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

• Published in: Journal of advanced research Vol. 7; no. 5; pp. 691 - 701
• Main Authors: Morsi, Nadia M., Aboelwafa, Ahmed A., Dawoud, Marwa H.S.
• Format: Journal Article
• Language: English
• Published: Egypt Elsevier B.V 01.09.2016; Elsevier
• Subjects: Antihypertensive; Factorial design; Optimization; Original; Timolol maleate; Transdermal; Transfersomes; Transfersomes; Antihypertensive; Timolol maleate; Transdermal; Factorial design; Optimization
• ISSN: 2090-1232; 2090-1224
• DOI: 10.1016/j.jare.2016.07.003

[Display omitted] 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 4h; 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 13mg drug amount with particle size of 2.722μm, %EE of 39.96%, and a release rate of 134.49μg/cm2/h. The permeation rate of the optimized formulation through the rat skin was excellent (151.53μg/cm2/h) and showed four times increase in relative bioavailability with prolonged plasma profile up to 72h 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.