Preparation of polymer microcapsules enclosing active agent with controlled-release property

本研究通过O/O乳剂法制备溶剂蒸发法制备包封生物活性物质的微颗粒药物，阐明工艺参数对其释放性能的影响。首先，在药物微粒分散于油滴的情况下，采用溶剂蒸发法制备可生物降解聚合物微胶囊。聚乳酸微胶囊的直径恒定在50μm左右，而微颗粒药物的载药量在很大范围内变化。聚乳酸微胶囊的直径随着分散油滴中聚合物溶解浓度的增加和溶剂蒸发搅拌速率的减小而增大。通过改变制备条件，如聚乳酸微胶囊的直径和载药量，我们成功地构建了释放模型，即核-壳模型，该模型很好地描述了初始破裂的程度和初始破裂后的释放速度。其次，我们试图阐明工艺参数对药物与聚合物相互作用的聚乳酸微胶囊的释放性能的影响。制备的聚乳酸微胶囊表面有许多折痕。聚合物微胶囊中药物含量越高，折痕越大。可以认为微胶囊上的折痕导致了初始破裂，因为初始破裂增加了聚合物微胶囊中药物含量的增加。即由于表面上的折痕而使表面积增加。这一事实对制备包涵新药的微粒药物时药物与聚合物之间的相互作用提出了警告。

This research was conducted to clarify the effect of process parameters which affected the release properties of microparticulate drugs encapsulating bioactive materials by solvent evaporation method via O/O emulsion preparation.At first, the experiment was carried out in the case that microparticle drug was dispersed in oil droplets, in the solvent evaporation method to prepare biodegradable polymer microcapsules. The diameter of polylactic acid microcapsules was constant to be ca. 50μm in spite that the loading amount of microparticle drug was varied in a wide range. whereas, the diameter of polylactic acid microcapsules increased in an increase in polymer concentration dissolved in dispersed oil droplets and in a decrease in stirring rate in solvent evaporation. From the release experiment in which preparation conditions, such as diameter of polylactic acid microcapsules and loading amount of drug, were varied, we successfully construct the release model, namely core-shell model, which well described the degree of initial burst and the release rate after initial burst.Secondly, we tried to clarify the effect of process parameter on release properties in the case of polylactic acid microcapsules enclosing drugs which had an interaction between drug and polymer. The prepared polylactic acid microcapsules showed many creases in their surface. The crease became more at higher drug content in polymer microcapsules. It was appropriate to consider that the crease on the microcapsule led the initial burst because the initial burst increase in an increase in drug content in polymer microcapsules. That is, the surface area increased due to crease on surface. This fact gave a warning about the interaction between drug and polymer in preparation of microparticulate drug enclosing a new drug.