Magnetic resonance imaging study on the physical stability of menthol and diphenhydramine cream for the treatment of chronic kidney disease-associated pruritus.

A cream that contains menthol and diphenhydramine is widely prepared in hospital pharmacies and prescribed to patients for the treatment of pruritus associated with chronic kidney disease. However, there is a serious concern regarding its physical stability; therefore, we investigated this issue using magnetic resonance imaging (MRI). For a sample preparation, a menthol-containing ethanol solution was mixed with a commercial diphenhydramine cream. After storage for 7 d at 40°C, substantial phase separation into two distinct layers (upper and lower layers) was observed in the sample. This study further examined the components of the phase-separated layers using magnetic resonance (MR) spectroscopy and chemical shift selective images, and it was verified that the upper layer consisted of packed oil droplet layers, whereas the lower was an aqueous phase. Subsequently, the time-dependent phase separation of the sample at different temperatures was investigated. From the MR images, including a T2 relaxation time map and apparent diffusion coefficient maps, it was obvious that the phase separation developed further with increasing temperature; the most substantial phase separation was observed from the sample stored at 40°C, while no phase separation was detected at 25°C. In the final phase of this study, we conducted a formulation study and succeeded in improving the cream's physical stability by adding a hydrophilic surfactant to the preparation.