Comparison of various pharmaceutical properties of clobetasol propionate cream formulations - considering stability of mixture with moisturizer

Yoshihisa Yamamoto; Yoshinori Onuki; Toshiro Fukami; Tatsuo Koide

doi:10.1186/s40780-020-0158-y

Comparison of various pharmaceutical properties of clobetasol propionate cream formulations - considering stability of mixture with moisturizer

J Pharm Health Care Sci. 2020 Jan 30:6:1. doi: 10.1186/s40780-020-0158-y. eCollection 2020.

Authors

Yoshihisa Yamamoto¹, Yoshinori Onuki², Toshiro Fukami³, Tatsuo Koide⁴

Affiliations

¹ 1Faculty of Pharmaceutical Sciences, Teikyo Heisei University, 4-21-2, Nakano, Nakano-ku, Tokyo, 164-8530 Japan.
² 2Faculty of Pharmacy and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194 Japan.
³ 3Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose, Tokyo 204-8588 Japan.
⁴ 4Division of Drugs, National Institute of Health Sciences, 3-25-26, Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-9501 Japan.

Abstract

Background: The clobetasol propionate cream formulations (CLB _Cr ) belong to the "strongest" group, and are used widely. In addition, those formulations are often used as a mixture with moisturizer. Recently, we evaluated pharmaceutical properties of the CLB _Cr using near infrared (NIR) spectroscopy, and characteristic NIR spectra depending on the formulation were observed. In the present study, we attempted to evaluate the more diverse pharmaceutical properties of CLB _Cr , including the stability of mixture of CLB _Cr and moisturizer.

Method: Pharmaceutical properties of CLB _Cr were evaluated using from rheological characteristics, microscopic observation, dye permeability observations, electrical conductivity method, thermogravimetry-differential thermal analysis (TG-DTA) and near infrared (NIR) spectroscopy. Stability of mixtures of CLB _Cr and moisturizer were evaluated using from dye method and NIR spectroscopy.

Results: The hardness of Dermovate® (DRM), Glydil® (GDL), and Myalone® (MYA) was greater than that of CLB _Cr . High concentrations of white beeswax were considered the reason for the hardness of DRM and GDL. On the other hand, the hardness of MYA may be due to the presence of macrogol 6000. After storage of the cream formulations discharged from the tube at room temperature, mass reduction and attenuation of the peak reflecting water of NIR spectroscopy occurred in a time-dependent manner, except for GDL and MYA. Only GDL was shown to be a w/o-type formulation by dye and electric conductivity measurements, which suggested that this was the reason for the lack of changes in the mass or NIR spectrum of samples after storage. In the NIR spectrum of MYA, the peak reflecting water slightly increased in a time-dependent manner, suggesting the water absorption of macrogol 6000. TG-DTA provided curves indicating the presence of water in each formulation, except for MYA, which was consistent with water quantification previously reported. Finally, when mixing the CLB _Cr with a moisturizer, in any CLB _Cr , the stability of the mixture with w/o-type moisturizer varies greatly depending on the each CLB _Cr .

Conclusion: Thus, even for cream formulations with the same active pharmaceutical ingredient, pharmaceutical properties and stability of mixture with moisturizer may different significantly.

Keywords: Clobetasol propionate; Cream; Generic; Mixture; Near infrared spectroscopy; Rheological property; TG-DTA.