed

    Bao, Jie; Xie, Zhi-Jun; Chen, Lei-Ming; Sun, Jing; Fan, Yong-Sheng

    2016-12-01

    To determine the effective dosage and formulation of agkistrodon in collagen-induced arthritis (CIA) rats. CIA was induced by injection of collagen in complete/incomplete Freund's adjuvant. Agkistrodon decoction, agkistrodon powder, and agkistrodon wine were administered daily starting from the onset of arthritis. Paw swelling degree was measured by using a volume-measuring instrument every 7 days after primary immunization. Arthritis index was measured and calculated using the "five scoring method" every 7 days. The levels of serum interleukin-1ß (IL-1ß) and type II collagen IgG antibodies were detected by enzyme-linked immunosorbent assay. Finally, all ankles were removed, and X-ray radiography was performed with In-vivo Imaging System FX. Samples were counterstained with hematoxylin and eosin for analysis. Among the various dosage formulations of agkistrodon, high-dose powder, which was equivalent to an amount of 6 g/day in adults, showed better effects on the inhibition of joint swelling and reduction of arthritis index score. The relatively low levels of serum IL-1 and anti-type II collagen IgG antibodies, as well as the X-ray radiography and pathology results, further proved the superiority of the high-dose powder over the other formulations. The effect of decoction on inhibiting joint swelling was inversely proportional to the dosage. Other effects, such as reduction of arthritis index score and the levels of serum IL-1 and anti-type II collagen IgG antibodies, were directly proportional to the dosage. While the use of large dose agkistrodon wine led to negative effects. These data highlight the potential function of high-dose agkistrodon powder, which was equivalent to an amount of 6 g/day in adults. The powder can quickly relieve the symptoms of rheumatoid arthritis and prevent aggravation of disease, especially during the early period.

  10. Ease of opening of blistered solid dosage forms in a senior citizens target group.

    PubMed

    Braun-Münker, Myriam; Ecker, Felix

    2016-10-30

    Blisters differing in design and handling are established as packaging material for solid dosage forms. The ease of opening of blisters influences application and patient's compliance. In this study the influence of visibility and movability of solid dosage forms in blister packaging on both, easy opening and patient's satisfaction, were investigated by target group testing according to ONR CEN/TS 15945. For each testing 20 participants in the age of 65-80 years were recruited randomly. They opened the blisters on realistic terms without any auxiliary devices. Video documentation of the hands' movements was recorded to analyze the opening procedure. To show the influence of visibility of the dosage form in the blister, capsules size 1 were packed in transparent and opaque blisters. A moderate influence of the visibility on both, the ease of opening and patient satisfaction, was observed. A second study dealt with the movability of solid dosage forms in blisters. Therefore, three different sizes of tablets with similar shapes were packed in identical cavities. Limited movability was found as major criterion on effectiveness and effectivity of opening as well as on satisfaction with the opening procedure. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Ethnic or racial differences revisited: impact of dosage regimen and dosage form on pharmacokinetics and pharmacodynamics.

    PubMed

    Chen, Mei-Ling

    2006-01-01

    Ethnic or racial differences in pharmacokinetics and pharmacodynamics have been attributed to the distinctions in the genetic, physiological and pathological factors between ethnic/racial groups. These pharmacokinetic/pharmacodynamic differences are also known to be influenced by several extrinsic factors such as socioeconomic background, culture, diet and environment. However, it is noted that other factors related to dosage regimen and dosage form have largely been ignored or overlooked when conducting or analysing pharmacokinetic/pharmacodynamic studies in relation to ethnicity/race. Potential interactions can arise between the characteristics of ethnicity/race and a unique feature of dosage regimen or dosage form used in the study, which may partly account for the observed pharmacokinetic/pharmacodynamic differences between ethnic/racial groups. Ethnic/racial differences in pharmacokinetics/pharmacodynamics can occur from drug administration through a specific route that imparts distinct pattern of absorption, distribution, transport, metabolism or excretion. For example, racial differences in the first-pass metabolism of a drug following oral administration may not be relevant when the drug is applied to the skin. On the other hand, ethnic/racial difference in pharmacokinetics/pharmacodynamics can also happen via two different routes of drug delivery, with varying levels of dissimilarity between routes. For example, greater ethnic/racial differences were observed in oral clearance than in systemic clearance of some drugs, which might be explained by the pre-systemic factors involved in the oral administration as opposed to the intravenous administration. Similarly, changes in the dose frequency and/or duration may have profound impact on the ethnic/racial differences in pharmacokinetic/pharmacodynamic outcome. Saturation of enzymes, transporters or receptors at high drug concentrations is a possible reason for many observed ethnic/racial discrepancies between single- and multiple-dose regimens, or between low- and high-dose administrations. The presence of genetic polymorphism of enzymes and/or transporters can further complicate the analysis of pharmacokinetic/pharmacodynamic data in ethnic/racial populations. Even within the same dosage regimen, the use of different dosage forms may trigger significantly different pharmacokinetic/pharmacodynamic responses in various ethnic/racial groups, given that different dosage forms may exhibit different rates of drug release, may release the drug at different sites, and/or have different retention times at specific sites of the body. It is thus cautioned that the pharmacokinetic/pharmacodynamic data obtained from different ethnic/racial groups cannot be indiscriminately compared or combined for analysis if there is a lack of homogeneity in the apparent 'extrinsic' factors, including dosage regimen and dosage form.

  12. A novel in-situ-gelling liquid suppository for site-targeting delivery of anti-colorectal cancer drugs.

    PubMed

    Lin, Hong-Ru; Tseng, Chao-Chih; Lin, Yiu-Jiuan; Ling, Ming-Hung

    2012-01-01

    In order to avoid anti-cancer drugs undergoing a first-pass effect and reduce their toxicity, and to solve conventional suppositories defects, we developed an in-situ-gelling and injectable Pluronic-poly(acrylic acid) (Pluronic-PAA) liquid suppository, which could gel fast in the physiological state and had suitable gel strength and bioadhesive force. The liquid suppositories were inserted into the rectum of rabbits without difficulty and leakage, and retained in the rectum for at least 6 h and while releasing the drug. The toxicity and cytotoxic tests indicated that Pluronic and PAA were non-toxic materials and could inhibit colon cancer cells when oxaliplatin was incorporated. C max and AUC0→12h values of oxaliplatin after rectal administration of a oxaliplatin suppository were higher than those for an oxaliplatin solution administered orally. These results suggest that an in-situ-gelling and injectable liquid suppository for humans can be further developed as a more convenient and effective rectal dosage form.

  13. Evaluation of a quail embryo model for the detection of botulinum toxin type A activity

    USDA-ARS?s Scientific Manuscript database

    The quail embryo was evaluated for use as a bioassay to detect biologically active botulinum toxin serotype A (BoNT/A). Day 15 of incubation embryos were injected with decreasing dosages of BoNT/A from 250 to 0.5 ng of toxin. At 1 day post-injection, embryos receiving 20 ng of BoNT or higher had m...

  14. Impact of release characteristics of sinomenine hydrochloride dosage forms on its pharmacokinetics in beagle dogs

    PubMed Central

    Sun, Jin; Shi, Jie-Ming; Zhang, Tian-Hong; Gao, Kun; Mao, Jing-Jing; Li, Bing; Sun, Ying-Hua; He, Zhong-Gui

    2005-01-01

    AIM: To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride (SM•HCl) on its pharmacokinetics in beagle dogs. METHODS: The in vitro release behavior of two SM•HCl dosage forms, including commercial 12-h sustained-release tablets and 24-h sustained-release pellets prepared in our laboratory, was examined. The two dosage forms were orally administrated to beagle dogs, and then the in vivo SM•HCl pharmacokinetics was investigated and compared. RESULTS: The optimal SM•HCl sustained-release formulation was achieved by mixing slow- and rapid-release pellets (9:1, w/w). The SM•HCl release profiles of the sustained-release pellets were scarcely influenced by the pH of the dissolution medium. Release from the 12-h sustained-release tablets was markedly quicker than that from the 24-h sustained-release pellets, the cumulative release up to 12-h was 99.9% vs 68.7%. From a pharmacokinetic standpoint, the 24-h SM•HCl sustained-release pellets had longer tmax and lower Cmax compared to the 12-h sustained-release tablets, the tmax being 2.67×0.52 h vs 9.83×0.98 h and the Cmax being 1 334.45±368.76 ng/mL vs 893.12±292.55 ng/mL, respectively. However, the AUC0-tn of two SM•HCl dosage forms was comparable and both preparations were statistically bioequivalent. Furthermore, the two preparations had good correlations between SM•HCl percentage absorption in vivo and the cumulative percentage release in vitro. CONCLUSION: The in vitro release properties of the dosage forms strongly affect their pharmacokinetic behavior in vivo. Therefore, managing the in vitro release behavior of dosage forms is a promising strategy for obtaining the optimal in vivo pharmacokinetic characteristics and safe therapeutic drug concentration-time curves. PMID:16052686

  15. Development and validation of multivariate calibration methods for simultaneous estimation of Paracetamol, Enalapril maleate and hydrochlorothiazide in pharmaceutical dosage form

    NASA Astrophysics Data System (ADS)

    Singh, Veena D.; Daharwal, Sanjay J.

    2017-01-01

    Three multivariate calibration spectrophotometric methods were developed for simultaneous estimation of Paracetamol (PARA), Enalapril maleate (ENM) and Hydrochlorothiazide (HCTZ) in tablet dosage form; namely multi-linear regression calibration (MLRC), trilinear regression calibration method (TLRC) and classical least square (CLS) method. The selectivity of the proposed methods were studied by analyzing the laboratory prepared ternary mixture and successfully applied in their combined dosage form. The proposed methods were validated as per ICH guidelines and good accuracy; precision and specificity were confirmed within the concentration range of 5-35 μg mL- 1, 5-40 μg mL- 1 and 5-40 μg mL- 1of PARA, HCTZ and ENM, respectively. The results were statistically compared with reported HPLC method. Thus, the proposed methods can be effectively useful for the routine quality control analysis of these drugs in commercial tablet dosage form.

  16. Tissue Engineering in Osteoarthritis: Current Status and Prospect of Mesenchymal Stem Cell Therapy.

    PubMed

    Im, Gun-Il

    2018-04-27

    Osteoarthritis (OA) is the most common form of arthritis. Over the last 20 years, attempts have been made to regenerate articular cartilage to overcome the limitations of conventional treatments. As OA is generally associated with larger and diffuse involvement of articular surfaces and alteration of joint homeostasis, a tissue engineering approach for cartilage regeneration is more difficult than in simple chondral defects. Autologous and allogeneic mesenchymal stem cells (MSCs) have rapidly emerged as investigational products for cartilage regeneration. This review outlines points to consider in MSC-based approaches for OA treatment, including allogeneic MSCs, sources of MSCs, dosages, feasibility of multiple injections, indication according to severity of OA lesion and patient age, and issues regarding implantation versus injection. We introduce possible mechanisms of action of implanted or injected MSCs as well as the immunological aspects of MSC therapy and provide a summary of clinical trials of MSCs in the treatment of OA. Given current knowledge, it is too early to draw conclusions on the ultimate effectiveness of intra-articular application of MSCs in terms of regenerative effects. Further radiological and histological data will be needed, with a larger pool of patients, before this question can be answered.

  17. Melts of Octaacetyl Sucrose as Oral-Modified Release Dosage Forms for Delivery of Poorly Soluble Compound in Stable Amorphous Form.

    PubMed

    Haznar-Garbacz, Dorota; Kaminska, Ewa; Zakowiecki, Daniel; Lachmann, Marek; Kaminski, Kamil; Garbacz, Grzegorz; Dorożyński, Przemysław; Kulinowski, Piotr

    2018-02-01

    The presented work describes the formulation and characterization of modified release glassy solid dosage forms (GSDFs) containing an amorphous nifedipine, as a model BCS (Biopharmaceutical Classification System) class II drug. The GSDFs were prepared by melting nifedipine together with octaacetyl sucrose. Dissolution profiles, measured under standard and biorelevant conditions, were compared to those obtained from commercially available formulations containing nifedipine such as modified release (MR) tablets and osmotic release oral system (OROS). The results indicate that the dissolution profiles of the GSDFs with nifedipine are neither affected by the pH of the dissolution media, type and concentration of surfactants, nor by simulated mechanical stress of biorelevant intensity. Furthermore, it was found that the dissolution profiles of the novel dosage forms were similar to the profiles obtained from the nifedipine OROS. The formulation of GSDFs is relatively simple, and the dosage forms were found to have favorable dissolution characteristics.

  18. Effects of injectable anticholinergic drugs on soman-induced lethality and convulsant/subconvulsant activity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Harris, L.W.; Anderson, D.R.; Lennox, W.J.

    1993-05-13

    FDA approved, injectable preparations of candidate compounds BENZTROPINE (BZT), 1.0 mg/ml; biperiden (BIP), 5.0 mg/ml; dicyclomine (DCL), 10 mg/ml; 1-hyoscyamine (HYO), 0.5 mg/ml; orphenadrine (ORP), 30 mg/ml; scopolamine (SCP), 1.0 mg/ml were tested in parallel with diazepam (DZ, the standard) in male guinea pigs against ongoing soman induced convulsive (CV)/sub-CV activity. Three trained graders concurrently assigned CV/sub-CV scores (12 - convulsions; 0 normal) to each animal. Animals received (im) pyridostigmine (PYR; 26 ug/kg) 30 min before soman (56 ug/kg; 2 LD50), atropine (2 mg/kg) admixed with 2-PAM (25 mg/kg) at one min after soman, and the candidate drug preparation atmore » 5.67 min post soman, a time when CV activity is assured. BIP and SCP demonstrated efficacy over dosage ranges between 10 and 0.3 and 1.0 and 0.13 mg/kg, respectively, while the other preparations were less effective at their respective maximum dosages. At optimal dosages of SCP (0.5 mg/kg) and BIP (10 mg/kg), the CV/sub-CV scores were significantly lower (p < 0.05) than those of DZ.« less

  19. The brain is a target organ after acute exposure to depleted uranium.

    PubMed

    Lestaevel, P; Houpert, P; Bussy, C; Dhieux, B; Gourmelon, P; Paquet, F

    2005-09-01

    The health effects of depleted uranium (DU) are mainly caused by its chemical toxicity. Although the kidneys are the main target organs for uranium toxicity, uranium can also reach the brain. In this paper, the central effects of acute exposure to DU were studied in relation to health parameters and the sleep-wake cycle of adult rats. Animals were injected intraperitoneally with 144+/-10 microg DU kg-1 as nitrate. Three days after injection, the amounts of uranium in the kidneys represented 2.6 microg of DU g-1 of tissue, considered as a sub-nephrotoxic dosage. The central effect of uranium could be seen through a decrease in food intake as early as the first day after exposure and shorter paradoxical sleep 3 days after acute DU exposure (-18% of controls). With a lower dosage of DU (70+/-8 microg DU kg-1), no significant effect was observed on the sleep-wake cycle. The present study intends to illustrate the fact that the brain is a target organ, as are the kidneys, after acute exposure to a moderate dosage of DU. The mechanisms by which uranium causes these early neurophysiological perturbations shall be discussed.

  20. Comparative effectiveness of botulinum toxin versus non-surgical treatments for treating lateral epicondylitis: a systematic review and meta-analysis.

    PubMed

    Lin, Yu-Ching; Wu, Wei-Ting; Hsu, Yu-Chun; Han, Der-Sheng; Chang, Ke-Vin

    2018-02-01

    To explore the effectiveness of botulinum toxin compared with non-surgical treatments in patients with lateral epicondylitis. Data sources including PubMed, Scopus, Embase and Airity Library from the earliest record to February 2017 were searched. Study design, patients' characteristics, dosage/brand of botulinum toxin, injection techniques, and measurements of pain and hand grip strength were retrieved. The standardized mean differences (SMDs) in pain relief and grip strength reduction were calculated at the following time points: 2-4, 8-12, and 16 weeks or more after injection. Six randomized controlled trials (321 participants) comparing botulinum toxin with placebo or corticosteroid injections were included. Compared with placebo, botulinum toxin injection significantly reduced pain at all three time points (SMD, -0.729, 95% confidence interval [CI], -1.286 to -0.171; SMD, -0.446, 95% CI, -0.740 to -0.152; SMD, -0.543, 95% CI, -0.978 to -0.107, respectively). Botulinum toxin was less effective than corticosteroid at 2-4 weeks (SMD, 1.153; 95% CI, 0.568-1.737) and both treatments appeared similar in efficacy after 8 weeks. Different injection sites and dosage/brand did not affect effectiveness. Botulinum toxin decreased grip strength 2-4 weeks after injection, and high equivalent dose could extend its paralytic effects to 8-12 weeks. When treating lateral epicondylitis, botulinum toxin was superior to placebo and could last for 16 weeks. Corticosteroid and botulinum toxin injections were largely equivalent, except the corticosteroid injections were better at pain relief in the early stages and were associated with less weakness in grip in the first 12 weeks.

  1. An overview of the cosmetic treatment of facial muscles with a new botulinum toxin.

    PubMed

    Wiest, Luitgard G

    2009-01-01

    Botulinum toxin (BTX) is used nowadays in a much more differentiated way with a much more individualized approach to the cosmetic treatment of patients. To the well known areas of the upper face new indications in the mid and lower face have been added. Microinjection techniques are increasingly used besides the classic intramuscular injection technique. BTX injections of the mid and lower face require small and smallest dosages. The perioral muscles act in concert to achieve the extraordinarily complex movements that control facial expressions, eating, and speech. As the mouth has horizontal as well as vertical movements, paralysis of these perioral muscles has a greater effect on facial function and appearance than does paralysis of muscles of the upper face, which move primarily in vertical direction. It is essential that BTX injections should achieve the desired cosmetic result with the minimum dose without any functional discomfort. In this paper the three-year clinical experience with average dosages for an optimal outcome in the treatment of facial muscles with a newly developed botulinum toxin type A (Xeomin) free from complexing proteins is presented.

  2. Priority Medicines for Maternal and Child Health: A Global Survey of National Essential Medicines Lists

    PubMed Central

    Hill, Suzanne; Yang, Annie; Bero, Lisa

    2012-01-01

    Background In April 2011, the World Health Organization (WHO) published a list of “priority medicines” for maternal and child health based on 1) the global burden of disease and 2) evidence of efficacy and safety. The objective of this study was to examine the occurrence of these priority medicines on national essential medicines lists. Methods and Findings All essential medicines lists published since 1999 were selected from the WHO website collection. The most-up-to date list for each country was then selected, resulting in 89 unique country lists. Each list was evaluated for inclusion of medicines (chemical entity, concentration, and dosage form) on the Priority Medicines List. There was global variation in the listing of the Priority Medicines. The most frequently listed medicine was paracetamol, on 94% (84/89) of lists. Sodium chloride, gentamicin and oral rehydration solution were on 93% (83/89) of lists. The least frequently listed medicine was the children's antimalarial rectal artesunate, on 8% of lists (7/89); artesunate injection was on 16% (14/89) of lists. Pediatric artemisinin combination therapy, as dispersible tablets or flexible oral solid dosage form, appeared on 36% (32/89) of lists. Procaine benzylpenicillin, for treatment of pediatric pneumonia and neonatal sepsis, was on 50% (45/89) of the lists. Zinc, for treatment of diarrhoea in children, was included on only 15% (13/89) of lists. For prevention and treatment of postpartum hemorrhage in women, oxytocin was more prevalent on the lists than misoprostol; they were included on 55 (62%) and 31 (35%) of lists, respectively. Cefixime, for treatment of uncomplicated anogenital gonococcal infection in woman was on 26% (23/89) of lists. Magnesium sulfate injection for treatment of severe pre-eclampsia and eclampsia was on 50% (45/89) of the lists. Conclusions The findings suggest that countries need to urgently amend their lists to provide all priority medicines as part of the efforts to improve maternal and child health. PMID:22675435

  3. METCAM/MUC18 promoted tumorigenesis of human breast cancer SK-BR-3 cells in a dosage-specific manner.

    PubMed

    Huang, Chang-Yu; Wu, Guang-Jer

    2016-04-01

    Overexpression of METCAM/MUC18, an immunoglobulin-like cell-adhesion molecule, promotes tumorigenesis and progression of human breast cancer cells. We also observed an intriguing phenomenon that a high-expressing SK-BR-3 clone manifested a transient tumor suppression effect in vivo. The purpose of this study was to understand if this was caused by clonal variation, METCAM/MUC18-dosage effect, or the number of cells injected. Several G418-resistant clones of SK-BR-3, expressing different levels of METCAM/MUC18, were obtained for testing effects of human METCAM/MUC18 on in vitro motility, invasiveness, and anchorage-independent colony formation (in vitro tumorigenicity) and in vivo tumorigenesis in female Balb/C athymic nude mice. Tumor sections were made for histology and immunohistochemistry analyses, and tumor lysates for Western blot analysis to determine the effects of human METCAM/MUC18 expression on levels of various downstream effectors. METCAM/MUC18 promoted in vitro motility, invasiveness, and in vitro tumorigenicity of SK-BR-3 cells in a dosage-specific manner. Overexpression of METCAM/MUC18 could promote in vivo tumorigenesis of SK-BR-3 cells even when one tenth of the previously used cell number (5 × 10(5)) was injected and in vivo tumorigenesis of SK-BR-3 cells was directly proportional to the dosage of the protein. The previously observed transient tumor suppression effect from the same clone was no longer observed. The downstream effector, such as phospho-AKT/AKT ratio, was elevated in the tumors. Transient suppression observed previously in the clone was caused by injection of a high cell number (2 × 10(6)-5 × 10(6)). METCAM/MUC18 positively promotes tumorigenesis of SK-BR-3 cells by increasing the survival and proliferation pathway. Copyright © 2016. Published by Elsevier B.V.

