Formulation and Optimization of Lyophilized Selexipag Nanocrystals to Improve the Saturation Solubility and Dissolution Rate

Abstract

Rusul M. Alwan, Nawal A. Raja, Areej W. Alhagiesa

Selexipag is first in class orally active, selective non-prostanoid prostacyclin receptor agonist with a long half-life. It has low oral bioavailability due to a poor dissolution rate, which is considered a rate-limiting step for drug absorption. Nanocrystals (NCs) formulation is an attractive approach for enhancing the poorly soluble drug's saturation solubility and dissolution rate. They offer the advantages of crystalline state, high drug loading capacity, and simple preparation method. This study aims to prepare and characterize Selexipag NCs, filled in hard gelatin capsule in attempt to improve its solubility and dissolution rate. The effect of stabilizer type and preparation methods on the NC particle size and polydispersity index were evaluated to select the most stable formula. The results revealed that the formula (F7) prepared by the solvent antisolvent precipitation with the ultrasonication method (which contain SLX: Soluplus® at a ratio of 1:2) has the smallest mean particle size (38.5 nm) and appropriate polydispersity index (0.12); hence it was selected as the optimal formula. Simultaneously, the data from powder X-ray diffraction shows no reduction in the crystallinity of drugs. SLX NCs exhibit increased saturation solubility by several folds than pure SLX. The hard gelatin capsule containing the lyophilized powder showed a faster dissolution profile (complete drug release in 15 min) relative to pure SLX (0.1% during the same time).