Stability of rifampicin in dissolution medium in presence of isoniazid.
Rifampicin (RIF) hydrolyzes in acidic medium to form insoluble and poorly absorbed 3-Formyl rifamycin SV (3-FRSV). This study describes development of two principally different methods, Dual Wavelength UV-Vis. spectrophotometry (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 method, a mixture of chloroform:methanol:water (80:20:2.5 v/v) was used as the 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 microg/ml and 50-250 ng/spot for DW spectrophotometric method and HPTLC method, respectively, and 5-50 microg/ml for RIF using DW spectrophotometric method. Both the methods were found to be specific, accurate and reproducible. The proposed methods were successfully applied to determine the rate of degradation of RIF to 3-FRSV in dissolution medium (0.1 N HCl) and also in presence of isoniazid (INH). The rate 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 RIF 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 formulations) while in presence of INH the degradation is catalyzed to about 21.5% (RIF+INH formulations), in 45 min. Thus, lower concentration of RIF may be available for absorption leading to poor bioavailability of RIF from combination dosage forms (RIF+INH) as compared to formulations containing only RIF. It is proposed that specific analytical method should be used to measure RIF in presence of 3-FRSV in a dissolution study.
Shishoo
C J
CJ
Department of Quality Assurance, L.M. College of Pharmacy, P.O. Box 4011, Navrangpura, Ahmedabad, India. cjsbcs@netscape.net
Shah
S A
SA
Rathod
I S
IS
Savale
S S
SS
Kotecha
J S
JS
Shah
P B
PB
D000995:Antitubercular Agents / Q000032:analysis / Q000737:chemistry*; D002855:Chromatography, Thin Layer / Q000379:methods; D004339:Drug Compounding; D004355:Drug Stability; D006851:Hydrochloric Acid / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007538:Isoniazid / Q000032:analysis / Q000737:chemistry*; D012044:Regression Analysis; D015203:Reproducibility of Results; D012293:Rifampin / Q000032:analysis / Q000737:chemistry*; D012294:Rifamycins / Q000032:analysis; D012680:Sensitivity and Specificity; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet / Q000379:methods
D000995:Antitubercular Agents; D012294:Rifamycins; C038966:3-formylrifamycin SV; D006851:Hydrochloric Acid; D007538:Isoniazid; D012293:Rifampin