  4. Specific aspects of gastro-intestinal transit in children for drug delivery design.

    PubMed

    Bowles, Alexandra; Keane, Joanne; Ernest, Terry; Clapham, David; Tuleu, Catherine

    2010-08-16

    This mini-review discusses relevant aspects of gastro-intestinal transit in different ages of paediatric patients with an attempt to highlight factors which should be considered in oral dosage form design, in particular multi-particulate dosage forms. This emphasis is due to multi-particulates possessing many of the benefits of liquid oral formulations (such as ease of swallowing and dose adaptability) without many of their drawbacks (such as stability issues and lack of enteric or modified release functionalities). It is commonly stated that children are not merely small adults with regards to medicines. However, there has been very little research regarding how different dosage forms transit through the gastro-intestinal tract in children compared to adults, due to both ethical and practical hurdles. Due to this lack of studies on dosage form transit in children, information which was available on the transit of food, milk and liquids (often dependent upon the age of the patient) has been used to look at how various aspects of transit vary with age and, where possible, when they reach adult values and how these may affect the fate of dosage forms in vivo: swallowability, oesophageal transit, gastric emptying and pH, intestinal and colonic transit are discussed. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  5. 3D printing of high drug loaded dosage forms using thermoplastic polyurethanes.

    PubMed

    Verstraete, G; Samaro, A; Grymonpré, W; Vanhoorne, V; Van Snick, B; Boone, M N; Hellemans, T; Van Hoorebeke, L; Remon, J P; Vervaet, C

    2018-01-30

    It was the aim of this study to develop high drug loaded (>30%, w/w), thermoplastic polyurethane (TPU)-based dosage forms via fused deposition modelling (FDM). Model drugs with different particle size and aqueous solubility were pre-processed in combination with diverse TPU grades via hot melt extrusion (HME) into filaments with a diameter of 1.75 ± 0.05 mm. Subsequently, TPU-based filaments which featured acceptable quality attributes (i.e. consistent filament diameter, smooth surface morphology and good mechanical properties) were printed into tablets. The sustained release potential of the 3D printed dosage forms was tested in vitro. Moreover, the impact of printing parameters on the in vitro drug release was investigated. TPU-based filaments could be loaded with 60% (w/w) fine drug powder without observing severe shark skinning or inconsistent filament diameter. During 3D printing experiments, HME filaments based on hard TPU grades were successfully converted into personalized dosage forms containing a high concentration of crystalline drug (up to 60%, w/w). In vitro release kinetics were mainly affected by the matrix composition and tablet infill degree. Therefore, this study clearly demonstrated that TPU-based FDM feedstock material offers a lot of formulation freedom for the development of personalized dosage forms. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Dropwise additive manufacturing of pharmaceutical products for solvent-based dosage forms.

    PubMed

    Hirshfield, Laura; Giridhar, Arun; Taylor, Lynne S; Harris, Michael T; Reklaitis, Gintaras V

    2014-02-01

    In recent years, the US Food and Drug Administration has encouraged pharmaceutical companies to develop more innovative and efficient manufacturing methods with improved online monitoring and control. Mini-manufacturing of medicine is one such method enabling the creation of individualized product forms for each patient. This work presents dropwise additive manufacturing of pharmaceutical products (DAMPP), an automated, controlled mini-manufacturing method that deposits active pharmaceutical ingredients (APIs) directly onto edible substrates using drop-on-demand (DoD) inkjet printing technology. The use of DoD technology allows for precise control over the material properties, drug solid state form, drop size, and drop dynamics and can be beneficial in the creation of high-potency drug forms, combination drugs with multiple APIs or individualized medicine products tailored to a specific patient. In this work, DAMPP was used to create dosage forms from solvent-based formulations consisting of API, polymer, and solvent carrier. The forms were then analyzed to determine the reproducibility of creating an on-target dosage form, the morphology of the API of the final form and the dissolution behavior of the drug over time. DAMPP is found to be a viable alternative to traditional mass-manufacturing methods for solvent-based oral dosage forms. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  7. Tilmicosin as a single injection treatment for respiratory disease of feedlot cattle

    PubMed Central

    Gorham, Paul E.; Carroll, Lamar H.; McAskill, Jack W.; Watkins, Lee E.; Ose, Earl E.; Tonkinson, Lealon V.; Merrill, John K.

    1990-01-01

    Tilmicosin, a new semi-synthetic macrolide antibiotic, was evaluated in eight field trials as a single subcutaneous injection at dosages of 0 (placebo), 5, 10 and 20 mg/kg for the treatment of naturally occurring respiratory disease in feedlot cattle. Animals for these trials were selected from large groups of recently-shipped feeder cattle at the time clinical signs of respiratory disease and body temperature of 40.6°C or higher were observed. Treated animals were evaluated daily for 10 days and finally at day 28. Each animal was weighed on the first day and again on day 28. Animals that died were necropsied. All treatment dosages were effective in significantly lowering mortality, improving weight gains, lowering body temperature, and reducing the severity of clinical signs when compared to the placebo-treated controls. Body temperature was the only variable with statistically significant differences among the dose levels. PMID:17423706

  8. Current opinions and recommendations of paediatric healthcare professionals – The importance of tablets: Emerging orally disintegrating versus traditional tablets

    PubMed Central

    Alyami, Hamad; Koner, Jasdip; Terry, David; Mohammed, Afzal R.

    2018-01-01

    The appropriate prescribing of paediatric dosage forms is paramount in providing the desired therapeutic effect alongside successful medication adherence with the paediatric population. Often it is the opinion of the healthcare practitioner that dictates which type of dosage form would be most appropriate for the paediatric patient, with liquids being both the most commonly available and most commonly used. Orally disintegrating tablets (ODTs) are an emerging dosage form which provide many benefits over traditional dosage forms for paediatric patients, such as rapid disintegration within the oral cavity, and the reduction in the risk of choking. However the opinion and professional use of healthcare practitioners regarding ODT’s is not known. This study was designed to assess the opinions of several types of healthcare professionals (n = 41) regarding ODTs, using a survey across two hospital sites. Results reaffirmed the popularity of liquids for prescribing in paediatrics, with 58.0% of participants preferring this dosage form. ODTs emerged as the second most popular dosage form (30.0%), with healthcare practitioners indicating an increasing popularity amongst patients in the hospital setting, belief with 63.0% of practitioners agreeing that many liquid formulations could be substituted with a suitable ODT. The desired properties of an ideal ODT were also identified by healthcare practitioners preferring a small, fast disintegrating tablet (90.2% and 95.1% respectively), with the taste, disintegration time and flavour being the three most important attributes identified (29.5%, 28.7% and 21.7% respectively). This study provided a pragmatic approach in assessing healthcare professional’s opinions on ODTs, highlighting the ideas and thoughts of practitioners who are on the frontline of paediatric prescribing and treatment and gave an indication to their preference for ODT properties. PMID:29489871

  9. Biowaiver monograph for immediate-release solid oral dosage forms: fluconazole.

    PubMed

    Charoo, Naseem; Cristofoletti, Rodrigo; Graham, Alexandra; Lartey, Paul; Abrahamsson, Bertil; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

    2014-12-01

    Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence (BE) testing requirements for the approval of immediate release (IR) solid oral dosage forms containing fluconazole as the only active pharmaceutical ingredient (API) are reviewed. The decision is based on solubility, dissolution, permeability, therapeutic index, pharmacokinetic parameters, pharmacodynamic properties, and other relevant data. BE/bioavailability (BA) problems and drug-excipients interaction data were also reviewed and taken into consideration. According to the biopharmaceutics classification system (BCS), fluconazole in polymorphic forms II and III is a BCS class I drug and has a wide therapeutic index. BE of test formulations from many different manufacturers containing different excipients confirmed that the risk of bioinequivalence because of formulation and manufacturing factors is low. It was inferred that risk can be further reduced if in vitro studies are performed according to biowaiver guidelines. Thus, it is concluded that a biowaiver can be recommended for fluconazole IR dosage forms if (a) fluconazole is present as polymorphic form II or III or any other form/mixture showing high solubility, (b) the selection of excipients be limited to those found in IR drug products approved in International Conference on Harmonisation (ICH) countries for the same dosage form and used in their usual amounts, and (c) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving throughout the shelf life with similar dissolution profiles at pH 1.2, 4.5, and 6.8. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  10. 21 CFR 206.3 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL IMPRINTING OF SOLID ORAL DOSAGE FORM DRUG PRODUCTS FOR HUMAN USE § 206.3 Definitions. The following... 600.3(t) of this chapter. Solid oral dosage form means capsules, tablets, or similar drug products...

  11. 21 CFR 206.3 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL IMPRINTING OF SOLID ORAL DOSAGE FORM DRUG PRODUCTS FOR HUMAN USE § 206.3 Definitions. The following... 600.3(t) of this chapter. Solid oral dosage form means capsules, tablets, or similar drug products...

  12. 21 CFR 206.3 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL IMPRINTING OF SOLID ORAL DOSAGE FORM DRUG PRODUCTS FOR HUMAN USE § 206.3 Definitions. The following... 600.3(t) of this chapter. Solid oral dosage form means capsules, tablets, or similar drug products...

  13. A report from the pediatric formulations task force: perspectives on the state of child-friendly oral dosage forms.

    PubMed

    Zajicek, Anne; Fossler, Michael J; Barrett, Jeffrey S; Worthington, Jeffrey H; Ternik, Robert; Charkoftaki, Georgia; Lum, Susan; Breitkreutz, Jörg; Baltezor, Mike; Macheras, Panos; Khan, Mansoor; Agharkar, Shreeram; MacLaren, David Douglas

    2013-10-01

    Despite the fact that a significant percentage of the population is unable to swallow tablets and capsules, these dosage forms continue to be the default standard. These oral formulations fail many patients, especially children, because of large tablet or capsule size, poor palatability, and lack of correct dosage strength. The clinical result is often lack of adherence and therapeutic failure. The American Association of Pharmaceutical Scientists formed a Pediatric Formulations Task Force, consisting of members with various areas of expertise including pediatrics, formulation development, clinical pharmacology, and regulatory science, in order to identify pediatric, manufacturing, and regulatory issues and areas of needed research and regulatory guidance. Dosage form and palatability standards for all pediatric ages, relative bioavailability requirements, and small batch manufacturing capabilities and creation of a viable economic model were identified as particular needs. This assessment is considered an important first step for a task force seeking creative approaches to providing more appropriate oral formulations for children.

  14. The influence of averaging procedure on the accuracy of IVIVC predictions: immediate release dosage form case study.

    PubMed

    Ostrowski, Michalł; Wilkowska, Ewa; Baczek, Tomasz

    2010-12-01

    In vivo-in vitro correlation (IVIVC) is an effective tool to predict absorption behavior of active substances from pharmaceutical dosage forms. The model for immediate release dosage form containing amoxicillin was used in the presented study to check if the calculation method of absorption profiles can influence final results achieved. The comparison showed that an averaging of individual absorption profiles performed by Wagner-Nelson (WN) conversion method can lead to lose the discrimination properties of the model. The approach considering individual plasma concentration versus time profiles enabled to average absorption profiles prior WN conversion. In turn, that enabled to find differences between dispersible tablets and capsules. It was concluded that in the case of immediate release dosage form, the decision to use averaging method should be based on an individual situation; however, it seems that the influence of such a procedure on the discrimination properties of the model is then more significant. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

  15. Topical cream-based dosage forms of the macrocyclic drug delivery vehicle cucurbit[6]uril.

    PubMed

    Seif, Marian; Impelido, Michael L; Apps, Michael G; Wheate, Nial J

    2014-01-01

    The macrocycle family of molecules called cucurbit[n]urils are potential drug delivery vehicles as they are able to form host-guest complexes with many different classes of drugs. This study aimed to examine the utility of Cucurbit[6]uril (CB[6]) in topical cream-based formulations for either localised treatment or for transdermal delivery. Cucurbit[6]uril was formulated into both buffered cream aqueous- and oily cream-based dosage forms. The solid state interaction of CB[6] with other excipients was studied by differential scanning calorimetry and the macrocycle's transdermal permeability was determined using rat skin. Significant solid state interactions were observed between CB[6] and the other dosage form excipients. At concentrations up to 32% w/w the buffered aqueous cream maintained its normal consistency and could be effectively applied to skin, but the oily cream was too stiff and is not suitable as a dosage form. Cucurbit[6]uril does not permeate through skin; as such, the results imply that cucurbituril-based topical creams may potentially only have applications for localised skin treatment and not for transdermal drug delivery.

  16. Development and in vitro evaluation of expandable gastroretentive dosage forms based on compressed collagen sponges.

    PubMed

    Gröning, R; Cloer, C; Müller, R S

    2006-07-01

    The objective of this study was to develop and evaluate new collagen gastroretentive dosage forms (GRDFs) which expand in the stomach after contact with gastric fluids. The GRDFs should remain in the stomach for a prolonged period of time due to their size. The dosage forms were prepared from collagen sponges. The sponges were manufactured by freeze-drying a riboflavin-containing collagen solution. A computer controlled material supply was constructed to transport precompressed collagen into a tablet machine. A second type of tablet was manufactured by combining compressed collagen sponges with hydrophilic matrix layers of hydroxypropylmethylcellulose. Matrix layers containing captopril or aciclovir were developed. In vitro experiments were performed with both types of dosage forms. The collagen tablets expand within a few minutes after contact with artificial gastric juice and form a drug delivery system with a size of 8 mm x 18 mm x 60 mm. Riboflavin is released over 16 h. If two layer tablets are used, the release of aciclovir or captopril can be controlled by the composition of the sustained release layer.

  17. Topical Cream-Based Dosage Forms of the Macrocyclic Drug Delivery Vehicle Cucurbit[6]uril

    PubMed Central

    Seif, Marian; Impelido, Michael L.; Apps, Michael G.; Wheate, Nial J.

    2014-01-01

    The macrocycle family of molecules called cucurbit[n]urils are potential drug delivery vehicles as they are able to form host-guest complexes with many different classes of drugs. This study aimed to examine the utility of Cucurbit[6]uril (CB[6]) in topical cream-based formulations for either localised treatment or for transdermal delivery. Cucurbit[6]uril was formulated into both buffered cream aqueous- and oily cream-based dosage forms. The solid state interaction of CB[6] with other excipients was studied by differential scanning calorimetry and the macrocycle's transdermal permeability was determined using rat skin. Significant solid state interactions were observed between CB[6] and the other dosage form excipients. At concentrations up to 32% w/w the buffered aqueous cream maintained its normal consistency and could be effectively applied to skin, but the oily cream was too stiff and is not suitable as a dosage form. Cucurbit[6]uril does not permeate through skin; as such, the results imply that cucurbituril-based topical creams may potentially only have applications for localised skin treatment and not for transdermal drug delivery. PMID:24454850

  18. Analgesic opioid dose is an important indicator of postoperative ileus following radical cystectomy with ileal conduit: experience in the robotic surgery era.

    PubMed

    Koo, Kyo Chul; Yoon, Young Eun; Chung, Byung Ha; Hong, Sung Joon; Rha, Koon Ho

    2014-09-01

    Postoperative ileus (POI) is common following bowel resection for radical cystectomy with ileal conduit (RCIC). We investigated perioperative factors associated with prolonged POI following RCIC, with specific focus on opioid-based analgesic dosage. From March 2007 to January 2013, 78 open RCICs and 26 robot-assisted RCICs performed for bladder carcinoma were identified with adjustment for age, gender, American Society of Anesthesiologists grade, and body mass index (BMI). Perioperative records including operative time, intraoperative fluid excess, estimated blood loss, lymph node yield, and opioid analgesic dose were obtained to assess their associations with time to passage of flatus, tolerable oral diet, and length of hospital stay (LOS). Prior to general anaesthesia, patients received epidural patient-controlled analgesia (PCA) consisted of fentanyl with its dose adjusted for BMI. Postoperatively, single intravenous injections of tramadol were applied according to patient desire. Multivariate analyses revealed cumulative dosages of both PCA fentanyl and tramadol injections as independent predictors of POI. According to surgical modality, linear regression analyses revealed cumulative dosages of PCA fentanyl and tramadol injections to be positively associated with time to first passage of flatus, tolerable diet, and LOS in the open RCIC group. In the robot-assisted RCIC group, only tramadol dose was associated with time to flatus and tolerable diet. Compared to open RCIC, robot-assisted RCIC yielded shorter days to diet and LOS; however, it failed to shorten days to first flatus. Reducing opioid-based analgesics shortens the duration of POI. The utilization of the robotic system may confer additional benefit.

  19. Analysis of molecular interactions in solid dosage forms; challenge to molecular pharmaceutics.

    PubMed

    Yamamoto, Keiji; Limwikrant, Waree; Moribe, Kunikazu

    2011-01-01

    The molecular states of active pharmaceutical ingredients (APIs) in pharmaceutical dosage forms strongly affect the properties and quality of a drug. Various important fundamental physicochemical studies were reviewed from the standpoint of molecular pharmaceutics. Mechanochemical effects were evaluated in mixtures of APIs and pharmaceutical additives. Amorphization, complex formation and nanoparticle formation are observed after grinding process depending on the combination of APIs and pharmaceutical additives. Sealed-heating method and mesoporous materials have been used to investigate drug molecular interactions in dosage forms. Molecular states have been investigated using powder X-ray diffraction, thermal analysis, IR, solid state fluorometry, and NMR. © 2011 Pharmaceutical Society of Japan

  20. 21 CFR 500.65 - Epinephrine injection 1:1,000 in 10-milliliter containers for emergency treatment of...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... symptoms of anaphylactoid shock including glassy eyes, increased salivation, grinding of the teeth, rapid... treating anaphylactoid shock. Usual Dosage: Cattle, horses, sheep, and swine—1 cubic centimeter per 100...

  1. 21 CFR 500.65 - Epinephrine injection 1:1,000 in 10-milliliter containers for emergency treatment of...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... symptoms of anaphylactoid shock including glassy eyes, increased salivation, grinding of the teeth, rapid... treating anaphylactoid shock. Usual Dosage: Cattle, horses, sheep, and swine—1 cubic centimeter per 100...

  2. 75 FR 21162 - Certain Other Dosage Form New Animal Drugs; Detomidine

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-23

    .... FDA-2010-N-0002] Certain Other Dosage Form New Animal Drugs; Detomidine AGENCY: Food and Drug... NADA provides for veterinary prescription use of detomidine hydrochloride oromucosal gel for sedation... prescription use of DORMOSEDAN GEL (detomidine hydrochloride) for sedation and restraint of horses. The...

  3. The knowledge, attitudes and beliefs of patients and their healthcare professionals around oral dosage form modification: A systematic review of the qualitative literature.

    PubMed

    Mc Gillicuddy, Aoife; Kelly, Maria; Crean, Abina M; Sahm, Laura J

    The objective of this systematic review was to synthesize the available qualitative evidence on the knowledge, attitudes and beliefs of adult patients, healthcare professionals and carers about oral dosage form modification. A systematic review and synthesis of qualitative studies was undertaken, utilising the thematic synthesis approach. The following databases were searched from inception to September 2015: PubMed, Medline (EBSCO), EMBASE, CINAHL, PsycINFO, Web of Science, ProQuest Databases, Scopus, Turning Research Into Practice (TRIP), Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews (CDSR). Citation tracking and searching the references lists of included studies was also undertaken. Grey literature was searched using the OpenGrey database, internet searching and personal knowledge. An updated search was undertaken in June 2016. Studies meeting the following criteria were eligible for inclusion; (i) used qualitative data collection and analysis methods; (ii) full-text was available in English; (iii) included adult patients who require oral dosage forms to be modified to meet their needs or; (iv) carers or healthcare professionals of patients who require oral dosage forms to be modified. Two reviewers independently appraised the quality of the included studies using the Critical Appraisal Skills Programme Checklist. A thematic synthesis was conducted and analytical themes were generated. Of 5455 records screened, seven studies were eligible for inclusion; three involved healthcare professionals and the remaining four studies involved patients. Four analytical themes emerged from the thematic synthesis: (i) patient-centred individuality and variability; (ii) communication; (iii) knowledge and uncertainty and; (iv) complexity. The variability of individual patient's requirements, poor communication practices and lack of knowledge about oral dosage form modification, when combined with the complex and multi-faceted healthcare environment complicate decision making regarding oral dosage form modification and administration. This systematic review has highlighted the key factors influencing the knowledge, attitudes and beliefs of patients and healthcare professionals about oral dosage form modifications. The findings suggest that in order to optimise oral medicine modification practices the needs of individual patients should be routinely and systematically assessed and decision-making should be supported by evidence based recommendations with multidisciplinary input. Further research is needed to optimise oral dosage form modification practices and the factors identified in this review should be considered in the development of future interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Correlation of ibuprofen bioavailability with gastrointestinal transit by scintigraphic monitoring of /sup 171/Er-labeled sustained-release tablets

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Parr, A.F.; Beihn, R.M.; Franz, R.M.

