丙酸倍氯米松及其溶剂化合物在三氯-氟甲烷的结晶生长动力学对定量气雾剂行为的影响

丙酸倍氯米松及其溶剂化合物在三氯-氟甲烷的结晶生长动力学对定量气雾剂行为的影响

毛磊, 王娟, 卞祖清, 张军

中国医药研究开发中心, 北京集爱制药有限公司, 北京 102206

收稿日期:1997-12-21 修回日期:1998-06-08 出版日期:1999-09-15 发布日期:1999-09-15

Kinetics of Crystal Growth of BDP and Its Solvates in Trichlorofluoromethane and Their Influence on the Performance of Metered Dose Inhalers

Mao Lei, Wang Juan, Bian Zuqing, Zhang Jun

The National Institure of Pharmaceutical Research and Development, Beijing 102206

Received:1997-12-21 Revised:1998-06-08 Online:1999-09-15 Published:1999-09-15

摘要/Abstract

摘要： 本文研究了丙酸倍氯米松及其醋酸乙酯和三氯-氟甲烷溶剂化物微粉在三氯-氟甲烷中的结晶生长行为。给出了结晶生长曲线并计算了结晶生长动力学参数、结晶生长的趋势及速度为丙酸倍氯米松>丙酸倍氯米松醋酸乙酯溶剂化物>丙酸借氯米松三氯-氟溶剂化物。15℃时丙酸信氯米松及40℃丙酸倍氯米松醋酸乙酯溶剂化物的结晶生长动力学参数限值成别为0.1637 μm·min^-1及0.0138 μm·min^-1。同时观察并计算了最终平衡粒径。双冲程实验结果表明用丙酸倍氯米松, 丙酸倍氯米松醋酸乙酯溶剂化物及丙酸倍氯米松三氯-氟甲烷溶剂化物微粉制备的定量气雾剂在深肺部的沉积为8%、54%及59%,在40%、75%RH条件下贮存两周后, 降至20、400及57%。

关键词: 丙酸倍氯米松, 溶剂化物, 晶体生长, 动力学参数, 气雾剂行为

Abstract: The purpose of this paper is to investigate the morphology change and crystalgrowth of fine particles of beclomethasone diopropionate (BDP), its ethyl acetate solvate (BDP-EtOAc) and trichlorofluoromethane solvate (BDP-P11) after contacting trichlorofluoromethane.Curves of crystal growth versus time were obtained and kinetic parameters of crystal growth were calcu1ated. The tendency and velocity of crystal growth were BDP>BDP-EtOAC>BDP-P11. K-values of crystal growth curves for BDP at 15℃ and BDP-EtOAc at 40 ℃ were 0.1637 μm·min^-1 and 0.0138 μm·min^-1 respectively. Final particle sizes of BDP were calculated and compared with measured values. Results of twin liquid impinger tests showed that BDP pressurized metered dose inhaler (pMDIs) prepared with BDP, BDP-EtOAc and BDP-P11 had deep lung drug deposition of 8%, 54% and 59%, dropping to 2%, 40%, and 57% after storage at 40℃, 75% RH for 2 weeks respectively.

Key words: Beclomethasone diopropionate, Solvates, Crystal growth, Kinetic parameter, Performance of inhalations

Supporting:

毛磊, 王娟, 卞祖清, 张军. 丙酸倍氯米松及其溶剂化合物在三氯-氟甲烷的结晶生长动力学对定量气雾剂行为的影响[J]. .

Mao Lei, Wang Juan, Bian Zuqing, Zhang Jun. Kinetics of Crystal Growth of BDP and Its Solvates in Trichlorofluoromethane and Their Influence on the Performance of Metered Dose Inhalers[J]. .

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