title: Solvent content and macroviscosity effects on the in vitro transcutaneous delivery and skin distribution of ketoprofen from simple gel formulations.
abstract: The effects of decreasing solvent content and macroviscosity of simple topical gel formulations on the transcutaneous delivery and distribution of ketoprofen through skin were studied. Simple topical gels, based on ketoprofen, PEG 400 and either Cabosil M-5 or hydroxypropylcellulose were formulated and applied to freshly excised pig ear skin in vitro. Receptor phase samples were taken to determine permeation and depth profiles of ketoprofen were constructed, following tape stripping and membrane separation. Reduction of solvent from the Cabosil-thickened gels resulted in a rank order reduction in the permeation and distribution of ketoprofen. Reduced amounts of ketoprofen were distributed through the skin, particularly the dermis, with decreasing solvent. Two gels sharing the same macroviscosity exhibited significantly different skin permeation and distribution characteristics. The rank order reduction in both permeation and distribution of ketoprofen was attributed to the physiochemical properties of the formulation and how they may change after application, in particular the increased adsorptivity of ketoprofen to the Cabosil relative to the amount of solvent present in the system. This effect appeared to be predominant over any interactions occurring between the formulation and the skin. The data provided further evidence that adsorption to the thickener, rather than changes in viscosity, were primarily responsible for reduced permeation and distribution in the system examined.
authors.affiliation: Welsh School of Pharmacy, Cardiff University, Cardiff, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Gallagher
authors.forename: C M
authors.initials: CM
authors.lastname: Heard
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002482:Cellulose / Q000031:analogs & derivatives; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005782:Gels; D066298:In Vitro Techniques; D007660:Ketoprofen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010592:Pharmaceutic Aids; D011092:Polyethylene Glycols; D012822:Silicon Dioxide; D012869:Skin Absorption; D012997:Solvents; D013552:Swine; D014783:Viscosity
chemical_list: D000893:Anti-Inflammatory Agents; D005782:Gels; D010592:Pharmaceutic Aids; D012997:Solvents; D011092:Polyethylene Glycols; D012822:Silicon Dioxide; D002482:Cellulose; D007660:Ketoprofen; C008079:hydroxypropylcellulose