Suitthimeathegorn, Orawan; (2006) Studies on non-aqueous emulsions. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis explores a neglected field in pharmacy, that of non-aqueous (o/o) emulsions and of multiple emulsions of the form o/o/w. Non-aqueous, oil-in-oil, or anhydrous emulsions composed of 'oil' droplets dispersed in another immiscible oil phase were formulated using different non-aqueous solvent and natural oils. Various types of surfactants were used to stabilise such systems including non-ionic, poloxamer, and silicone surfactants. Among all formulations studied, the most stable emulsions could be formed with castor oil as the disperse phase and dimethicone or cyclopentasiloxane as the continuous phase. Only silicone surfactants which were miscible in silicone oil stabilised such systems. Emulsions formulated using these surfactants were found to be stable against phase separation and exhibited least globule growth over 168 h. An oil-in-oil-in-water (o/o/w) emulsion was formulated using a castor oil-in-silicone oil (co/so) emulsion as the disperse phase and nonylphenol ethoxy 7 as hydrophilic surfactant. Slow release patterns of 3H-dehydroepiandrosterone and 3H-dexamethasone solubilised in the disperse castor oil phase into an aqueous dialyzing medium were observed up to 48 h in in vitro. Intramuscular administration of 3H-dexamethasone in a co/so non-aqueous emulsion in rats confirmed slower absorption than from co/w emulsions with a longer Tmax and lower Cmax together with an increase of MRT and t1/2. In addition, slow clearance of the drug from the muscle injection site was observed. Non-aqueous emulsions may be considered as depot formulations for sustained release delivery, but further studies of these formulations are necessary for optimal effect. Magnetic nanoparticles were synthesized and characterised using TEM and powder X-ray crystallography. When the disperse phase is loaded with 10 nm magnetic nanoparticles, magnetic non-aqueous emulsions could be formulated. The use of an external magnetic field to immobilize or control the movement of magnetite carrying globules was also studied. Finally, flow behaviour non-aqueous emulsions in the microchannels of microfluidic devices was investigated. The phenomenological results of flow behaviour such as chain-like aggregation, oscillatory movement of droplets as well as the breakup of droplets were observed. These findings may provide a better understanding in the stabilisation and production of emulsion systems.

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