Institute of Pharmaceutical Technology, Technische Universität Braunschweig, Braunschweig, Germany.
Eur J Pharm Biopharm. 2013 Nov;85(3 Pt B):1215-8. doi: 10.1016/j.ejpb.2013.02.018. Epub 2013 Apr 6.
Hydrogel microspheres, e.g. for the use as protein carriers, can be prepared without the use of organic solvents via an emulsified aqueous two-phase system (ATPS) that is based on two immiscible polymer solutions. The type and concentration of the polymers can affect the ATPS and finally the distribution of incorporated drugs between the aqueous phases. For the preparation of hydrogel microspheres based on hydroxyethyl starch-hydroxyethyl methacrylate (HES-HEMA), hydroxyethyl starch-methacrylate (HES-MA), and hydroxyethyl starch-polyethylene glycol methacrylate (HES-P(EG)6MA), polyethylene glycol 12,000 (PEG 12,000) was used as second polymer. The particle size distribution and encapsulation efficiency of the microspheres depended dramatically on the type of PEG 12,000 that was used in the second phase of the ATPS. Analysis of different PEG 12,000 brands by various methods revealed differences in the salt composition and molecular weight distribution of the polymers which can explain the effects on the production process. The results illustrate that the range of product specifications may not always be tight enough to avoid variability in pharmaceutical processes like the preparation of hydrogel microspheres by an aqueous two-phase preparation process.
水凝胶微球，例如用作蛋白质载体，可以通过基于两种不混溶聚合物溶液的乳化双水相体系（ATPS）在不使用有机溶剂的情况下制备。聚合物的类型和浓度会影响 ATPS，最终影响水相间包埋药物的分布。为了制备基于羟乙基淀粉-羟乙基甲基丙烯酸酯（HES-HEMA）、羟乙基淀粉-甲基丙烯酸酯（HES-MA）和羟乙基淀粉-聚乙二醇甲基丙烯酸酯（HES-P(EG)6MA）的水凝胶微球，使用聚乙二醇 12,000（PEG 12,000）作为第二聚合物。微球的粒径分布和包封效率取决于 ATPS 第二相中使用的 PEG 12,000 的类型。通过各种方法对不同 PEG 12,000 品牌进行分析，发现聚合物的盐组成和分子量分布存在差异，这可以解释对生产工艺的影响。结果表明，产品规格范围可能不够严格，无法避免像通过双水相制备工艺制备水凝胶微球这样的药物工艺中的可变性。
