羟丙基-β-环糊精的包合作用对前列腺素E1溶解度、溶出速率及稳定性的影响

羟丙基-β-环糊精的包合作用对前列腺素E₁溶解度、溶出速率及稳定性的影响

谷福根, 崔福德^*, 高永良

1.沈阳药科大学药剂教研室, 辽宁沈阳 110016;
2.军事医学科学院毒物药物研究所制剂室, 北京 100850

收稿日期:2004-04-19 修回日期:2004-08-10 出版日期:2004-09-15 发布日期:2004-09-15
通讯作者: 崔福德*

Effect of Complexation with Hydroxylpropyl-β-Cyclodextrin on Solubility, Dissolution Rate and Chemical Stability of Prostaglandin E₁

GU Fu-gen, CUI Fu-de^*, GAO Yong-liang

1.Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China;
2.Department of Pharmaceutics, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China

Received:2004-04-19 Revised:2004-08-10 Online:2004-09-15 Published:2004-09-15
Contact: CUI Fu-de*

摘要/Abstract

摘要： 目的研究羟丙基-β-环糊精(HP-β-CD)对前列腺素E1(PGE1)溶解度、溶出速率及化学稳定性的影响, 为制备稳定的PGE1-HP-β-CD包合物固体以及溶液型制剂提供依据. 方法采用相溶解度法研究HP-β-CD对PGE1溶解度的影响; 分别采用紫外吸收光谱法(UV)、圆二色谱法(CD)与红外吸收光谱法(IR)、X-射线衍射法研究PGE1与HP-β-CD在溶液中的包合作用及PGE1固体包合物的物相; 采用冷冻干燥法制备PGE1-HP-β-CD固体包合物并测定其溶出速度及化学稳定性; 同时研究在不同pH值条件下HP-β-CD对PGE1溶液稳定性的影响. 结果相溶解度法表明, 在不同pH条件下, PGE1的溶解度均随HP-β-CD浓度的增加而呈线性增加, 相溶解度图为A1-型; UV与CD法证实了PGE1与HP-β-CD在溶液中可形成包合物; IR与X-射线衍射法证明了PGE1包合物已形成一新的物相; PGE1与HP-β-CD形成包合物后, 其溶解速率及化学稳定性显著增加; 在酸、碱性pH条件下, HP-β-CD可明显增加PGE1溶液的稳定性, 但在中性pH条件下, HP-β-CD的上述稳定作用并不存在. 结论 HP-β-CD可明显增加PGE1的溶解度、溶出速率及化学稳定性.完全有可能制备一种稳定性良好的PGE1-HP-β-CD包合物固体制剂, 但制备稳定性良好的PGE1-HP-β-CD包合物溶液型制剂的可能性较小, 因为尽管HP-β-CD可明显增加PGE1水溶液的稳定性, 但降解速率仍很快.

关键词: 前列腺素E1, 前列腺素E1, 前列腺素E1, 羟丙基-β-环糊精, 羟丙基-β-环糊精, 羟丙基-β-环糊精, 包合物, 包合物, 包合物, 溶解度, 溶解度, 溶解度, 溶出速率, 溶出速率, 溶出速率, 稳定性, 稳定性, 稳定性

Abstract: Aim To study the effect of complexation with hydroxylpropyl-β-cyclodextrin (HP-β-CD) on the solubility,dissolution rate and chemical stability of prostaglandin E1 (PGE1), thereby providing a basis for preparing a stable solid or aqueous preparation of PGE1 formulated with HP-β-CD. Methods The effect of HP-β-CD on the solubility of PGE1 was studied by phase solubility method. The formation of inclusion complexes of PGE1 with HP-β-CD in the aqueous solution was confirmed by UV spectra, circular dichroism spectroscopy, and that in the solid state by IR spectra and X-ray diffractometry. An solid inclusion complex of PGE1 with HP-β-CD was prepared by lyophilization. The dissolution rate and stability of the inclusion complex were determined and compared with those of PGE1 alone. Meanwhile, the stability of PGE1 aqueoussolutions in the presence of HP-β-CD was studied under different pH conditions. Results The solubility of PGE1 increased linearly with increasing HP-β-CD concentration in various pH buffered solutions, showing typical AL-type phase solubility diagrams. The stability and dissolution rate of the solid inclusion complex of PGE1 were significantly increased, compared with those of pure PGE1. The stability of PGE1 in HP-β-CD solutions was also obviously improved under acidic and basic conditions, but the stabilizing effect was absent under neutral conditions. Conclusions The solubility,dissolution rate and chemical stability of PGE1 are markedly improved by complexation with HP-β-CD. It is quite possible to prepare a stable PGE1 inclusion complex-containing solid dosage forms, but almost impossible to obtain a stable aqueous preparation of PGE1 formulated with HP-β-CD.

Key words: PGE1, PGE1, HP-β-CD, HP-β-CD, inclusion complex, inclusion complex, solubility, solubility, dissolution rate, dissolution rate, stability, stability

中图分类号:

R912

R943.4

Supporting: ^*Corresponding author. Tel.: 86-24-23843711-3736

谷福根, 崔福德^*, 高永良. 羟丙基-β-环糊精的包合作用对前列腺素E₁溶解度、溶出速率及稳定性的影响[J]. .

GU Fu-gen, CUI Fu-de^*, GAO Yong-liang. Effect of Complexation with Hydroxylpropyl-β-Cyclodextrin on Solubility, Dissolution Rate and Chemical Stability of Prostaglandin E₁[J]. .

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羟丙基-β-环糊精的包合作用对前列腺素E₁溶解度、溶出速率及稳定性的影响

Effect of Complexation with Hydroxylpropyl-β-Cyclodextrin on Solubility, Dissolution Rate and Chemical Stability of Prostaglandin E₁

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