雌二醇聚乳酸类微囊的制备与体外评价

雌二醇聚乳酸类微囊的制备与体外评价

周新腾^*, 朱峰, 潘卫三, 王磊, 张汝华

1.沈阳药科大学药剂教研室, 沈阳 110016;
2.北京博泰康宁医药有限公司, 北京 100054

收稿日期:2003-01-12 修回日期:2003-05-10 出版日期:2003-06-15 发布日期:2003-06-15
通讯作者: 周新腾*

Preparation and in Vitro Evaluation of Polylactic Acid (PLA) or Polylactic-co-Glycolic Acid (PLGA) Microcapsules Loaded with Estradiol

ZHOU Xin-teng^*, ZHU Feng, PAN Wei-san, WANG Lei, ZHANG Ru-hua

1.Department of pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China;
2.Beijing Botaikangning Medical Co., Ltd., Beijing 100054, China

Received:2003-01-12 Revised:2003-05-10 Online:2003-06-15 Published:2003-06-15
Contact: ZHOU Xin-teng*

摘要/Abstract

摘要： 目的以聚乳酸或乳酸-乙醇酸共聚物为载体材料制备雌二醇缓释微囊. 方法实验中采用乳化-溶剂萃取法制备微囊, 考察了影响微囊特性以及体外释药的各种因素, 采用单因素试验方差分析进行因素影响的显著性检验, 并在此基础上采用T方法进行两两间多重比较, 进一步考察因素各水平间差异的显著性. 结果结果表明, 粒径和加水萃取速度对雌二醇微囊的包封率有显著性影响(P<0.01); 随油相载体的浓度以及加水萃取速度对微囊的粒径影响显著(P<0.01). 体外释外研究表明, 加水萃取速度和载体的型号和分子量对微囊释药影响显著(P<0.01).但这些因素的各水平之间的差异性并不都具有显著性. 结论通过改变处方以及制备工艺可以得到具有不同性质的雌二醇聚乳酸类缓释微囊.

关键词: 微囊, 雌二醇, 聚乳酸, 乳酸-乙醇酸共聚物, 乳化-溶剂萃取法

Abstract: Aim PLA/PLGA was used as biodegradable and biocompatible carriers to achieve sustained release of estradiol (E2). Methods Microcapsules (MC) were prepared by an emulsification-solvent extraction method, and then the properties and in vitro drug release behavior of MC were examined. An analysis of variance (ANOVA) was used to test the statistical significance. Then, multiple comparisons were made with a T-method between levels to examine the significance of difference further. For all the results a P value>0.05 was considered statistically insignificant. Results Under the same conditions, the water-adding speed and the particle size had significant effects (P<0.01) on the entrapment efficiency of MC; the water-adding speed and the concentration of PLA in the oil phase had significant effects (P<0.01) on the diameter MC in medium. Release of E2 from MC was influenced significantly (P<0.01) by the water-adding speed and the type and molecule weight of the polymers. But the differences between levels of the variates were not all significant. Conclusion E2-PLA/PLGA-MC with various properties can be formed when the formulation and the technology were changed accordingly.

Key words: microcapsules, microcapsules, estradiol, estradiol, PLA, PLA, PLGA, PLGA, emulsification solvent extraction, emulsification solvent extraction

中图分类号:

R945

Supporting: ^*Corresponding author. Tel.: 020-23843711-3811

周新腾^*, 朱峰, 潘卫三, 王磊, 张汝华. 雌二醇聚乳酸类微囊的制备与体外评价[J]. .

ZHOU Xin-teng^*, ZHU Feng, PAN Wei-san, WANG Lei, ZHANG Ru-hua . Preparation and in Vitro Evaluation of Polylactic Acid (PLA) or Polylactic-co-Glycolic Acid (PLGA) Microcapsules Loaded with Estradiol[J]. .

参考文献

[1] Zheng JM. Textbook of Pharmaceutical Polymers [M]. Beijing: Chinese Medical Technology Press, 1992. 117.
[2] Yasuaki O, Hiroaki O, Masaki Y. In vivo release profiles of leuprolide acetate from microcapsules prepared with polylactic acids or copoly (lactic/glycotic) acids and in vivo degradation of these polymers [J]. Chem Pharm Bull, 1988, 36: 2576.
[3] Tae GP. Degradation of poly (lactic-co-glycolic acid) microspheres : effects of copolymers composition [J]. Biomaterials, 1995, 16: 1123-1130.
[4] Atkins TJ, Lewis DH, Rickey ME. An injectable, 30 d naltrexone delivery system [J]. Proc Int Symp Controlled Release Bioact Mater, 1992, 19th: 54-55.
[5] Kobayashi D, Tsubuku S, Yamanaka H, et al. In vivo characteristics of injectable poly (DL-lactic acid) microspheres for long-acting drug delivery [J]. Drug Dev Ind Pharm, 1998, 24 (9): 819-825.
[6] Maria T, Jessica N, Yuyi G, et al. A novel system based on a poloxamer/PLGA blend as a tetanus toxoid delivery vehicle [J]. Pharm Res, 1999, 16 (5): 682-688.
[7] Falk RF, Randolph TW. Process variable implication for residual solvent removal and polymer morphology in the formation of gentamycin-loaded poly (L-lactide) microparticles [J]. Pharm Res, 1998, 15 (8): 1233-1237.
[8] Benita S, Benoit JP, Puisteux F, et al. Characterization of drug-loaded poly ( d, l-lactide) microspheres [J]. J Pharm Sci, 1984, 73 (12): 1721-1724.
[9] Hiroaki O, Masaki Y, Toshiro H, et al. Drug delivery using biodegradable microspheres [J]. J Controlled Release, 1994, 28: 121-129.
[10] Duane TB, Jacqueline DK, David BH, et al. Controlled release of β-estradiol from PLGA microparticles: the effect of organic phase solvent on encapsulation and release [J]. J Controlled Release, 2000, 65: 375-387.
[11] Hongkee S. Microencapsulation techniques using ethyl acetate as a dispersed solvent: effects of its extraction rate on the characteristics of PLGA microcapsules [J]. J Controlled Release, 1997, 47: 233-245.
[12] Zhou XT, Pan WS, Zhang RH, et al. Preparation and evaluation of poly (d,l-lactic acid) (PLA) or d,l-lactide/glycolide copolymer (PLGA) microspheres with estradiol [J]. Die Pharmazie, 2002, 10: 695-697.
[13] Huang ZH and Fang JQ. Mathematical Statistical Methods [M]. Beijing: People’s Health Press, 1990. 141-152.
[14] Manger JW, Chilko D, Howard S. On the analysis of dissolution rate [J]. Drug Dev Ind Pharm, 1986, 12 (7): 969-992.
[15] Joachim H, Roland B. Somatostatin containing biodegradable microcapsules prepared by a modified solvent evaporation method based on w/o/w-multiple emulsion [J]. Int J Pharm,1995, 126: 129-138.