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氟比洛芬从尤特奇RS和RL水纳米混悬液中的释放:通过差示扫描量热法和透析实验进行的动力学研究

Flurbiprofen release from Eudragit RS and RL aqueous nanosuspensions: a kinetic study by DSC and dialysis experiments.

作者信息

Castelli Francesco, Messina Chiara, Sarpietro Maria Grazia, Pignatello Rosario, Puglisi Giovanni

机构信息

Dipartimento di Scienze Chimiche, Universita di Catania, Viale Andrea Doria, 6, Citta Universitaria, I-95125 Catania, Italy.

出版信息

AAPS PharmSciTech. 2002;3(2):E9. doi: 10.1208/pt030209.

Abstract

The present work investigated the release of Flurbiprofen (FLU) from Eudragit RS100 (RS) and Eudragit RL100 (RL) nanosuspensions to a biological model membrane consisting of Dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles (MLV). This release was compared with those observed from solid drug particles as well as with dialysis experiments. Nanosuspensions were prepared by a modification of Quasi-Emulsion Solvent Diffusion technique. Drug release was monitored by the Differential Scanning Calorimetry (DSC). FLU dispersed in MLV affects the transition temperature (T(m)) of DMPC liposomes, causing a shift towards lower values. The temperature shift is modulated by the drug fraction present in the aqueous lipid bilayer suspension. DSC was also performed, after increasing incubation periods at 37 degrees C, on suspensions of blank liposomes added to fixed amounts of unloaded and FLU-loaded nanosuspensions, as well as to powdered free drug. T(m) shifts, caused by the drug released from the polymeric system or by free-drug dissolution during incubation cycles, were compared with those caused by free drug increasing molar fractions dispersed directly in the membrane during their preparation. These results were compared with the drug release and were followed by a classical dialysis technique. Comparing the suitability of the 2 different techniques in order to follow the drug release as well as the differences between the 2 RL and RS polymer systems, it is possible to confirm the efficacy of DSC in studying the release from polymeric nanoparticulate systems compared with the "classical" release test by dialysis. The different rate of kinetic release could be due to void liposomes, which represent a better uptaking system than aqueous solution in dialysis experiments.

摘要

本研究考察了氟比洛芬(FLU)从乙基纤维素RS100(RS)和乙基纤维素RL100(RL)纳米混悬液释放至由二肉豆蔻酰磷脂酰胆碱(DMPC)多层脂质体(MLV)组成的生物模型膜的情况。将该释放情况与从固体药物颗粒观察到的释放情况以及透析实验进行了比较。纳米混悬液通过改进的准乳液溶剂扩散技术制备。通过差示扫描量热法(DSC)监测药物释放。分散在MLV中的FLU会影响DMPC脂质体的转变温度(T(m)),导致其向较低值偏移。温度偏移受水性脂质双层混悬液中药物分数的调节。在37℃下延长孵育时间后,还对添加了固定量未负载和负载FLU的纳米混悬液以及游离药物粉末的空白脂质体混悬液进行了DSC测定。将聚合物系统释放的药物或孵育周期中游离药物溶解引起的T(m)偏移与制备过程中直接分散在膜中的游离药物摩尔分数增加引起的T(m)偏移进行了比较。将这些结果与药物释放情况进行比较,并采用经典透析技术跟踪。比较这两种不同技术在跟踪药物释放方面的适用性以及两种RL和RS聚合物系统之间的差异,可以确认与通过透析进行的“经典”释放试验相比,DSC在研究聚合物纳米颗粒系统释放方面的有效性。不同的动力学释放速率可能归因于空脂质体,在透析实验中,空脂质体是比水溶液更好的摄取系统。

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