Evaluation of a spray-dried amorphous solid dispersion formulation of ID11916, a new molecular entity with dual inhibition mechanisms targeting the androgen receptor and phosphodiesterase type-5

PurposeThe objective of this study is to develop an amorphous solid dispersion (ASD) formulation that enhances the oral bioavailability of ID11916, a novel molecular entity with dual inhibition mechanisms targeting the androgen receptor and phosphodiesterase type-5, by improving its very low solubility.MethodsThe ASD formulations were prepared after screening the solubility of ID11916 using different solvents and assessing kinetic solubility using polymers. The stability of the formulations was assessed using assay (%), purity (%), X-ray powder diffraction, and morphology. Moreover, the in vivo pharmacokinetic studies were performed in mice for the final formulations selected through in vitro dissolution tests.ResultsBased on the results of screening solvents and polymers, ID11916 and hypromellose phthalate were dissolved at a 1:2 weight ratio in a dichloromethane and methanol mixture (1:1, v/v), and then the formulation was prepared via spray drying. After 4 weeks of exposure to high temperature and humidity conditions, the formulation was stable with no significant changes in any of the evaluated results. Additionally, the formulation improved the in vitro dissolution of ID11916 at pH 1.6 and pH 6.5. In the in vivo pharmacokinetic studies in mice at doses of 30 and 100 mg/kg, Cmax and AUC values were significantly enhanced in a dose-dependent manner, resulting in a 26- and 90-fold increase in relative oral bioavailability compared to the suspension.ConclusionThe ASD formulation is a promising strategy for enhancing the oral bioavailability of ID11916.