Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles, Belgium.
Int J Pharm. 2012 Nov 1;437(1-2):20-8. doi: 10.1016/j.ijpharm.2012.08.006. Epub 2012 Aug 9.
This work describes the encapsulation of a small, hydrophilic molecule (clonidine) into a PLGA matrix to provide sustained release over more than one month after intra-articular administration. The microparticles were prepared using a double emulsion (w(1)/o/w(2)) method followed by evaporation of the organic solvent. To optimize the efficiency of encapsulation and the mean size of the microparticles, which was targeted around 30 μm, the following parameters were modulated: the viscosity and the volume of the organic phase, the molecular weight of the polymer, the volume of the internal and external aqueous phases, the drug loading, the concentration of surfactant, and the stirring parameters. Blends of polymers characterized by different molecular weights (34000-96000 Da) as well as copolymers of PLGA-PEG were used to enhance the entrapment of the drug. The pH of the aqueous phases was adjusted to obtain suitable encapsulation efficiency. Characterization was made of the physico-chemical properties of the microparticles, such as their crystallinity (DSC and PXRD) and microstructure (SEM). When performing in vitro dissolution studies, controlled release for up to approximately 30 days was achieved with several of the formulations developed. Diffusion was found to be the dominant drug release mechanism at early time points.
本工作描述了将一种小的亲水性分子（可乐定）封装到 PLGA 基质中，以便在关节内给药后超过一个月的时间内提供持续释放。采用双乳液（w(1)/o/w(2)）法制备微球，然后蒸发有机溶剂。为了优化包封效率和微球的平均粒径（目标粒径约为 30 μm），对以下参数进行了调节：有机相的粘度和体积、聚合物的分子量、内水相和外水相的体积、载药量、表面活性剂的浓度和搅拌参数。使用具有不同分子量（34000-96000 Da）的聚合物混合物以及 PLGA-PEG 共聚物来提高药物的包封效率。调节水相的 pH 值以获得合适的包封效率。对微球的物理化学性质进行了表征，例如结晶度（DSC 和 PXRD）和微观结构（SEM）。在进行体外释放研究时，开发的几种制剂可实现长达约 30 天的控制释放。在早期，扩散被发现是药物释放的主要机制。
