Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
Drug Dev Ind Pharm. 2011 Dec;37(12):1387-93. doi: 10.3109/03639045.2011.576426. Epub 2011 May 5.
A novel transdermal delivery of sumatriptan (ST) was attempted by application of dissolving microneedle (DM) technology. Dextran DM (d-DM) and hyaluronate DM (h-DM) were prepared by adding ST solution to dextran solution or hyaluronic acid solution. One DM chip, 1.0 × 1.0 cm, contains 100 microneedle arrays in a 10 × 10 matrix. The mean lengths of DMs were 496.6 ± 2.9 μm for h-DM and 494.5 ± 1.3 μm for d-DM. The diameters of the array basement were 295.9 ± 3.9 μm (d-DM) and 291.7 ± 3.0 μm (h-DM), where ST contents were 31.6 ± 4.5 μg and 24.1 ± 0.9 μg. These results suggest that ST was stable in h-DM. Each DM was administered to rat abdominal skin. The maximum plasma ST concentrations, Cmax, and the areas under the plasma ST concentration versus time curves (AUC) were 44.6 ± 4.9 ng/ml and 24.6 ± 3.9 ng · h/ml for h-DM and 38.4 ± 2.7 ng/ml and 14.1 ± 1.5 ng · h/ml for d-DM. The bioavailabilities of ST from DMs were calculated as 100.7 ± 18.8% for h-DM and 93.6 ± 10.2% for d-DM. Good dose dependency was observed on Cmax and AUC. The stability study of ST in DM was performed for 3 months under four different conditions, −80, 4, 23, and 50°C. At the end of incubation period, they were, respectively, 100.0 ± 0.3%, 97.8 ± 0.2%, 98.8 ± 0.2%, and 100.7 ± 0.1%. These suggest the usefulness of DM as a noninvaisive transdermal delivery system of ST to migraine therapy.
尝试通过应用溶解微针 (DM) 技术来实现舒马曲坦 (ST) 的新型透皮给药。葡聚糖 DM(d-DM) 和透明质酸 DM(h-DM) 是通过将 ST 溶液加入葡聚糖溶液或透明质酸溶液中制备的。一个 DM 芯片，1.0×1.0cm，包含 100 个微针阵列，呈 10×10 矩阵排列。h-DM 的平均长度为 496.6±2.9μm，d-DM 的平均长度为 494.5±1.3μm。阵列基底的直径为 295.9±3.9μm(d-DM) 和 291.7±3.0μm(h-DM)，其中 ST 含量分别为 31.6±4.5μg 和 24.1±0.9μg。这些结果表明 ST 在 h-DM 中稳定。将每个 DM 施用于大鼠腹部皮肤。h-DM 的最大血浆 ST 浓度 Cmax 和血浆 ST 浓度与时间曲线下面积 (AUC) 分别为 44.6±4.9ng/ml 和 24.6±3.9ng·h/ml，d-DM 分别为 38.4±2.7ng/ml 和 14.1±1.5ng·h/ml。DM 中 ST 的生物利用度分别计算为 h-DM 的 100.7±18.8%和 d-DM 的 93.6±10.2%。Cmax 和 AUC 表现出良好的剂量依赖性。在 4 种不同条件下（−80、4、23 和 50°C）对 DM 中 ST 的稳定性进行了 3 个月的研究。孵育期结束时，分别为 100.0±0.3%、97.8±0.2%、98.8±0.2%和 100.7±0.1%。这些结果表明 DM 作为一种非侵入性的舒马曲坦透皮给药系统用于偏头痛治疗是有用的。
