title: Novel perspectives in the tuberculosis treatment: Administration of isoniazid through the skin.
abstract: Despite its high efficacy in anti-tuberculosis therapy, the oral administration of isoniazid (INH) may lead to poor patient compliance due to hepatotoxicity events. In this context, the transdermal administration of INH was evaluated, for the first time, since this route avoids hepatic first pass effect. INH was applied to porcine skin in Franz diffusion chambers alone and with 5% menthol, limonene or Transcutol(®). Infrared and DSC analyses were selected for mechanistic studies. The transdermal absorption of INH was sufficient to ensure a systemic therapeutic effect. Menthol was not able to improve the absorption of INH, but it increased the drug accumulation in skin compared to the control (1.4-fold). Transcutol(®) reduced permeation flux of INH (2.2-fold) and also increased the amount of drug retained in skin (1.7-fold). Limonene was the most effective excipient since it increased permeation flux of INH (1.5-fold) and lag time was greatly shortened (2.8-fold). DSC and FTIR analyses of limonene-treated skin suggest higher degree of disorder in lipid bilayers. Transdermal delivery of INH was positively correlated with logP of chemical enhancers. INH can be efficiently delivered by skin route and specific excipients may be selected depending on intended use.
authors: Programa de Pós-Graduação em Farmácia (PGFAR), Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900 Florianópolis, SC, Brazil. Electronic address: thiagocaon@gmail.com.
authors: Thiago
authors: T
authors: Caon
authors: Laboratório de Difração de Raios-X, Departamento de Física, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900 Florianópolis, SC, Brazil.
authors: Carlos Eduardo Maduro
authors: CE
authors: Campos
authors: Programa de Pós-Graduação em Farmácia (PGFAR), Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900 Florianópolis, SC, Brazil.
authors: Cláudia Maria Oliveira
authors: CM
authors: Simões
authors: Programa de Pós-Graduação em Farmácia (PGFAR), Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900 Florianópolis, SC, Brazil.
authors: Marcos Antônio Segatto
authors: MA
authors: Silva
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002152:Calorimetry, Differential Scanning; D053138:Cyclohexenes / Q000008:administration & dosage / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics; D005026:Ethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics; D005079:Excipients / Q000008:administration & dosage / Q000493:pharmacokinetics; D007538:Isoniazid / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000077222:Limonene; D008610:Menthol / Q000008:administration & dosage / Q000493:pharmacokinetics; D012869:Skin Absorption / Q000187:drug effects*; D017550:Spectroscopy, Fourier Transform Infrared; D013552:Swine; D013729:Terpenes / Q000008:administration & dosage / Q000493:pharmacokinetics; D013997:Time Factors
chemical_list: D053138:Cyclohexenes; D004337:Drug Carriers; D005026:Ethylene Glycols; D005079:Excipients; D013729:Terpenes; D008610:Menthol; D000077222:Limonene; C010111:carbitol; D007538:Isoniazid
keywords: Chemical penetration enhancer; Isoniazid; Skin permeation; Transdermal delivery