    1987-12-01

    External gamma scintigraphy was used to monitor the gastrointestinal (GI) transit of radiolabeled sustained-release tablets containing 800 mg ibuprofen in eight fasted healthy volunteers. Ibuprofen serum concentrations were determined from blood samples drawn sequentially over a 24-hr period. Serum concentrations and related parameters were correlated to the position of the dosage form in the GI tract from the scintiphotos. The sustained-release tablets were radiolabeled intact utilizing a neutron activation procedure, by incorporating 0.18% of /sup 170/Er2O3 (enriched to greater than 96% /sup 170/Er) into the bulk formulation. After manufacture of the final dosage forms, the tablets were irradiated in amore » neutron flux (4.4 x 10(13) n/cm2.sec) for 2 min, converting the stable /sup 170/Er to radioactive /sup 171/Er (t1/2 = 7.5 hr). Each tablet contained 50 microCi of /sup 171/Er at the time of administration. The scintigraphy studies suggested that the greatest proportion of ibuprofen was absorbed from this dosage form while the tablet was in the large bowel. The dosage forms eroded slowly in the small bowel and appeared to lose their integrity in the large bowel. In vitro studies showed only minimal effects of the neutron irradiation procedure on the dosage form performance.« less

  5. Evolution of a detailed physiological model to simulate the gastrointestinal transit and absorption process in humans, part II: extension to describe performance of solid dosage forms.

    PubMed

    Thelen, Kirstin; Coboeken, Katrin; Willmann, Stefan; Dressman, Jennifer B; Lippert, Jörg

    2012-03-01

    The physiological absorption model presented in part I of this work is now extended to account for dosage-form-dependent gastrointestinal (GI) transit as well as disintegration and dissolution processes of various immediate-release and modified-release dosage forms. Empirical functions of the Weibull type were fitted to experimental in vitro dissolution profiles of solid dosage forms for eight test compounds (aciclovir, caffeine, cimetidine, diclofenac, furosemide, paracetamol, phenobarbital, and theophylline). The Weibull functions were then implemented into the model to predict mean plasma concentration-time profiles of the various dosage forms. On the basis of these dissolution functions, pharmacokinetics (PK) of six model drugs was predicted well. In the case of diclofenac, deviations between predicted and observed plasma concentrations were attributable to the large variability in gastric emptying time of the enteric-coated tablets. Likewise, oral PK of furosemide was found to be predominantly governed by the gastric emptying patterns. It is concluded that the revised model for GI transit and absorption was successfully integrated with dissolution functions of the Weibull type, enabling prediction of in vivo PK profiles from in vitro dissolution data. It facilitates a comparative analysis of the parameters contributing to oral drug absorption and is thus a powerful tool for formulation design. Copyright © 2011 Wiley Periodicals, Inc.

  6. [Pharmaceutical counseling of non-conventional dosage forms concerning the health-literacy and the patient adherence in public medication dispensing -Questionnaire surveys in Hungarian community pharmacies.

    PubMed

    Somogyi, O; Zelko, R

    Although the non-conventional dosage forms (e.g. modified release per oral systems or transdermal patches) have more significant advantages than other conventional dosage forms, the pa- tients have to apply them correctly in their home medicine using to reach the effective and safe therapy. A guideline of relevant application instructions contribute to development of an effective pharmaceutical counseling in community pharmacies. The counseling and advices can improve the patients' knowledge concerning application rules of different new dosage forms (health- literacy) with patient adherence. Finally it will result more effective and safer therapies. The aim of our Hungarian questionnaire surveys was to explore the patients' drug application habits or application errors and improve special verbal counseling of mentioned non-conventional dosage forms in community pharmacies. Understandable patient information leaflets were developed about application rules and besides the levels of patients' reading comprehension was evaluated in case of the leaflet of medicinal patches. The results show that a properly developed text is useful for the majority of patients but they need the verbal explanation as well, moreover there is a demand for the verbal counseling in community pharmacies. The most common application errors were explored and the most effective instructions or application rules were collected for the pharmacists and patients concerning the modified release tablets or capsules and transdermal patches.

  7. Age-appropriate and acceptable paediatric dosage forms: Insights into end-user perceptions, preferences and practices from the Children's Acceptability of Oral Formulations (CALF) Study.

    PubMed

    Ranmal, Sejal R; Cram, Anne; Tuleu, Catherine

    2016-11-30

    A lack of evidence to guide the design of age-appropriate and acceptable dosage forms has been a longstanding knowledge gap in paediatric formulation development. The Children's Acceptability of Oral Formulations (CALF) study captured end-user perceptions and practices with a focus on solid oral dosage forms, namely tablets, capsules, chewables, orodispersibles, multiparticulates (administered with food) and mini-tablets (administered directly into the mouth). A rigorous development and testing phase produced age-adapted questionnaires as measurement tools with strong evidence of validity and reliability. Overall, 590 school children and adolescents, and 428 adult caregivers were surveyed across hospitals and various community settings. Attitudes towards dosage forms primarily differed based on age and prior use. Positive attitudes to tablets and capsules increased with age until around 14 years. Preference was seen for chewable and orodispersible preparations across ages, while multiparticulates were seemingly less favourable. Overall, 59.6% of school children reported willingness to take 10mm diameter tablets, although only 32.1% of caregivers perceived this size to be suitable. While not to be taken as prescriptive guidance, the results of this study provide some evidence towards rational dosage form design, as well as methodological approaches to help design tools for further evaluation of acceptability within paediatric studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Biowaiver monograph for immediate-release solid oral dosage forms: bisoprolol fumarate.

    PubMed

    Charoo, Naseem A; Shamsher, Areeg A A; Lian, Lai Y; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

    2014-02-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing bisoprolol as the sole active pharmaceutical ingredient (API) are reviewed. Bisoprolol is classified as a Class I API according to the current Biopharmaceutics Classification System (BCS). In addition to the BCS class, its therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability problems are taken into consideration. Qualitative compositions of IR tablet dosage forms of bisoprolol with a marketing authorization (MA) in ICH (International Conference on Harmonisation) countries are tabulated. It was inferred that these tablets had been demonstrated to be bioequivalent to the innovator product. No reports of failure to meet BE standards have been made in the open literature. On the basis of all these pieces of evidence, a biowaiver can currently be recommended for bisoprolol fumarate IR dosage forms if (1) the test product contains only excipients that are well known, and used in normal amounts, for example, those tabulated for products with MA in ICH countries and (2) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving with similarity of the dissolution profiles demonstrated at pH 1.2, 4.5, and 6.8. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  9. Issues impacting therapeutic outcomes in pediatric patients: an overview.

    PubMed

    Kalra, Atin; Goindi, Shishu

    2014-01-01

    The quest for achieving optimal therapeutic outcomes in pediatric patients has evaded the healthcare professionals for long and often lack of child specific dosage forms and the associated events that follow with it have been considered to be major contributor towards suboptimal outcomes. Consequently, there have been sustained efforts over the years to address this issue with the enactment of legislations like Best Pharmaceutical for Children Act (BPCA), Pediatric Research Equity Act (PREA) and Pediatric Regulation by European Union (EU) to incentivise the participation of pharmaceutical industry towards development of child friendly dosage forms. Initiatives taken in past by organisations like World Health Organisation (WHO) and Drugs for Neglected Diseases Initiative (DNDi) to spur the development of child friendly dosage forms has helped to address issues pertaining to management of Human Immunodeficiency Virus (HIV) and malaria in pediatric patients. Present efforts aimed at developing child friendly dosage forms include oro-dispersible platforms including thin films and mini-tablets. Despite these leaps and advancements in developing better dosage forms for children, lower therapeutic outcomes in pediatric patients continue to remain an unresolved issue because of detrimental effects of additional factors such as parents understanding of label instructions and complexities involved in executing pediatric clinical studies thus requiring a concerted effort from pharmaceutical companies, academic researchers, parents and healthcare providers to work for better treatment outcomes in children.

  10. Analytical Method Development and Validation for the Simultaneous Estimation of Abacavir and Lamivudine by Reversed-phase High-performance Liquid Chromatography in Bulk and Tablet Dosage Forms.

    PubMed

    Raees Ahmad, Sufiyan Ahmad; Patil, Lalit; Mohammed Usman, Mohammed Rageeb; Imran, Mohammad; Akhtar, Rashid

    2018-01-01

    A simple rapid, accurate, precise, and reproducible validated reverse phase high performance liquid chromatography (HPLC) method was developed for the determination of Abacavir (ABAC) and Lamivudine (LAMI) in bulk and tablet dosage forms. The quantification was carried out using Symmetry Premsil C18 (250 mm × 4.6 mm, 5 μm) column run in isocratic way using mobile phase comprising methanol: water (0.05% orthophosphoric acid with pH 3) 83:17 v/v and a detection wavelength of 245 nm and injection volume of 20 μl, with a flow rate of 1 ml/min. In the developed method, the retention times of ABAC and LAMI were found to be 3.5 min and 7.4 min, respectively. The method was validated in terms of linearity, precision, accuracy, limits of detection, limits of quantitation, and robustness in accordance with the International Conference on Harmonization guidelines. The assay of the proposed method was found to be 99% - 101%. The recovery studies were also carried out and mean % recovery was found to be 99% - 101%. The % relative standard deviation from reproducibility was found to be <2%. The proposed method was statistically evaluated and can be applied for routine quality control analysis of ABAC and LAMI in bulk and in tablet dosage form. Attempts were made to develop RP-HPLC method for simultaneous estimation of Abacavir and Lamivudine for the RP-HPLC method. The developed method was validated according to the ICH guidelines. The linearity, precision, range, robustness were within the limits as specified by the ICH guidelines. Hence the method was found to be simple, accurate, precise, economic and reproducible. So the proposed methods can be used for the routine quality control analysis of Abacavir and Lamivudine in bulk drug as well as in formulations. Abbreviations Used: HPLC: High-performance liquid chromatography, UV: Ultraviolet, ICH: International Conference on Harmonization, ABAC: Abacavir, LAMI: Lamivudine, HIV: Human immunodeficiency virus, AIDS: Acquired immunodeficiency syndrome, NRTI: Nucleoside reverse transcriptase inhibitors, ARV: Antiretroviral, RSD: Relative standard deviation, RT: Retention time, SD: Standard deviation.

  11. 76 FR 40808 - Oral Dosage Form New Animal Drugs; Amprolium

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-12

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Amprolium AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  12. 77 FR 15961 - Oral Dosage Form New Animal Drugs; Phenylpropanolamine

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Phenylpropanolamine AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal...

  13. 76 FR 59023 - Oral Dosage Form New Animal Drugs; Tylosin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-23

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Tylosin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  14. 75 FR 67031 - Oral Dosage Form New Animal Drugs; Domperidone

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Domperidone AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  15. 77 FR 3927 - Oral Dosage Form New Animal Drugs; Deracoxib

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-26

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Deracoxib AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  16. 77 FR 15960 - Oral Dosage Form New Animal Drugs; Pergolide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Pergolide AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  17. 76 FR 18648 - Oral Dosage Form New Animal Drugs; Robenacoxib

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Robenacoxib AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  18. 76 FR 78149 - Oral Dosage Form New Animal Drugs; Estriol

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Estriol AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  19. 21 CFR 206.10 - Code imprint required.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL IMPRINTING OF SOLID ORAL DOSAGE FORM DRUG PRODUCTS FOR HUMAN USE § 206.10 Code imprint required. (a) Unless exempted under § 206.7, no drug product in solid oral dosage form may be introduced or...

  20. 21 CFR 206.10 - Code imprint required.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL IMPRINTING OF SOLID ORAL DOSAGE FORM DRUG PRODUCTS FOR HUMAN USE § 206.10 Code imprint required. (a) Unless exempted under § 206.7, no drug product in solid oral dosage form may be introduced or...

  1. 21 CFR 206.10 - Code imprint required.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL IMPRINTING OF SOLID ORAL DOSAGE FORM DRUG PRODUCTS FOR HUMAN USE § 206.10 Code imprint required. (a) Unless exempted under § 206.7, no drug product in solid oral dosage form may be introduced or...

  2. 76 FR 38554 - Oral Dosage Form New Animal Drugs; Amprolium

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-01

    .... FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Amprolium AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original abbreviated new animal drug application (ANADA) filed by Cross...

  3. 77 FR 4226 - Oral Dosage Form New Animal Drugs; Gentamicin Sulfate

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-27

    .... FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Gentamicin Sulfate AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original abbreviated new animal drug application (ANADA...

  4. 75 FR 76259 - Oral Dosage Form New Animal Drugs; Tylosin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-08

    .... FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Tylosin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original abbreviated new animal drug application (ANADA) filed by...

  5. 75 FR 54492 - Oral Dosage Form New Animal Drugs; Tiamulin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-08

    .... FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Tiamulin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a supplemental new animal drug application (NADA) filed by Novartis Animal...

  6. 76 FR 16533 - Certain Other Dosage Form New Animal Drugs; Detomidine; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-24

    .... FDA-2010-N-0002] Certain Other Dosage Form New Animal Drugs; Detomidine; Correction AGENCY: Food and... paragraph describing limitations to the approved conditions of use for detomidine hydrochloride oromucosal... conditions of use for detomidine hydrochloride oromucosal gel in horses. This correction is being made to...

  7. 76 FR 72619 - Ophthalmic and Topical Dosage Form New Animal Drugs; Eprinomectin

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-25

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 524 [Docket No. FDA-2011-N-0003] Ophthalmic and Topical Dosage Form New Animal Drugs; Eprinomectin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule; technical amendment. SUMMARY: The Food and Drug...

  8. Efficacy of 2-Hydroxypropyl-β-cyclodextrin in Niemann-Pick Disease Type C Model Mice and Its Pharmacokinetic Analysis in a Patient with the Disease.

    PubMed

    Tanaka, Yuta; Yamada, Yusei; Ishitsuka, Yoichi; Matsuo, Muneaki; Shiraishi, Koki; Wada, Koki; Uchio, Yushiro; Kondo, Yuki; Takeo, Toru; Nakagata, Naomi; Higashi, Taishi; Motoyama, Keiichi; Arima, Hidetoshi; Mochinaga, Sakiko; Higaki, Katsumi; Ohno, Kousaku; Irie, Tetsumi

    2015-01-01

    Niemann-Pick type C disease (NPC), an autosomal recessive lysosomal storage disorder, is an inherited disease characterized by the accumulation of intracellular unesterified cholesterol. A solubilizing agent of lipophilic compounds, 2-hydroxypropyl-β-cyclodextrin (HPBCD), is an attractive drug candidate against NPC disease. However, establishment of the optimum dosage of HPBCD remains to be determined. In this study, we evaluated the effective dosage of HPBCD in NPC model (Npc1(-/-)) mice, and determined serum HPBCD concentrations. Subcutaneous injection of 1000-4000 mg/kg HPBCD improved the lifespan of Npc1(-/-) mice. In addition, liver injury and cholesterol sequestration were significantly prevented by 4000 mg/kg HPBCD in Npc1(-/-) mice. Serum HPBCD concentrations, when treated at the effective dosages (1000-4000 mg/kg), were approximately 1200-2500 µg/mL at 0.5 h after subcutaneous injection, and blood HPBCD concentrations were immediately eliminated in Npc1(-/-) mice. Furthermore, we examined serum HPBCD concentrations when treated at 40000 mg (approximately 2500 mg/kg) in a patient with NPC. We observed that the effective concentration in the in vivo study using Npc1(-/-) mice was similar to that in the patient. In the patient, systemic clearance and the volume of distribution of HPBCD were in accordance with the glomerular filtration rate and extracellular fluid volume, respectively. These results could provide useful information for developing the optimal dosage regimen for HPBCD therapy when administered intravenously to NPC patients.

  9. Efficacy of PLD-118, a Novel Inhibitor of Candida Isoleucyl-tRNA Synthetase, against Experimental Oropharyngeal and Esophageal Candidiasis Caused by Fluconazole-Resistant C. albicans

    PubMed Central

    Petraitis, Vidmantas; Petraitiene, Ruta; Kelaher, Amy M.; Sarafandi, Alia A.; Sein, Tin; Mickiene, Diana; Bacher, John; Groll, Andreas H.; Walsh, Thomas J.

    2004-01-01

    PLD-118, formerly BAY 10-8888, is a synthetic antifungal derivative of the naturally occurring β-amino acid cispentacin. We studied the activity of PLD-118 in escalating dosages against experimental oropharyngeal and esophageal candidiasis (OPEC) caused by fluconazole (FLC)-resistant Candida albicans in immunocompromised rabbits. Infection was established by fluconazole-resistant (MIC > 64 μg/ml) clinical isolates from patients with refractory esophageal candidiasis. Antifungal therapy was administered for 7 days. Study groups consisted of untreated controls; animals receiving PLD-118 at 4, 10, 25, or 50 mg/kg of body weight/day via intravenous (i.v.) twice daily (BID) injections; animals receiving FLC at 2 mg/kg/day via i.v. BID injections; and animals receiving desoxycholate amphotericin B (DAMB) i.v. at 0.5 mg/kg/day. PLD-118- and DAMB-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, and esophagus in comparison to untreated controls (P ≤ 0.05, P ≤ 0.01, P ≤ 0.001, respectively), while FLC had no significant activity. PLD-118 demonstrated nonlinear plasma pharmacokinetics across the investigated dosage range, as was evident from a dose-dependent increase in plasma clearance and a dose-dependent decrease in the area under the plasma concentration-time curve. The biochemical safety profile was similar to that of FLC. In summary, PLD-118 demonstrated dosage-dependent antifungal activity and nonlinear plasma pharmacokinetics in treatment of experimental FLC-resistant oropharyngeal and esophageal candidiasis. PMID:15388459

  10. Efficacy of PLD-118, a novel inhibitor of candida isoleucyl-tRNA synthetase, against experimental oropharyngeal and esophageal candidiasis caused by fluconazole-resistant C. albicans.

    PubMed

    Petraitis, Vidmantas; Petraitiene, Ruta; Kelaher, Amy M; Sarafandi, Alia A; Sein, Tin; Mickiene, Diana; Bacher, John; Groll, Andreas H; Walsh, Thomas J

    2004-10-01

    PLD-118, formerly BAY 10-8888, is a synthetic antifungal derivative of the naturally occurring beta-amino acid cispentacin. We studied the activity of PLD-118 in escalating dosages against experimental oropharyngeal and esophageal candidiasis (OPEC) caused by fluconazole (FLC)-resistant Candida albicans in immunocompromised rabbits. Infection was established by fluconazole-resistant (MIC > 64 microg/ml) clinical isolates from patients with refractory esophageal candidiasis. Antifungal therapy was administered for 7 days. Study groups consisted of untreated controls; animals receiving PLD-118 at 4, 10, 25, or 50 mg/kg of body weight/day via intravenous (i.v.) twice daily (BID) injections; animals receiving FLC at 2 mg/kg/day via i.v. BID injections; and animals receiving desoxycholate amphotericin B (DAMB) i.v. at 0.5 mg/kg/day. PLD-118- and DAMB-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, and esophagus in comparison to untreated controls (P

  11. Chemical Restraint of Free-ranging South American Coatis ( Nasua nasua ) with a Combination of Tiletamine and Zolazepam.

    PubMed

    Conforti, Valéria Amorim; de Azevedo, Fernando Cesar Cascelli; de Oliveira Henriques Paulo, Otávio Luís; de Moraes, Wanderlei; Deddens, James Albert

    2017-01-01

    We describe the use of a combination of tiletamine and zolazepam (Zoletil®) for chemical restraint of South American coatis ( Nasua nasua ) under field conditions. We immobilized 53 coatis from a free-ranging population at Iguaçu National Park, Brazil, with Zoletil. Males and females (1.0-8.7 kg) of different age groups participated in the study. Four dosage (milligram per kilogram body weight) groups were created based on quartiles as follows: 1) 4.76-6.68 mg/kg (n=13), 2) 6.83-7.71 mg/kg (n=13), 3) 7.72-8.68 mg/kg (n=18), and 4) 8.98-11.57 mg/kg (n=9). Variables analyzed were sex, age, body weight, dosage, induction time, handling time (HT: time elapsed between the onset of immobilization and first signs of recovery), time from injection to first stand-up posture after anesthesia, heart and respiratory rates, and body temperature. Mean (±SD) induction time was 2.9 (±1.4) min and was positively correlated with age. In dosage groups 1-4, mean HTs were 40.3 (±24.0), 64.5 (±19.1), 54.8 (±15.0), and 60.3 (±12.0), respectively. Handling time had a positive linear relationship with age and body weight, but the relationship between HT and dosage was nonlinear. Group 1 had a shorter HT compared to the other groups combined. Time from injection to first stand-up was 105.0 (±33.5) min. Zoletil was quick acting and safe for immobilization of coatis in the wild.

  12. Analytical Enantio-Separation of Linagliptin in Linagliptin and Metformin HCl Dosage Forms by Applying Two-Level Factorial Design.

    PubMed

    Jadhav, Sushant B; Mane, Rahul M; Narayanan, Kalyanraman L; Bhosale, Popatrao N

    2016-10-17

    A novel, stability indicating, reverse phase high-performance liquid chromatography (RP-HPLC) method was developed to determine the S -isomer of linagliptin (LGP) in linagliptin and metformin hydrochloride (MET HCl) tablets (LGP-MET HCl) by implementing design of experiment (DoE), i.e., two-level, full factorial design (2³ + 3 centre points = 11 experiments) to understand the critical method parameters (CMP) and its relation with the critical method attribute (CMA), and to ensure robustness of the method. The separation of the S -isomer, LGP and MET HCl in the presence of their impurities was achieved on Chiralpak ® IA-3 ( Amylose tris (3, 5-dimethylphenylcarbamate ), immobilized on 3 µm silica gel) stationary phase (250 × 4.6 mm, 3 µm) using isocratic elution and detector wavelength at 225 nm with a flow rate of 0.5 mL·min -1 , an injection volume of 10 µL with a sample cooler (5 °C) and column oven temperature of 25 °C. Ethanol:Methanol:Monoethanolamine (EtOH:MeOH:MEA) in the ratio of 60:40:0.2 v / v / v was used as a mobile phase. The developed method was validated in accordance with international council for harmonisation (ICH) guidelines and was applied for the estimation of the S -isomer of LGP in LGP-MET HCl tablets. The same method also can be extended for the estimation of the S -isomer in LGP dosage forms.

