Preparation And Characterization Of Ultrafine Beclomethasone Dipropionate By Anti-Solvent Precipitation

Beclomethasone dipropionate (BDP), a member in the inhaled glucocorticosteroid (IGCS) class, is commonly used in clinics for the treatment of asthma. For IGCS, the particle size and corresponding size distribution are the key factors, which determine if drug particles can reach the site of action. Drug particles with smaller diameter are easier to enter the respiratory tract and reach the alveol. Therefore, the particle size reduction of beclomethasone dipropionate is a very effective method to improve the efficiency of pulmonary drug delivery. In this study, ultrafine BDP particles were successfully prepared by anti-solvent precipitation method in an inside circulation rotating packed bed (RPB). Furthermore, the multi-stage liquid impinger was utilized to study the efficiency of pulmonary drug delivery. The main contents and findings are summarized as follows.1. The effects of experimental parameters on particle size and morphology were investigated in beaker, such as the solvent and anti-solvent, the volume ratio of solution to anti-solvent, temperature, concentration of BDP solution and stirring speed, etc. New solvent and anti-solvent system was discovered, and the optimum condition was obtained:the volume ratio of solution to anti-solvent1/L5, temperature of4℃, BDP solution concentration of0.03g/ml, stirring time of4min, stirring speed of2000rpm, vacuum drying at105℃. The as-prepared BDP particles had a mean length of850nm and a narrow particle size distribution. In addition, the specific surface area was increased by43.1%compared with raw material, and the process recovery rate reached over99.99%. The Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) analysis indicated that no chemical decomposition took place during the process, and the crystal structures of the drug were not changed.2. It is well-known that the micro-mixing situation between solvent and anti-solvent is an important factor affecting the particle size of products when ultrafine BDP was prepared by anti-solvent precipitation. Well micro-mixing condition can be achieved in several reactors such as continuous RPB, inside circulation RPB and micro reactor. Therefore, the above-mentioned BDP preparation procedures in these equipments were explored. The results indicated that the BDP particles prepared in inside circulation RPB possessed the smallest particle size and narrow size distribution. The mean length was810nm and the specific surface area was increased by58.8%compared with raw material. It could be concluded that inside circulation RPB was better than other reactors.3. The results of pulmonary deposition experiments showed that the fine partial fraction (FPFemit dose) of drug powder obtained in inside circulation RPB was77.2%, twice than that of raw material. Therefore, ultrafine BDP powder respirable can be obtained by anti-solvent precipitation in inside circulation RPB.