Effects of Various Storage Conditions and Alterations of Antioxidant Contents on Chromatic Aberration of Hydroquinone Ointment.

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. [1][2][3][4][5][6][7][8] In our hospital, HQ ointments consisting of 5 or 10% HQ, 1.6% L(ϩ)-ascorbic acid (AsA), 0.5% Na 2 SO 3 , 10% (v/w) glycerin and hydrophilic ointment have been prepared (Table 1). 9) However, various problems have been observed during usage for about 4 years including chromatic aberration of the ointments, a relatively large variability of efficacy, and mild side effects. In our previous report, the pharmaceutical and clinical properties of HQ ointments were evaluated, and the following observations were made: 1) HQ ointments were highly effective in the treatment of various types of skin pigmentations; 2) Chromatic aberration occurred during 3 months of storage; 3) Chromatic aberration was independent of the prescribed HQ content; 4) Removal of both antioxidants resulted in the suppression of chromatic aberration; 5) Removal of Na 2 SO 3 only was further effective in suppressing chromatic aberration; 6) Chromatic aberration was due to a newly developed water-soluble material and insoluble noncovalent complex formed by HQ and p-benzoquinone, which was formed from HQ.In this paper, the effects of various storage conditions on the chromatic aberration and HQ content of HQ ointments for clinical use were evaluated to clarify the conditions that encourage or discourage the chromatic aberration. The storage conditions were chosen to imitate the actual situation during usage by patients. In addition, various types of HQ ointments were also prepared to find a formulation to minimize chromatic aberration. A relationship between the acidity of ointments and chromatic aberration was also demon-strated by addition of HCl or NaOH to the ointments.

Effects of hydroquinone and its glucoside derivatives on melanogenesis and antioxidation: Biosafety as skin whitening agents

“…Of note, topical preparations of hydroquinone are extremely unstable and rapidly discolor in appearance and increase the skin irritation if the hydroquinone-contained formula is exposed to UV irradiation [19]. In this study, we determined the cell viabilities and intracellular ROS levels in monophenol-treated melanocytes in the presence or absence of 3 J/cm 2 UVA exposure, emphasizing whether it is safe to use such skin-lightening ingredients daily in a clinical setting.…”

Regulation of Melanin Synthesis by Selenium-Containing Carbohydrates

“…Hydroquinones and their derivatives are widely used to treat hyperpigmentation in many countries but, they are unstable and easily oxidized. 34) Therefore a new tyrosinase inhibitor is needed. SG-8 showed so much cytotoxicity that it could not be considered as a melanin regulator.…”

Intradermal Concentration of Hydroquinone after Application of Hydroquinone Ointments Is Higher than Its Cytotoxic Concentration

“…9,10) p-BQ was detected at a level of 0.1-0.5% of HQ in antioxidant-free HQ ointments, but this decreased to 0-0.05% on addition of AsA and Na 2 SO 3 . 9,10) Here, it was also demonstrated that the cytotoxicity of HQ was not altered by antioxidants, AsA and Na 2 SO 3 . Consequently, it was suggested that p-BQ was not extensively cytotoxic in FR cells.…”

“…9,10) However, various problems have been observed during usage including chromatic aberration of the ointments, a relatively large variability of efficacy, and undesirable topical side effects, e.g., irritation, although they were mild. The pharmaceutical and clinical properties of HQ ointments prepared in our hospital have been evaluated, 9,10) and the following observations were made: 1) HQ ointments were highly effective in the treatment of various types of skin pigmentations; 2) Chromatic aberration occurred during 3 months of storage at room temperature, and was accelerated by exposure to high temperature, air and light; 3) Chromatic aberration was independent of the prescribed HQ content, and was not explained by alterations in the content of HQ or p-benzoquinone (p-BQ), which was formed from HQ; 4) Removal of both antioxidants resulted in the suppression of chromatic aberration; 5) Removal of Na 2 SO 3 only was further effective in suppressing chromatic aberration, and the protective effect of AsA was mainly due to its acidifying effect; 6) Chromatic aberration was due to a newly developed water-soluble material and insoluble non-covalent complex both formed by HQ and p-BQ.In this paper, to evaluate whether the topical side effects including irritation after application of the HQ ointments are due to HQ, AsA and Na 2 SO 3 , their cytotoxicity was assessed in vitro using rat skin fibroblasts as the concentration with 50% survival after 24 h exposure. 11,12) Results were compared with the intradermal concentrations after application of the HQ ointments, which were estimated by an in vitro rat skin permeation study with rat full-thickness abdominal skin and Franz-type diffusion cells.…”