多尺度下超细粉静电沉积构建渗透泵包衣膜机制研究

渗透泵制剂是目前最理想的、可实现药物匀速释放的膜控型口服控释制剂，其包衣膜（半透膜）厚度及均匀性是其质量和疗效的关键，目前仅溶剂包衣可制备出合格的包衣膜，但有机溶剂易燃易爆易挥发等问题给其产业化生产造成了极大困难。申请人所在课题组利用粉末静电沉积构建出口服固体制剂，解决了溶剂包衣的诸多缺陷，但仍无法制备出质量合格的渗透泵制剂。本项目将集中探究多尺度下超细粉静电沉积构建渗透泵制剂机制，剖析微纳尺度包衣粉在宏尺度制剂片芯表面的吸附沉积及塑性变形行为，着重研究多尺度下包衣粉的流动、聚集等特性对其均匀沉积和快速成膜的影响，解决微纳尺度下超细粉高表面能、易团聚等关键问题。建立超细包衣粉尺度、渗透泵制剂包衣膜厚度及均匀性、药物释放速率三者之间的量化关系，实现通过调整超细包衣粉的尺度从而精准控制半透膜厚度及均匀性继而精准控制药物释放速率的目标，为规模化制备质量和疗效可控的新型渗透泵制剂提供理论依据。

As the only oral drug delivery system capable achieving constant drug release rate, osmotic pump tablet (OPT) is considered as the ultimate ideal drug delivery system. Presently, only organic solvent coating can be used to prepare OPT due to the high glass transition temperature (Tg) of the coating materials, causing many problems such as toxicity and environmental concerns. Our earlier attempts reported dry powder coated pharmaceutical tablets through an electrostatic deposition of coating powders, which eliminated the shortcomings of solvent coating. But still, it cannot achieve OPT owing to the difficulties in uniformly and precisely controlling the electrostatic deposition of ultrafine powders onto the surface of the OPT cores in a complicated multiscale system. .The present study aims to investigate the mechanism of the electrostatic deposition and deformation of ultrafine coating powders during the preparation of osmotic pump tablets in a multiscale system, analyzing the adhesion and deformation of micro-nano scaled ultrafine powders onto those macro scaled osmotic pump tablet cores. Also to in-depth explore how the motion properties of ultrafine coating powders affect the deposition, deformation and the uniformity of the film, eliminating or reducing the agglomeration of the ultrafine powders. And to quantitatively establish the relationship among the particle size and distribution of the ultrafine powders, the thickness of the coating film and the drug release rate from the osmotic pump tablet, providing theoretical basis for the industrialization of the electrostatic powder coated osmotic pump tablets.