Preparation, characterization and pharmacological evaluation of tolterodine hydrogels for the treatment of overactive bladder

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• 作者：Fengying Sun ; Cheng Sui ; Yulin Zhou ; Ximing Liu ; Yanan Shi ; Yi Wu ; Youxin Li
• 关键词：Tolterodine ; Hydrogels ; Transdermal ; Pharmacokinetics ; Pharmacodynamics
• 刊名：International Journal of Pharmaceutics
• 出版年：2013
• 出版时间：15 September, 2013
• 年：2013
• 卷：454
• 期：1
• 页码：532-538
• 全文大小：1003 K

文摘

In this study, transdermal gel formulations for tolterodine were developed to investigate the effects of gel matrix and chemical enhancers on drug skin permeation from tolterodine hydrogels. In vitro permeation studies of tolterodine through excised mouse skin were carried out using Franz-type diffusion cells. In the optimum gel formulation, Carbopol 940 was selected as the gel matrix. Compared to gels without enhancer, tolterodine hydrogels with N-methyl pyrrolidone (NMP) showed significant enhancing effect on transdermal permeation of tolterodine (p < 0.05). The results of in vitro percutaneous delivery experiment showed that the relationship of the steady accumulative percutaneous amount (Q, ¦Ìg cm^?2) of tolterodine hydrogels and time was Q_4-12h = 770.19t^1/2 ? 966.99. Tolterodine permeated at the steady-state speed of 770.19 ¦Ìg cm^?2 h^?1 and its release coincided with Higuchi Equation. The pharmacokinetic properties of the optimized tolterodine formulation were studied in rabbits. The absolute bioavailability of tolterodine was 11.47 % . Since the absence of hepatic first-pass metabolism, only a single active compound-tolterodine was detected in the plasma. A skin irritation study was also carried out on rabbits, and the results showed tolterodine hydrogels had no skin irritation. In the pharmacodynamic study, the significant effects of tolterodine hydrogels on the inhibition of pilocarpine-induced rat urinary bladder contraction were last to 12 h, indicating that tolterodine hydrogels could produce prolonged pharmacological responses. In conclusion, tolterodine hydrogels were formulated successfully using Carbopol 940 and NMP and these results helped in finding the optimum formulation for percutaneous drug release. It is quite evident that tolterodine hydrogels may offer a possibility to avoid the first-pass effect, resulting in a single active compound of tolterodine in plasma, which may profit on the patient under the dose control and the reduction of potential adverse effect from two active compounds in the body.