Self-organizing Map Analysis for Understanding Comprehensive Relationships between Formulation Variables, State of Water, and the Physical Stability of Pharmaceutical Emulsions.

The physical stability of pharmaceutical emulsions is an important quality attribute to be considered. To obtain a better understanding of this issue, this study investigated the contribution of the state of water to the physical stability of pharmaceutical emulsions. The key technology to evaluate the state of water was magnetic resonance imaging (MRI). For sample preparation, model emulsions with different formulation variables (surfactant content, water content, and hydrophilic-lipophilic balance) were prepared. The T1 relaxation time, diffusion coefficient, and viscosity were measured as physical properties. The physical stability of the samples was evaluated using apparent diffusion coefficient maps acquired by MRI. Data analysis of the observed data was performed using the nonlinear response surface method and Kohonen's self-organizing map (SOM). It was determined that, depending on the formulation variables, the state of water was substantially changed and it played a significant role in the physical stability. SOM analysis successfully classified the conditions of formulation variables into four distinct clusters in terms of the similarity of the physical properties of the resultant emulsions, and then clarified the characteristics of the stable emulsions. This study provided us with a comprehensive understanding of the formulation variables, physical properties, and stability concerning the preparation of the model emulsion.

Non-destructive monitoring of creaming of oil-in-water emulsion-based formulations using magnetic resonance imaging.

A non-destructive method for monitoring creaming of emulsion-based formulations is in great demand because it allows us to understand fully their instability mechanisms. This study was aimed at demonstrating the usefulness of magnetic resonance (MR) techniques, including MR imaging (MRI) and MR spectroscopy (MRS), for evaluating the physicochemical stability of emulsion-based formulations. Emulsions that are applicable as the base of practical skin creams were used as test samples. Substantial creaming was developed by centrifugation, which was then monitored by MRI. The creaming oil droplet layer and aqueous phase were clearly distinguished by quantitative MRI by measuring T1 and the apparent diffusion coefficient. Components in a selected volume in the emulsions could be analyzed using MRS. Then, model emulsions having different hydrophilic-lipophilic balance (HLB) values were tested, and the optimal HLB value for a stable dispersion was determined. In addition, the MRI examination enables the detection of creaming occurring in a polyethylene tube, which is commonly used for commercial products, without losing any image quality. These findings strongly indicate that MR techniques are powerful tools to evaluate the physicochemical stability of emulsion-based formulations. This study will make a great contribution to the development and quality control of emulsion-based formulations.

Feasibility of deep-inspiration breath-hold PET/CT with short-time acquisition: detectability for pulmonary lesions compared with respiratory-gated PET/CT.

OBJECTIVES: Deep-inspiration breath-hold (DIBH) PET/CT with short-time acquisition and respiratory-gated (RG) PET/CT are performed for pulmonary lesions to reduce the respiratory motion artifacts, and to obtain more accurate standardized uptake value (SUV). DIBH PET/CT demonstrates significant advantages in terms of rapid examination, good quality of CT images and low radiation exposure. On the other hand, the image quality of DIBH PET is generally inferior to that of RG PET because of short-time acquisition resulting in poor signal-to-noise ratio. In this study, RG PET has been regarded as a gold standard, and its detectability between DIBH and RG PET studies was compared using each of the most optimal reconstruction parameters. METHODS: In the phantom study, the most optimal reconstruction parameters for DIBH and RG PET were determined. In the clinical study, 19 cases were examined using each of the most optimal reconstruction parameters. RESULTS: In the phantom study, the most optimal reconstruction parameters for DIBH and RG PET were different. Reconstruction parameters of DIBH PET could be obtained by reducing the number of subsets for those of RG PET in the state of fixing the number of iterations. In the clinical study, high correlation in the maximum SUV was observed between DIBH and RG PET studies. The clinical result was consistent with that of the phantom study surrounded by air since most of the lesions were located in the low pulmonary radioactivity. CONCLUSION: DIBH PET/CT may be the most practical method which can be the first choice to reduce respiratory motion artifacts if the detectability of DIBH PET is equivalent with that of RG PET. Although DIBH PET may have limitations in suboptimal signal-to-noise ratio, most of the lesions surrounded by low background radioactivity could provide nearly equivalent image quality between DIBH and RG PET studies when each of the most optimal reconstruction parameters was used.