Tsukada Yusuke, Hara Kaori, Bando Yohei, Huang C C, Kousaka Yasuo, Kawashima Yoshiaki, Morishita Ryuichi, Tsujimoto Hiroyuki
Hosokawa Powder Technology Research Institute, 1-9 Shoudai, Tajika, Hirakata, Osaka 573-1132, Japan.
Int J Pharm. 2009 Mar 31;370(1-2):196-201. doi: 10.1016/j.ijpharm.2008.11.019. Epub 2008 Nov 28.
Parameters affecting the particle sizes of poly(DL-lactide-co-glycolide) (PLGA) nanospheres produced by the Emulsion Solvent Diffusion (ESD) method were evaluated in this study, so that suitable PLGA nanospheres could be prepared to pass through a membrane filter with 0.2 microm pore size and used as a sterile product. Experimental results demonstrated that the particle sizes of PLGA nanospheres could be reduced by the following efforts. (1) Increase stirring rate of poor solvent. (2) Decrease feed rate of good solvent. (3) Increase poor solvent ratio. (4) Increase the temperature of poor solvent. (5) Decrease polyvinyl alcohol concentration in poor solvent. (6) Increase ethanol concentration in good solvent. (7) Decrease PLGA concentration in good solvent. After optimization, PLGA nanospheres with a mean particle size of 102-163 nm and the 100-98% of filtration fraction could be produced and passed the bacteria challenge tests. This study found PLGA nanospheres can be efficiently prepared as a sterile product.
本研究评估了影响通过乳液溶剂扩散（ESD）法制备的聚（DL-丙交酯-共-乙交酯）（PLGA）纳米球粒径的参数，以便制备出合适的PLGA纳米球，使其能够通过孔径为0.2微米的膜过滤器并用作无菌产品。实验结果表明，可通过以下措施减小PLGA纳米球的粒径。（1）提高不良溶剂的搅拌速率。（2）降低良溶剂的进料速率。（3）提高不良溶剂比例。（4）提高不良溶剂的温度。（5）降低不良溶剂中聚乙烯醇的浓度。（6）提高良溶剂中乙醇的浓度。（7）降低良溶剂中PLGA的浓度。优化后，可制备出平均粒径为102-163 nm且过滤率为100-98%的PLGA纳米球，并通过细菌挑战试验。本研究发现PLGA纳米球可有效地制备成无菌产品。
