Study of the Technological Methods Effect on Dissolution of the X-ray Amorphous Efavirenz-mesoporous Carrier System

Abstract

Introduction. The low solubility of active pharmaceutical ingredients (APIs) in the physiological pH range of the intestinal tract can adversely affect their absorption and bioavailability. Various methods of increasing the solubility of APIs have been proposed in recent decades. Among them there are preparation of solid dispersions, micronization, solubilization and other methods, including ones based on the amorphization of the crystalline substances, such as, spray drying, hot melt extrusion, absorption on mesoporous carriers such as magnesium aluminosilicate, silica, etc.Aim. Study the technological methods effect on dissolution at physiological temperature and pH range of practically insoluble API efavirenz amorphized by absorption on mesoporous carriers.Materials and methods. Efavirenz form І (EFA) (LLC "AMEDART", Russia, batch 010520). Efavirenz reference standard (USP № R09740). Mesoporous carriers (MC): Silica – Syloid® 244FP (244), Syloid® XDP 3150 (3150) (W.R. Grace&Co.-Conn, USA); FujiSil™ (FSL) (Fuji Chemical Industries Co., Ltd., Japan); Aeroperl® 300 (APL) (Evonik, Germany); Parteck® SLC (SLC) (Merck Millipore, USA); Synthetic magnesium aluminometasilicate – Neusilin® US2 (US2), Neusilin® UFL (UFL) (Fuji Chemical Industry Co., Ltd., Japan). The API absorption on MC was performed via solvent wetting and hot melt extrusion methods.Results and discussion. The dissolution increases in the MC series as the following: SLC > FSL > UFL = US2 > 244 = 3150. The data are consistent with an increase in the surface area and a decrease in the pore size of MC. The crystalline state of the system API efavirenz-Aeroperl® is caused by the largest pore size. It is obvious according to the data that the solvent wetting method gives better results in comparison with the hot melt extrusion as the method of obtaining X-ray amorphous systems API efavirenz-MC.Conclusion. Solvent wetting technology is recommended for increasing the dissolution of practically insoluble APIs. The preferable mesoporous carriers are silica Parteck® SLC or synthetic magnesium aluminometasilicate Neusilin® US2.