title: Topical delivery of diclofenac into and across equine skin from a novel liquid diclofenac epolamine formulation.
abstract: The aim was to investigate diclofenac delivery into and across equine skin in vitro using Franz diffusion cells from a novel diclofenac epolamine (DIC-EP; 1.3%) formulation and to compare the results to those of Surpass®(1% diclofenac sodium liposomal cream) and a 1% aqueous solution of diclofenac sodium. Skin was harvested from the lower legs of Freiberger geldings immediately after slaughter and sliced to a thickness of ~2 mm. Skin samples were divided into two groups [Group 1: 1 year old (n = 2) and Group 2: 6-8 years old (n = 3)]. Cumulative permeation of diclofenac in Groups 1 and 2 after 24 h using diclofenac sodium solution was 1.91 ± 0.27 and 1.76 ± 0.34 μg/cm2, respectively. The values for Surpass®and DIC-EP were 3.2 ± 0.8/3.3 ± 0.7 μg/cm2and 230 ± 59/89.2 ± 32.5 μg/cm2, respectively. Thus, diclofenac permeation from DIC-EP was significantly greater and appeared to show an age-dependent effect. Mathematical modelling showed that the DIC-EP formulation significantly increased diclofenac partitioning into the skin and a linear correlation was observed between steady-state flux and the partition parameter. Greater skin deposition of diclofenac was also observed with DIC-EP. These preliminary results suggest that the DIC-EP formulation may be effective in treating inflammatory conditions in horses.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, Geneva, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Del Río-Sancho
authors.affiliation: Wezen Bio AG, Fondation pour Recherches Médicales, Geneva, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Concas
authors.affiliation: Glycores 2000 Srl, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Oreste
authors.affiliation: Glycores 2000 Srl, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Zoppetti
authors.affiliation: Alkhalediah Equine Hospital, Riyadh, Kingdom of Saudi Arabia.
authors.forename: P H
authors.initials: PH
authors.lastname: Briggs
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, Geneva, Switzerland. yogi.kalia@unige.ch.
authors.forename: Y N
authors.initials: YN
authors.lastname: Kalia
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004008:Diclofenac / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006736:Horses; D012867:Skin / Q000187:drug effects*; D012879:Skin Physiological Phenomena
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C064142:diclofenac hydroxyethylpyrrolidine; D004008:Diclofenac