  13. Development and Validation of a Precise, Single HPLC Method for the Determination of Tolperisone Impurities in API and Pharmaceutical Dosage Forms.

    PubMed

    Raju, Thummala Veera Raghava; Seshadri, Raja Kumar; Arutla, Srinivas; Mohan, Tharlapu Satya Sankarsana Jagan; Rao, Ivaturi Mrutyunjaya; Nittala, Someswara Rao

    2013-01-01

    A novel, sensitive, stability-indicating HPLC method has been developed for the quantitative estimation of Tolperisone-related impurities in both bulk drugs and pharmaceutical dosage forms. Effective chromatographic separation was achieved on a C18 stationary phase with a simple mobile phase combination delivered in a simple gradient programme, and quantitation was by ultraviolet detection at 254 nm. The mobile phase consisted of a buffer and acetonitrile delivered at a flow rate 1.0 ml/min. The buffer consisted of 0.01 M potassium dihydrogen phosphate with the pH adjusted to 8.0 by using diethylamine. In the developed HPLC method, the resolution between Tolperisone and its four potential impurities was found to be greater than 2.0. Regression analysis showed an R value (correlation coefficient) of greater than 0.999 for the Tolperisone impurities. This method was capable of detecting all four impurities of Tolperisone at a level of 0.19 μg/mL with respect to the test concentration of 1000 μg/mL for a 10 µl injection volume. The tablets were subjected to the stress conditions of hydrolysis, oxidation, photolysis, and thermal degradation. Considerable degradation was found to occur in base hydrolysis, water hydrolysis, and oxidation. The stress samples were assayed against a qualified reference standard and the mass balance was found to be close to 100%. The established method was validated and found to be linear, accurate, precise, specific, robust, and rugged.

  14. Dry coating, a novel coating technology for solid pharmaceutical dosage forms.

    PubMed

    Luo, Yanfeng; Zhu, Jesse; Ma, Yingliang; Zhang, Hui

    2008-06-24

    Dry coating is a coating technology for solid pharmaceutical dosage forms derived from powder coating of metals. In this technology, powdered coating materials are directly coated onto solid dosage forms without using any solvent, and then heated and cured to form a coat. As a result, this technology can overcome such disadvantages caused by solvents in conventional liquid coating as serious air pollution, high time- and energy-consumption and expensive operation cost encountered by liquid coating. Several dry coating technologies, including plasticizer-dry-coating, electrostatic-dry-coating, heat-dry-coating and plasticizer-electrostatic-heat-dry-coating have been developed and extensively reported. This mini-review summarized the fundamental principles and coating processes of various dry coating technologies, and thoroughly analyzed their advantages and disadvantages as well as commercialization potentials.

  15. Solid-state NMR as an effective method of polymorphic analysis: solid dosage forms of clopidogrel hydrogensulfate.

    PubMed

    Pindelska, Edyta; Szeleszczuk, Lukasz; Pisklak, Dariusz Maciej; Mazurek, Andrzej; Kolodziejski, Waclaw

    2015-01-01

    Clopidogrel hydrogensulfate (HSCL) is an antiplatelet agent, one of top-selling drugs in the world. In this paper, we have described a rapid and convenient method of verification which polymorph of HSCL is present in its final solid dosage form. Our methodology based on solid-state NMR spectroscopy and ab initio gauge-including projector-augmented wave calculations of NMR shielding constants is appropriate for currently available commercial solid dosage forms of HSCL. Furthermore, such structural characterization can assist with the development of new pharmaceutical products containing HSCL and also be useful in the identification of counterfeit drugs. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. Novel depots of buprenorphine have a long-acting effect for the management of physical dependence to morphine.

    PubMed

    Liu, Kuo-Sheng; Kao, Cheng-Hsiung; Liu, Shyun-Yeu; Sung, K C; Kuei, Chun-Hsiung; Wang, Jhi-Joung

    2006-03-01

    Buprenorphine is a promising new pharmacotherapy for the management of physical dependence to opioids. The aim of the study was to evaluate the duration of action of several novel depots of buprenorphine in the treatment of physical dependence to morphine in mice. Following intramuscular injection, the duration of action of several novel oil-based depots of buprenorphine base in morphine-dependent mice were evaluated. The traditional dosage form of buprenorphine hydrochloride in saline was used as control. We found that the depot of buprenorphine base in sesame oil produced a dose-related long-lasting effect. On an equimolar basis of 6 micromol kg(-1), its effect was 5.7-fold longer than that of buprenorphine hydrochloride in saline. When prepared in several other oleaginous vehicles (castor oil, cottonseed oil, peanut oil and soybean oil), buprenorphine base also produced a long-lasting effect, which was similar to buprenorphine base in sesame oil. In conclusion, buprenorphine base, when prepared in oleaginous vehicles and injected intramuscularly in mice, produced a long-lasting effect on physical dependence to morphine.

  17. 21 CFR 520.1448 - Monensin oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Monensin oral dosage forms. 520.1448 Section 520.1448 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... layer chromatography, the R f value must be comparable to a reference standard (the R f value is the...

  18. 21 CFR 520.1448 - Monensin oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Monensin oral dosage forms. 520.1448 Section 520.1448 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... layer chromatography, the R f value must be comparable to a reference standard (the R f value is the...

  19. 75 FR 12981 - Oral Dosage Form New Animal Drugs; Tetracycline Powder

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-18

    .... FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Tetracycline Powder AGENCY: Food and Drug... amending the animal drug regulations to reflect approval of a supplemental new animal drug application... approval of this product. This change is being made to improve the accuracy of the animal drug regulations...

  20. 76 FR 40229 - Oral Dosage Form New Animal Drugs; Change of Sponsor

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-08

    .... FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Change of Sponsor AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect a change of sponsor for a new animal drug application (NADA) from Virbac AH...

  1. 75 FR 54018 - Oral Dosage Form New Animal Drugs; Praziquantel and Pyrantel

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-03

    .... FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Praziquantel and Pyrantel AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a supplemental new animal drug application (NADA) filed by...

  2. Intracoronary Adenosine: Dose-Response Relationship With Hyperemia.

    PubMed

    Adjedj, Julien; Toth, Gabor G; Johnson, Nils P; Pellicano, Mariano; Ferrara, Angela; Floré, Vincent; Di Gioia, Giuseppe; Barbato, Emanuele; Muller, Olivier; De Bruyne, Bernard

    2015-09-01

    The present study sought to establish the dosage of intracoronary (IC) adenosine associated with minimal side effects and above which no further increase in flow can be expected. Despite the widespread adoption of IC adenosine in clinical practice, no wide-ranging, dose-response study has been conducted. A recurring debate still exists regarding its optimal dose. In 30 patients, Doppler-derived flow velocity measurements were obtained in 10 right coronary arteries (RCAs) and 20 left coronary arteries (LCAs) free of stenoses >20% in diameter. Flow velocity was measured at baseline and after 8 ml bolus administrations of arterial blood, saline, contrast medium, and 9 escalating doses of adenosine (4 to 500 μg). The hyperemic value was expressed in percent of the maximum flow velocity reached in a given artery (Q/Qmax, %). Q/Qmax did not increase significantly beyond dosages of 60 μg for the RCA and 160 μg for LCA. Heart rate did not change, whereas mean arterial blood pressure decreased by a maximum of 7% (p < 0.05) after bolus injections of IC adenosine. The incidence of transient A-V blocks was 40% after injection of 100 μg in the RCA and was 15% after injection of 200 μg in the LCA. The duration of the plateau reached 12 ± 13 s after injection of 100 μg in the RCA and 21 ± 6 s after the injection of 200 μg in the LCA. A progressive prolongation of the time needed to return to baseline was observed. Hyperemic response after injection of 8 ml of contrast medium reached 65 ± 36% of that achieved after injection of 200 μg of adenosine. This wide-ranging, dose-response study indicates that an IC adenosine bolus injection of 100 μg in the RCA and 200 μg in the LCA induces maximum hyperemia while being associated with minimal side effects. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  3. Progesterone PLGA/mPEG-PLGA Hybrid Nanoparticle Sustained-Release System by Intramuscular Injection.

    PubMed

    Xie, Bin; Liu, Yang; Guo, Yuting; Zhang, Enbo; Pu, Chenguang; He, Haibing; Yin, Tian; Tang, Xing

    2018-02-14

    To prepare sustained-release PLGA/mPEG-PLGA hybrid nanoparticles of progesterone (PRG), and evaluate the descending required administration dosage in vivo. PRG hybrid nanoparticles (PRG H-NPs) based on PLGA/mPEG-PLGA were compared with PRG nanoparticles (PRG-NPs) of pure PLGA as the matrix and PRG-oil solutions. Nanoparticles (NPs) were formed by the method of nanoemulsion, and the pharmacokinetics of the sustained-release PRG H-NPs in male Sprague dawley (SD) rats were investigated. The rats were randomly divided into four groups, each group received: single dose of PRG H-NPs (14.58 mg/kg, i.m.) and PRG-NPs (14.58 mg/kg, i.m.), repeated dosing for 7 days of PRG-oil (2.08 mg/kg, i.m.) solution (Oil-L) and a higher dosage of PRG-oil (6.24 mg/kg, i.m.) solution (Oil-H), respectively. In the pharmacokinetic test, the PRG H-NPs exhibited a comparatively good sustained-release effect against the PRG-NPs without mPEG-PLGA and PRG-oil solution. The pharmacokinetic parameters of the PRG H-NPs, PRG-NPs, Oil-L and Oil-H were AUC 0-t (ng·h·mL -1 ) 8762.1, 1546.1, 1914.5, and 12,138.9, t 1/2 (h)52.7, 44.1, 8.4 and 44.6 respectively. Owing to the modification of PEG, PRG H-NPs can act as safe delivery platforms for sustained-release of drugs with a lower dosage required.

  4. The effect of morphine on the biosynthesis of catecholamines in the rat brain.

    PubMed

    Malini, M; Kwan, T K; Perumal, R

    1994-02-01

    In vivo studies involved monitoring the effect of morphine administration on catecholamine biosynthesis by the brain while in vitro studies involved studying the effect of morphine on the uptake of tritiated tyrosine by synaptosomes and its subsequent incorporation into the catecholamines. The extremely low levels of these endogenous compounds required the use of High Performance Liquid Chromatography with electrochemical detection. Intra-peritoneal injection of morphine at a dosage of 10 mg/kg did not produce appreciable changes in the catecholamine levels but a dosage of 30 mg/kg morphine was found to elevate dihydroxy phenylacetic acid content. At a dosage of 60 mg/kg, dopamine levels were elevated while noradrenaline was depleted. Morphine, at a concentration of 1 x 10(-5)M increases the incorporation of tritiated tyrosine into dopamine and dihydroxy phenylacetic acid in synaptosomal preparations.

  5. Can dosage form-dependent food effects be predicted using biorelevant dissolution tests? Case example extended release nifedipine.

    PubMed

    Andreas, Cord J; Tomaszewska, Irena; Muenster, Uwe; van der Mey, Dorina; Mueck, Wolfgang; Dressman, Jennifer B

    2016-08-01

    Food intake is known to have various effects on gastrointestinal luminal conditions in terms of transit times, hydrodynamic forces and/or luminal fluid composition and can therefore affect the dissolution behavior of solid oral dosage forms. The aim of this study was to investigate and detect the dosage form-dependent food effect that has been observed for two extended-release formulations of nifedipine using in vitro dissolution tests. Two monolithic extended release formulations, the osmotic pump Adalat® XL 60mg and matrix-type Adalat® Eins 30mg formulation, were investigated with biorelevant dissolution methods using the USP apparatus III and IV under both simulated prandial states, and their corresponding quality control dissolution method. In vitro data were compared to published and unpublished in vivo data using deconvolution-based in vitro - in vivo correlation (IVIVC) approaches. Quality control dissolution methods tended to overestimate the dissolution rate due to the excessive solubilizing capabilities of the sodium dodecyl sulfate (SDS)-containing dissolution media. Using Level II biorelevant media the dosage form dependent food effect for nifedipine was described well when studied with the USP apparatus III, whereas the USP apparatus IV failed to detect the positive food effect for the matrix-type dosage form. It was demonstrated that biorelevant methods can serve as a useful tool during formulation development as they were able to qualitatively reflect the in vivo data. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Predicting the oral pharmacokinetic profiles of multiple-unit (pellet) dosage forms using a modeling and simulation approach coupled with biorelevant dissolution testing: case example diclofenac sodium.

    PubMed

    Kambayashi, Atsushi; Blume, Henning; Dressman, Jennifer B

    2014-07-01

    The objective of this research was to characterize the dissolution profile of a poorly soluble drug, diclofenac, from a commercially available multiple-unit enteric coated dosage form, Diclo-Puren® capsules, and to develop a predictive model for its oral pharmacokinetic profile. The paddle method was used to obtain the dissolution profiles of this dosage form in biorelevant media, with the exposure to simulated gastric conditions being varied in order to simulate the gastric emptying behavior of pellets. A modified Noyes-Whitney theory was subsequently fitted to the dissolution data. A physiologically-based pharmacokinetic (PBPK) model for multiple-unit dosage forms was designed using STELLA® software and coupled with the biorelevant dissolution profiles in order to simulate the plasma concentration profiles of diclofenac from Diclo-Puren® capsule in both the fasted and fed state in humans. Gastric emptying kinetics relevant to multiple-units pellets were incorporated into the PBPK model by setting up a virtual patient population to account for physiological variations in emptying kinetics. Using in vitro biorelevant dissolution coupled with in silico PBPK modeling and simulation it was possible to predict the plasma profile of this multiple-unit formulation of diclofenac after oral administration in both the fasted and fed state. This approach might be useful to predict variability in the plasma profiles for other drugs housed in multiple-unit dosage forms. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals

    PubMed Central

    Bellinger, Andrew M.; Jafari, Mousa; Grant, Tyler M.; Zhang, Shiyi; Slater, Hannah C.; Wenger, Edward A.; Mo, Stacy; Lee, Young-Ah Lucy; Mazdiyasni, Hormoz; Kogan, Lawrence; Barman, Ross; Cleveland, Cody; Booth, Lucas; Bensel, Taylor; Minahan, Daniel; Hurowitz, Haley M.; Tai, Tammy; Daily, Johanna; Nikolic, Boris; Wood, Lowell; Eckhoff, Philip A.; Langer, Robert; Traverso, Giovanni

    2017-01-01

    Efforts at elimination of scourges, such as malaria, are limited by the logistic challenges of reaching large rural populations and ensuring patient adherence to adequate pharmacologic treatment. We have developed an oral, ultra–long-acting capsule that dissolves in the stomach and deploys a star-shaped dosage form that releases drug while assuming a geometry that prevents passage through the pylorus yet allows passage of food, enabling prolonged gastric residence. This gastric-resident, drug delivery dosage form releases small-molecule drugs for days to weeks and potentially longer. Upon dissolution of the macrostructure, the components can safely pass through the gastrointestinal tract. Clinical, radiographic, and endoscopic evaluation of a swine large-animal model that received these dosage forms showed no evidence of gastrointestinal obstruction or mucosal injury. We generated long-acting formulations for controlled release of ivermectin, a drug that targets malaria-transmitting mosquitoes, in the gastric environment and incorporated these into our dosage form, which then delivered a sustained therapeutic dose of ivermectin for up to 14 days in our swine model. Further, by using mathematical models of malaria transmission that incorporate the lethal effect of ivermectin against malaria-transmitting mosquitoes, we demonstrated that this system will boost the efficacy of mass drug administration toward malaria elimination goals. Encapsulated, gastric-resident dosage forms for ultra–long-acting drug delivery have the potential to revolutionize treatment options for malaria and other diseases that affect large populations around the globe for which treatment adherence is essential for efficacy. PMID:27856796

  8. Development and evaluation of a monolithic floating dosage form for furosemide.

    PubMed

    Menon, A; Ritschel, W A; Sakr, A

    1994-02-01

    The poor bioavailability of orally dosed furosemide (60%), a weakly acidic drug, is due to the presence of a biological window comprised of the upper gastrointestinal tract. The purpose of the present study was to develop and optimize in vitro a monolithic modified-release dosage form (MMR) for furosemide with increased gastric residence time and to evaluate the in vivo performance of the dosage form. The principle of floatation was used to restrict the MMR to the stomach. A two-factor three-level full factorial experimental design was employed for formulation development. A flow-through cell was designed to evaluate in vitro dissolution parameters. Quadratic regression models indicated the polymer viscosity and polymer:drug ratio to be significant (p < 0.05) formulation factors in determining the duration of buoyancy and the release profile. Statistical optimization using response surface methodology with certain physiological constraints relating to gastric emptying time predicted an optimal MMR. In vivo evaluation of the optimized MMR in beagle dogs resulted in a significant increase (p < 0.05) in the absolute bioavailability for the MMR dosage form (42.9%) as compared to the commercially available tablet (33.4%) and enteric product (29.5%). Significant in vitro/in vivo correlations (p < 0.05) were obtained for the MMR using deconvolution analysis normalized for bioavailability. The floating dosage form was found to be a feasible approach in delivering furosemide to the upper gastrointestinal tract to maximize drug absorption.

  9. Analgesic Opioid Dose Is an Important Indicator of Postoperative Ileus Following Radical Cystectomy with Ileal Conduit: Experience in the Robotic Surgery Era

    PubMed Central

    Koo, Kyo Chul; Yoon, Young Eun; Chung, Byung Ha; Hong, Sung Joon

    2014-01-01

    Purpose Postoperative ileus (POI) is common following bowel resection for radical cystectomy with ileal conduit (RCIC). We investigated perioperative factors associated with prolonged POI following RCIC, with specific focus on opioid-based analgesic dosage. Materials and Methods From March 2007 to January 2013, 78 open RCICs and 26 robot-assisted RCICs performed for bladder carcinoma were identified with adjustment for age, gender, American Society of Anesthesiologists grade, and body mass index (BMI). Perioperative records including operative time, intraoperative fluid excess, estimated blood loss, lymph node yield, and opioid analgesic dose were obtained to assess their associations with time to passage of flatus, tolerable oral diet, and length of hospital stay (LOS). Prior to general anaesthesia, patients received epidural patient-controlled analgesia (PCA) consisted of fentanyl with its dose adjusted for BMI. Postoperatively, single intravenous injections of tramadol were applied according to patient desire. Results Multivariate analyses revealed cumulative dosages of both PCA fentanyl and tramadol injections as independent predictors of POI. According to surgical modality, linear regression analyses revealed cumulative dosages of PCA fentanyl and tramadol injections to be positively associated with time to first passage of flatus, tolerable diet, and LOS in the open RCIC group. In the robot-assisted RCIC group, only tramadol dose was associated with time to flatus and tolerable diet. Compared to open RCIC, robot-assisted RCIC yielded shorter days to diet and LOS; however, it failed to shorten days to first flatus. Conclusion Reducing opioid-based analgesics shortens the duration of POI. The utilization of the robotic system may confer additional benefit. PMID:25048497

  10. Bioavailability of AREDS1 micronutrients from softgel capsules and tablets: a pilot study

    PubMed Central

    Johnson, Elizabeth J.; Vishwanathan, Rohini; Rasmussen, Helen M.

    2014-01-01

    Purpose The benefits of antioxidant micronutrients in slowing progression to advanced stages of age-related macular degeneration (AMD) was supported by the 4/day tablet form investigated in the Age-related Eye Disease Study 1 (AREDS1) and the 2/day softgel form in the Age-related Eye Disease Study 2 (AREDS2). However, the choices of excipient, dosage form, and ingredient chemistry as well as the patient physiologies and pathologies can influence bioavailability and efficacy. The objective of the study was to explore the influence of dosage form on the bioavailability of the five primary AREDS1 and Tier-2 AREDS2 micronutrients: the metals zinc and copper, β-carotene, and vitamins E and C. The intent was to establish by chemical analysis the relative bioavailabilities of these five micronutrients in plasma, or serum for the metals, as well as to identify any opportunities for improvements. Methods A total of 15 healthy men (5) and women (10) were recruited for a controlled, randomized, three-arm, crossover trial of the AREDS1 micronutrients. The study investigated responses in bioabsorption to a single dose of either four tablets or two softgels at the full dose level, or one softgel at the half-dose level. The bioavailability of each micronutrient was based on the pharmacokinetic profiles established through 15 samplings for each ingredient/dosage form in plasma/serum over the course of one week. Results Bioavailability was estimated using model-independent and model-dependent procedures. A statistical advantage of the dosage form was observed in only two cases from the exaggerated effects using the half-dose softgel and for the tablet dosage form for β-carotene and vitamin E. An unanticipated complexity was suggested by the bimodal absorption of zinc. For these micronutrients, no disadvantage (though potential advantage) was inferred for the water-soluble components presented in a softgel formulation. Increased fractional absorption was observed for the smaller dose (one capsule versus two), but it was not sufficient to reach the level achieved by the full dose of either four tablets or two softgels. A model-dependent analysis permitted an estimation of the percentage of micronutrients absorbed, with zinc, the single most important ingredient, absorbed at about a 10% level. Conclusions The results suggest modestly contradictory requirements in the dosage form for water-soluble and lipid-soluble ingredients, as based on a goal of improved bioavailability. Comparative consistency in bioavailability was observed across dosage forms, and most nutrients between AREDS1 and AREDS2 (full dose) formulations relative to the significant variations observed within this controlled population. The results emphasize the importance of defining the requisite bioavailability of each micronutrient and the influence of the dosage form that provides it. With the recognition of global and population-specific micronutrient deficiencies, notably in the elderly populations afflicted with AMD and their significant metabolic and health consequences, establishing efficient means of supplementation are of continuing epidemiologic interest. PMID:25352732

  11. Response of Low Birthweight Infants to Treatment with Folic Acid

    PubMed Central

    Burland, W. L.; Simpson, K.; Lord, Juliet

    1971-01-01

    Folate deficiency, detected by measuring serum and red cell levels, was seen within a group of low birthweight infants who had been followed for a period of 9 months. A similar group treated with 14 × 100 μg folic acid by intramuscular injection over a period of 28 days during the first 5 weeks of life had significantly higher folate levels. There was no evidence of megaloblastic anaemia in the untreated group and no differences from the treated group in haemoglobin concentration or other haematological index except for a significant increase in neutrophils with 5-lobed nuclei at 3 months. We conclude that folate should be given from birth to all infants of low birthweight, but its form, and the route, dosage, and duration of treatment merit further investigation. PMID:5108386

  12. Preformulation considerations for controlled release dosage forms. Part I. Selecting candidates.

    PubMed

    Chrzanowski, Frank

    2008-01-01

    The physical-chemical properties of interest for controlled release (CR) dosage form development presented are based on the author's experience. Part I addresses selection of the final form based on a logical progression of physical-chemical properties evaluation of candidate forms and elimination of forms with undesirable properties from further evaluation in order to simplify final form selection. Several candidate forms which could include salt, free base or acid, polymorphic and amorphic forms of a new chemical entity (NCE) or existing drug substance (DS) are prepared and evaluated for critical properties in a scheme relevant to manufacturing processes, predictive of problems, requiring small amounts of test materials and simple analytical tools. A stability indicating assay is not needed to initiate the evaluation. This process is applicable to CR and immediate release (IR) dosage form development. The critical properties evaluated are melting, crystallinity, solubilities in water, 0.1 N HCl, and SIF, hygrodymamics, i.e., moisture sorption and loss at extremes of RH, and LOD at typical wet granulation drying conditions, and processability, i.e., corrosivity, and filming and/or sticking upon compression.

