Université de Lyon, F-69622, Lyon, France.
Int J Pharm. 2010 Jan 4;383(1-2):236-43. doi: 10.1016/j.ijpharm.2009.09.023. Epub 2009 Sep 23.
The evolution of regulation on chemical substances (i.e. REACH regulation) calls for the progressive substitution of toxic chemicals in formulations when suitable alternatives have been identified. In this context, the method of Hansen solubility parameters was applied to identify an alternative solvent less toxic than methylene chloride used in a microencapsulation process. During the process based on a multiple emulsion (W/O/W) with solvent evaporation/extraction method, the solvent has to dissolve a polymer, poly(epsilon-caprolactone) (PCL), which forms a polymeric matrix encapsulating or entrapping a therapeutic protein as the solvent is extracted. Therefore the three partial solubility parameters of PCL have been determined by a group contribution method, swelling experiments and turbidimetric titration. The results obtained allowed us to find a solvent, anisole, able to solubilize PCL and to form a multiple emulsion with aqueous solutions. A feasibility test was conducted under standard operating conditions and allowed the production of PCL microspheres.
化学物质法规的演变（即 REACH 法规）要求在确定合适的替代品时，逐步用毒性更小的化学品替代制剂中的有毒化学品。在这种情况下，应用 Hansen 溶解度参数方法来确定一种替代溶剂，该溶剂要比在微胶囊化过程中使用的二氯甲烷毒性更小。在基于多乳剂（W/O/W）的溶剂蒸发/提取方法的过程中，溶剂必须溶解聚合物聚己内酯（PCL），聚合物形成聚合物基质，包封或困住治疗性蛋白质，因为溶剂被提取。因此，通过基团贡献法、溶胀实验和浊度滴定法确定了 PCL 的三个部分溶解度参数。得到的结果使我们能够找到一种溶剂，即苯甲醚，它能够溶解 PCL 并与水溶液形成多乳剂。在标准操作条件下进行了可行性测试，从而能够生产 PCL 微球。
