Preparation of water-soluble altrenogest inclusion complex with β-cyclodextrin derivatives and in vitro sustained-release test

Abstract

To improve the solubility of the insoluble drug Altrenogest in water, the water-soluble inclusion complexes of altrenogest-β-cyclodextrin derivatives hydroxypropyl-β-cyclodextrin, 2,6-dimethyl-β-cyclodextrin, and sulfobutyl ether-β-cyclodextrin inclusion complexes were prepared by the freeze-drying method, to solve the limitation of altrenogest in clinical application due to its water-insoluble and then broaden the way of altrenogest medicine. The inclusion complexes were prepared by the freeze-drying method and characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, and microscopy imaging. The solubility of altrenogest in the inclusion complex was determined by the solubility method. Taking the yield and encapsulation efficiency of the inclusion complex as evaluation indexes, the optimum preparation conditions of the inclusion complex were screened by orthogonal experimental design. The solubility test showed that the solubility of altrenogest was increased 1012 times, 1354 times, and 988 times in inclusion complex, respectively. It is indicated that the inclusion complex can effectively increase the solubility of altrenogest. Additionally, in vitro sustained-release test of the sustained-release silica gel suppositories of the altrenogest-sulfobutyl ether-β-cyclodextrin and the altrenogest-hydroxypropyl-β-cyclodextrin inclusion complex had better sustained-release effects. The inclusion complex has good stability, and it has a simple preparation method, and easy to industrialized production. • The molar ratio of influencing factors has great influence on the preparation of inclusion complex. • Three inclusion complexes of ALT-β-cyclodextrin derivatives all improved the solubility of ALT drugs. • The sustained-release effect of ALT-SBE-β-CD and ALT-HP -β-CD sustained-release silicone suppositories ware better.