Department of Pharmaceutical Science, School of Pharmacy, Shenyang Pharmaceutical University, PR China.
Drug Dev Ind Pharm. 2012 Aug;38(8):1008-14. doi: 10.3109/03639045.2011.637049. Epub 2011 Nov 29.
To design and optimize a drug-in-adhesive (DIA) type transdermal patch for tolterodine (TOL) based on acrylic and silicone matrixes.
Initial in vitro studies were conducted to optimize the formulations. Two types of adhesive matrixes, drug loading, and enhancers were evaluated on the TOL transport across rabbit skin. For in vivo studies, patches were administered to rabbit abdominal skin. Pharmacokinetic assessments were performed based on plasma level of TOL up to 28 h for acrylic patch and 52 h for silicone patch after topical application.
The final formulation of acrylic adhesive type patch consisted of 10% TOL (w/w) and 5.8 × 10(-4) mol isopropyl myristate (IPM) and 2.9 × 10(-4) mol Span 80 in per unit gram (mol/g) of adhesive, while 2.5% TOL (w/w) and 2.9 × 10(-4) mol/g IPM for silicone adhesive type patch. Comparison of the pharmacokinetic parameters between two types of patches showed that the steady-state concentration of silicone type patch was 2-fold higher than that of acrylic type patch being 0.97 mg/L versus 0.49 mg/L, and the absolute bioavailability was 27.5% for silicone type patch and 6.3% for acrylic type patch, respectively. In addition, the prediction of in vivo drug level from the in vitro permeation data of silicone adhesive formulation was in good agreement with actual observed concentration data in rabbits.
These results indicate that the silicone type of TOL patch is an appropriate delivery system for the treatment of overactive bladder (OAB).
设计并优化一种基于丙烯酸和硅酮基质的托特罗定（TOL）透皮贴剂（DIA）。
进行初步的体外研究以优化配方。两种类型的粘合基质、药物负载和增强剂都在兔皮中评估了 TOL 的转运情况。对于体内研究，将贴片施用于兔腹部皮肤。基于 TOL 的血浆水平进行药代动力学评估，直至经皮应用后 28 小时的丙烯酸贴片和 52 小时的硅酮贴片。
丙烯酸粘合型贴片的最终配方包括 10%的 TOL（w/w）和 5.8×10（-4）mol 的肉豆蔻异丙酯（IPM）和 2.9×10（-4）mol 的司盘 80，每克（mol/g）粘合剂，而硅酮粘合型贴片的 2.5%的 TOL（w/w）和 2.9×10（-4）mol/g 的 IPM。两种类型贴片的药代动力学参数比较表明，硅酮型贴片的稳态浓度是丙烯酸型贴片的 2 倍，分别为 0.97mg/L 和 0.49mg/L，绝对生物利用度分别为 27.5%的硅酮型贴片和 6.3%的丙烯酸型贴片。此外，硅酮粘合制剂体外渗透数据对体内药物水平的预测与兔体内实际观察到的浓度数据吻合良好。
这些结果表明，硅酮型 TOL 贴片是治疗膀胱过度活动症（OAB）的合适的给药系统。
