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1.
Chem Pharm Bull (Tokyo) ; 62(1): 64-71, 2014.
Article in English | MEDLINE | ID: mdl-24390494

ABSTRACT

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.


Subject(s)
Emulsions/chemistry , Oils/chemistry , Pharmaceutical Preparations/chemistry , Water/chemistry , Hydrogen-Ion Concentration , Micelles , Surface-Active Agents/chemistry
2.
Ultrason Sonochem ; 15(6): 988-94, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18534893

ABSTRACT

The generation of hydroxyl (OH) radicals was investigated during ultrasonic irradiation and in the presence of TiO(2). The effect of TiO(2) on an ultrasonic system's oxidation power was evaluated by examining the oxidation of salicylic acid. The generation of the salicylic acid derivatives, 2,3-dihydroxybenzoic acid (DHBA) and 2,5-DHBA, was measured by high-performance liquid chromatography coupled with electrochemical detection under different experimental conditions. The presence of TiO(2) enhanced the generation of DHBA during ultrasonic irradiation, thus indicating a higher oxidation power in the ultrasonic system. Al(2)O(3) also increased the generation of DHBA during irradiation; however, the effect of TiO(2) was found to be higher than that of Al(2)O(3). The addition of OH radical scavengers such as dimethylsulfoxide (DMSO), methanol and mannitol significantly suppressed the production of DHBA, and DMSO was found to have the highest suppressive effect among all scavengers. The effects of dissolved gases on the generation of OH radicals were further studied, and their power was found to be in the order Xe > Ar > O(2) > N(2). The degassing of the irradiation solution completely suppressed the generation of OH radicals. These results indicate that the presence of TiO(2) accelerates the generation of OH radicals during ultrasonic irradiation, and that the process may be mediated through the induction of cavitation bubbles in irradiating solutions.


Subject(s)
Hydroxyl Radical/chemistry , Titanium/chemistry , Aluminum Oxide/chemistry , Catechols/chemistry , Chromatography, High Pressure Liquid , Electrochemistry , Electron Spin Resonance Spectroscopy , Free Radical Scavengers/chemistry , Gases/chemistry , Hydroxybenzoates , Hydroxyl Radical/radiation effects , Salicylates/chemistry , Salicylates/radiation effects , Spin Trapping , Titanium/radiation effects , Ultrasonics , X-Ray Diffraction
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