title: Efficacy of a new topical gel-spray formulation of ketoprofen lysine salt in the rat: percutaneous permeation in vitro and in vivo and pharmacological activity.
abstract: The aim of this study was to evaluate the percutaneous permeation of a new topical Gel-Spray formulation, containing 15% of ketoprofen lysine salt (KLS), both in vitro, using the Franz-type diffusion cells and in vivo, by evaluating urinary recovery after topical administration and to correlate the absorption data with KLS pharmacological activity in the rat. Concentrations of ketoprofen free acid (KFA) were determined by HPLC in the receptor compartment (in vitro), or in urine (in vivo). The permeation of ketoprofen evaluated in vitro after the application of KLS Gel-Spray was higher than that observed with the marketed formulation Profénid gel (containing KFA at 2.5%). The same evidence was found in vivo, except when the ratio between the administered dose and the area treated was higher than 1 mg cm-2. Thus, the difference between the two formulations seems to be the resultant of two opposing components: a positive gradient of concentration that favours the absorption of ketoprofen from KLS Gel-Spray and the presence of the enhancer ethanol that could favour the efficacy of Profénid gel. Under our conditions the former prevailed. As for the efficacy, evaluated in the carrageenan-induced oedema and hyperalgesia model, KLS Gel-Spray confirmed the data obtained for in vivo absorption, being more efficient than the reference standard Profénid gel. The observed inhibitory effects were due only to dermal absorption, oral absorption was excluded by an Elizabethan collar applied around the neck of the rat. In these experimental conditions, no significant damage of the rat stomach mucosa was observed. These results indicate that KLS Gel-Spray, due to its high KLS concentration, allows a very high efficiency in delivering ketoprofen to the inflamed area using a minimal amount of formulation, even in the absence of permeation enhancers.
authors.affiliation: Dompé S.p.A., Research Center, L'Aquila, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Porzio
authors.forename: G
authors.initials: G
authors.lastname: Caselli
authors.forename: L
authors.initials: L
authors.lastname: Pellegrini
authors.forename: V
authors.initials: V
authors.lastname: Pallottini
authors.forename: M
authors.initials: M
authors.lastname: Del Rosario
authors.forename: A
authors.initials: A
authors.lastname: Coppola
authors.forename: L
authors.initials: L
authors.lastname: Boltri
authors.forename: M
authors.initials: M
authors.lastname: Gentile
authors.forename: G
authors.initials: G
authors.lastname: Clavenna
authors.forename: G
authors.initials: G
authors.lastname: Melillo
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D005260:Female; D005782:Gels; D066298:In Vitro Techniques; D007249:Inflammation / Q000188:drug therapy*; D007660:Ketoprofen / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008239:Lysine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013270:Stomach / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005782:Gels; C029946:ketoprofen lysine; D007660:Ketoprofen; D008239:Lysine