title: Study of tolnaftate release from fatty acids containing ointment and penetration into human skin ex vivo.
abstract: Five fatty acids (oleic, linoleic, myristic, lauric and capric) were incorporated in 10% (w/w) into ointment formulation and their influence on lipophilic model drug tolnaftate release in vitro and enhancing effect on tolnaftate penetration into epidermis and dermis of human skin ex vivo were investigated. The prepared ointments were tested for homogeneity, pH and theological properties. In vitro release studies and ex vivo skin penetration experiments were carried out using Hanson and Bronaugh-type flow-through diffusion cells, respectively. Tolnaftate cumulative amount liberated from semisolids was assayed using UV-Vis spectrophotometer. After in vitro skin penetration studies, appropriately extracted human skin layers were analyzed for tolnaftate content using a validated HPLC method. Statistical analysis revealed that release rate of tolnaftate from control ointment and ointments with fatty acids was not significantly different and only 7.34-8.98% of drug was liberated into an acceptor medium after 6 h. Tolnaftate amount penetrating into 1 cm2 of epidermis from ointments containing oleic, linoleic, myristic and lauric acids was significantly greater (p < 0.05) than from the control ointment. Penetration enhancing ratios for these fatty acids for tolnaftate penetration into epidermis ranged from 1.48 to 1.75. In conclusion, fatty acids did not increase the liberation of tolnaftate from ointment formulation, but demonstrated their enhancing effect on tolnaftate penetration into human epidermis in vitro. Results from in vitro release experiments do not suit for prediction of the situation in the skin in vitro, if chemical penetration enhancers are incorporated into the ointment formulation.
authors: Department of Pharmaceutical Technology and Social Pharmacy, Faculty of Pharmacy, Lithuanian University of Health Sciences, A. Mickeviciaus 9, 44307 Kaunas, Lithuania. tomakezutyte@yahoo.com
authors: Toma
authors: T
authors: Kezutyte
authors: Tomas
authors: T
authors: Drevinskas
authors: Audrius
authors: A
authors: Maruska
authors: Rytis
authors: R
authors: Rimdeika
authors: Vitalis
authors: V
authors: Briedis
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003652:Decanoic Acids / Q000494:pharmacology; D004339:Drug Compounding; D005227:Fatty Acids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007850:Lauric Acids / Q000494:pharmacology; D019787:Linoleic Acid / Q000494:pharmacology; D008875:Middle Aged; D019814:Myristic Acid / Q000494:pharmacology; D009824:Ointments; D019301:Oleic Acid / Q000494:pharmacology; D010539:Permeability; D012212:Rheology; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013678:Technology, Pharmaceutical / Q000379:methods; D014047:Tolnaftate / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D003652:Decanoic Acids; D005227:Fatty Acids; D007850:Lauric Acids; D009824:Ointments; D014047:Tolnaftate; D019814:Myristic Acid; C030358:lauric acid; D019301:Oleic Acid; C031071:decanoic acid; D019787:Linoleic Acid