醋酸烯诺孕酮透皮贴剂的制备及不同促渗剂对其促渗作用考察

Preparation of Nestorone Transdermal Patches and Study on the Effect of Different Permeation Enhancer on It

目的:制备醋酸烯诺孕酮透皮贴剂,并考察5种促渗剂单用和联用对贴剂的促渗作用。方法:采用正交试验,以初黏力和累积渗透量(Q)为指标,优化Druo-tak87-2287压敏胶、聚维酮(PVP)K30、乙酰丙酮铝的用量,考察250h内的平均Q;比较质量分数均为5%的氮酮(Azone)、油酸(OA)、肉豆蔻酸异丙酯(IPM)、桉叶油(OE)和丙二醇(PG)及1%、3%、5%、7%OE和3%OE+1%Azone、3%OE+3%Azone、3%OE+5%Azone的贴剂250h内的Q、透皮速率常数(Jss)及增渗倍数。结果:压敏胶、PVPK30、乙酰丙酮铝的用量分别为15、2、0.03g,250h的平均Q为60.83μg/cm2;5%OE单用时250h内的Q最大,为118.12μg/cm2,Jss为0.71μg/(cm2·h),增渗倍数为2.2;3%OE+5%Azone联用时250h内的Q最大,为175.96μg/cm2,Jss为1.102μg(/cm2·h),增渗倍数为3.22。结论:所制备的贴剂初黏力符合要求,3%OE+5%Azone对醋酸烯诺孕酮透皮贴剂有明显促渗作用。

OBJECTIVE： To prepare Nestorone transdermal patches, and to investigate the effect of 5 kinds of enhancing permeation by enhancers used alone or combined. METHODS： Druo-tak 87-2287 PSA, PVP K 30, amount of aluminum acetylacetonate and 250 h average cumulative permeation quantity （Q） were optimized with orthogonal design using Q and the initial adhesive force as index. Q within 250 h, percutaneous rate constant （Jss） and enhancing rate were compared among 5% Azone, 5% OA, 5% IPM, 5% OE and 5% PG, 1% OE, 3% OE, 5% OE and 7% OE, 3% OE＋1% Azone, 3% OE＋3% Azone, 3% OE＋5% Azone. RESULTS： The amounts ofPSA, PVP K 30 and aluminum acetylacetonate were 15 g, 2 g and 0.03 g, and average Q within 250 h was 60.83 μg/cm2; the maximum Q within 250 h of 5% OE used alone was 118.12 μg/cm2, and Jss and enhancing rate were 0.71 μg/（cm2.h） and 2.2; the maximum Q within 250 h of 3% OE＋5% Azone was 175.96 μg/cm^2, and Jss and enhancing rate were 1.102 μg/（cm2. h） and 3.22. CONCLUSIONS： The initial adhesive force of prepared patches is in line with the requirement, and 3 % OE＋5 % Azone promote the permeation of Nestorone transdermal patches significantly.