  13. Feasibility and optimal dosage of indocyanine green fluorescence for sentinel lymph node detection using robotic single-site instrumentation: preclinical study.

    PubMed

    Levinson, Kimberly L; Mahdi, Haider; Escobar, Pedro F

    2013-01-01

    The present study was performed to determine the optimal dosage of indocyanine green (ICG) to accurately differentiate the sentinel node from surrounding tissue and then to test this dosage using novel single-port robotic instrumentation. The study was performed in healthy female pigs. After induction of anesthesia, all pigs underwent exploratory laparotomy, dissection of the bladder, and colpotomy to reveal the cervical os. With use of a 21-gauge needle, 0.5 mL normal saline solution was injected at the 3- and 9-o'clock positions as control. Four concentrations of ICG were constituted for doses of 1000, 500, 250, and 175 μg per 0.5 mL. ICG was then injected at the 3- and 9-o'clock positions on the cervix. The SPY camera was used to track ICG into the sentinel nodes and to quantify the intensity of light emitted. SPY technology uses an intensity scale of 1 to 256; this scale was used to determine the difference in intensity between the sentinel node and surrounding tissues. The optimal dosage was tested using single-port robotic instrumentation with the same injection techniques. A sentinel node was identified at all doses except 175 μg, at which ICG stayed in the cervix and vasculature only. For both the 500- and 250-μg doses, the sentinel node was identified before reaching maximum intensity. At maximum intensity, the difference between the surrounding tissue and the node was 207 (251 vs 44) for the 500-μg dose and 159 (251 vs 92) for the 250-μg dose. Sentinel lymph node (SLN) biopsy was successfully performed using single-port robotic technology with both the 250- and 500-μg doses. For SLN detection, the dose of ICG is related to the ability to differentiate the sentinel node from the surrounding tissue. An ICG dose of 250 to 500 μg enables identification of a SLN with more distinction from the surrounding tissues, and this procedure is feasible using single-port robotics instrumentation. Copyright © 2013 AAGL. Published by Elsevier Inc. All rights reserved.

  14. Hormone preparation, dosage calculation, and injection technique for induced spawning of foodfish

    USDA-ARS?s Scientific Manuscript database

    Reliable spawning and fry production of food species is critical for successful commercial production. Environmental stimuli often fail to trigger the requisite hormone cascades for gamete formation, final oocyte maturation, and ovulation in fish held under captive conditions. In general, enviro...

  15. Regulatory perspectives on acceptability testing of dosage forms in children.

    PubMed

    Kozarewicz, Piotr

    2014-08-05

    Current knowledge about the age-appropriateness of different dosage forms is still fragmented or limited. Applicants are asked to demonstrate that the target age group(s) can manage the dosage form or propose an alternative strategy. However, questions remain about how far the applicant must go and what percentage of patients must find the strategy 'acceptable'. The aim of this overview is to provide an update on current thinking and understanding of the problem, and discuss issues relating to the acceptability testing. This overview should be considered as means to start a wider discussion which hopefully will result in a harmonised, globally acceptable approach for confirmation of the acceptability in the future. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Fourth-order derivative spectrophotometric method for simultaneous determination of pseudoephedrine and naproxen in pharmaceutical dosage forms

    PubMed Central

    Souri, Effat; Mosafer, Amir; Tehrani, Maliheh Barazandeh

    2016-01-01

    Combination dosage forms of naproxen sodium and pseudoephedrine hydrochloride are used for symptomatic treatment of cold and sinus disorders. In this study, fourth-order derivative spectrophotometric method was used for simultaneous determination of naproxen sodium and pseudoephedrine hydrochloride. The method was linear over the range of 2-28 μg/ml for pseudoephedrine hydrochloride and 4-200 μg/ml for naproxen sodium. The within-day and between-day coefficient of variation values were less than 5.8% and 2.5% for pseudoephedrine hydrochloride and naproxen sodium, respectively. The application of the proposed method for simultaneous determination of naproxen and pseudoephedrine in dosage forms was demonstrated without any special pretreatment. PMID:27168748

  17. Using the technique of computed tomography for nondestructive analysis of pharmaceutical dosage forms

    NASA Astrophysics Data System (ADS)

    de Oliveira, José Martins, Jr.; Mangini, F. Salvador; Carvalho Vila, Marta Maria Duarte; ViníciusChaud, Marco

    2013-05-01

    This work presents an alternative and non-conventional technique for evaluatingof physic-chemical properties of pharmaceutical dosage forms, i.e. we used computed tomography (CT) technique as a nondestructive technique to visualize internal structures of pharmaceuticals dosage forms and to conduct static and dynamical studies. The studies were conducted involving static and dynamic situations through the use of tomographic images, generated by the scanner at University of Sorocaba - Uniso. We have shown that through the use of tomographic images it is possible to conduct studies of porosity, densities, analysis of morphological parameters and performing studies of dissolution. Our results are in agreement with the literature, showing that CT is a powerful tool for use in the pharmaceutical sciences.

  18. In-vitro tomography and non-destructive imaging at depth of pharmaceutical solid dosage forms.

    PubMed

    Zeitler, J Axel; Gladden, Lynn F

    2009-01-01

    Tomographic imaging techniques offer new prospects for a better understanding of the quality, performance and release mechanisms of pharmaceutical solid dosage forms. It is only over the last fifteen years that tomography has been applied for the in-vitro characterisation of dosage forms. This review aims to introduce the concept of tomography in a pharmaceutical context, and describes the current state-of-the-art of the four most promising techniques: X-ray computed microtomography, magnetic resonance imaging, terahertz imaging and optical coherence tomography. The basic working principles of the techniques are introduced and the current pharmaceutical applications of the technologies are discussed, together with a comparison of their specific strengths and weaknesses. Possible future developments in these fields are also discussed.

  19. [Oral disintegrating tablets. A new, modern, solid dosage form].

    PubMed

    Popa, Graţiela; Gafiţanu, Eliza

    2003-01-01

    The pharmaceutical market shows lately an increasing interest in orally disintegrating tablets, due to their good acceptability among certain age categories (ex. elderly, children), and other patients with difficulties in swallowing classic solid dosage forms. Some of the methods of preparing such tablets have gained industrial applicability: molding, lyophilization, direct compression with highly soluble excipients, super disintegrants and/or effervescent systems. Some of the patients have had a good impact on the pharmaceutical market and more improvements are expected in the next few years, with new drugs to be formulated as fast dissolving dosage formulations.

  20. Hydrophilic thermoplastic polyurethanes for the manufacturing of highly dosed oral sustained release matrices via hot melt extrusion and injection molding.

    PubMed

    Verstraete, G; Van Renterghem, J; Van Bockstal, P J; Kasmi, S; De Geest, B G; De Beer, T; Remon, J P; Vervaet, C

    2016-06-15

    Hydrophilic aliphatic thermoplastic polyurethane (Tecophilic™ grades) matrices for high drug loaded oral sustained release dosage forms were formulated via hot melt extrusion/injection molding (HME/IM). Drugs with different aqueous solubility (diprophylline, theophylline and acetaminophen) were processed and their influence on the release kinetics was investigated. Moreover, the effect of Tecophilic™ grade, HME/IM process temperature, extrusion speed, drug load, injection pressure and post-injection pressure on in vitro release kinetics was evaluated for all model drugs. (1)H NMR spectroscopy indicated that all grades have different soft segment/hard segment ratios, allowing different water uptake capacities and thus different release kinetics. Processing temperature of the different Tecophilic™ grades was successfully predicted by using SEC and rheology. Tecophilic™ grades SP60D60, SP93A100 and TG2000 had a lower processing temperature than other grades and were further evaluated for the production of IM tablets. During HME/IM drug loads up to 70% (w/w) were achieved. In addition, Raman mapping and (M)DSC results confirmed the homogenous distribution of mainly crystalline API in all polymer matrices. Besides, hydrophilic TPU based formulations allowed complete and sustained release kinetics without using release modifiers. As release kinetics were mainly affected by drug load and the length of the PEO soft segment, this polymer platform offers a versatile formulation strategy to adjust the release rate of drugs with different aqueous solubility. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Vitamin B12-Loaded Buccoadhesive Films as a Noninvasive Supplement in Vitamin B12 Deficiency: In Vitro Evaluation and In Vivo Comparative Study With Intramuscular Injection.

    PubMed

    Mohamad, Soad A; Sarhan, Hatem A; Abdelkader, Hamdy; Mansour, Heba F

    2017-07-01

    This study aimed to formulate and evaluate vitamin B12-loaded buccal mucoadhesive hydrogel films. Various film formulations were prepared using chitosan and polyvinyl alcohol. The prepared films were characterized for thickness, weight variation, drug content, percentage moisture uptake and moisture content, surface pH, mechanical properties, in vitro release, and mucoadhesion. Vitamin B12 bioavailability from the optimized formulation was studied on rabbits by the aid of enzyme-linked immunosorbent assay. Neuroton ® I.M. injection was used for comparison. The films had acceptable mechanical and mucoadhesion properties. The percentages of moisture content of the optimized formulation were 3.2 ± 0.95, whereas the percentage drug released was 98.59 ± 1.41% at the end of 40 min. FTIR revealed the incidence of drug/polymer interaction. Differential scanning calorimetry revealed the possibility of the dispersion of cyanocobalamin in a molecular state with complete amorphization in the polymers. The estimated AUC 0-8h showed 1.5-fold increases in the bioavailability of cyanocobalamin from the optimized formulation compared with the marketed I.M. injection. These findings warrant that vitamin B12 buccal film formulation can be considered as an effective alternative portal with noninvasive and more convenient characteristics compared with the I.M. injection dosage form. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  2. Validation of a stability-indicating hydrophilic interaction liquid chromatographic method for the quantitative determination of vitamin k3 (menadione sodium bisulfite) in injectable solution formulation.

    PubMed

    Ghanem, Mashhour M; Abu-Lafi, Saleh A; Hallak, Hussein O

    2013-01-01

    A simple, specific, accurate, and stability-indicating method was developed and validated for the quantitative determination of menadione sodium bisulfite in the injectable solution formulation. The method is based on zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) coupled with a photodiode array detector. The desired separation was achieved on the ZIC-HILIC column (250 mm × 4.6 mm, 5 μm) at 25°C temperature. The optimized mobile phase consisted of an isocratic solvent mixture of 200mM ammonium acetate (NH4AC) solution and acetonitrile (ACN) (20:80; v/v) pH-adjusted to 5.7 by glacial acetic acid. The mobile phase was fixed at 0.5 ml/min and the analytes were monitored at 261 nm using a photodiode array detector. The effects of the chromatographic conditions on the peak retention, peak USP tailing factor, and column efficiency were systematically optimized. Forced degradation experiments were carried out by exposing menadione sodium bisulfite standard and the injectable solution formulation to thermal, photolytic, oxidative, and acid-base hydrolytic stress conditions. The degradation products were well-resolved from the main peak and the excipients, thus proving that the method is a reliable, stability-indicating tool. The method was validated as per ICH and USP guidelines (USP34/NF29) and found to be adequate for the routine quantitative estimation of menadione sodium bisulfite in commercially available menadione sodium bisulfite injectable solution dosage forms.

  3. Corticosteroid injection for adhesive capsulitis in primary care: a systematic review of randomised clinical trials

    PubMed Central

    Koh, Kim Hwee

    2016-01-01

    Adhesive capsulitis is a common cause of shoulder pain and limited movement. The objectives of this review were to assess the efficacy and safety of corticosteroid injections for adhesive capsulitis and to evaluate the optimum dose and anatomical site of injections. PubMed and CENTRAL databases were searched for randomised trials and a total of ten trials were included. Results revealed that corticosteroid injection is superior to placebo and physiotherapy in the short-term (up to 12 weeks). There was no difference in outcomes between corticosteroid injection and oral nonsteroidal anti-inflammatory drugs at 24 weeks. Dosages of intra-articular triamcinolone 20 mg and 40 mg showed identical outcomes, while subacromial and glenohumeral corticosteroid injections had similar efficacy. The use of corticosteroid injections is also generally safe, with infrequent and minor side effects. Physicians may consider corticosteroid injection to treat adhesive capsulitis, especially in the early stages when pain is the predominant presentation. PMID:27570870

  4. Corticosteroid injection for adhesive capsulitis in primary care: a systematic review of randomised clinical trials.

    PubMed

    Koh, Kim Hwee

    2016-12-01

    Adhesive capsulitis is a common cause of shoulder pain and limited movement. The objectives of this review were to assess the efficacy and safety of corticosteroid injections for adhesive capsulitis and to evaluate the optimum dose and anatomical site of injections. PubMed and CENTRAL databases were searched for randomised trials and a total of ten trials were included. Results revealed that corticosteroid injection is superior to placebo and physiotherapy in the short-term (up to 12 weeks). There was no difference in outcomes between corticosteroid injection and oral nonsteroidal anti-inflammatory drugs at 24 weeks. Dosages of intra-articular triamcinolone 20 mg and 40 mg showed identical outcomes, while subacromial and glenohumeral corticosteroid injections had similar efficacy. The use of corticosteroid injections is also generally safe, with infrequent and minor side effects. Physicians may consider corticosteroid injection to treat adhesive capsulitis, especially in the early stages when pain is the predominant presentation. Copyright: © Singapore Medical Association.

  5. The effect of Houttuynia cordata injection on pseudorabies herpesvirus (PrV) infection in vitro.

    PubMed

    Ren, Xiaofeng; Sui, Xiuwen; Yin, Jiechao

    2011-02-01

    Pseudorabies herpesvirus (PrV) belongs to the Alphaherpesvirinae. Piglets infected with PrV die within a few days. Development of effective antiviral agents is one alternative or complementary method to prevent PrV infection. Houttuynia cordata Thunb. (Saururaceae), H. cordata, a traditional Chinese medicine, is often used to relieve lung abnormal symptoms, infectious disease, refractory hemoptysis and malignant pleural effusion in China. The present study aimed to investigate the effect of H. cordata injection on cell infection by PrV using Vero cells (a monkey kidney cell line) and swine testis cells (ST) as models. The infectivity of PrV was determined by plaque assays when H. cordata was applied to the virus, to the virus infected cells, and to the cells prior to infection. The genomic DNA copies post-drug treatment were confirmed by PCR and reverse transcription PCR. The cell apoptosis caused by the virus was analyzed. H. cordata efficiently inhibited cell infection after incubating the drug with PrV. Nevertheless, H. cordata was more efficient in Vero cells than in ST cells in terms of its inhibitory effect. Low-dosage drug inhibited cell apoptosis induced by PrV; nevertheless, high-dosage drug alone resulted in cell apoptosis. H. cordata has a direct inhibitory activity against PrV in vitro. H. cordata may be used as an anti-PrV agent or combined with other anti-PrV agents. PrV infection induces cell apoptosis and H. cordata inhibits cell infection. The optimal administration dosage of H. cordata should be taken into account in the future, because high-dosage H. cordata alone causes cell apoptosis.

  6. Use of medetomidine and ketamine for immobilization of free-ranging giraffes.

    PubMed

    Bush, M; Grobler, D G; Raath, J P; Phillips, L G; Stamper, M A; Lance, W R

    2001-01-15

    To develop a dosage correlated with shoulder height (SH) in centimeters for effective immobilization of free-ranging giraffes, using a combination of medetomidine (MED) and ketamine (KET) and reversal with atipamezole (ATP). Prospective study. 23 free-ranging giraffes. The drug combination (MED and KET) was administered by use of a projectile dart. Quality of induction, quality of immobilization, and time to recovery following injection of ATP were evaluated. Physiologic variables measured during immobilization included PaO2, PaCO2, oxygen saturation, end-tidal CO2, blood pH, indirect arterial blood pressure, heart and respiratory rates, and rectal temperature. Sixteen giraffes became recumbent with a dosage (mean +/- SD) of 143 +/- 29 microg of MED and 2.7 +/- 0.6 mg of KET/cm of SH. Initially, giraffes were atactic and progressed to lateral recumbency. Three giraffes required casting with ropes for data collection, with dosages of 166 +/- 5 microg of MED and 3.2 +/- 0.6 mg of KET/cm of SH. Four giraffes required administration of etorphine (n = 2) or were cast with ropes (2) for capture but remained dangerous to personnel once recumbent, precluding data collection. In giraffes successfully immobilized, physiologic monitoring revealed hypoxia and increased respiratory rates. Values for PaCO2, end-tidal CO2, and heart rate remained within reference ranges. All giraffes were hypertensive and had a slight increase in rectal temperature. Atipamezole was administered at 340 +/- 20 microg/cm of SH, resulting in rapid and smooth recoveries. Medetomidine and KET was an effective immobilizing combination for free-ranging giraffes; however, at the dosages used, it does not induce adequate analgesia for major manipulative procedures. Quality of induction and immobilization were enhanced if the giraffe was calm. Reversal was rapid and complete following injection of ATP.

  7. Pharmaceutical Additive Manufacturing: a Novel Tool for Complex and Personalized Drug Delivery Systems.

    PubMed

    Zhang, Jiaxiang; Vo, Anh Q; Feng, Xin; Bandari, Suresh; Repka, Michael A

    2018-06-25

    Inter-individual variability is always an issue when treating patients of different races, genders, ages, pharmacogenetics, and pharmacokinetic characteristics. However, the development of novel dosage forms is limited by the huge investments required for production line modifications and dosages diversity. Additive manufacturing (AM) or 3D printing can be a novel alternative solution for the development of controlled release dosages because it can produce personalized or unique dosage forms and more complex drug-release profiles. The primary objective of this manuscript is to review the 3D printing processes that have been used in the pharmaceutical area, including their general aspects, materials, and the operation of each AM technique. Advantages and shortcomings of the technologies are discussed with respect to practice and practical applications. Thus, this review will provide an overview and discussion on advanced pharmaceutical AM technologies, which can be used to produce unique controlled drug delivery systems and personalized dosages for the future of personalized medicine.

  8. 21 CFR 522.960b - Flumethasone acetate solution.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... noted. Dosage by injection should not exceed 3 days of therapy. With chronic conditions intramuscular....25 mg per animal. (2) Indications for use. For use in certain acute and chronic canine dermatoses of varying etiology to help control the pruritus, irritation, and inflammation associated with these...

  9. Extemporaneous compounding in a sample of New Zealand hospitals: a retrospective survey.

    PubMed

    Kairuz, Therése; Chhim, Srey; Hasan, Fhazeel; Kumar, Karishma; Lal, Aarti; Patel, Roshni; Singh, Ranjani; Dogra, Mridula; Garg, Sanjay

    2007-03-23

    To determine the extent and nature of extemporaneous compounding of liquid preparations in a sample of New Zealand hospitals. Retrospective data were collected from eight hospitals known to provide compounding services during the period 1 June 2004 to 31 December 2004; including dosage form, volume, and quantity prepared. Data were collected on site from compounding logbooks and batch sheets. Demographic patient data was limited to age and was only collected from pharmacy departments where this information was readily available. Off-label use was analysed where appropriate data were available. 2015 products were compounded over the 7-month period; an average of 251.9 per month. More oral dosage forms were compounded (n=152) compared to topical dosage forms (n=100); 74 drugs required extemporaneous preparation for oral use. There were 16 drugs used in an off-label manner on 144 occasions for paediatric patients. Most off-label drugs were reformulated as suspensions; omeprazole suspension was compounded at all of the hospitals. Off-label use of four drugs (sotalol, labetalol, diazoxide, and clonidine) was analysed for different paediatric age groups. Suspensions are the most frequently compounded dosage form and omeprazole is the drug that is most frequently reformulated. Off-label medicines form a small but integral role in the supply of medicinal products.

