title: A novel transdermal delivery system for the anti-inflammatory lumiracoxib: influence of oleic acid on in vitro percutaneous absorption and in vivo potential cutaneous irritation.
abstract: Transdermal delivery of non-steroidal anti-inflammatory drugs may be an interesting strategy for delivering these drugs to the diseased site, but it would be ineffective due to low skin permeability. We investigated whether oleic acid (OA), a lipid penetration enhancer in poloxamer gels named poloxamer-based delivery systems (PBDS), can improve lumiracoxib (LM) delivery to/through the skin. The LM partition coefficient (K) studies were carried out in order to evaluate the drug lipophilicity grade (K(octanol/buffer)), showing values >1 which demonstrated its high lipophilicity. Both in vitro percutaneous absorption and skin retention studies of LM were measured in the presence or absence of OA (in different concentrations) in PBDS using porcine ear skin. The flux of in vitro percutaneous absorption and in vitro retention of LM in viable epidermis increased in the presence of 10.0% (w/w) OA in 25.0% (w/w) poloxamer gel. In vivo cutaneous irritation potential was carried out in rabbits showing that this formulation did not provide primary or cumulative cutaneous irritability in animal model. The results showed that 25.0% poloxamer gel containing 10.0% OA is potential transdermal delivery system for LM.
authors.affiliation: School of Pharmacy, Pharmaceutical Technology Laboratory, Department of Medicine, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, 373, 21.941.590, Rio de Janeiro, Brazil.
authors.forename: Tailane Sant'Anna
authors.initials: TS
authors.lastname: Moreira
authors.forename: Valéria Pereira
authors.initials: VP
authors.lastname: de Sousa
authors.forename: Maria Bernadete Riemma
authors.initials: MB
authors.lastname: Pierre
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004008:Diclofenac / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D003875:Drug Eruptions / Q000209:etiology / Q000517:prevention & control; D019301:Oleic Acid / Q000737:chemistry*; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000502:physiology*; D013552:Swine
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D004008:Diclofenac; D019301:Oleic Acid; C473384:lumiracoxib