MRI as a promising tool for evaluation of the stability of cosmetic emulsions

The admixture of a steroid ointment and a moisturizing cream is frequently prescribed to patients suffering from atopic dermatitis. For the mixing operation, a revolution/rotation-type hybrid mixer is widely used in pharmacy. The purpose of this study was to monitor the mixed state of the admixtures during the mixing process of the hybrid mixer. The key technology used in this study was magnetic resonance imaging (MRI). Two different commercial mometasone furoate-containing ointments were used as a test steroid ointment. After layering the moisturizing cream and the steroid ointment in an ointment bottle, the sample was mixed for a predetermined period using the hybrid mixer. According to MRI transverse relaxation time (T 2 ) mapping for nondestructive monitoring, it was confirmed that the Flumeta ® ointment-containing admixture became homogeneous by mixing for 60 s or more. As for the mometasone furoate ointment 0.1%-containing admixture, the mixed state, after becoming homogeneous, was separated into two layers again by the prolonged mixing process. From the 1 H-NMR spectra of the phase-separated layers, re-separation was caused by removing aqueous components from the bottom of the samples. MRI is a powerful tool for monitoring the mixed state of the admixture during the mixing process. We believe that our findings offer profound insights into the clinical practice of the mixing operation using a hybrid mixer.

Section: Resultsmentioning

confidence: 94%

“…During the accelerated testing, their emulsion states were monitored by T 2 mapping. 9,10) From these studies, T 2 mapping proved to be effective for detecting the change in emulsion state (e.g., creaming and phase separation).…”

mentioning

confidence: 99%

MRI Monitoring of the Mixed State of Admixtures Consisting of Moisturizing Cream and Steroid Ointment during the Mixing Process by a Revolution/Rotation-Type Hybrid Mixer

Yokokawa

Setoyama

Okada

et al. 2018

“…We have already found that T 2 mapping is a powerful tool with which to evaluate the stability of emulsions. [8][9]12) The acquired T 2 maps clearly display the phase separation with distinct T 2 values (Figs. 5a, c).…”

Section: Resultsmentioning

confidence: 97%

Stability of Mixed Preparations Consisting of Commercial Moisturizing Creams with an Ointment Base Investigated by Magnetic Resonance Imaging

Onuki

Funatani

Yamamoto

et al. 2017

A moisturizing cream mixed with a steroid ointment is frequently prescribed to patients suffering from atopic dermatitis. However, there is a concern that the mixing operation causes destabilization. The present study was performed to investigate the stability of such preparations closely using magnetic resonance imaging (MRI). As sample preparations, five commercial moisturizing creams that are popular in Japan were mixed with an ointment base, a white petrolatum, at a volume ratio of 1 : 1. The mixed preparations were stored at 60°C to accelerate the destabilization processes. Subsequently, the phase separations induced by the storage test were monitored using MRI. Using advanced MR technologies including spin-spin relaxation time (T 2 ) mapping and MR spectroscopy, we successfully characterized the phase-separation behavior of the test samples. For most samples, phase separations developed by the bleeding of liquid oil components. From a sample consisting of an oil-in-water-type cream, Urepearl Cream 10%, a distinct phase-separation mode was observed, which was initiated by the aqueous component separating from the bottom part of the sample. The resultant phase separation was the most distinct among the test samples. To investigate the phase separation quantitatively and objectively, we conducted a histogram analysis on the acquired T 2 maps. The water-in-oil type creams were found to be much more stable after mixing with ointment base than those of oil-in-water type creams. This finding strongly supported the validity of the mixing operation traditionally conducted in pharmacies.Key words mixed external preparation; magnetic resonance imaging; quantitative T 2 map; emulsion stability Atopic dermatitis is one of the most common skin disorders in Japan. Dermatologists frequently prescribe moisturizing creams mixed with steroid ointments.1-4) This treatment approach is based on the concept that moisture retention of the skin is important for the treatment of atopic dermatitis, as is steroid therapy. To facilitate application of the cream and ointment, they are mixed in an operation that is widely performed at pharmacy level.Moisturizing creams are classified into two types: oilin-water (o/w) emulsions, which are composed of small oil droplets dispersed in a continuous aqueous phase, while water-in-oil (w/o) creams are composed of small water droplets dispersed in a continuous oily phase.5) The basic concept concerning the compatibility of the different types of emulsions with steroid ointments is described in the dispensing guidelines in Japan, Chozai Shishin.6) The guidelines show a greater preference for w/o-type moisturizing creams in mixing creams with ointments than for o/w-type creams. This description is often used as a rationale to argue that the mixing operation performed in the pharmacy is appropriate. However, as a whole, pharmaceutical emulsions are not designed under the assumption that they would be mixed with other preparations. Therefore, it remains a concern that the mixing operation could be a...

“…From our previous studies, it has been confirmed that T 2 maps are a powerful tool to detect phase separation in pharmaceutical emulsions. 10,11,15) As far as oil-in-water (o/w)-type emulsion is concerned, the state of water is substantially changed depending on its surroundings.…”

Section: Effects Of Surfactants On the Emulsion Stability Of The Creammentioning

confidence: 99%

“…It is worth noting that the detection sensitivity of change in the emulsion state is much superior to that by visible observation. 12,15) The creams containing various surfactants were stored at 40°C, and their phase separations were monitored continuously. As shown in Fig.…”

Section: Effects Of Surfactants On the Emulsion Stability Of The Creammentioning

confidence: 99%

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

Onuki

Yokokawa

Utsumi

et al. 2016

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.