Preparation Of Nanosized Bicalutamide And Its Process-Induced Crystalline Control

In this study, nanosized bicalutamide was produced by anti-solvent precipitation. The experimental parameters such as the ratio of volume of solution to anti-solvent, temperature, concentration of bicalutamide in solvent, stirring time, stirring speed, drying methods were studied for their effects on the particle size and morphologies.The results in beaker demonstrated that, of these systems,(DMSO+EtOH)/deionised (DI) water was the best to obtain fine particles, and the optimal condition was:the volume ratio of solution to anti-solvent1/20, temperature20-30℃, concentration of Bicalutamide solution0.06g/ml, stirring time2min, stirring speed10000rpm, and vacuum drying at60℃. Under the optimal condition, the longest dimension was about500nm.Subsequently, the preparation of nanosized bicalutamide without addition of surfactants was carried out by combing rotating packed bed (RPB) with precipitation method. Under the optimal condition, the longest dimension of particles prepared from internal circulating RPB was about600nm.Other experimental affecting factors such as stirring style (homogenizing) and speed were studied for investigation. It was shown that the mean particle size was closely dependent on the type of energy induced. The as-prepared bicalutamide possessed sharply decreased particle size with narrow size distribution, as well as preferable dissolution profile (dissolved about85%in120min) comparing with those of crude drug.The conformational polymorphism of bicalutamide has been investigated. Two crystalline forms and amorphous of this drug were obtained and preliminary analysis on this point was performed. The detailed exploration of affecting parameters including temperature and solvents on bicalutamide polymorphs selection in precipitation process was also investigated. Increasing the temperature promotes the conversion of crystalline; at middle temperature (25-40℃), the crystal mixture was obtained. The roles of solvents and co-solvents as crystal and morphology mediators during crystalline control process were under study. Besides, the drying style, stirring style, reserving condition exerted no influence on the polymorphs formation during the preparation process of nanosized bicalutamide.