Improved bioavailability of timolol maleate via transdermal transfersomal gel: Statistical optimization, characterization, and pharmacokinetic assessment

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• 作者：Nadia M. Morsi^a ; Ahmed A. Aboelwafa^a ; Marwa H.S. Dawoud^b ; ^{marwa.hamdy@yahoo.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Antihypertensive ; Transfersomes ; Transdermal ; Timolol maleate ; Factorial design ; Optimization
• 刊名：Journal of Advanced Research
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：7
• 期：5
• 页码：691-701
• 全文大小：1380 K

文摘

Timolol maleate (TiM), a nonselective β-adrenergic blocker, is a potent highly effective agent for management of hypertension. The drug suffers from extensive first pass effect, resulting in a reduction of oral bioavailability (F%) to 50% and a short elimination half-life of 4 h; parameters necessitating its frequent administration. The current study was therefore, designed to formulate and optimize the transfersomal TiM gel for transdermal delivery. TiM loaded transfersomal gel was optimized using two 2³ full factorial designs; where the effects of egg phosphatidyl choline (PC): surfactant (SAA) molar ratio, solvent volumetric ratio, and the drug amount were evaluated. The formulation variables; including particle size, drug entrapment efficiency (%EE), and release rate were characterized. The optimized transfersomal gel was prepared with 4.65:1 PC:SAA molar ratio, 3:1 solvent volumetric ratio, and 13 mg drug amount with particle size of 2.722 μm, %EE of 39.96%, and a release rate of 134.49 μg/cm²/h. The permeation rate of the optimized formulation through the rat skin was excellent (151.53 μg/cm²/h) and showed four times increase in relative bioavailability with prolonged plasma profile up to 72 h compared with oral aqueous solution. In conclusion, a potential transfersomal transdermal system was successfully developed and the factorial design was found to be a smart tool, when optimized.