Assessing drug-excipient interactions in the formulation of isoniazid tablets

Abstract

A suitable and efficient high-performance liquid chromatography (HPLC) method was developed for the simultaneous determination of tuberculostatic isoniazid and its related impurities, isonicotinic acid and isonicotinamide, in oral solid dosage forms. We studied the influence on chromatographic separation of mobile phase parameters, such as pH, ion pairing and ionic strength, as well as column bonded phase and brands. The use of buffer solution pH 6.8:acetonitrile 96:4 (v/v) at 0.8 mL min-1, C18 column (250 × 4.6 mm, 5 μm), allowed proper separation of these ionizable analytes without the need of ion pairing agents. The limit of quantification of the method (0.1 μg mL-1) was suitable for the analysis of impurities. A drug-excipient compatibility study was carried out with the anaytical method proposed in this work and addressed frequent excipients used in isoniazid coated tablets. The dye FD & C blue 2 lake promoted the highest degradation of the tuberculostatic agent.