Effect of Surfactants and Thickeners on the Stability of Menthol–Diphenhydramine Cream Identified by Magnetic Resonance Imaging

• Onuki Yoshinori

  Department of Pharmaceutical Technology, Graduate School of Medical and Pharmaceutical Science, University of Toyama

• Yokokawa Masamitsu

  Department of Pharmaceutics, Hoshi University

• Utsumi Shunichi

  Department of Pharmaceutics, Hoshi University

• Obata Yasuko

  Department of Pharmaceutics, Hoshi University

• Machida Yoshiaki

  Division of Applied Pharmaceutical Education and Research, Hoshi University

• Seike Chieko

  Pharmaceutical Department, Odawara Circulatory Organ Hospital

• Hayashi Yoshihiro

  Department of Pharmaceutical Technology, Graduate School of Medical and Pharmaceutical Science, University of Toyama

• Takayama Kozo

  Department of Pharmaceutics, Hoshi University

Abstract

A menthol–diphenhydramine cream is prepared in hospital pharmacies and then prescribed to patients for the treatment of pruritus associated with chronic kidney disease. The purpose of this study is to design a stable formulation without any concern about phase separation during its clinical use on patients. As a preventive measure against phase separation, various surfactants and thickeners were incorporated into the creams. The test creams were stored at 40°C, and then their phase separation behaviors were monitored. The key technology was magnetic resonance imaging T₂ mapping. From the T₂ maps, some surfactants showed a certain stabilizing effect. In addition, the data analysis using Kohonen’s self-organizing map revealed that hydrophilic–lipophilic balance of the surfactant is an important factor for the stabilizing effects of the surfactants. However, as a whole, the effect of surfactant was not sufficient to improve completely the low stability. By contrast, the creams were significantly stabilized by addition of thickeners. In particular, the stabilizing effect of carbomer Hiviswako105^® (H105) was very high; no phase separation was observed from the cream containing H105 even after 30 d storage at 40°C. This study also verified the combination effect of surfactants and thickeners on the improvement of the emulsion stability. In conclusion, we successfully established a stable formulation of menthol–diphenhydramine cream.

Journal

• Chemical and Pharmaceutical Bulletin

  Chemical and Pharmaceutical Bulletin 64 (11), 1616-1621, 2016

  The Pharmaceutical Society of Japan

Keywords

• magnetic resonance imaging
• <i>T</i>₂ map
• menthol–diphenhydramine cream
• surfactant
• thickener
• Kohonen’s self-organizing map

Details

• CRID: 1390001204178571264
• NII Article ID: 130005268072
• NII Book ID: AA00602100
• DOI: 10.1248/cpb.c16-00562
• ISSN: 13475223
• ISSN: 00092363
• NDL BIB ID: 027684792
• PubMed: 27803472
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I027684792
• Web Site: https://www.jstage.jst.go.jp/article/cpb/64/11/64_c16-00562/_pdf
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed