Stability of rifampicin in dissolution medium in presence of isoniazid

Rifampicin (RIF) hydrolyzes in acidic medium to form insoluble and poorly a bsorbed 3-Formyl rifamycin SV (3-FRSV). This study describes development of two principally different methods, Dual Wavelength UV-Vis. spectrophotomet ry (DW spectrophotometry) and HPTLC, to determine 3-FRSV in presence of RIF . Using DW spectrophotometry, RIF was estimated by using wavelengths 475.0 and 507.0 nm and 3-FRSV was estimated using 457.0 and 492.0 nm. In HPTLC me thod, a mixture of chloroform:methanol:water (80:20:2.5 v/v) was used as th e mobile phase to resolve 3-FRSV from RIF and 3-FRSV was quantified at 333 nm. The linearity range for 3-FRSV was 2-10 mu g/ml and 50-250 ng/spot for DW spectrophotometric method and HPTLC method, respectively, and 5-50 mu g/ ml for RIF using DW spectrophotometric method. Both the methods were found to be specific, accurate and reproducible. The proposed methods were succes sfully applied to determine the rate of degradation of RIF to 3-FRSV in dis solution medium (0.1 N HCl) and also in presence of isoniazid (INH). The ra te of degradation of RIF in presence of INH was almost two times more than that of RIF alone. These methods were utilized to study the stability of RI F in market formulations of RIF and RIF with INH in dissolution medium. It has been observed that RIF degrades by 12.4% to form 3-FRSV (RIF formulatio ns) while in presence of INH the degradation is catalyzed to about 21.5% (R IF + INH formulations), in 45 min. Thus, lower concentration of RIF may be available for absorption leading to poor bioavailability of RIF from combin ation dosage forms (RIF + INH) as compared to formulations containing only RIF. It is proposed that specific analytical method should be used to measu re RIF in presence of 3-FRSV in a dissolution study. (C) 1999 Elsevier Scie nce B.V. All rights reserved.