title: Preparation and valuation of a topical solution containing eutectic mixture of itraconazole and phenol.
abstract: The purposes of this study were to prepare a topical solution containing itraconazole (ITR)-phenol eutectic mixture and to evaluate its ex vivo skin permeation, in vivo deposition and in vivo irritation. The eutectic mixture was prepared by agitating ITR and phenol (at a weight ratio of 1:1) together at room temperature. The effects of additives on the skin permeation of ITR were evaluated using excised hairless mouse skin. The in vivo skin deposition and skin irritation studies were performed in Sprague-Dawley rat and New Zealand white rabbit model. The permeability coefficient of ITR increased with addition of oleic acid in the topical solution. Otherwise, the permeability coefficient was inversely proportional to the concentration of the thickening agent, HPMC. The optimized topical solution contained 9 wt% of the ITR-phenol eutectic mixture, 9.0 wt% of oleic acid, 5.4 wt% of hydroxypropylmethyl cellulose and 76.6 wt% of benzyl alcohol. The steady-state flux and permeability coefficient of the optimized topical solution were 0.90 ± 0.20 μg/cm(2)·h and 22.73 ± 5.73 × 10(6) cm/h, respectively. The accumulated of ITR in the epidermis and dermis at 12 h was 49.83 ± 9.02 μg/cm(2). The topical solution did not cause irritation to the skins of New Zealand white rabbits. Therefore, the findings of this study indicate the possibilities for the topical application of ITR via an external preparation.
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea.
authors.forename: Chun-Woong
authors.initials: CW
authors.lastname: Park
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Yun-Seok
authors.initials: YS
authors.lastname: Rhee
authors.forename: Tack-Oon
authors.initials: TO
authors.lastname: Oh
authors.forename: Jung-Myung
authors.initials: JM
authors.lastname: Ha
authors.forename: Na-Young
authors.initials: NY
authors.lastname: Choi
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Chi
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Park
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D019905:Benzyl Alcohol / Q000737:chemistry; D005079:Excipients / Q000737:chemistry*; D065347:Hypromellose Derivatives; D017964:Itraconazole / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D051379:Mice; D008812:Mice, Hairless; D008813:Mice, Inbred ICR; D019301:Oleic Acid / Q000737:chemistry; D010539:Permeability; D019800:Phenol / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption
chemical_list: D000935:Antifungal Agents; D005079:Excipients; D019301:Oleic Acid; D017964:Itraconazole; D019800:Phenol; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D019905:Benzyl Alcohol