Ensslin Simon, Moll Klaus Peter, Metz Hendrik, Otz Markus, Mäder Karsten
Technical Research & Development, Novartis Pharma AG, Basel, Switzerland.
Eur J Pharm Biopharm. 2009 May;72(1):111-8. doi: 10.1016/j.ejpb.2008.11.005. Epub 2008 Nov 27.
The aim of the study was to clarify the influences of three coating parameters on the drug release from chlorpheniramine maleate (CPM) pellets, coated with blends of poly(vinyl acetate) (PVAc) and poly(vinyl alcohol)-poly(ethylene glycol) (PVA-PEG) graft copolymer. A central composite design was implemented to investigate the effect of the polymer blend ratio, the film coat thickness and the plasticizer concentration on the drug release. The solubilization inside the pellets was monitored by EPR spectroscopy. The blending ratio of both the polymers and the film thickness were found to have a major influence on the drug release and the solubilization speed, in contrast to the plasticizer concentration. A pH-independent release profile was adjustable via modulating the polymer blend ratio and the coating thickness. A mathematical model was developed, providing a good predictability of the release profile, based on the film coat composition. This model offers the possibility to achieve a defined drug-release profile by selective adaptation of the film coat composition, in view of process times, feasibility or polymer costs.
本研究的目的是阐明三个包衣参数对用聚醋酸乙烯酯（PVAc）和聚乙烯醇-聚乙二醇（PVA-PEG）接枝共聚物混合物包衣的马来酸氯苯那敏（CPM）微丸药物释放的影响。采用中心复合设计来研究聚合物共混比例、薄膜包衣厚度和增塑剂浓度对药物释放的影响。通过电子顺磁共振光谱监测微丸内部的溶解情况。与增塑剂浓度相比，聚合物的共混比例和薄膜厚度对药物释放和溶解速度有重大影响。通过调节聚合物共混比例和包衣厚度可实现与pH无关的释放曲线。基于薄膜包衣组成建立了一个数学模型，该模型对释放曲线具有良好的预测性。鉴于加工时间、可行性或聚合物成本，该模型提供了通过选择性调整薄膜包衣组成来实现特定药物释放曲线的可能性。
