Morsi N.M.Aboelwafa A.A.Dawoud M.H.S.Department of Pharmaceutics and Industrial PharmacyFaculty of PharmacyCairo UniversityCairoEgypt; Department of PharmaceuticsFaculty of PharmacyOctober University for Modern Sciences and ArtsDokkiEgypt2020-01-092020-01-0920188982104https://doi.org/10.1080/08982104.2017.1295989PubMed ID 28264602https://t.ly/py7xbScopusMSA Google ScholarTimolol Maleate (TiM), a nonselective ?-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 2 3 full 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 ?g/cm 2 /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. � 2017 Informa UK Limited, trading as Taylor & Francis Group.EnglishAntihypertensivedesign-expertliposomespermeationultra-flexible vesiclesphosphatidylcholinesurfactanttimolol maleateantihypertensive agentdrug carrierliposomenanoparticletimololanimal cellanimal experimentanimal tissuearea under the curve ratioArticledrug absorptiondrug bioavailabilitydrug determinationdrug formulationdrug penetrationelimination half-lifefactorial designhigh performance liquid chromatographyhydrationin vitro studyin vivo studylipid bilayermalemaximum plasma concentrationnonhumanparticle sizepharmacokinetic parameterspriority journalquantitative analysisratsustained drug releasetime to maximum plasma concentrationtransdermal drug administrationtransdermal protransfersomal systemanimalbioavailabilitychemistrycutaneous drug administrationdrug formulationdrug releasemetabolismoral drug administrationproceduresskinskin absorptionsurface propertyWistar ratAdministration, CutaneousAdministration, OralAnimalsAntihypertensive AgentsBiological AvailabilityDrug CarriersDrug CompoundingDrug LiberationLiposomesMaleNanoparticlesParticle SizePhosphatidylcholinesRats, WistarSkinSkin AbsorptionSurface PropertiesSurface-Active AgentsTimololArticlehttps://doi.org/10.1080/08982104.2017.1295989PubMed ID 28264602