  10. Influence of Postprandial Intragastric Pressures on Drug Release from Gastroretentive Dosage Forms.

    PubMed

    Schneider, Felix; Hoppe, Melanie; Koziolek, Mirko; Weitschies, Werner

    2018-05-29

    Despite extensive research in the field of gastroretentive dosage forms, this "holy grail" of oral drug delivery yet remained an unmet goal. Especially under fasting conditions, the reproducible retention of dosage forms in the stomach seems to be an impossible task. This is why such systems are often advised to be taken together with food. But also the postprandial motility can contribute significantly to the failure of gastroretentive dosage forms. To investigate the influence of postprandial pressure conditions on drug release from such systems, we used a novel in vitro dissolution tool, the dissolution stress test device. With the aid of this device, we simulated three different intragastric pressure profiles that may occur after postprandial intake. These transit scenarios were based on recently obtained, postprandial SmartPill® data. The tested systems, Glumetza® 1000 and Madopar® HBS 125, are marketed dosage forms that are based on different approaches to achieve proper gastric retention. All three transit scenarios revealed a highly pressure-sensitive drug release behavior, for both drugs. For Madopar® HBS 125, nearly complete drug release was observed even after early occurring pressures. Glumetza® 1000 seemed to be more resistant to these, most likely due to incomplete wetting of the system. On the contrary to these findings, data from standard dissolution tests using the paddle apparatus displayed controlled drug release for both systems for about 6 h. Based on these results, it can be doubted that established gastroretentive systems stay intact over a longer period of time, even under postprandial conditions.

  11. A novel approach for the preparation of highly loaded polymeric controlled release dosage forms of diltiazem HCl and diclofenac sodium.

    PubMed

    Kakish, Hanan F; Tashtoush, Bassam; Ibrahim, Hussein G; Najib, Naji M

    2002-07-01

    In this investigation, modified-release dosage forms of diltiazem HCl (DT) and diclofenac sodium (DS) were prepared. The development work comprised two main parts: (a) loading the drug into ethylene vinyl acetate (EVA) polymer, and (b) generation of a non-uniform concentration distribution of the drug within the polymer matrix. Phase separation technique was successfully used to load DT and DS into the polymer at significantly high levels, up to 81 and 76%, respectively. Size diameter of the resultant microspheres was between 1.6 and 2.0mm. Controlled-extraction of loaded microspheres and high vacuum freeze-drying were used to generate the non-uniform concentration distribution and to immobilize the new drug distribution within the matrix. Parameters controlling the different processes were investigated, and hence optimal processing conditions were used to prepare the dosage forms. Rates of drug release from the two dosage forms in water and in media having different pH were found to be constant for an appreciable length of time (>8h) followed by a slow decline; a characteristic of a non-Fickian diffusion process. Scanning electron microscopy studies suggested that the resultant release behavior was the outcome of the combined effects of the non-uniform distribution of the drug in the matrix and the apparent changes in the pores and surface characteristics of the microspheres. Comparison of release rate-time plots of dissolution data of marketed products with the newly developed dosage forms indicated the ability of the latter to sustain more zero order release.

  12. Dual Wavelength RP-HPLC Method for Simultaneous Determination of Two Antispasmodic Drugs: An Application in Pharmaceutical and Human Serum.

    PubMed

    Hasan, Najmul; Chaiharn, Mathurot; Khan, Sauleha; Khalid, Hira; Sher, Nawab; Siddiqui, Farhan Ahmed; Siddiqui, Muhammad Zain

    2013-01-01

    A reverse phase stability indicating HPLC method for simultaneous determination of two antispasmodic drugs in pharmaceutical parenteral dosage forms (injectable) and in serum has been developed and validated. Mobile phase ingredients consist of Acetonitrile : buffer : sulfuric acid 0.1 M (50 : 50 : 0.3 v/v/v), at flow rate 1.0 mL/min using a Hibar μ Bondapak ODS C18 column monitored at dual wavelength of 266 nm and 205 nm for phloroglucinol and trimethylphloroglucinol, respectively. The drugs were subjected to stress conditions of hydrolysis (oxidation, base, acid, and thermal degradation). Oxidation degraded the molecule drastically while there was not so much significant effect of other stress conditions. The calibration curve was linear with a correlation coefficient of 0.9999 and 0.9992 for PG and TMP, respectively. The drug recoveries fall in the range of 98.56% and 101.24% with 10 pg/mL and 33 pg/mL limit of detection and limit of quantification for both phloroglucinol and trimethylphloroglucinol. The method was validated in accordance with ICH guidelines and was applied successfully to quantify the amount of trimethylphloroglucinol and phloroglucinol in bulk, injectable form and physiological fluid. Forced degradation studies proved the stability indicating abilities of the method.

  13. 76 FR 49649 - Oral Dosage Form New Animal Drugs; Change of Sponsor; Chlortetracycline; Sulfamethazine

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-11

    ...;Prices of new books are listed in the first FEDERAL REGISTER issue of each #0;week. #0; #0; #0; #0;#0... wholly owned subsidiary of Pfizer, Inc., 235 East 42d St., New York, NY 10017 has informed FDA that it...-0003] Oral Dosage Form New Animal Drugs; Change of Sponsor; Chlortetracycline; Sulfamethazine AGENCY...

  14. Dosage form design and in vitro/in vivo evaluation of cevimeline extended-release tablet formulations.

    PubMed

    Tajiri, Shinichiro; Kanamaru, Taro; Kamada, Makoto; Makoto, Kamada; Konno, Tsutomu; Nakagami, Hiroaki

    2010-01-04

    The objective of the present work is to develop an extended-release dosage form of cevimeline. Two types of extended-release tablets (simple matrix tablets and press-coated tablets) were prepared and their potential as extended-release dosage forms were assessed. Simple matrix tablets have a large amount of hydroxypropylcellulose as a rate-controlling polymer and the matrix is homogeneous throughout the tablet. The press-coated tablets consisted of a matrix core tablet, which was completely surrounded by an outer shell containing a large amount of hydroxypropylcellulose. The simple matrix tablets could not sustain the release of cevimeline effectively. In contrast, the press-coated tablets showed a slower dissolution rate compared with simple matrix tablets and the release curve was nearly linear. The dissolution of cevimeline from the press-coated tablets was not markedly affected by the pH of the dissolution medium or by a paddle rotating speed over the range of 50-200 rpm. Furthermore, cevimeline was constantly released from the press-coated tablets in the gastrointestinal tract and the steady-state plasma drug levels were maintained in beagle dogs. These results suggested that the designed PC tablets have a potential for extended-release dosage forms.

  15. Dissolution testing of orally disintegrating tablets.

    PubMed

    Kraemer, Johannes; Gajendran, Jayachandar; Guillot, Alexis; Schichtel, Julian; Tuereli, Akif

    2012-07-01

    For industrially manufactured pharmaceutical dosage forms, product quality tests and performance tests are required to ascertain the quality of the final product. Current compendial requirements specify a disintegration and/or a dissolution test to check the quality of oral solid dosage forms. These requirements led to a number of compendial monographs for individual products and, at times, the results obtained may not be reflective of the dosage form performance. Although a general product performance test is desirable for orally disintegrating tablets (ODTs), the complexity of the release controlling mechanisms and short time-frame of release make such tests difficult to establish. For conventional oral solid dosage forms (COSDFs), disintegration is often considered to be the prerequisite for subsequent dissolution. Hence, disintegration testing is usually insufficient to judge product performance of COSDFs. Given the very fast disintegration of ODTs, the relationship between disintegration and dissolution is worthy of closer scrutiny. This article reviews the current status of dissolution testing of ODTs to establish the product quality standards. Based on experimental results, it appears that it may be feasible to rely on the dissolution test without a need for disintegration studies for selected ODTs on the market. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  16. QR encoded smart oral dosage forms by inkjet printing.

    PubMed

    Edinger, Magnus; Bar-Shalom, Daniel; Sandler, Niklas; Rantanen, Jukka; Genina, Natalja

    2018-01-30

    The use of inkjet printing (IJP) technology enables the flexible manufacturing of personalized medicine with the doses tailored for each patient. In this study we demonstrate, for the first time, the applicability of IJP in the production of edible dosage forms in the pattern of a quick response (QR) code. This printed pattern contains the drug itself and encoded information relevant to the patient and/or healthcare professionals. IJP of the active pharmaceutical ingredient (API)-containing ink in the pattern of QR code was performed onto a newly developed porous and flexible, but mechanically stable substrate with a good absorption capacity. The printing did not affect the mechanical properties of the substrate. The actual drug content of the printed dosage forms was in accordance with the encoded drug content. The QR encoded dosage forms had a good print definition without significant edge bleeding. They were readable by a smartphone even after storage in harsh conditions. This approach of efficient data incorporation and data storage combined with the use of smart devices can lead to safer and more patient-friendly drug products in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Simultaneous determination of Fluticasone propionate and Azelastine hydrochloride in the presence of pharmaceutical dosage form additives

    NASA Astrophysics Data System (ADS)

    Merey, Hanan A.; El-Mosallamy, Sally S.; Hassan, Nagiba Y.; El-Zeany, Badr A.

    2016-05-01

    Fluticasone propionate (FLU) and Azelastine hydrochloride (AZE) are co-formulated with phenylethyl alcohol (PEA) and Benzalkonium chloride (BENZ) (as preservatives) in pharmaceutical dosage form for treatment of seasonal allergies. Different spectrophotometric methods were used for the simultaneous determination of cited drugs in the dosage form. Direct spectrophotometric method was used for determining of AZE, while Derivative of double divisor of ratio spectra (DD-RS), Ratio subtraction coupled with ratio difference method (RS-RD) and Mean centering of the ratio spectra (MCR) are used for the determination of FLU. The linearity of the proposed methods was investigated in the range of 5.00-40.00 and 5.00-80.00 μg/mL for FLU and AZE, respectively. The specificity of the developed methods was investigated by analyzing laboratory prepared mixtures containing different ratios of cited drugs in addition to PEA and their pharmaceutical dosage form. The validity of the proposed methods was assessed using the standard addition technique. The obtained results were statistically compared with those obtained by official or the reported method for FLU or AZE, respectively showing no significant difference with respect to accuracy and precision at p = 0.05.

  18. Comparative drug release measurements in limited amounts of liquid: a suppository formulation study.

    PubMed

    Welch, Ken; Ek, Ragnar; Strømme, Maria

    2006-07-01

    A novel method for the investigation of drug formulations in limited liquid volumes is presented. The experimental setup consists of a measurement cell containing an absorbent sponge cloth placed between two parallel electrodes. Conductivity measurements are used to monitor the drug release from the dosage form. By varying the amount of water contained in the absorbent cloth surrounding the dosage form, it is possible to measure the drug release performance of the dosage form in very limited amounts of water. The method was employed to test four different tablet formulations consisting of the model drug NaCl incorporated in excipient matrices of hard fat, polyethylene glycol, microcrystalline cellulose and a mixture of microcrystalline cellulose and croscarmellose sodium (Ac-Di-Sol). The drug release rates of the different formulations in limited water volumes differed markedly from the release rates in an excess of water. Whereas the release rates from all tablet types in an excess of water showed only minor differences among the tablet types, the release rates from the tablets formulated with disintegrating excipients were clearly superior in limited water volumes. The developed method for drug release in limited volumes of liquid should be suitable for evaluation of rectal dosage forms.

  19. Terahertz pulsed imaging as an advanced characterisation tool for film coatings--a review.

    PubMed

    Haaser, Miriam; Gordon, Keith C; Strachan, Clare J; Rades, Thomas

    2013-12-05

    Solid dosage forms are the pharmaceutical drug delivery systems of choice for oral drug delivery. These solid dosage forms are often coated to modify the physico-chemical properties of the active pharmaceutical ingredients (APIs), in particular to alter release kinetics. Since the product performance of coated dosage forms is a function of their critical coating attributes, including coating thickness, uniformity, and density, more advanced quality control techniques than weight gain are required. A recently introduced non-destructive method to quantitatively characterise coating quality is terahertz pulsed imaging (TPI). The ability of terahertz radiation to penetrate many pharmaceutical materials enables structural features of coated solid dosage forms to be probed at depth, which is not readily achievable with other established imaging techniques, e.g. near-infrared (NIR) and Raman spectroscopy. In this review TPI is introduced and various applications of the technique in pharmaceutical coating analysis are discussed. These include evaluation of coating thickness, uniformity, surface morphology, density, defects and buried structures as well as correlation between TPI measurements and drug release performance, coating process monitoring and scale up. Furthermore, challenges and limitations of the technique are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Analysis of coating structures and interfaces in solid oral dosage forms by three dimensional terahertz pulsed imaging.

    PubMed

    Zeitler, J Axel; Shen, Yaochun; Baker, Colin; Taday, Philip F; Pepper, Michael; Rades, Thomas

    2007-02-01

    Three dimensional terahertz pulsed imaging (TPI) was evaluated as a novel tool for the nondestructive characterization of different solid oral dosage forms. The time-domain reflection signal of coherent pulsed light in the far infrared was used to investigate film-coated tablets, sugar-coated tablets, multilayered controlled release tablets, and soft gelatin capsules. It is possible to determine the spatial and statistical distribution of coating thickness in single and multiple coated products using 3D TPI. The measurements are nondestructive even for layers buried underneath other coating structures. The internal structure of coating materials can be analyzed. As the terahertz signal penetrates up to 3 mm into the dosage form interfaces between layers in multilayered tablets can be investigated. In soft gelatin capsules it is possible to measure the thickness of the gelatin layer and to characterize the seal between the gelatin layers for quality control. TPI is a unique approach for the nondestructive characterization and quality control of solid dosage forms. The measurements are fast and fully automated with the potential for much wider application of the technique in the process analytical technology scheme. Copyright (c) 2006 Wiley-Liss, Inc.

  1. Floating dosage forms to prolong gastro-retention--the characterisation of calcium alginate beads.

    PubMed

    Stops, Frances; Fell, John T; Collett, John H; Martini, Luigi G

    2008-02-28

    Floating calcium alginate beads, designed to improve drug bioavailability from oral preparations compared with that from many commercially available and modified release products, have been investigated as a possible gastro-retentive dosage form. A model drug, riboflavin, was also incorporated into the formula. The aims of the current work were (a) to obtain information regarding the structure, floating ability and changes that occurred when the dosage form was placed in aqueous media, (b) to investigate riboflavin release from the calcium alginate beads in physiologically relevant media prior to in vivo investigations. Physical properties of the calcium alginate beads were investigated. Using SEM and ESEM, externally the calcium alginate beads were spherical in shape, and internally, air filled cavities were present thereby enabling floatation of the beads. The calcium alginate beads remained buoyant for times in excess of 13h, and the density of the calcium alginate beads was <1.000gcm(-3). Riboflavin release from the calcium alginate beads showed that riboflavin release was slow in acidic media, whilst in more alkali media, riboflavin release was more rapid. The characterisation studies showed that the calcium alginate beads could be considered as a potential gastro-retentive dosage form.

  2. A Review of Disintegration Mechanisms and Measurement Techniques.

    PubMed

    Markl, Daniel; Zeitler, J Axel

    2017-05-01

    Pharmaceutical solid dosage forms (tablets or capsules) are the predominant form to administer active pharmaceutical ingredients (APIs) to the patient. Tablets are typically powder compacts consisting of several different excipients in addition to the API. Excipients are added to a formulation in order to achieve the desired fill weight of a dosage form, to improve the processability or to affect the drug release behaviour in the body. These complex porous systems undergo different mechanisms when they come in contact with physiological fluids. The performance of a drug is primarily influenced by the disintegration and dissolution behaviour of the powder compact. The disintegration process is specifically critical for immediate-release dosage forms. Its mechanisms and the factors impacting disintegration are discussed and methods used to study the disintegration in-situ are presented. This review further summarises mathematical models used to simulate disintegration phenomena and to predict drug release kinetics.

  3. Preparation of microcapsules with self-microemulsifying core by a vibrating nozzle method.

    PubMed

    Homar, Miha; Suligoj, Dasa; Gasperlin, Mirjana

    2007-02-01

    Incorporation of drugs in self-microemulsifying systems (SMES) offers several advantages for their delivery, the main one being faster drug dissolution and absorption. Formulation of SMES in solid dosage forms can be difficult and, to date, most SMES are applied in liquid dosage form or soft gelatin capsules. This study has explored the incorporation of SMES in microcapsules, which could then be used for formulation of solid dosage forms. An Inotech IE-50 R encapsulator equipped with a concentric nozzle was used to produce alginate microcapsules with a self-microemulsifying core. Retention of the core phase was improved by optimization of encapsulator parameters and modification of the shell forming phase and hardening solution. The mean encapsulation efficiency of final batches was more than 87%, which resulted in 0.07% drug loading. It was demonstrated that production of microcapsules with a self-microemulsifying core is possible and that the process is stable and reproducible.

  4. Intravesical treatment of bladder pain syndrome/interstitial cystitis: from the conventional regimens to the novel botulinum toxin injections.

    PubMed

    Dellis, Athanasios; Papatsoris, Athanasios G

    2014-06-01

    Bladder pain syndrome (BPS) includes interstitial cystitis (IC) and is often used as a synonym of it (i.e., BPS/IC). It is associated with lower urinary tract symptoms as well as with negative cognitive, behavioral, sexual and/or emotional consequences. Unfortunately, none of the numerous existing oral and intravesical treatments have been effective for all of the BPS subtypes and therefore relevant research is ongoing. In this review, the authors analyze the existing literature for the intravesical treatment of BPS/IC with focus on the novel administration of botulinum toxin (BTX). Several intravesical drugs have been studied in the past, including lidocaine, heparin, pentosan polysulfate sodium, dimethyl sulfoxide, chondroitin sulfate, hyaluronic acid as well as investigational drugs such as GM-0111. Recently, intravesical submucosal injections of BTX have been studied in patients with BPS/IC. Most of the recent studies use BTX-A with no serious adverse effects and with satisfactory results in patients who do not respond to oral or standard intravesical therapy. Nevertheless, there is no consensus regarding the best dosage scheme of BTX, the injection sites and the treatment intervals. BTX intravesical administration in patients with BPS/IC is a safe and efficient treatment option; yet the level of evidence of the initial studies is not high. There is still the need for large randomized controlled studies so that a consensus can be reached for the ideal BTX dosage, injection sites and intervals between treatments.

  5. Microwave freeze-thaw technique of injectable drugs. A review from 1980 to 2014.

    PubMed

    Hecq, J-D; Godet, M; Jamart, J; Galanti, L

    2015-11-01

    Microwave freeze-thaw treatment (MFTT) of injectable drugs can support the development of centralized intravenous admixtures services (CIVAS). The aim of the review is to collect information and results about this method. A systematic review of the scientific literature about injectable drug stability studies was performed. The data are presented in a table and describe name of the drug, producer, final concentration, temperature and time of freezing storage, type of microwave oven, thawing power, method of dosage and results after treatment or final long-term storage at 5±3 °C. From 1980 to 2014, 59 drugs were studied by MFTT and the results were presented in 49 publications. Forty papers were presented by 8 teams (2 to 18 by team). The temperatures of freezing storage vary from -70 °C to -10 °C, the time storage from 4 hours to 12 months, the thaw from low to full power. Dosages are mainly made by high performance liquid chromatography. Most of the 59 drugs are stable during and after treatment. Only 3 teams have tested the long-term stability after MFTT, the first for ganciclovir after 7 days, the second for ceftizoxime after 30 days and the third for 19 drugs after 11 to 70 days. This review can help CIVAS to take in charge the productions of ready-to-use injectable drugs. Copyright © 2015 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

  6. Toxic corneal epitheliopathy after intravitreal methotrexate and its treatment with oral folic acid.

    PubMed

    Gorovoy, Ian; Prechanond, Tidarat; Abia, Maravillas; Afshar, Armin R; Stewart, Jay M

    2013-08-01

    To determine whether oral folic acid can ameliorate an iatrogenic, visually significant corneal epitheliopathy, which commonly occurs with intravitreal injections of methotrexate for the treatment of intraocular lymphoma. We report 2 cases of visually significant corneal epitheliopathy occurring after intravitreal injections of methotrexate for intraocular lymphoma. The first patient did not receive any treatment for the corneal disease, and the second patient with bilateral intraocular lymphoma received 1 mg of oral folic acid daily, a commonly used dosage for patients on systemic methotrexate. In the first patient without treatment, there was a complete regression of the corneal epithelial disease only when the frequency of intravitreal methotrexate was reduced from weekly to monthly as per a commonly used dosage regimen for methotrexate. In the second patient, the corneal disease improved 80% within 1 week of initiating oral folic acid for her eye already experiencing severe epitheliopathy during her weekly dosing regimen of methotrexate and also had significantly decreased epithelial disease in her second eye that started weekly intravitreal methotrexate several weeks after beginning oral folic acid. Currently, oral folic acid supplements are recommended for patients using systemic methotrexate to minimize drug toxicity. We suggest a similar use in patients undergoing intravitreal methotrexate injections to decrease toxic effects on the corneal epithelium.

  7. Green approach towards the determination of hydroxyzine dihydrochloride in pure and pharmaceutical dosage forms.

    PubMed

    Mumtaz, Amina; Hussain, Shahid; Yasir, Muhammad

    2014-09-01

    A simple eco-friendly method has been developed for detection of hydroxyzine dihydrochloride in pure and pharmaceutical dosage forms. Both conventional system and microwave assisted procedures are used for the development of color. The blue coloured complex is measured spectrophotometrically at 750nm. Peak shift in FT-IR spectra also indicated the formation of complex. The reaction obeys Beer's law over the concentration range of 50- 250βg/mL of hydroxyzine dihydrochloride. The precision value (intra-day and inter-day RSD) for the drug is not greater than 0.79% and recoveries were found to be in range of 99.01-99.99%. The designed method is applicable for periodic determination of hydroxyzine dihydrochloride in pure and pharmaceutical dosage forms.

