Investigation of ethylene oxide-co-propylene oxide for dissolution enhancement of hot-melt extruded solid dispersions.

Abstract

The optimal design of amorphous solid dispersion (ASD) formulations requires the use of excipients to maintain supersaturation and improve physical stability in order to ensure shelf-life stability and better absorption during intestinal transit, respectively. Blends of excipients (surfactants and polymers) are often used within pharmaceutical products to improve the oral delivery of BCS class II drugs. Therefore in this study, a dissolution enhancer, poloxamer 407 (P407), was investigated to determine its effect on the dissolution properties and on the amorphous nature of the API contained in the formulation. Phase solubility studies of indomethacin (INM) in aqueous solutions of P407 and PVP VA64 showed an increase in the kinetic solubility of INM compared with the pure drug at 37°C with a Ka value of 0.041 μg/ml. The solid dispersions showed a higher dissolution rate when compared to pure and amorphous drug when performed in pH buffer 1.2 with a kinetic solubility of 21 μg/ml. The stability data showed that the amorphous drug in solid solutions with PVP VA64 and P407 remained amorphous and the % P407 loading had no effect on the amorphous stability of INM. This study concluded that the amorphous solid dispersion contributed to the increased solubility of INM.