复方屈螺酮/炔雌醇长效避孕贴剂的研制与体外评价

Preparation and in vitro evaluation of prolonged-release transdermal contraceptive patch containing drospirenone and ethinylestradiol

目的:制备含屈螺酮(drospirenone,DRSP)与炔雌醇(ethinylestradiol,EE)的长效控释避孕贴剂,并对其体外释放度和经皮渗透性进行考察,为体内评价和临床应用提供依据。方法:分别建立屈螺酮和炔雌醇的体外含量HPLC测定法,用溶剂挥发法制备贴剂,以体外透皮性能为指标对压敏胶型号、载药量和促渗剂进行筛选,优化处方。结果:以DURO-TAK 87-2510型压敏胶为骨架材料,制得含药量质量分数为11%、氮酮质量分数为5%的复方避孕贴剂,在7 d内屈螺酮和炔雌醇能以稳定的速率透过离体裸鼠皮肤,稳态透皮速率分别为0. 95μg·cm-2·h-1和5. 2 ng·cm-2·h-1。体外48 h的释放度分别为92. 3%和90. 6%。结论:制得复方避孕贴,在7 d内能维持较稳定的药物经皮渗透速率,有望成为一种新型非口服避孕制剂。

Objective: To develop a prolonged-release contraceptive patch containing drospirenone(DRSP)and ethinylestradiol(EE),and to investigate the release degree in vitro and the transdermal permeation of the patch,providing the basis for in vivo evaluation and clinical application. Methods: HPLC method for determination of DRSP and EE in vitro was established. Solvent evaporation technique was used to prepare the contraceptive patches. To optimize the prescription,in vitro transdermal properties were used as indicators to screen the adhesive matrixes,drug loadings and penetration enhancers. Results: Steady transdermal permeation parameters of both drugs were achieved by the formulation consisted of 11% drug,5% azone,and adhesive of DURO-TAK 87-2510.The DRSP and EE permeated through hairless mouse skin for 7 days with different rates at 0. 95 μg·cm^-2·h^-1 and5. 2 ng·cm^-2·h^-1 respectively. The cumulative release percentages in vitro in 48 hours were 90. 6% for DRSP,and 92. 3% for EE. Conclusion: The prolonged-release contraceptive patch containing DRSP and EE could maintain a stable drug transdermal permeation rate for 7 days,which was expected to be a novel non-oral contraceptive preparation.