THE FORMATION AND CHARACTERIZATION OF HYDROCORTISONE-LOADED POLY((+/-)-LACTIDE) MICROSPHERES
THE FORMATION AND CHARACTERIZATION OF HYDROCORTISONE-LOADED POLY((+/-)-LACTIDE) MICROSPHERES
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DOI：
10.1111/j.2042-7158.1986.tb04561.x
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发表时间：
1986-04-01
影响因子：
3.3
通讯作者：
THIES, C
中科院分区：
文献类型：
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作者：
CAVALIER, M;BENOIT, JP;THIES, C
采用溶剂蒸发法制备了负载氢化可的松的聚（+-）微球。-丙交酯)（PLA）和丙交酯-乙醇酸共聚物（65/35）。二氯甲烷是铸造溶剂。采用部分水解（88%）的聚乙烯醇和甲基纤维素作为水相乳化剂。甲基纤维素是首选，因为随着氢化可的松包封量的增加，它会产生稳定的乳液，而聚乙烯醇则不会。以甲基纤维素为乳化剂，可制备含氢化可的松50% （w/w）的球形微球。热分析和x射线分析证实聚(（.+-）。含有氢化可的松的微球保留了两种材料的热事件特征。这证明这种微球在一定程度上含有分散在聚乳酸基质中的结晶氢化可的松结构域。但大部分被包封的药物分子分散在PLA玻璃中。考察了氢化可的松微球在不同贮存条件下的稳定性：未见药物降解现象。250-350亩氢化可的松释放量。M直径微球搅拌成37度。用高效液相色谱法测定C水（氮气氛）。评估的微球初始氢化可的松有效载荷为12 - 47% （w/w）。药物释放速率随微球初始载药量的增加而增加。释放数据不能用零级、一阶或时间平方根释放动力学来充分描述。含有12% （w/w）氢化可的松的微球的药物释放接近平台值，远低于微球实际携带的药物量。对于包封在丙交酯-乙醇酸聚合物中的氢化可的松尤其如此。
The solvent evaporation process has been used to form hydrocortisone-loaded microspheres from poly ((.+-.)-lactide) (PLA) and a lactide-glycolide copolymer (65/35). Methylene chloride was the casting solvent. Partialy hydrolysed (88%) poly(vinyl alcohol) and methylcellulose were used as aqueous phase emulsifiers. Methylcellulose was preferred, because it gave stable emulsions as the amount of hydrocortisone being encapsulated increased whereas poly(vinyl alcohol) did not. With methylcellulose as the emulsifier, a broad size range of spherical microspheres containing up to 50% (w/w) hydrocortisone could be prepared. Thermal and X-ray analyses established that poly((.+-.)-lactide) microspheres containing hydrocortisone retained thermal events characteristic of both materials. This is evidence that such microspheres contain, to some extent, crystalline hydrocortisone domains dispersed in a PLA matrix. But most of the encapsulated drug was molecularly dispersed in the PLA glass. The stability of hydrocortisone in microspheres was evaluted in different storage conditions: no degradation of drug was found. The release of hydrocortisone from 250-350 .mu.m diameter microspheres into agitated 37.degree. C water (nitrogen atmosphere) was determined by HPLC analysis. The microspheres evaluated had initial hydrocortisone payloads of 12 to 47% (w/w). The rate of drug release increased as the initial drug payload carried by the microspheres increased. The release data are not adequately described by zero order, first order, or square-root-of-time release kinetics. Drug release from microspheres that contain 12% (w/w) hydrocortisone approached a plateau value well below the amount of drug actually carried by the microspheres. This is particularly true for hydrocortisone encapsulated in lactide-glycolide polymer.