Co-Amorphous Solid Dispersion System for Improvement in Dissolution Profile of -(((1,4)-4-((6-fluorobenzo[]oxazol-2-yl)amino)cyclohexyl)methyl)-2-methylpropane-2-sulfonamide as a Neuropeptide Y5 Receptor Antagonist.

Brick dust molecules exhibit high melting points and ultralow solubility. Overcoming this solubility issue is challenging. Previously, we formulated a co-amorphous system for a neuropeptide Y5 receptor antagonist (NP) as a brick dust drug using sodium taurocholate (ST) to improve its dissolution profile. In this study, we have designed a ternary amorphous system involving polymer addition to further improve a co-amorphous system. The amorphous samples were prepared by the ball milling. The thermal and spectroscopic analyses were performed, and the isothermal crystallization and dissolution profiles were evaluated. The ball milling of NPs, ST, and each of the three types of polymers successfully converted crystalline NPs to amorphous NPs. Thermal analysis confirmed the formation of a single amorphous phase. The infrared spectra revealed a specific interaction between an NP and ST in the co-amorphous system. Moreover, the intermolecular interactions of NP-ST were maintained in the ternary amorphous systems, suggesting the miscible dispersion of the co-amorphous system into the polymer via weak interactions as co-amorphous solid dispersions. The dissolution profile of co-amorphous NP-ST was 4.1- and 6.7-fold higher than that of crystalline NPs in pH 1.2 and 6.8 buffers, respectively. The drug concentration in the ternary amorphous system in pH 1.2 and 6.8 buffers became 1.1-1.2- and 1.4-2.7-fold higher than that seen in the co-amorphous system, respectively. Co-amorphous solid dispersion is a promising method for enhancing the solubility of brick dust molecules.