title: Enhancement of the bioavailability of an antihypertensive drug by transdermal protransfersomal system: formulation and in vivo study.
abstract: Timolol Maleate (TiM), a nonselective β-adrenergic blocker, is a potent highly effective agent for management of hypertension. The drug suffers from poor oral bioavailability (50%) due to its first pass effect and a short elimination half-life of 4 h; resulting in its frequent administration. Transdermal formulation may circumvent these problems in the form of protransfersomes. The aim of this study is to develop and optimize transdermal protransfersomal system of Timolol Maleate by film deposition on carrier method where protransfersomes were converted to transfersomes upon skin hydration following transdermal application under occlusive conditions. Two 23full factorial designs were employed to investigate the influence of three formulation variables which were; phosphatidyl choline: surfactant molar ratio, carrier: mixture and the type of SAA each on particle size, drug entrapment efficiency and release rate. The optimized formulation was evaluated regarding permeation through hairless rat skin and compared with oral administration of aqueous solution on male Wistar rats. Optimized protransfersomal system had excellent permeation rate through shaved rat skin (780.69 μg/cm2/h) and showed six times increase in relative bioavailability with prolonged plasma profile up to 72 h. A potential protransfresomal transdermal system was successfully developed and factorial design was found to be a smart tool in its optimization.
authors.affiliation: a Department of Pharmaceutics and Industrial Pharmacy , Faculty of Pharmacy, Cairo University , Cairo , Egypt and.
authors.forename: Nadia M
authors.initials: NM
authors.lastname: Morsi
authors.affiliation: a Department of Pharmaceutics and Industrial Pharmacy , Faculty of Pharmacy, Cairo University , Cairo , Egypt and.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Aboelwafa
authors.affiliation: b Department of Pharmaceutics , Faculty of Pharmacy, October University for Modern Sciences and Arts , Dokki , Egypt.
authors.forename: Marwa H S
authors.initials: MHS
authors.lastname: Dawoud
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D065546:Drug Liberation; D008081:Liposomes / Q000737:chemistry; D008297:Male; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry; D013999:Timolol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D000959:Antihypertensive Agents; D004337:Drug Carriers; D008081:Liposomes; D010713:Phosphatidylcholines; D013501:Surface-Active Agents; D013999:Timolol
keywords: Antihypertensive; design-expert; liposomes; permeation; ultra-flexible vesicles