Dissolution Methodology for Evaluation of Rifampicin-Containing Fixed-Dose Combinations Using Biopharmaceutic Classification System Based Approach

Abstract

The purpose of this investigation was to develop the dissolution methodology for evaluation of rifampicin-containing fixed-dose combinations of antituberculosis (anti-TB) drugs using BCS-based approach. In this investigation, dissolution studies were conducted at agitation intensities of 30, 50, 75, and 100 rpm and also in various media recommended by United States Pharmocopeia (USP) as well as media proposed based on Biopharmaceutic Classification System (BCS) for class II drugs. Equilibrium solubility of rifampicin was also determined. BCS-based predictions indicated that use of 0.1 N HCl as dissolution medium reflects 100% bioavailability, whereas 0.01 N HCl shows 70% to 90% bioavailability, which is more nearer to the in vivo bioavailability of rifampicin of 90%. Hence, 0.01 N HCl may be more discriminatory medium to distinguish good and bad formulations. Thus a dissolution methodology with 0.01 N HCl and pH 6.8 phosphate buffer using USP apparatus II at 50 rpm is being proposed.

Key words: :

• Anti-TB FDCs
• BCS
• Rifampicin
• Dissolution
• Biorelevant Dissolution Media

Notes

[4] FDA. Guidance for Industry: Waiver of in vivo bioavailability and bioequivalence studies for immediate release solid oral dosage forms based on a Biopharmaceutics Classification System. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research; 2000.

[6] FDA. Guidance for Industry: Dissolution testing of immediate release solid oral dosage forms. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research; 1997.