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

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 T 2 mapping. From the T 2 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.

Nondestructive Monitoring of the Dispersion State of Titanium Dioxide Nanoparticles in Concentrated Suspensions Using Magnetic Resonance Imaging

“…In addition to the nondestructive monitoring of the interior of samples, MRI enables the visualization of the molecular mobility of major components of the sample (e.g., water in the body) by using MR parameters including the T 1 and T 2 relaxation times and the apparent diffusion coefficient. Recently, we succeeded in nondestructive monitoring of the destabilization process of pharmaceutical emulsions (e.g., creaming behavior) using MRI. − The key technology is the visualization of the molecular mobility of water. For instance, the creaming of an emulsion is accompanied by a change in the volume fractions of oil and water between the upper and lower regions of the sample.…”