Formulation and Evaluation of Fixed Dose Combination Products of Rifampicin and Isoniazid with Improved Rifampicin Stability

Introduction: One of the main reasons for the development of the resistance in the therapy for Tuberculosis is the mono drug therapy. This may be due to the drug-drug interactions as the therapy includes combination of various drugs leading to poor bioavailability of these drugs. One such reported interaction is between Rifampicin and Isoniazid which leads to poor bioavailability of Rifampicin. Objective: The aim of the present study is to formulate and evaluate fixed dose combination tablets of Rifampicin and Isoniazid with improved Rifampicin stability in invitro conditions. Methodology: 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 the Isoniazid tablets were enteric coated with Eudragit L-100 using pan coating technique. Dissolution studies for the Rifampicin tablets were performed along with uncoated Isoniazid (Formulation I) and as well in combination withenteric coated Isoniazid (Formulation II) tablets separately. Results: The cumulative percentage drug release for Rifampicin was found to be around 80% in case of Formulation I (when it was taken along with uncoated immediate release Isoniazid tablets) whereas it has been increased to91% for Formulation II (when it is with enteric coated Isoniazid tablets). Conclusion: This study proves that Rifampicin interacts with Isoniazid and undergoes degradation to a phenomenal extent in presence of Isoniazid at pH 1.2. This interaction and degradation of Rifampicin can be reduced and the stability can be enhanced by enteric coating of Isoniazid with suitable polymers.