The Effects of Internal and Receptor pH on the Rate of Drug Release from Water-in-Oil Emulsions
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概要
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We evaluated the effects of internal phase and receptor solution pH on the rate of drug release from water-in-oil emulsions using methylene blue as a model drug. The water-in-oil emulsions were prepared using an aqueous solution of methylene blue, squalene, and a non-ionic-lipophilic surfactant. The methylene blue release rate was strongly dependent on both internal phase and receptor solution pH. Methylene blue dissolved in squalene in the presence of a surfactant. The water–squalene distribution of methylene blue changed with pH, whereas its ionic state did not. The pH dependence of the methylene blue release rate may have been due to this distribution change. We also investigated the pH dependence in terms of the mobility of water molecules using time-domain NMR. The mobility of water in water-in-oil emulsions was also dependent on the internal phase pH. Water-in-oil emulsions that showed high water mobility also released drug more rapidly. These results suggest that methylene blue is released from the water-in-oil emulsion through a reverse micelle mechanism. Methylene blue moves from the internal phase to a soluble reverse micelle of the surfactant, diffuses through the oil phase within this reverse micelle, and is transferred to the receptor solution. It appeared that the reverse micelles could diffuse in oil more freely than water droplets of the water-in-oil emulsion because the micelles were much smaller than the droplets. We found that the drug release rate from a water-in-oil emulsion comprising squalene and a non-ionic surfactant could be controlled by pH optimization.
著者
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Shimizu Nobuaki
Institute of Natuare and Environmental Technology, Kanazawa University
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Fujihira Atsushi
Formulation Development Center, CMC Development Laboratories, Shionogi & Co., Ltd.
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