The compatibility of formulation components is crucial for safe and high-quality medicines. To detect the potential for incompatibility and to assess formulation stability, it is beneficial to conduct a compatibility study during the drug development phase. The therapy of tuberculosis normally consists of two or more medicines taken together. Consequently, different antituberculotic fixed-dose combination (FDC) formulations have been developed. Isoniazid is first-line medicine and present in several FDCs. Low bioavailability due to the active substances' incompatibility in acidic medium was reported for some of these FDC forms. Rifabutin, also a first-line antituberculotic, is available in the market as a single component formulation. This study presents compatibility testing of these two active substances for a new FDC and evaluates the impact of the most common solid dosage forms' excipients on the stability of two active substances. The potential for interaction between the formulation components was analyzed by the UHPLC method. One degradation product and one interaction product were observed and further characterized by high-resolution mass spectrometry. Still, significant degradation of two active substances, such as reported in marketed FDC formulations was not detected for this combination. The stability and drug delivery of the proposed combination were confirmed by the dissolution test in acidic medium.
Keywords: Compatibility; FDC; MS/MS; characterization; dissolution; impurities; isoniazid; rifabutin.