title: Gel formulations containing catanionic vesicles composed of alprenolol and SDS: effects of drug release and skin penetration on aggregate structure.
abstract: To fully utilize the extended contact time of gel formulations a novel formulation with drug containing catanionic aggregates offering prolonged drug release and skin penetration were investigated. This study aimed to further explore the drug release process from catanionic vesicles in gels. Catanionic vesicles were formed from alprenolol and sodium dodecyl sulphate. Physical gels composed of catanionic vesicles and a SoftCAT polymer were used as well as covalent Carbopol gels. Drug release was measured in vitro using a modified USP paddle method and the skin penetration was studied using dermatomized pig ear skin mounted in horizontal Ussing chambers. The aggregate structure was visualized with cryo-TEM during the drug release and skin penetration process. The study results show that catanionic vesicles are present in the formulations throughout the drug release process and during the clinically relevant skin application time. Hence, the decreased skin penetration rate stems from the prolonged release of drug substance from the gels. The rheological investigation shows that the gel structure of the physically cross-linked gels is maintained even as the drug substance is released and the gel volume is decreased. These findings indicate that the applicability of formulations like these is a future possibility.
authors.affiliation: Department of Pharmacy, Uppsala University, Uppsala, Sweden. noel.dew@aconordic.com
authors.forename: Noel
authors.initials: N
authors.lastname: Dew
authors.forename: Katarina
authors.initials: K
authors.lastname: Edwards
authors.forename: Jonny
authors.initials: J
authors.lastname: Eriksson
authors.forename: Katarina
authors.initials: K
authors.lastname: Edsman
authors.forename: Erik
authors.initials: E
authors.lastname: Björk
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000526:Alprenolol / Q000008:administration & dosage*; D000818:Animals; D002412:Cations; D002851:Chromatography, High Pressure Liquid; D005782:Gels; D046529:Microscopy, Electron, Transmission; D012212:Rheology; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry*; D013552:Swine
chemical_list: D000319:Adrenergic beta-Antagonists; D002412:Cations; D005782:Gels; D012967:Sodium Dodecyl Sulfate; D000526:Alprenolol