Formulation and evaluation of fixed dose combination tablets of Rifampicin and Isoniazid with improved Rifampicin stability

The aim of the present study is to formulate and evaluate enteric coated combination tablets of Rifampicin and Isoniazid with improved Rifampicin stability in in-vitro conditions. Rifampicin and Isoniazid were formulated separately as immediate release tablets. Then these tablets were evaluated for the various physical parameters like appearance, weight variation, hardness, friability and disintegration. Then Rifampicin and Isoniazid were mixed and formulated as combination tablets which were enteric coated with Eudragit L-100 using pan coating technique after evaluating them for physical parameters. This is mainly done to prevent isoniazid from interacting with Rifampicin in acidic medium and to improve the stability of Rifampicin. Dissolution studies for the uncoated tablets and enteric coated combination tablets were performed and the cumulative percentage drug release for Rifampicin was calculated. The cumulative percentage drug release for Rifampicin was found to be around 80% when it was taken along with uncoated immediate release Isoniazid tablets for the dissolution study whereas it has been increased to 88% when it is formulated as enteric coated combination tablet. This study proves that Rifampicin interacts with Isoniazid and undergoes degradation to a significant extent in presence of Isoniazid in acidic medium. This interaction and degradation of Rifampicin can be reduced and the stability can be enhanced by preventing the physical contact between these two drugs in the stomach and by making them to release in Intestinal pH.