  8. Biopharmaceutical Evaluation and CMC Aspects of Oral Modified Release Formulations.

    PubMed

    Chang, Rong-Kun; Mathias, Neil; Hussain, Munir A

    2017-09-01

    This article discusses the range of outcomes from biopharmaceutical studies of specific modified release (MR) product examples in preclinical models and humans. It touches upon five major biopharmaceutical areas for MR drug products: (1) evidence for regional permeability throughout the GI tract, (2) susceptibility to food-effect, (3) susceptibility to pH-effect, (4) impact of chronopharmacology in designing MR products, and (5) implications to narrow therapeutic index products. Robust bioperformance requires that product quality is met through a thorough understanding of the appropriate critical quality attributes that ensure reliable and robust manufacture of a MR dosage form. The quality-by-design (QbD) aspects of MR dosage form design and development are discussed with the emphasis on the regulatory view of the data required to support dosage form development.

  9. 21 CFR 522.2002 - Propiopromazine hydrochloride injection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Section 522.2002 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... administered either intravenously or intramuscularly to dogs and cats for tranquilization at a dosage level of 0.05-0.5 milligram per pound of body weight and is also administered intravenously to dogs and cats...

  10. Essential medicines lists for children of WHO, India, South Africa, and EML of China: A comparative study.

    PubMed

    Liu, Dan; Cheng, Jing; Zhang, Ling-Li; Li, You-Ping; Zeng, Li-Nan; Zhang, Chuan; Gui, Ge

    2017-11-01

    Comparing the essential medicine lists for children and China national essential medicine list 2012, to provide the evidence for establishing essential medicine list for children in China. Search the official websites of WHO and some other countries' ministry of health to get essential medicine lists for children (EMLc) that have already established. Compare the situation of updating, the number and classification of medicines, and the dosage forms in essential medicine lists for children and China national essential medicine list 2012. By December 2013, the WHO, India, and South Africa have established EMLc. The list of China was for people in all ages, so the number of medicines ranked first in four lists. WHO, India, and China classified the medicines by pharmacologic action, South Africa classified by ATC classification. Except for WHO, India, South Africa, and China did not have specific medicines for neonatal care or medicines for diseases of joints. The main administration routes in these four lists were oral administration, injection, and topical application. There were medicine restrictions in lists of WHO and India, but there were no medicine restrictions in the lists of South Africa and China. Compared with EMLs for children, the 2012 National Essential Medicine List for China is not suitable for children in China. Development of Chinese EMLc should be based on the burden of diseases for children, and should select applicable dosage forms and specifications. © 2016 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.

  11. Nursing home medication administration cost minimization analysis.

    PubMed

    Hamrick, Irene; Nye, Ann Marie; Gardner, Casey K

    2007-03-01

    To assess the time it takes nurses to administer medications in the nursing home setting, to calculate nursing cost of medication administration, and to determine whether using extended-release products are justified by decreasing nursing costs. Cost-minimization analysis using observational data from a time-motion analysis. Two 150-bed nursing homes in rural eastern North Carolina. Nurses working during first and second shifts. Nurses were timed as they each administered medications to 12 patients. The mean time required to administer each dosage form was calculated. The cost of nursing time was based on the average nursing staff salary of $20.45 per hour as reported by the directors of nursing. Time and cost to dispense one more medication during an existing medication pass and an additional medication pass are calculated. The time to administer an additional dose of an oral medication to one patient was 45.01 seconds during an already scheduled medication pass and 63.05 seconds during a new medication pass. The cost of adding an oral medication once a day for a patient will cost $7.67 per month if administered at the same time as other medications or $10.74 per month if a new medication pass is required. The administration of other dosage forms, such as crushed, percutaneous enteroscopic gastrostomy, injection, and patch was more time involved and, thus, costlier. Formulas are provided to calculate medication administration cost based on local salary. Nursing time and costs for medication administration in the nursing home are great and should be considered when selecting a product. This may justify the selection of higher cost extended-release products.

  12. Use of two sulfonthalein dyes in the extraction-free spectrophotometric assay of tramadol in dosage forms and in spiked human urine based on ion-pair reaction.

    PubMed

    Vinay, Kanakapura B; Revannasiddappa, Hosakere D; Rajendraprasad, Nagaraju; Ramesh, Pavagada J; Xavier, Cijo M; Basavaiah, Kanakapura

    2012-02-01

    Tramadol is a centrally acting analgesic used in the prevention and treatment of moderate to severe pain. Two sensitive, selective, and rapid spectrophotometric methods are described for the determination of tramadol in its dosage forms and in spiked human urine. The methods are based on formation of yellow ion-pairs between tramadol and two sulfonthalein dyes; bromocresol purple (BCP) and bromocresol green (BCG) in dichloromethane medium followed by absorbance measurement at 400 and 410 nm, respectively. Under the optimum conditions, tramadol could be assayed in the concentration ranges, 1-15 and 1-16 µg ml(-1) with correlation coefficient greater than 0.999 in both cases. The molar absorptivity values are calculated to be 1.84 × 10(4) and 1.97 × 10(4) l mol(-1) cm(-1) for BCP and BCG methods, respectively; and the corresponding Sandell sensitivity values are 0.0143 and 0.0134 µg cm(-2). The limits of detection (LOD) and quantification (LOQ) have also been reported. The stoichiometry of the reaction was found to be 1:1 in both cases and the conditional stability constant (K(f)) values of the ion pairs have been calculated. The within-day and between-day RSD were 0.9-1.96% and 1.56-3.21%, respectively. The methods were successfully applied to the determination of tramadol in tablets and injections and also in spiked human urine with good recoveries. The procedures are simple, accurate, and suitable for quality control application. Copyright © 2011 John Wiley & Sons, Ltd.

  13. Botulinum toxin uses in strabismus: A review of the injections performed during one year in a general hospital.

    PubMed

    Jarrín, E; Arranz Márquez, E; Yebra González, L; García Gil de Bernabé, J

    2016-03-01

    To analyse the indications, dosage and efficacy of botulinum toxin A injection performed in patients in a Strabismus Department. In this prospective study, botulinum toxin A was injected into 28 patients diagnosed with strabismus. Data was obtained from the records of patients that were evaluated during 2013 in the Strabismus Unit of Rey Juan Carlos Hospital (Móstoles, Madrid, Spain) in order to assess the indications and dosage of botulinum toxin A use in strabismus, as well as its clinical effect and differences in paediatric and adult patients. The outcomes in the last visit, at least 14 months after the injections, were analysed. An analysis was performed on the data from 11 children, 6 females (54.5%), and 17 adults, 11 males (64%). The mean age was 4.42±3.48 years and 58.71±18.07 years in the children and adult groups, respectively. The majority of cases in both groups were esotropia (81.8% in children and 47.1% in adults). However the pathologies in the adult group were quite heterogeneous, including 4 patients with exotropia (26.5%), 4 with hypertropia (26.5%), and one with isolated nystagmus (5.9%). The mean number of the botulinum toxin injections in children was 1.45±0.93, although 72.7% received a single injection. In the adult group, the mean number of injections was 3.27±1.41. There was a statistically significant difference between pre- and post-injection in the tropia and phoria measurements in children and adults group (P<.05). In both groups there was a statistically significant improvement in post-injection torticollis when compared with the pre-injection measurement (P<.05). An improvement in the stereoacuity could be detected in 4 children. Two children (18.2%) and 5 adults (29.4%) required subsequent surgical intervention. Eight adult patients (49.1%) complained of diplopia in the primary position, which was resolved in 6 cases with toxin injection, whereas 2 needed surgery for diplopia correction. Botulinum toxin is a very useful tool in the management of strabismus, obtaining better sensory and motor results in children, but it is also effective as a symptomatic treatment in some types of strabismus in adults. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  14. Solid oral forms availability in children: a cost saving investigation

    PubMed Central

    Lajoinie, Audrey; Henin, Emilie; Kassai, Behrouz; Terry, David

    2014-01-01

    Aim To assess the suitability and potential cost savings, from both the hospital and community perspective, of prescribed oral liquid medicine substitution with acceptable solid forms for children over 2 years. Method Oral liquid medicines dispensed from a paediatric hospital (UK) in 1 week were assessed by screening for existence of the solid form alternative and evaluating the acceptability of the available solid form, firstly related to the prescribed dose and secondly to acceptable size depending on the child's age. Costs were calculated based on providing treatment for 28 days or prescribed duration for short term treatments. Results Over 90% (440/476) of liquid formulations were available as a marketed solid form. Considering dosage acceptability (maximum of 10% deviation from prescribed dosage or 0% for narrow therapeutic range drugs, maximum tablet divisions into quarters) 80% of liquids could be substituted with a solid form. The main limitation for liquid substitution would be solid form size. However, two-thirds of prescribed liquids could have been substituted with a suitable solid form for dosage and size, with estimated savings being of £5K and £8K in 1 week, respectively based on hospital and community costs, corresponding to a projected annual saving of £238K and £410K (single institution). Conclusion Whilst not all children over 2 years will be able to swallow tablets, drug cost savings if oral liquid formulations were substituted with suitable solid dosage forms would be considerable. Given the numerous advantages of solid forms compared with liquids, this study may provide a theoretical basis for investing in supporting children to swallow tablets/capsules. PMID:24965935

  15. A double-blind, randomized, placebo-controlled comparison of botulinum toxin type a injection sites and doses in the prevention of episodic migraine.

    PubMed

    Saper, Joel R; Mathew, Ninan T; Loder, Elizabeth W; DeGryse, Ronald; VanDenburgh, Amanda M

    2007-09-01

    Several randomized, controlled studies have reported benefits of botulinum toxin type A (BoNTA; Allergan Inc., Irvine, CA, USA) over placebo in the treatment of migraine. Some studies reported significant benefits at dosages as low as 16 U, while other studies reported safety, tolerability, and efficacy at dosages up to 260 U. However, the optimal treatment paradigm and patient population have yet to be defined. To compare different injection sites and doses of BoNTA in the prevention of episodic migraine. This was a randomized, double-blind, placebo-controlled study of 232 patients with a history of four to eight moderate to severe migraines per month, with or without aura. Patients were randomized to placebo or one of four BoNTA groups that received injections into different muscle regions: frontal (10 U), temporal (6 U), glabellar (9 U), or all three areas (total dose 25 U). For 3 months following a single treatment, patients recorded migraine-related variables in a daily diary. BoNTA and placebo produced comparable decreases from baseline in the frequency of migraines (P > or = 0.411). In general, no statistically significant differences were observed for any efficacy variable. The overall rates of adverse events (any type) or treatment-related adverse events were similar among the groups. In this exploratory study of episodic migraine patients, low-dose injections of BoNTA into the frontal, temporal, and/or glabellar muscle regions were not more effective than placebo. BoNTA was safe and well tolerated. Future studies may examine higher BoNTA doses, flexible injection sites, multiple treatments, and disallow concomitant prophylactic medications.

  16. Pharmacokinetics of buprenorphine after single-dose subcutaneous administration in red-eared sliders (Trachemys scripta elegans).

    PubMed

    Kummrow, Maya S; Tseng, Florina; Hesse, Leah; Court, Michael

    2008-12-01

    Buprenorphine, a mu opioid receptor agonist, is expected to be a suitable analgesic drug for use in reptiles. However, to date, dosage recommendations have been based on anecdotal observations. The aim of this study was to provide baseline pharmacokinetic data in red-eared sliders (Trachemys scripta elegans) targeting a plasma level of 1 ng/ml reported effective for analgesia in humans. Serial blood samples were taken after subcutaneous injection of buprenorphine, and plasma buprenorphine levels were measured by radioimmunoassay. Pharmacokinetic parameters of a lower dose (0.02 mg/kg) injected into the forelimb were compared with a higher dose (0.05 mg/kg) given in the same forelimb as well as a lower dose (0.02 mg/kg) given in the hind limb of the same animals with 2 wk between studies. After administration of 0.05 mg/kg in the front limb, 85% of animals maintained the minimum effective plasma level for 24 hr, while only 43% of animals maintained this level after 0.02 mg/kg. After hind limb injection at 0.02 mg/kg, maximum plasma concentrations and areas under the buprenorphine concentration-time curve were less than 20% and 70%, respectively, of values after forelimb injection, consistent with substantial first pass extraction by the liver. Furthermore, a secondary rise in the buprenorphine level was found after having only a hind limb injection, probably from enterohepatic recirculation of glucuronidated drug. In conclusion, buprenorphine dosages of at least 0.075 mg/kg s.i.d. should be appropriate for evaluation of analgesia efficacy, and front limb administration may be preferable to hind limb administration for optimal drug exposure.

  17. Chemical stability of diphenhydramine hydrochloride from an elixir and lidocaine hydrochloride from a viscous solution when mixed together.

    PubMed

    Gupta, Vishnu D

    2006-01-01

    The stability of diphenhydramine hydrochloride (from an elixir) and lidocaine hydrochloride (from a viscous solution) in a mixture (1:1) was studied using a stability-indicating high-peformance liquid chromatographic assay method. The concentrations of the drugs were related directly to peak heights and the percent relative standard deviations based on five injections were 1.4 for diphenhydramine and 1.3 for lidocaine. The products of hydrolysis from the both the drugs and a number of excipients present in the dosage forms did not interfere with the developed assay procedure. The mixture was stable for at least 21 days when stored in amber-colored bottles at room temperature. The pH value of the mixture remained constant, and the physical appearance did not change during the study period.

  18. [Analysis of Kudiezi injection's security literature].

    PubMed

    Chang, Yan-Peng; Xie, Yan-Ming

    2012-09-01

    By retrieving the relevant database, aim was to achieve the security reported of Kudiezi injection (Yueanxin). To analysis the gender, age, underlying disease, medication dosage, solvent, adverse event/adverse reaction time of occurrence, clinical presentation of patients, It was found the adverse event/adverse reaction usually occur in older people, involving the organs and systems include skin and its appendages, digestive system, nervous system, circulatory system, respiratory system, systemic reaction, part of the adverse event/adverse reaction's cause were not according to the instructions. It was found on the adverse event/adverse reaction of the judgment on the lack of objective evidence, to produce certain effect for objective evaluation of security of Kudiezi injection (Yueanxin).

  19. Inhibition of Androgen-Independent Growth of Prostate Cancer by siRNA-Mediated Androgen Receptor Gene Silencing

    DTIC Science & Technology

    2006-02-01

    was gradually increased along with increasing dosage of the AAV.ARHP8 particles injected. No GFP expression was observed in PBS-injected xenograft...receptor. Cancer Gene Ther 2002;9:117–25. 16. Craft N, Shostak Y , Carey M, Sawyers CL. A mechanism for hormone- independent prostate cancer through...modulation of androgen receptor signaling by the HER-2/neu tyrosine kinase. Nat Med 1999;5:280–5. 17. Wen Y , Hu MC, Makino K, et al. HER-2/neu promotes

  20. Derivative spectrophotometric method for simultaneous determination of clindamycin phosphate and tretinoin in pharmaceutical dosage forms.

    PubMed

    Barazandeh Tehrani, Maliheh; Namadchian, Melika; Fadaye Vatan, Sedigheh; Souri, Effat

    2013-04-10

    A derivative spectrophotometric method was proposed for the simultaneous determination of clindamycin and tretinoin in pharmaceutical dosage forms. The measurement was achieved using the first and second derivative signals of clindamycin at (1D) 251 nm and (2D) 239 nm and tretinoin at (1D) 364 nm and (2D) 387 nm.The proposed method showed excellent linearity at both first and second derivative order in the range of 60-1200 and 1.25-25 μg/ml for clindamycin phosphate and tretinoin respectively. The within-day and between-day precision and accuracy was in acceptable range (CV<3.81%, error<3.20%). Good agreement between the found andadded concentrations indicates successful application of the proposed method for simultaneous determination of clindamycin and tretinoin in synthetic mixtures and pharmaceutical dosage form.

  1. Semi-Solid and Solid Dosage Forms for the Delivery of Phage Therapy to Epithelia.

    PubMed

    Brown, Teagan L; Petrovski, Steve; Chan, Hiu Tat; Angove, Michael J; Tucci, Joseph

    2018-02-26

    The delivery of phages to epithelial surfaces for therapeutic outcomes is a realistic proposal, and indeed one which is being currently tested in clinical trials. This paper reviews some of the known research on formulation of phages into semi-solid dosage forms such as creams, ointments and pastes, as well as solid dosage forms such as troches (or lozenges and pastilles) and suppositories/pessaries, for delivery to the epithelia. The efficacy and stability of these phage formulations is discussed, with a focus on selection of optimal semi-solid bases for phage delivery. Issues such as the need for standardisation of techniques for formulation as well as for assessment of efficacy are highlighted. These are important when trying to compare results from a range of experiments and across different delivery bases.

  2. Practical issues of hyperspectral imaging analysis of solid dosage forms.

    PubMed

    Amigo, José Manuel

    2010-09-01

    Hyperspectral imaging techniques have widely demonstrated their usefulness in different areas of interest in pharmaceutical research during the last decade. In particular, middle infrared, near infrared, and Raman methods have gained special relevance. This rapid increase has been promoted by the capability of hyperspectral techniques to provide robust and reliable chemical and spatial information on the distribution of components in pharmaceutical solid dosage forms. Furthermore, the valuable combination of hyperspectral imaging devices with adequate data processing techniques offers the perfect landscape for developing new methods for scanning and analyzing surfaces. Nevertheless, the instrumentation and subsequent data analysis are not exempt from issues that must be thoughtfully considered. This paper describes and discusses the main advantages and drawbacks of the measurements and data analysis of hyperspectral imaging techniques in the development of solid dosage forms.

  3. Semi-Solid and Solid Dosage Forms for the Delivery of Phage Therapy to Epithelia

    PubMed Central

    Petrovski, Steve; Chan, Hiu Tat; Angove, Michael J.; Tucci, Joseph

    2018-01-01

    The delivery of phages to epithelial surfaces for therapeutic outcomes is a realistic proposal, and indeed one which is being currently tested in clinical trials. This paper reviews some of the known research on formulation of phages into semi-solid dosage forms such as creams, ointments and pastes, as well as solid dosage forms such as troches (or lozenges and pastilles) and suppositories/pessaries, for delivery to the epithelia. The efficacy and stability of these phage formulations is discussed, with a focus on selection of optimal semi-solid bases for phage delivery. Issues such as the need for standardisation of techniques for formulation as well as for assessment of efficacy are highlighted. These are important when trying to compare results from a range of experiments and across different delivery bases. PMID:29495355

  4. Particle Engineering Via Mechanical Dry Coating in the Design of Pharmaceutical Solid Dosage Forms.

    PubMed

    Qu, Li; Morton, David A V; Zhou, Qi Tony

    2015-01-01

    Cohesive powders are problematic in the manufacturing of pharmaceutical solid dosage forms because they exhibit poor flowability, fluidization and aerosolization. These undesirable bulk properties of cohesive powders represent a fundamental challenge in the design of efficient pharmaceutical manufacturing processes. Recently, mechanical dry coating has attracted increasing attention as it can improve the bulk properties of cohesive powders in a cheaper, simpler, safer and more environment-friendly way than the existing solvent-based counterparts. In this review, mechanical dry coating techniques are outlined and their potential applications in formulation and manufacturing of pharmaceutical solid dosage forms are discussed. Reported data from the literature have shown that mechanical dry coating holds promise for the design of superior pharmaceutical solid formulations or manufacturing processes by engineering the interfaces of cohesive powders in an efficient and economical way.

  5. Pharmacokinetics of orally administered DL-α-lipoic acid in dogs.

    PubMed

    Zicker, Steven C; Avila, Albert; Joshi, Dinesh K; Gross, Kathy L

    2010-11-01

    To determine the pharmacokinetics of DL-α-lipoic acid in dogs when administered at 3 dosages via 3 methods of delivery. 27 clinically normal Beagles. In a 3 × 3 factorial Latin square design, 3 dosages (2.5, 12.5, and 25 mg/kg) of DL-α-lipoic acid were administered orally in a capsule form and provided without a meal, in a capsule form and provided with a meal, and as an ingredient included in an extruded dog food. Food was withheld for 12 hours prior to DL-α-lipoic acid administration. Blood samples were collected before (0 minutes) and at 15, 30, 45, 60, and 120 minutes after administration. Plasma concentrations of DL-α-lipoic acid were determined via high-performance liquid chromatography. A generalized linear models procedure was used to evaluate the effects of method of delivery and dosage. Noncompartmental analysis was used to determine pharmacokinetic parameters of DL-α-lipoic acid. Nonparametric tests were used to detect significant differences between pharmacokinetic parameters among treatment groups. A significant effect of dosage was observed regardless of delivery method. Method of delivery also significantly affected plasma concentrations of DL-α-lipoic acid, with extruded foods resulting in lowest concentration for each dosage administered. Maximum plasma concentration was significantly affected by method of delivery at each dosage administered. Other significant changes in pharmacokinetic parameters were variable and dependent on dosage and method of delivery. Values for pharmacokinetic parameters of orally administered DL-α-lipoic acid may differ significantly when there are changes in dosage, method of administration, and fed status.

