Morita T, Horikiri Y, Suzuki T, Yoshino H
DDS Research Department, Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., 3-16-89 Kashima, Yodogawa-ku, 532-8505, Osaka, Japan.
Int J Pharm. 2001 May 21;219(1-2):127-37. doi: 10.1016/s0378-5173(01)00642-1.
Gelatin microparticles were prepared by co-lyophilization with poly(ethylene glycol) (PEG) as a protein micronization adjuvant. Aqueous solutions containing gelatin and PEG at various mixing ratios were freeze-dried. The lyophilizates were dispersed in methylene chloride and subjected to particle size analysis. The particle size decreased as the PEG/gelatin ratio increased. The microparticles isolated from the suspension had spherical microdomains with sizes ranging from 1 to 10 microm, which indicated that phase separation between PEG and gelatin during freezing was involved in the formation mechanism of gelatin microparticles. By using this technology, gelatin microparticles with an average size of less than 10 microm, with high purity of more than 90% and with good dispersibility could be obtained with high yield. The gelatin microparticles with average sizes from 5 to 20 microm were applied to encapsulation into biodegradable PLGA/PLA microspheres via a solid-in-oil-in-water emulsion process. The entrapment efficiency was highly dependent on the particle size and the size distribution, signifying that solid microparticles with an average diameter of less than 5 m and an maximal diameter of less than 10 microm would be required for effective encapsulation. These gelatin microparticles would be useful for studying and developing various drug delivery systems.
通过与作为蛋白质微粉化助剂的聚乙二醇（PEG）共冻干制备明胶微粒。将含有不同混合比例的明胶和PEG的水溶液进行冻干。将冻干产物分散在二氯甲烷中并进行粒度分析。随着PEG/明胶比例的增加，粒径减小。从悬浮液中分离出的微粒具有尺寸范围为1至10微米的球形微区，这表明冷冻过程中PEG和明胶之间的相分离参与了明胶微粒的形成机制。通过使用该技术，可以高产率获得平均尺寸小于10微米、纯度高于90%且具有良好分散性的明胶微粒。将平均尺寸为5至20微米的明胶微粒通过水包油包固乳液法包封到可生物降解的PLGA/PLA微球中。包封效率高度依赖于粒径和尺寸分布，这表明有效包封需要平均直径小于5微米且最大直径小于10微米的固体微粒。这些明胶微粒将有助于研究和开发各种药物递送系统。
