Formulation of dispersible isoniazid/pyridoxine fixed-dose combination tablets for isoniazid preventive therapy in pediatrics

Abstract

Abstract Objective: Oral dispersible isoniazid 50 mg/pyridoxine 6.25 mg fixed-dose combination (FDC) tablets were formulated for Isoniazid Preventive Therapy in pediatrics weighing less than 5 kg. Significance: The Kenyan clinical market lacks age-appropriate isoniazid/pyridoxine formulations for pediatrics whose dose requirements are catered extemporaneously. The proposed oral dispersible FDC tablets would improve the treatment outcomes of the drug combination by ensuring accurate dosing, reduce pill burden, prolonged shelf life, and circumvent individual drug stock-outs. Method: Nine batches of isoniazid/pyridoxine FDC tablets with an average weight of 125 mg differing in the composition of three superdisintegrants were formulated. Pre-formulation studies were done on the powder blend using Fourier transform infra-red spectroscopy before the blend was directly compressed. Pharmaceutical parameters of the tablets were assessed against compendial specifications. Results: Pre-formulation studies showed no predictable incompatibilities between the drugs and excipients. All batches complied with compendial specifications for weight uniformity, hardness and disintegration, while three batches complied with the friability test. Only Batch Nine tablets containing croscarmellose and sodium starch glycolate superdisintegrants in the ratio of 3:5 complied with the assay specification. Batch Nine tablets contained 96% of isoniazid and 95% of pyridoxine complying with the United States Pharmacopeia (USP) 2016 monograph limits of 90–110% and 95–115% of the labelled isoniazid and pyridoxine, respectively. In the in-vitro dissolution studies, 88.7% and 105.3% of isoniazid and pyridoxine contained in Batch Nine tablets dissolved within 30 min complying with the USP 2016 specifications for dissolution test. Conclusion: The isoniazid/pyridoxine FDC incorporating croscarmellose sodium and sodium starch glycolate superdisintegrants was the most successful formulation since the formulated tablets complied with all the evaluated compendial specifications implying potential clinical utility of the formulation.