孕二烯酮固体分散体微丸的工艺研究  

Process study of gestodene solid dispersion pellets

作　　者：曾佳[1] 普天磊 黄婷[1] 薛嫚[1,2] 李芳[1] 潘峰[1] 侯安国[2] 俸灵林[1] 陈建兴[1] Zeng Jia Pu Tianlei Huang Ting Xue Man Li Fang Pan Feng Hou Anguo Feng Linglin Chen Jianxing(Shanghai Institute of Planned Parenthood Research, Key Laboratory of Contraceptives and Devices Research, Shanghai Engineer and Technology Research Center of Reproductive Health Drug and Devices, Shanghai 200032, Chin Colloge of TCM,, Yunnan University of Traditional Chinese Medicine, Kunming, 650500, Chin)

机构地区：[1]上海市计划生育科学研究所,国家人口和计划生育委员会计划生育药具重点实验室,上海生殖健康药具工程技术研究中心,200032 [2]云南中医学院中药学院,昆明650500

出　　处：《生殖与避孕》2017年第1期39-45,共7页Reproduction and Contraception

基　　金：上海市计划生育科学研究所青年科技创新基金(Q2013-3)~~

摘　　要：目的旨在提高孕激素孕二烯酮(gestodene,GSD)口服固体制剂的溶出度和含量均匀度。方法以羟丙基-β-环糊精(HP-β-CD)和聚氧乙烯蓖麻油(Cremophor EL)为载体材料,采用流化床技术制备GSD固体分散体微丸。以微丸上药率和溶出度为主要评价指标,单因素考察了药物载体比例、乙醇浓度和上药液体积等处方因素及进风风量、进风温度和雾化压力等工艺因素对微丸性质的影响;并采用二因素五水平星点设计效应面法优化处方制备工艺。结果药物载体比例和上药液体积对GSD固体分散体微丸的性质影响较显著。处方最优区域为药物载体比例1︰25~1︰35,上药液体积25~55 m L。结论星点设计优化制备的GSD固体分散体微丸5 min溶出度达90%以上。该优化区域与单因素考察结果基本一致,表明该法具有较好的可靠性和预测性。Objective To improve dissolution and content uniformity of oral gestodene （GSD） solid formulations. Methods GSD solid dispersion pellets were prepared by the fluid-bed coating technology with hydroxypropyl-β-cyclodextrin （HP-β-CD） and Cremophor EL as carrier. The criteria to evaluate the pellets included the drug loading efficiency assay and dissolution rate. The influence of formulation factors such as the ratio of drug to carrier, the concentration of ethanol and the volume of solution were investigated based on single factor test. In addition, the process factors included the air volume, temperature and atomization pressure were investigated as well. Central composite design and response surface methodology （CCD-RSM） with two factors and five levels was used to optimize the formulation and process of GSD pellets. Results The ratio of drug and the volume of the solution had a significant effect on the properties of the pellets. The optimal region of formulation was 1 ： 25-1 ： 35 for the ratio of drug to carrier, and 25-55 mL for the volume of drug solution. Conclusion The dissolution of GSD solid dispersion pellets prepared by CCD-RSM optimized formulation and process was more than 90% in 5 min. The result of optimization region was consistent with the results of single factor test, which indicated that CCD-RSM has a good predictability and reliability.

关 键 词：孕二烯酮(GSD) 流化床 固体分散体 微丸 星点设计 

分 类 号：TQ460.6[化学工程—制药化工]