title: Pharmaceutical and clinical assessment of hydroquinone ointment prepared by extemporaneous nonsterile compounding.
abstract: Ointments of the skin depigmentation agent hydroquinone (HQ) have been prepared by extemporaneous nonsterile compounding in Japan by imitating skin lightening creams commercially available in the U.S.A. and European Union. In our hospital, HQ ointments consisting of 5 or 10% HQ, 1.6% L(+)-ascorbic acid (AsA), 0.5% (w/w) Na2SO3, 10% (v/w) glycerin and hydrophilic ointment have been prepared. However, various problems have been observed including chromatic aberration of HQ ointments, relatively large variability of efficacy, and undesirable side effects although they were mild. Herein, the pharmaceutical and clinical properties of the HQ ointments were evaluated. HQ ointments were highly effective for treatment of various types of skin pigmentation. Chromatic aberration occurred during 3 months of storage, but this could be suppressed by storage at 4 degrees C. Chromatic aberration was independent of prescribed HQ content, and was not explained by alterations of HQ or p-benzoquinone (p-BQ) contents. Unexpectedly, removal of both antioxidants resulted in suppression of chromatic aberration, but an increase in p-BQ content. Acidification by removal of Na2SO3 only was further effective for the suppression of chromatic aberration, but with a decrease of p-BQ content except in the initial period. Chromatic aberration was due to water soluble material and insoluble material both formed by co-existence of HQ and p-BQ at a molecular ratio of 5:3 to 1:1. 1H-NMR analysis elucidated that the water soluble material was not HQ or p-BQ, and the insoluble material was a complex of HQ and p-BQ with non-covalent binding.
authors.affiliation: Department of Hospital Pharmacy, School of Medicine, Kobe University, Japan. tmatuba-kob@umin.ac.jp
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Matsubayashi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakaeda
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kita
authors.forename: Michiyo
authors.initials: M
authors.lastname: Nara
authors.forename: Yoko
authors.initials: Y
authors.lastname: Funasaka
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Ichihashi
authors.forename: Takuya
authors.initials: T
authors.lastname: Fujita
authors.forename: Fumio
authors.initials: F
authors.lastname: Kamiyama
authors.forename: Akira
authors.initials: A
authors.lastname: Yamamoto
authors.forename: James J
authors.initials: JJ
authors.lastname: Nordlund
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kaneko
authors.forename: Akira
authors.initials: A
authors.lastname: Iida
authors.forename: Midori
authors.initials: M
authors.lastname: Hirai
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Okumura
mesh_terms: D000975:Antioxidants / Q000737:chemistry; D016227:Benzoquinones / Q000737:chemistry; D003116:Color; D003879:Dermatologic Agents / Q000737:chemistry* / Q000494:pharmacology*; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006873:Hydroquinones / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D009824:Ointments; D010084:Oxidation-Reduction; D011310:Preservatives, Pharmaceutical; D013242:Sterilization
chemical_list: D000975:Antioxidants; D016227:Benzoquinones; D003879:Dermatologic Agents; D006873:Hydroquinones; D009824:Ointments; D011310:Preservatives, Pharmaceutical