Behavior of decomposition of rifampicin in the presence of isoniazid in the pH range 1-3.
The extent of decomposition of rifampicin in the presence of isoniazid was determined in the pH range 1-3 at 37 degrees C in 50 min, the mean stomach residence time. With increase in pH, the degradation initially increased from pH 1 to 2 and then decreased, resulting in a bell-shaped pH-decomposition profile. This showed that rifampicin degraded in the presence of isoniazid to a higher extent at pH 2, the maximum pH in the fasting condition, under which antituberculosis fixed-dose combination (FDC) products are administered. At this pH and in 50 min, rifampicin decomposed by approximately 34%, while the fall of isoniazid was 10%. The extent of decomposition for the two drugs was also determined in marketed formulations, and the values ranged between 13-35% and 4-11%, respectively. The extents of decomposition at stomach residence times of 15 min and 3 h were 11.94% and 62.57%, respectively, for rifampicin and 4.78% and 11.12%, respectively, for isoniazid. The results show that quite an extensive loss of rifampicin and isoniazid can occur as a result of interaction between them in fasting pH conditions. This emphasizes that antituberculosis FDC formulations, which contain both drugs, should be designed in a manner that the interaction of the two drugs is prevented when the formulations are administered on an empty stomach.
Sankar
R
R
Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, India.
Sharda
Nishi
N
Singh
Saranjit
S
D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D004338:Drug Combinations; D004344:Drug Incompatibility; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007538:Isoniazid / Q000737:chemistry / Q000378:metabolism*; D012293:Rifampin / Q000737:chemistry / Q000378:metabolism*; D013607:Tablets; D013997:Time Factors
D002214:Capsules; D004338:Drug Combinations; D013607:Tablets; D007538:Isoniazid; D012293:Rifampin