Development studies on the orodispersible freeze-dried platforms for lurasidone hydrochloride − Understanding the effect of amino acid additive and lyophilization stage

In this study, lyophilizates with the second-class antipsychotic agent lurasidone hydrochloride were developed as orodispersible platforms to improve patients' adherence. The primary aim was to evaluate the effect of the amino acid additive (L-arginine, L-lysine, L-histidine) and the freeze-drying stage on the pharmaceutical performance of the designed formulations. The composition was initially optimized using an experimental design approach. The amino acids (in particular L-histidine) acted as dispersing agents, prevented drug aggregation and assured high drug content uniformity within the lyophilizate matrix. The freeze-drying stage reduced the particles dimensions which significantly increased solubility of lurasidone hydrochloride, and consequently, it's dissolution rate. The presence of L-arginine in lyophilizate composition balanced out sufficient compression strength with a rapid drug release. Despite the fact that L-lysine enhanced the mechanical strength, it also caused delayed drug release. Notably, L-histidine and L-arginine accelerated transport of lurasidone hydrochloride through the porcine buccal epithelium with approximately 100% and 50% increase in absorption, respectively, when compared to commercial reference drug. Overall, the designed lyophilizates containing L-histidine and L-arginine, hold promise as orodispersible platforms for improved performance of lurasidone hydrochloride.