Two-phase amorphous-amorphous solid drug dispersion with enhanced stability, solubility and bioavailability resulting from ultrasonic dispersion of an immiscible system
Martínez, L.M.ía.; Videa, M.; López Silva, T.; Castro, S.; Caballero, A.; Lara-Díaz, V.íc.J.; Castorena-Torres, F.
European Journal of Pharmaceutics and Biopharmaceutics: Official Journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik E.V 119: 243-252
Amorphization of active pharmaceutical ingredients (APIs) and the preparation of solid dispersions are strategies that can be synergized to improve the solubility of oral drugs. Immiscibility between an API and a carrier in the molten state that could be perceived as a problem in the preparation of solid dispersions, may actually introduce an advantage. In the present work, a two-phase amorphous-amorphous solid dispersion (AASD) was prepared by ultrasonicating a molten immiscible mixture of indomethacin (IND) and glucose (GLU) prior quenching. By introducing this novel ultrasound assisted method, the immiscible API particles were uniformly dispersed as microscopic glassy clusters of the drug in the solid amorphous GLU matrix; particle sizes of IND in the AASD range from 600nm to 1.4μm. As a result of the amorphization and particle size reduction of IND, its aqueous solubility increased to reach almost 40ppm (8 times more soluble compared to indomethacin in its crystalline state). In addition, the oral bioavailability and its resistance against crystallization were also enhanced; AASD samples have remained amorphous for more than two years of storage.