  6. The Quality of Selected Essential Medicines Sold in Accredited Drug Dispensing Outlets and Pharmacies in Tanzania.

    PubMed

    Kaale, Eliangiringa; Manyanga, Vicky; Chambuso, Mhina; Liana, Jafary; Rutta, Edmund; Embrey, Martha; Layloff, Thomas; Johnson, Keith

    2016-01-01

    The purpose of this study was to investigate the quality of a select group of medicines sold in accredited drug dispensing outlets (ADDOs) and pharmacies in different regions of Tanzania as part of an in-depth cross-sectional assessment of community access to medicines and community use of medicines. We collected 242 samples of amoxicillin trihydrate, artemether-lumefantrine (ALu), co-trimoxazole, ergometrine maleate, paracetamol, and quinine from selected ADDOs and pharmacies in Mbeya, Morogoro, Singida, and Tanga regions. The analysis included physical examination and testing with validated analytical techniques. Assays for eight of nine products were conducted using high-performance thin-layer chromatography (HPTLC). For ALu tablets, we used a two-tiered approach, where tier 1 was a semi-quantitative Global Pharma Health Fund-Minilab® method and tier 2 was high-performance liquid chromatography (HPLC) as described in The International Pharmacopoeia's monograph for artemether-lumefantrine. The physical examination of samples revealed no defects in the solid and oral liquid dosage forms, but unusual discoloration in an injectable solution, ergometrine maleate. For ALu, the results showed that of 38 samples, 31 (81.6%) passed tier 1 testing and 7 (18.4%) gave inconclusive drug content results. The inconclusive ALu samples were submitted for tier 2 testing and all met the quality standards. The pass rate using the HPTLC and TLC/HPLC assays was 93.8%; the failures were the ergometrine maleate samples purchased from both ADDOs and pharmacies. The disintegration testing of the solid dosage forms was conducted in accordance with US Pharmacopeia monographs. Only two samples of paracetamol, 1.2% of the solid dosage forms, failed to comply to standards. The study revealed a high overall rate of 92.6% of samples that met the quality standards. Although the overall failure rate was 7.4%, it is important to note that this was largely limited to one product and likely due to poor distribution and storage rather than poor manufacturing practices. Over 90% of the medicines sold in ADDOs and pharmacies met quality standards. Policy makers need to reconsider ergometrine maleate's place on the list of medicines that ADDOs are allowed to dispense, by either substituting a more temperature-stable therapeutically equivalent product or requiring those sites to have refrigerators, which is not a feasible option for rural Tanzania.

  7. The Quality of Selected Essential Medicines Sold in Accredited Drug Dispensing Outlets and Pharmacies in Tanzania

    PubMed Central

    Manyanga, Vicky; Chambuso, Mhina; Liana, Jafary; Rutta, Edmund; Embrey, Martha; Layloff, Thomas; Johnson, Keith

    2016-01-01

    Introduction The purpose of this study was to investigate the quality of a select group of medicines sold in accredited drug dispensing outlets (ADDOs) and pharmacies in different regions of Tanzania as part of an in-depth cross-sectional assessment of community access to medicines and community use of medicines. Methods We collected 242 samples of amoxicillin trihydrate, artemether-lumefantrine (ALu), co-trimoxazole, ergometrine maleate, paracetamol, and quinine from selected ADDOs and pharmacies in Mbeya, Morogoro, Singida, and Tanga regions. The analysis included physical examination and testing with validated analytical techniques. Assays for eight of nine products were conducted using high-performance thin-layer chromatography (HPTLC). For ALu tablets, we used a two-tiered approach, where tier 1 was a semi-quantitative Global Pharma Health Fund-Minilab® method and tier 2 was high-performance liquid chromatography (HPLC) as described in The International Pharmacopoeia’s monograph for artemether-lumefantrine. Results and Discussion The physical examination of samples revealed no defects in the solid and oral liquid dosage forms, but unusual discoloration in an injectable solution, ergometrine maleate. For ALu, the results showed that of 38 samples, 31 (81.6%) passed tier 1 testing and 7 (18.4%) gave inconclusive drug content results. The inconclusive ALu samples were submitted for tier 2 testing and all met the quality standards. The pass rate using the HPTLC and TLC/HPLC assays was 93.8%; the failures were the ergometrine maleate samples purchased from both ADDOs and pharmacies. The disintegration testing of the solid dosage forms was conducted in accordance with US Pharmacopeia monographs. Only two samples of paracetamol, 1.2% of the solid dosage forms, failed to comply to standards. The study revealed a high overall rate of 92.6% of samples that met the quality standards. Although the overall failure rate was 7.4%, it is important to note that this was largely limited to one product and likely due to poor distribution and storage rather than poor manufacturing practices. Conclusions Over 90% of the medicines sold in ADDOs and pharmacies met quality standards. Policy makers need to reconsider ergometrine maleate’s place on the list of medicines that ADDOs are allowed to dispense, by either substituting a more temperature-stable therapeutically equivalent product or requiring those sites to have refrigerators, which is not a feasible option for rural Tanzania. PMID:27846216

  8. Confectionery-based dose forms.

    PubMed

    Tangso, Kristian J; Ho, Quy Phuong; Boyd, Ben J

    2015-01-01

    Conventional dosage forms such as tablets, capsules and syrups are prescribed in the normal course of practice. However, concerns about patient preferences and market demands have given rise to the exploration of novel unconventional dosage forms. Among these, confectionery-based dose forms have strong potential to overcome compliance problems. This report will review the availability of these unconventional dose forms used in treating the oral cavity and for systemic drug delivery, with a focus on medicated chewing gums, medicated lollipops, and oral bioadhesive devices. The aim is to stimulate increased interest in the opportunities for innovative new products that are available to formulators in this field, particularly for atypical patient populations.

  9. Treatment efficacy of electromyography versus fiberscopy-guided botulinum toxin injection in adductor spasmodic dysphonia patients: a prospective comparative study.

    PubMed

    Kim, Jae Wook; Park, Jae Hong; Park, Ki Nam; Lee, Seung Won

    2014-01-01

    This study prospectively evaluates and compares the treatment efficacy of botulinum toxin injection under electromyography guidance (EMG group) and percutaneous botulinum toxin injection under flexible fiberscopic guidance (fiberscopy group). Thirty patients with adductor spasmodic dysphonia (ADSD), who had never received treatment, were randomly allocated into EMG- or fiberscopy-guided botulinum toxin injections between March 2008 and February 2010. We assessed acoustic and aerodynamic voice parameters, and the voice handicap index (VHI) before injection and at 1, 3, and 6 months after injection. The mean total dosage of botulinum toxin was similar for both groups: 1.7 ± 0.5 U for the EMG group and 1.8 ± 0.4 U for the fiberscopy group (P > 0.05). There were no significant differences in outcomes between the two groups in either the duration of effectiveness or complications such as breathy voice and aspiration. Botulinum toxin injection under fiberscopic guidance is a viable alternative to EMG-guided botulinum toxin injection for the treatment of adductor spasmodic dysphonia when EMG equipment is unavailable.

  10. Treatment Efficacy of Electromyography versus Fiberscopy-Guided Botulinum Toxin Injection in Adductor Spasmodic Dysphonia Patients: A Prospective Comparative Study

    PubMed Central

    Kim, Jae Wook; Park, Jae Hong; Park, Ki Nam; Lee, Seung Won

    2014-01-01

    Introduction. This study prospectively evaluates and compares the treatment efficacy of botulinum toxin injection under electromyography guidance (EMG group) and percutaneous botulinum toxin injection under flexible fiberscopic guidance (fiberscopy group). Methods. Thirty patients with adductor spasmodic dysphonia (ADSD), who had never received treatment, were randomly allocated into EMG- or fiberscopy-guided botulinum toxin injections between March 2008 and February 2010. We assessed acoustic and aerodynamic voice parameters, and the voice handicap index (VHI) before injection and at 1, 3, and 6 months after injection. Results. The mean total dosage of botulinum toxin was similar for both groups: 1.7 ± 0.5 U for the EMG group and 1.8 ± 0.4 U for the fiberscopy group (P > 0.05). There were no significant differences in outcomes between the two groups in either the duration of effectiveness or complications such as breathy voice and aspiration. Conclusion. Botulinum toxin injection under fiberscopic guidance is a viable alternative to EMG-guided botulinum toxin injection for the treatment of adductor spasmodic dysphonia when EMG equipment is unavailable. PMID:25383369

  11. Thermoplastic polyurethanes for the manufacturing of highly dosed oral sustained release matrices via hot melt extrusion and injection molding.

    PubMed

    Claeys, Bart; Vervaeck, Anouk; Hillewaere, Xander K D; Possemiers, Sam; Hansen, Laurent; De Beer, Thomas; Remon, Jean Paul; Vervaet, Chris

    2015-02-01

    This study evaluated thermoplastic polyurethanes (TPUR) as matrix excipients for the production of oral solid dosage forms via hot melt extrusion (HME) in combination with injection molding (IM). We demonstrated that TPURs enable the production of solid dispersions - crystalline API in a crystalline carrier - at an extrusion temperature below the drug melting temperature (Tm) with a drug content up to 65% (wt.%). The release of metoprolol tartrate was controlled over 24h, whereas a complete release of diprophylline was only possible in combination with a drug release modifier: polyethylene glycol 4000 (PEG 4000) or Tween 80. No burst release nor a change in tablet size and geometry was detected for any of the formulations after dissolution testing. The total matrix porosity increased gradually upon drug release. Oral administration of TPUR did not affect the GI ecosystem (pH, bacterial count, short chain fatty acids), monitored via the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). The high drug load (65 wt.%) in combination with (in vitro and in vivo) controlled release capacity of the formulations, is noteworthy in the field of formulations produced via HME/IM. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Inferring Core Tungsten Behavior Using SPRED During the DIII-D Metal Rings Campaign

    NASA Astrophysics Data System (ADS)

    Thomas, D. M.; Kaplan, D.; Groebner, R.; Grierson, B.; Unterberg, Z.; Victor, B.

    2016-10-01

    The GA SPRED EUV spectrometer was used to study core emission of highly charged tungsten ions (W40+-W45+) in the 120-135Å region during the recent Metal Rings Campaign. These experiments used two 5-cm wide toroidal rings of W-coated metal inserts exposed to a variety of DIII-D discharges to study effects of high-Z divertor erosion, migration, core uptake, and effects on advanced tokamak performance. For the proper core temperature range (2-4 keV), the measured multistate W emission forms a well defined spectral pattern that can be used to study the relative importance of strike point location, flux expansion, injected power, ELM characteristics and magnetic drift direction for high-Z core contamination in DIII-D. The spectra are fit using simple Gaussians to estimate concentrations using the historical SPRED intensity calibration. Calibration shots using known core dosages of pellet injected W are used to help infer the relative response of the instrument. Supported by US DOE under DE-FC02-04ER54698, DE-AC02-09CH11466, DE-AC05-00OR22725, DE-AC52-07NA27344.

  13. General public knowledge, preferred dosage forms, and beliefs toward medicines in western Saudi Arabia.

    PubMed

    Alhaddad, Mahmoud S; Abdallah, Qasem M; Alshakhsheer, Sami M; Alosaimi, Salman B; Althmali, Ahmed R; Alahmari, Solaiman A

    2014-06-01

    To measure general public knowledge, source of knowledge, preferred dosage forms, and beliefs toward medicines. A cross-sectional study design using convenience-sampling technique was used. A pre-validated questionnaire was designed and distributed to the general public through face-to-face interviews. All data were analyzed, and p-values less than 0.05 were considered significant. The study took place in the Clinical Pharmacy Department, Taif University, Taif, Kingdom of Saudi Arabia between August 2012 and February 2013 RESULTS: Nine hundred participants successfully responded to this study. Males represented two-thirds of the respondents (66.8%). In addition, 52% of respondents were of high education level. Modern (74.2%) and alternative medicines (88.7%) were understood by most respondents. Tablets (69.6%) and capsules (37.6%) represented the highest preferred dosage forms. In addition, physicians (66.6%) and pharmacists (46.2%) were the main sources of information regarding medicines. In terms of beliefs, respondents showed wrong beliefs in many statements used in this study. There is a need to improve public knowledge and beliefs toward medicines as well as utilizing public preferred dosage forms. In addition, pharmacists should play a major role in these programs since they are experts on medicines and play a more active role in patient education and counseling.

  14. Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Levetiracetam.

    PubMed

    Petruševska, Marija; Berglez, Sandra; Krisch, Igor; Legen, Igor; Megušar, Klara; Peternel, Luka; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Kopp, Sabine; Langguth, Peter; Mehta, Mehul; Polli, James E; Shah, Vinod P; Dressman, Jennifer

    2015-09-01

    Literature and experimental data relevant for the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing levetiracetam are reviewed. Data on solubility and permeability suggest that levetiracetam belongs to class I of the biopharmaceutical classification system (BCS). Levetiracetam's therapeutic use, its wide therapeutic index, and its favorable pharmacokinetic properties make levetiracetam a valid candidate for the BCS-based biowaiver approach. Further, no BE studies with levetiracetam IR formulations in which the test formulation failed to show BE with the comparator have been reported in the open literature. On the basis of the overall evidence, it appears unlikely that a BCS-based biowaiver approach for levetiracetam IR solid oral dosage forms formulated with established excipients would expose patients to undue risks. Thus, the BCS-based biowaiver approach procedure is recommended for IR solid oral dosage form containing levetiracetam, provided the excipients in the formulation are also present in products that have been approved in countries belonging to or associated with the International Committee on Harmonization and are used in their usual quantities, and provided the dissolution profiles of the test and reference product comply with the current requirements for BCS-based biowaivers. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  15. Barrier coated drug layered particles for enhanced performance of amorphous solid dispersion dosage form.

    PubMed

    Puri, Vibha; Dantuluri, Ajay K; Bansal, Arvind K

    2012-01-01

    Amorphous solid dispersions (ASDs) may entail tailor-made dosage form design to exploit their solubility advantage. Surface phenomena dominated the performance of amorphous celecoxib solid dispersion (ACSD) comprising of amorphous celecoxib (A-CLB), polyvinylpyrrolidone, and meglumine (7:2:1, w/w). ACSD cohesive interfacial interactions hindered its capsule dosage form dissolution (Puri V, Dhantuluri AK, Bansal AK 2011. J Pharm Sci 100:2460-2468). Furthermore, ACSD underwent significant devitrification under environmental stress. In the present study, enthalpy relaxation studies revealed its free surface to contribute to molecular mobility. Based on all these observations, barrier coated amorphous CLB solid dispersion layered particles (ADLP) were developed by Wurster process, using microcrystalline cellulose as substrate and polyvinyl alcohol (PVA), inulin, and polyvinyl acetate phthalate (PVAP) as coating excipients. Capsule formulations of barrier coated-ADLP could achieve rapid dispersibility and high drug release. Evaluation under varying temperature and RH conditions suggested the crystallization inhibitory efficiency in order of inulin < PVA ≈ PVAP; however, under only temperature treatment, crystallization inhibition increased with increase in T(g) of the coating material. Simulated studies using DSC evidenced drug-polymer mixing at the interface as a potential mechanism for surface stabilization. In conclusion, surface modification yielded a fast dispersing robust high drug load ASD based dosage form. Copyright © 2011 Wiley-Liss, Inc.

  16. Gastric emptying of multi-particulate dosage forms.

    PubMed

    Newton, J Michael

    2010-08-16

    The evidence in the literature for the concept that multi-particulate dosage forms below a specific size empty from the stomach as if they were liquids and hence have the potential to provide the best solution to the formulation of controlled release oral dosage forms, has been considered. There is some evidence that particles less than 1.0mm provide a more rapid response than larger size particles but there is also evidence that this is not always the case and that rapid and reproducible gastric emptying of small particles does not always occur when they are administered. There is strong evidence that food can delay the gastric emptying of multi-particulate systems. Some of the misconception for gastric emptying performance of multi-particulate system is shown to be related to the limitation of the study design and limitation of the way the data is processed. Nevertheless, there is clear evidence that multi-particulate systems can provide effective oral controlled release dosage forms. There is still some way to go with experimental techniques which would allow a definitive answer to the issue of how the variability of the gastric emptying of multi-particulate systems of less than 2.0mm arises. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  17. Current status of amorphous formulation and other special dosage forms as formulations for early clinical phases.

    PubMed

    Kawakami, Kohsaku

    2009-09-01

    Although most chemists in the pharmaceutical industry have a good understanding on favorable physicochemical properties for drug candidates, formulators must still deal with many challenging candidates. On the other hand, formulators are not allowed to spend much time on formulation development for early phases of the clinical studies. Thus, it is basically difficult to apply special dosage form technologies to the candidates for the first-in-human formulations. Despite the availability of numerous reviews on oral special dosage forms, information on their applicability as the early phase formulation has been limited. This article describes quick review on the oral special dosage forms that may be applied to the early clinical formulations, followed by discussion focused on the amorphous formulations, which still has relatively many issues to be proved for the general use. The major problems that inhibit the use of the amorphous formulation are difficulty in the manufacturing and the poor chemical/physical stability. Notably, the poor physical stability can be critical, because of not the poor stability itself but the difficulty in the timely evaluation in the preclinical developmental timeframes. Research directions of the amorphous formulations are suggested to utilize this promising technology without disturbing the preclinical developmental timelines.

  18. Development of extended release dosage forms using non-uniform drug distribution techniques.

    PubMed

    Huang, Kuo-Kuang; Wang, Da-Peng; Meng, Chung-Ling

    2002-05-01

    Development of an extended release oral dosage form for nifedipine using the non-uniform drug distribution matrix method was conducted. The process conducted in a fluid bed processing unit was optimized by controlling the concentration gradient of nifedipine in the coating solution and the spray rate applied to the non-pareil beads. The concentration of nifedipine in the coating was controlled by instantaneous dilutions of coating solution with polymer dispersion transported from another reservoir into the coating solution at a controlled rate. The USP dissolution method equipped with paddles at 100 rpm in 0.1 N hydrochloric acid solution maintained at 37 degrees C was used for the evaluation of release rate characteristics. Results indicated that (1) an increase in the ethyl cellulose content in the coated beads decreased the nifedipine release rate, (2) incorporation of water-soluble sucrose into the formulation increased the release rate of nifedipine, and (3) adjustment of the spray coating solution and the transport rate of polymer dispersion could achieve a dosage form with a zero-order release rate. Since zero-order release rate and constant plasma concentration were achieved in this study using the non-uniform drug distribution technique, further studies to determine in vivo/in vitro correlation with various non-uniform drug distribution dosage forms will be conducted.

  19. Electrokinetic delivery of persulfate to remediate PCBs polluted soils: effect of injection spot.

    PubMed

    Fan, Guangping; Cang, Long; Fang, Guodong; Qin, Wenxiu; Ge, Liqiang; Zhou, Dongmei

    2014-12-01

    Persulfate-based in situ chemical oxidation (ISCO) is a promising technique for the remediation of organic compounds contaminated soils. Electrokinetics (EK) provides an alternative method to deliver oxidants into the target zones especially in low permeable-soil. In this study, the flexibility of delivering persulfate by EK to remediate polychlorinated biphenyls (PCBs) polluted soil was investigated. 20% (w/w) of persulfate was injected at the anode, cathode and both electrodes to examine its transport behaviors under electrical field, and the effect of field inversion process was also evaluated. The results showed that high dosage of persulfate could be delivered into S4 section (near cathode) by electroosmosis when persulfate was injected from anode, 30.8% of PCBs was removed from the soil, and the formed hydroxyl precipitation near the cathode during EK process impeded the transportation of persulfate. In contrast, only 18.9% of PCBs was removed with the injection of persulfate from cathode, although the breakthrough of persulfate into the anode reservoir was observed. These results indicated that the electroosmotic flow is more effective for the transportation of persulfate into soil. The addition of persulfate from both electrodes did not significantly facilitate the PCBs oxidation as well as the treatment of electrical field reversion, the reinforced negative depolarization function occurring in the cathode at high current consumed most of the oxidant. Furthermore, it was found that strong acid condition near the anode favored the oxidation of PCBs by persulfate and the degradation of PCBs was in consistent with the oxidation of Soil TOC in EK/persulfate system. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Consumption of baits containing raccoon pox-based plague vaccines protects black-tailed prairie dogs (Cynomys ludovicianus).

    PubMed

    Rocke, Tonie E; Pussini, Nicola; Smith, Susan R; Williamson, Judy; Powell, Bradford; Osorio, Jorge E

    2010-01-01

    Baits containing recombinant raccoon poxvirus (RCN) expressing plague antigens (fraction 1 [F1] and a truncated form of the V protein-V307) were offered for voluntary consumption several times over the course of several months to a group of 16 black-tailed prairie dogs (Cynomys ludovicianus). For comparison, another group of prairie dogs (n = 12) was injected subcutaneously (SC) (prime and boost) with 40 microg of F1-V fusion protein absorbed to alum, a vaccine-adjuvant combination demonstrated to elicit immunity to plague in mice and other mammals. Control animals received baits containing RCN without the inserted antigen (n = 8) or injected diluent (n = 7), and as there was no difference in their survival rates by Kaplan-Meier analysis, all of them were combined into one group in the final analysis. Mean antibody titers to Yersinia pestis F1 and V antigen increased (p < 0.05) in the vaccinated groups compared to controls, but titers were significantly higher (p < 0.0001) in those receiving injections of F1-V fusion protein than in those orally vaccinated with RCN-based vaccine. Interestingly, upon challenge with approximately 70,000 cfu of virulent Y. pestis, oral vaccination resulted in survival rates that were significantly higher (p = 0.025) than the group vaccinated by injection with F1-V fusion protein and substantially higher (p < 0.0001) than the control group. These results demonstrate that oral vaccination of prairie dogs using RCN-based plague vaccines provides significant protection against challenge at dosages that simulate simultaneous delivery of the plague bacterium by numerous flea bites.

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