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PLGA 分子量差异对微球中利培酮释放的影响。

The effect of PLGA molecular weight differences on risperidone release from microspheres.

机构信息

University of Connecticut, School of Pharmacy, Storrs, CT 06269, United States.

Qrono Inc., Pittsburgh, PA 15213, United States.

出版信息

Int J Pharm. 2020 May 30;582:119339. doi: 10.1016/j.ijpharm.2020.119339. Epub 2020 Apr 17.

Abstract

The objective of the present study was to investigate the effect of molecular weight differences of poly (lactic-co-glycolic acid) (PLGA) on the in vitro release profile of risperidone microspheres. Four different PLGA molecular weights were investigated and all the microsphere formulations were prepared using the same manufacturing process. Physicochemical properties (particle size, drug loading, morphology and molecular weight) as well as in vitro degradation profiles of the prepared microspheres were investigated in addition to in vitro release testing. The in vitro release tests were performed using a previously developed flow through cell (USP apparatus 4) method. The particle size of the four prepared microsphere formulations varied, however there were no significant differences in the drug loading. Interestingly, the in vitro release profiles did not follow the molecular weight of the polymers used. Instead, the drug release appeared to be dependent on the glass transition temperature of the polymers as well as the porosity of the prepared formulations. The catalytic effect of risperidone (an amine drug) on PLGA during manufacturing and release testing, minimized the differences in the molecular weights of the four formulations, explaining the independence of the release profiles on PLGA molecular weight.

摘要

本研究旨在探讨聚(乳酸-共-乙醇酸)(PLGA)分子量差异对利培酮微球体外释放特性的影响。研究考察了四种不同的 PLGA 分子量,所有微球制剂均采用相同的制造工艺制备。除体外释放试验外,还对制备的微球的理化性质(粒径、载药量、形态和分子量)以及体外降解特性进行了考察。体外释放试验采用先前开发的流动池(USP 装置 4)法进行。四种制备的微球制剂的粒径不同,但载药量无显著差异。有趣的是,体外释放曲线并不遵循所使用聚合物的分子量。相反,药物释放似乎取决于聚合物的玻璃化转变温度以及所制备制剂的孔隙率。在制造和释放试验过程中,利培酮(一种胺类药物)对 PLGA 的催化作用最小化了四种制剂分子量的差异,解释了释放曲线与 PLGA 分子量无关。

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