Nanosuspensions of Selexipag: Formulation, Characterization, and in vitro Evaluation

Abstract

Selexipag(SLP) is an orally selective long-acting prostacyclin receptor agonist indicated for pulmonary arterial hypertension treatment. It is practically insoluble in water (class II, according to BCS). This work aims to prepare and optimize Selexipag nanosuspensions (SLPNS) to enhance the saturation solubility and in vitro dissolution rate. The solvent antisolvent precipitation method was used for the production of NS, and the effect of formulation parameters (stabilizer type, drug: Stabilizer ratio, and use of co-stabilizer) and process parameter (stirring speed) on the particle size (P.S) and polydispersity index (PDI) were studied. The result revealed that the P.S of all prepared SLPNS formulation was in the nanometer range, except for the formulas that stabilized by Poloxamer. The optimal SLPNS (F15), which is stabilized by Soluplus® (SLP: Stabilizer ratio 1:2) and prepared at a stirring speed of 1000 rpm, showed the smallest P.S and appropriate PDI, which are 47 nm and 0.073. The formula F5 exhibits 136 folds, an increase in the saturation solubility, and an enhancement in the dissolution rate in phosphate buffer pH 6.8 (100% drug release during 60 min) compared to the pure drug. This result indicates that SLPNS is an efficient way for improving the saturation solubility and the dissolution rate of SLP.