Morita T, Horikiri Y, Yamahara H, Suzuki T, Yoshino H
DDS Research Department, Tanabe Seiyaku Co. Ltd., Osaka, Japan.
Pharm Res. 2000 Nov;17(11):1367-73. doi: 10.1023/a:1007526301331.
Preparation of spherical fine protein microparticles by the lyophilization of a protein-poly(ethylene glycol) (PEG) aqueous mixture was investigated. The main objective was to establish a method for preparing protein microparticles suitable for pharmaceutical production.
Aqueous solutions containing bovine serum albumin (BSA) and PEG at various mixing ratios were freeze-dried. The lyophilizates were dispersed in methylene chloride and subjected to particle size analysis. Analogous studies were performed using several model proteins. A phase diagram of the PEG-BSA aqueous system was obtained by the titration method.
The particle size of BSA decreased as the PEG-BSA ratio increased. A bending point was observed in this relationship, at which the PEG-BSA ratio coincided with that of the critical point on the phase diagram of the PEG-BSA system. These results were explained by the freezing-induced condensation, followed by phase separation in the PEG-BSA system.
Spherical fine protein microparticles were successfully obtained at high yield and without any activity loss under optimum conditions. This new technology could be applicable to proteins with a wide range of molecular weights, and is expected to be developed for dry powder inhalations or long-term sustained release microsphere formulations.
研究通过冻干蛋白质 - 聚乙二醇（PEG）水溶液混合物制备球形精细蛋白质微粒。主要目的是建立一种适合药物生产的蛋白质微粒制备方法。
将含有不同混合比例牛血清白蛋白（BSA）和PEG的水溶液进行冻干。将冻干物分散在二氯甲烷中并进行粒度分析。使用几种模型蛋白进行了类似研究。通过滴定法获得了PEG - BSA水体系的相图。
随着PEG - BSA比例的增加，BSA的粒径减小。在这种关系中观察到一个转折点，此时PEG - BSA比例与PEG - BSA体系相图上的临界点比例一致。这些结果通过冷冻诱导凝聚，随后在PEG - BSA体系中发生相分离来解释。
在最佳条件下成功获得了高产率且无任何活性损失的球形精细蛋白质微粒。这项新技术可应用于广泛分子量的蛋白质，并有望开发用于干粉吸入剂或长期缓释微球制剂。
