Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Piroxicam. Issue 2 (2nd December 2013)

• Record Type: Journal Article
• Authors: Shohin, Igor E.; Kulinich, Julia I.; Ramenskaya, Galina V.; Abrahamsson, Bertil; Kopp, Sabine; Langguth, Peter; Polli, James E.; Shah, Vinod P.; Groot, D. W.; Barends, Dirk M.; Dressman, Jennifer B.
• Is Part Of: Journal of pharmaceutical sciences. Volume 103:Issue 2(2014:Feb.)
• Page Start: 367
• Page End: 377
• Publication Date: 2013-12-02
• Subjects: Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.23799
• Languages: English
• ISSNs: 0022-3549

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Literature and experimental data relevant to the decision to allow a waiver of <italic>in vivo</italic> bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing piroxicam in the free acid form are reviewed. Piroxicam solubility and permeability, its therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA), and corresponding dissolution data are taken into consideration. The available data suggest that according to the current biopharmaceutics classification system (BCS) and all current guidances, piroxicam would be assigned to BCS Class II. The extent of piroxicam absorption seems not to depend on manufacturing conditions or excipients, so the risk of bio<italic>in</italic>equivalence in terms of area under the curve (AUC) is very low, but the rate of absorption (i.e., BE in terms of <italic>C</italic><sub>max</sub>) can be affected by the formulation. Current <italic>in vitro</italic> dissolution methods may not always reflect differences in terms of <italic>C</italic><sub>max</sub> for BCS Class II weak acids; however, minor differences in absorption rate of piroxicam would not subject the patient to unacceptable risks: as piroxicam products may be taken before or after meals, the rate of absorption cannot be considered crucial to drug action. Therefore, a biowaiver for IR piroxicam solid oral dosage form is considered feasible, provided that (a) the test product contains only excipients, which are also present in IR solid oral drug products containing piroxicam, which have been approved in ICH or associated countries, for instance, those presented in Table 3 of this paper; (b) both the test and comparator drug products dissolve 85% in 30 min or less at pH 1.2, 4.5, and 6.8; and (c) the test product and comparator show dissolution profile similarity in pH 1.2, 4.5, and 6.8. When not all of these conditions can be fulfilled, BE of the products should be established <italic>in vivo</italic>. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:367–377, 2014</p> </abstract>