盐酸雷尼替丁中空缓释微球的制备及其特性

Preparation and characteristics of ranitidine hydrochloride hollow microspheres

目的:以盐酸雷尼替丁(RH)为模型药物,研究中空微球的制备,并对制备过程中的影响因素进行考察。方法:以乙基纤维素(EC)为载体材料,乙醇/乙醚为混合溶剂,采用溶剂扩散-挥发法制备盐酸雷尼替丁中空微球。以产率、平均粒径、载药量和微球形态为指标,考察了处方工艺对微球性能的影响。并考察了EC粘度,RH/EC比例以及粒径对微球释药速率的影响。结果:中空微球产率为84.51%,粒径分布均匀,平均粒径632μm,载药量13.71%,包封率55.86%。电镜扫描显示:微球外观圆整光滑,内部为中空结构。体外释药研究表明随着EC粘度的增加释药速率降低;随着RH/EC比例和搅拌速度的增加释药速率增加。最终所得到的中空微球缓释可达24h,体外漂浮实验表明在人工胃液中可持续漂浮48h以上。结论:该处方工艺简便可行,制得的盐酸雷尼替丁中空微球在人工胃液中缓释性和漂浮性良好。中空微球有望成为吸收窗药物的又一新型给药系统。

OBJECTIVE The study involves preparation and evaluation of hollow microspheres with ranitidine hydrochloride （RH） as a model drug. METHODS Hollow microspheres containing ranitidine hydrochloride were prepared by a solvent diffusion and evaporation method using ethyl cellulose （EC） as carrier material and ethanol/ether as organic solvents. The yield, mean diameter （MD）, drug loading efficiency（LE）and shape of microspheres were used to evaluate the influence of different formulations and preparation factors. Effects of the EC viscidity, RH/EC ratio and diameter during preparation on the drug release from microspheres were also observed. RESULTS The yield of the hollow microspheres was 84.51%, the mean diameter was 632 μm, the drug loading efficiency was 13.71% and the encapsulation efficiency was 55.86%. The scanning electron microscope confirmed their hollow structures,with smooth surfaces. The in vitro release study showed that the drug release rate decreased with increasing the EC viscidity,while increased with increasing the RH/EC ratio and the diameter. The prepared mi- crospheres exhibited prolonged drug release （approximately 24 h） and remained buoyant more than 48 h in artificial gastric juice. CONCLUSION The prepared RH hollow microspheres showed prolonged drug release and excellent floatability. Those results suggest that the hollow microspheres have good potential for some absorption window drugs.