Effects of roll mixing with beta-cyclodextrin on enhancing solubilities of water insoluble drugs

To increase a solubility of water insoluble drugs by the use of roll mixing with beta-cyclodextrin (CyD), equilibrium concentrations of ten medicinal drugs indomethacin, griseofulvin, nifedipine and so on were examined in comparison with those of different mixed systems as kneading with water and physical mixing. The equilibrium concentration of drug in the roll mixed systems was more advantageous than the others excluding the systems of cortisone acetate (CA), and it increased apparently as compared to the solubility of the drugs except for kitasamycin. Almost all of drugs being a crystalline state turned readily to an amorphous form by the procedures of roll mixing with CyD. The amorphous product roll mixed with CA or diethylstilbestrol (DB) changed to the crystalline form due to the inclusion complexes of CyD in X-ray diffraction patterns, when these were exposed on humidifing atmospheres of relative humidity (RH) 97% for 24 hours. The another roll mixed products exhibited the crystalline pattern of the hydrated CyD. Apparent increases in the solubility of drug roll mixed were expected to relate a formation of inclusion compounds or certain molecular interactions between the drug and CyD, which was based upon slight changes in absorption bands on IR spectra.