Abstract
High kinetic stability water-in-oil high internal phase ratio emulsions (W/O-HIPREs) have been obtained in a 0.5% Theophylline (TP) aqueous solution/Cremophor WO7/liquid paraffin system at 25°C. The release of TP has been studied from HIPREs with pH values of the dispersed phase ranging between 2 and 12. Although the release from aqueous solutions was not influenced by pH, the release from HIPREs depended strongly on the pH of the dispersed phase. Increasing the solubility of TP in the dispersed phase, its apparent diffusion coefficient decreased over two orders of magnitude. Two different physico-chemical models have been applied to describe the diffusion of TP, showing an excellent agreement with experiments and confirming the role of the structure of the emulsions and the solubility of the drug. It has been shown that only non-ionized species are able to cross the interfacial film. Therefore, at pH>pKa diffusion is limited by the concentration of non-ionized species inside the emulsion droplets, while at pH<pKa diffusion is determined by the interfacial film. This demonstrates that solubility of the diffusing molecule can have a higher effect on release from HIPREs than the interfacial film properties.
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