Preparation and Evaluation of Immediate-Release Oral Tablets Using Solid Dispersion of Selexipag

Abstract

Selexipag is an oral drug for pulmonary arterial hypertension with limited aqueous solubility, which can adversely affect its dissolution behavior, and it is classified as a biopharmaceutics classification system (BCS) class II drug. The present study aimed to prepare immediate-release tablets loaded with selexipag solid dispersion to enhance its solubility and dissolution. Poloxamer 407 was used as a carrier in combination with the drug at a 1:3 ( drug:polymer, w/w) ratio, and the solid dispersion was prepared using the solvent evaporation method. The resulting solid dispersion was assessed for percentage of yield, drug content, and saturation solubility in phosphate buffer pH=6.8. Using the direct compression method, the produced solid dispersion was incorporated into immediate-release tablets employing three diluents, namely mannitol, microcrystalline cellulose and starch, along with three superdisintegrants, croscarmellose sodium, sodium starch glycolate, and crospovidone. Six immediate-release tablet formulations were prepared and subsequently evaluated for weight variation, drug content uniformity, hardness, friability, disintegration time, and dissolution behavior. Formulation T4, composed of a mannitol–microcrystalline cellulose(40:60) as diluent and croscarmellose sodium (3%) as a superdisintegrant, containing 4 mg of selexipag solid dispersion, exhibited rapid disintegration and achieved approximately 99% drug release within 15 minutes compared to pure selexipag immediate-release tablet.