目的 考察多西他赛囊袋张力环加速释放度试验条件,并优化多西他赛囊袋张力环的处方工艺。方法 通过考察释放介质中乙醇含量(0%、5%、10%)和不同温度(37和45 ℃)对多西他赛囊袋张力环释药速度的影响,建立制剂体外加速释放度试验条件。利用加速释放度试验方法考察多西他赛囊袋张力环的体外释放度,筛选最优处方。结果 在介质为含5%乙醇pH 7.4磷酸盐缓冲溶液、温度为(45±0.5) ℃的加速释放条件下,药物释放速度提高了4倍,加速释放度与长期释放度用二项式拟合最好(y=0.004 6x2+0.437 4x+9.683 7,r2=0.998 4);载药量为30%,载体为PLGA5050(60K-100K=1:1,W/W)的处方释药平稳,可持续释药30 d,符合Peppas equation释药模型。结论 多西他赛囊袋张力环的释药特性可用加速释放度试验快速考察,该制剂体外释药平稳缓慢,具有临床应用前景。
Abstract
OBJECTIVE To develop the accelerated release test method of docetaxel capsule tension ring and optimize its formulation. METHODS The effects of ethanol concentration in the medium (0%, 5%, 10%) and temperature (37 and 45 ℃) on the release rate of docetaxel capsule tension ring were investigated, and the correlation regression equation between the accelerated release rate and the long-term release was established. Then, the best prescription was screened out with the accelerated release test method.RESULTS The drug release rate of these preparations could be increased by four times under the accelerated conditions, i.e.,using pH 7.4 phosphate buffer solution containing 5% ethanol as the release medium and operating at (45±0.5)℃. The accelerated release and long-term release were fitted the best using binomial model (y=0.004 6x2+0.437 4x+9.683 7, r2=0.998 4). The preparation using PLGA5050 (60K-100K=1:1, W/W) with drug-loading of 30% released drug stably and sustainedly for 30 d, and its release behavior was consistent with Peppas equation drug release model. CONCLUSION Accelerated release testing can be employed as a rapid screening test to facilitate the formulation optimization of docetaxel capsule tension ring. This preparation has been proven to have sustained-release characteristics, suggesting a good clinical application prospect.
关键词
聚乳酸-羟基乙酸共聚物 /
多西他赛 /
囊袋张力环 /
加速释放度 /
体外释放
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Key words
polylactic-co-glycolic acid /
docetaxel /
capsule tension ring /
accelerated release test /
in vitro release
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中图分类号：
R944
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参考文献
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脚注
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基金
广东省医学科学技术研究基金资助项目(B2014083);广东食品药品职业学院自然科学研究资助项目(2013YZ011)
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