Biowaiver monographs for immediate release solid oral dosage forms: acetaminophen (paracetamol).

School of Pharmacy, National & Kapodistrian University of Athens, Athens, Greece.
Journal of Pharmaceutical Sciences (Impact Factor: 3.13). 02/2006; 95(1):4-14. DOI: 10.1002/jps.20477
Source: PubMed

ABSTRACT Literature data are reviewed on the properties of acetaminophen (paracetamol) related to the biopharmaceutics classification system (BCS). According to the current BCS criteria, acetaminophen is BCS Class III compound. Differences in composition seldom, if ever, have an effect on the extent of absorption. However, some studies show differences in rate of absorption between brands and formulations. In particular, sodium bicarbonate, present in some drug products, was reported to give an increase in the rate of absorption, probably caused by an effect on gastric emptying. In view of Marketing Authorizations (MAs) given in a number of countries to acetaminophen drug products with rapid onset of action, it is concluded that differences in rate of absorption were considered therapeutically not relevant by the Health Authorities. Moreover, in view of its therapeutic use, its wide therapeutic index and its uncomplicated pharmacokinetic properties, in vitro dissolution data collected according to the relevant Guidances can be safely used for declaring bioequivalence (BE) of two acetaminophen formulations. Therefore, accepting a biowaiver for immediate release (IR) acetaminophen solid oral drug products is considered scientifically justified, if the test product contains only those excipients reported in this paper in their usual amounts and the test product is rapidly dissolving, as well as the test product fulfils the criterion of similarity of dissolution profiles to the reference product.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study illustrates the application of experimental design and multivariate data analysis in defining design space for granulation and tableting processes. According to the quality by design concepts, critical quality attributes (CQAs) of granules and tablets, as well as critical parameters of granulation and tableting processes, were identified and evaluated. Acetaminophen was used as the model drug, and one of the study aims was to investigate the possibility of the development of immediate- or extended-release acetaminophen tablets. Granulation experiments were performed in the fluid bed processor using polyethylene oxide polymer as a binder in the direct granulation method. Tablets were compressed in the laboratory excenter tablet press. The first set of experiments was organized according to Plackett-Burman design, followed by the full factorial experimental design. Principal component analysis and partial least squares regression were applied as the multivariate analysis techniques. By using these different methods, CQAs and process parameters were identified and quantified. Furthermore, an in-line method was developed to monitor the temperature during the fluidized bed granulation process, to foresee possible defects in granules CQAs. Various control strategies that are based on the process understanding and assure desired quality attributes of the product are proposed. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
    Journal of Pharmaceutical Sciences 04/2013; · 3.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The present study examines how drug's inherent properties and product design influence the evaluation and applications of in vitro-in vivo correlation (IVIVC) for modified-release (MR) dosage forms consisting of extended-release (ER) and immediate-release (IR) components with bimodal drug release. Three analgesic drugs were used as model compounds, and simulations of in vivo pharmacokinetic profiles were conducted using different release rates of the ER component and various IR percentages. Plasma concentration-time profiles exhibiting a wide range of tmax and maximum observed plasma concentration (Cmax ) were obtained from superposition of the simulated IR and ER profiles based on a linear IVIVC. It was found that depending on the drug and dosage form design, direct use of the superposed IR and ER data for IVIVC modeling and prediction may (1) be acceptable within errors, (2) become unreliable and less meaningful because of the confounding effect from the non-negligible IR contribution to Cmax , or (3) be meaningless because of the insensitivity of Cmax to release rate change of the ER component. Therefore, understanding the drug, design and drug release characteristics of the product is essential for assessing the validity, accuracy, and reliability of IVIVC of complex MR products obtained via directly modeling of in vivo data. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
    Journal of Pharmaceutical Sciences 12/2013; · 3.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Paracetamol (APAP), a frequently used antipyretic drug, has poor compression moldability. In this study, we identified a novel cocrystal consisting of APAP and trimethylglycine (TMG) that exhibits improved tabletability. TMG was used instead of oxalic acid (OXA), which is a coformer reported previously. The cocrystal (APAP-TMG at a molar ratio of 1:1) was characterized by X-ray analysis, infrared spectroscopy, and thermal analysis. The crystal structure of APAP-TMG revealed that it was a cocrystal, since no proton was transferred between the APAP and TMG molecules. The compression and dissolution properties of APAP-TMG were similar to that of the APAP-OXA cocrystal. In addition, taste sensing measurements suggested that TMG has a sweet and umami taste, indicating that TMG should suppress the bitterness of APAP. From these results, TMG could be a safe and promising cocrystal former that could replace OXA, which can irritate tissues.
    International Journal of Pharmaceutics 07/2014; · 3.99 Impact Factor

Full-text (3 Sources)

Available from
May 26, 2014