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聚(丙交酯-乙交酯)和聚(丙交酯)多储库型微球的破裂及药物释放特性

Rupture and drug release characteristics of multi-reservoir type microspheres with poly(dl-lactide-co-glycolide) and poly(dl-lactide).

作者信息

Matsumoto Akihiro, Matsukawa Yasuhisa, Horikiri Yuji, Suzuki Takehiko

机构信息

Pharamaceutical Development Laboratory, Tanabe Seiyaku Co. Ltd., Kashima 3-chome, Yodogawa-ku, Osaka 532, Japan.

出版信息

Int J Pharm. 2006 Dec 11;327(1-2):110-6. doi: 10.1016/j.ijpharm.2006.07.055. Epub 2006 Aug 4.

Abstract

For the multi-reservoir type microspheres composed of polylactide (PLA) and poly(dl-lactide-co-glycolide) (PLGA), the influence of inner drug-holding layer/outer layer ratio on drug release profiles was studied. The microspheres were prepared by the O/W type emulsion-solvent evaporation technique, and cisplatin was used as a model drug. The water-uptake and the erosion of each polymer were evaluated to clarify the mechanism of drug release for multi-reservoir type microspheres. The formulations were classified by the influence of the blending ratio on drug-release profiles: the formulations with the drug-release profiles independent of the blending ratio (Typel group) and the formulations with drug-release profiles depending on the blending ratio (type 2 group). The formulations of type 1 group showed the uniform swelling during drug-release test, and provided the drug-release governed by the erosion of the inner drug-holding layer. On the other hand, the formulations of Type2 group showed the rupture of outer layer which was induced by the swelling of inner drug-holding layer, and the microspheres with the low ratio of the PLGA provided the drug-release rate which exceeded the estimate from the erosion profiles. The results of present study revealed that two types of drug-release mechanism exist for multi-reservoir type microspheres.

摘要

对于由聚丙交酯(PLA)和聚(丙交酯-共-乙交酯)(PLGA)组成的多储库型微球,研究了内部药物包封层/外层比例对药物释放曲线的影响。微球采用水包油(O/W)型乳液溶剂蒸发技术制备,顺铂用作模型药物。评估了每种聚合物的吸水率和侵蚀情况,以阐明多储库型微球的药物释放机制。根据混合比例对药物释放曲线的影响对制剂进行分类:药物释放曲线与混合比例无关的制剂(类型1组)和药物释放曲线取决于混合比例的制剂(类型2组)。类型1组的制剂在药物释放试验中表现出均匀膨胀,并呈现出由内部药物包封层侵蚀控制的药物释放。另一方面,类型2组的制剂显示出由于内部药物包封层膨胀而导致的外层破裂,并且PLGA比例低的微球提供的药物释放速率超过了根据侵蚀曲线的估计值。本研究结果表明,多储库型微球存在两种药物释放机制。

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