Faculty of Chemistry, Physical Chemistry Division, Warsaw University of Technology, Warsaw, Poland.
Eur J Pharm Biopharm. 2013 Sep;85(1):151-7. doi: 10.1016/j.ejpb.2013.02.012.
In the field of drug delivery systems, microparticles made of polymeric matrix appear as an attractive approach. The in vitro release kinetic profile is crucial information when developing new particulate formulations. These data are essential for batch to batch comparison, quality control as well as for anticipation of in vivo behavior to select the best formulation to go further in preclinical investigations. The methods available present common drawbacks such as the time- and compound-consumption that does not fit with formulation screening requirements in early development stages. In this study, a new microscale high throughput screening (HTS) method has been developed to investigate drug release kinetic from piroxicam-loaded polylactic acid (PLA) and polylactic-co-glycolic acid (PLGA) microparticles. The method is a sample- and separation-based method where separation is performed by filtration using 96-well micro filter plates. 96 experiments can therefore be performed on one plate in one time in a fully automated way and with a very low sample and particle consumption. The influence of different parameters controlling release profiles was also investigated using this technique. The HTS method gave the same release profile than the standard dialysis method. Shaking, particle concentration, and the nature of the release medium were found to be of influence. The HTS method appears as a reliable method to evaluate drug release from particles with smaller standard deviation and less consumption of material.
在药物传递系统领域,聚合物基质微球作为一种有吸引力的方法出现了。开发新的颗粒制剂时,体外释放动力学特征是关键信息。这些数据对于批间比较、质量控制以及预测体内行为以选择最佳制剂以进一步进行临床前研究至关重要。现有的方法存在一些共同的缺点,例如时间和化合物消耗,这不符合早期开发阶段制剂筛选的要求。在这项研究中,开发了一种新的微尺度高通量筛选(HTS)方法,用于研究载比罗昔康的聚乳酸(PLA)和聚乳酸-共-羟基乙酸(PLGA)微球的药物释放动力学。该方法是一种基于样品和分离的方法,分离是通过使用 96 孔微孔滤板进行过滤来完成的。因此,可以在一个平板上一次自动进行 96 个实验,并且样品和颗粒的消耗量非常低。还使用该技术研究了控制释放曲线的不同参数的影响。HTS 方法给出了与标准透析方法相同的释放曲线。发现搅拌、颗粒浓度和释放介质的性质有影响。HTS 方法似乎是一种可靠的方法,可以评估具有较小标准偏差和较少材料消耗的颗粒的药物释放。