释药吸液避孕膜稳定性与体外释放度研究

Study on stability and release rate of release drug imbibition contraceptive membranes

目的:考察新研制释药吸液避孕膜的稳定性,体外释放度和体、内外溶化时限。方法:稳定性试验在40℃±1℃、相对湿度75%±5%的恒温恒湿培养箱内和室温自然条件下放置样品,使用高效液相色谱法(HPLC),在设定的时间测定样品中壬苯醇醚-9(NP-9)含量;分别将释药吸液避孕膜放入37℃±0.5℃水浴中及女性阴道内测定体外释放度并观察体内外溶化时限,在不同的时间点采样,采用HPLC测定释放介质中NP-9累积释放量。结果:在设定的时间内,样品中NP-9含量无明显变化,稳定性良好。药膜中NP-9累积释放量随着时间的延长而增加,0min及80min时累积释放率分别为28.93%、98.10%。释药吸液避孕膜在妇女阴道内溶化时限为8～12h,在体外溶化时限平均为61.48±0.16min。结论:释药吸液避孕膜具有良好的稳定性,可在室温条件下存放24个月。释药吸液避孕膜中N-9体外释放量随着时间的延长而增加。体内、外溶化时间不一致的特性,表明释药吸液避孕膜溶化速度可能与液体量有关,这一特点可使药膜在遇到精液时迅速释放出N-9,以提高杀精效果。

Objective：To investigate the stability and the release rate of the new release drug imbibition contraceptive membranes in vitro and its dissolution time in vivo and in vitro. Methods：The samples were retained in the constant humidity incubator with the （40±1）℃ of temperature and （75±5）% of relative humidity. The contents of nonoxinol-9 （N-9） were measured by high performance liquid chromatography （HPLC） at the target time. The release drug imbibition contraceptive membranes were put in the （37±0.5）℃ water bath and interposed in the vagina of the women respectively,then the release rate and its dissolution time were determined in vivo and in vitro. The cumulative release amounts of N-9 in the release medium at different time were measured. Results：There were no significant differences in the N-9 contents at the target time; the stability was good as well. The cumulative release of N-9 in the release mediums raised as time increased,with 28.93% and 98.10% of the cumulative percentages at 0,80 min respectively. On average,the dissolution time of the release drug imbibition contraceptive membrane was between 8 and 12 hours in the vagina of the women,and its dissolution time was （61.48±0.16） minutes in vitro. Conclusion：The release drug imbibition contraceptive membranes have well stability and may be preserved at the room temperature for 24 months. The different property of the dissolution time in vitro and in vivo indicates that its dissolved rate was related to amount of liquid around,resulting in improvement of their spermicidal effects with rapid release of N-9 when melt with the sperm.