Strategy for the development of a thermodynamically stable oral microemulsion.
Microemulsions, being thermodynamically stable systems, with low viscosity and elegant in appearance have attracted interest not only for the delivery of single drug substances with low water solubility but for the stabilization of drugs in combination due to their preferential solubility in either the water or oil phases. Microemulsion design involves the solubilisation of an optimum amount of the dispersed phase in the continuous phase, utilizing the minimum amount of surfactant/mixture of surfactants/cosurfactants. It is the choice of the surfactant/surfactant mixture and/or cosurfactants, which poses the greatest challenge in the design of a thermodynamically stable microemulsion formulation. This paper will present a strategy for choosing surfactants to achieve a stable, dilutable microemulsion formulation for oral administration. Ternary and pseudo-ternary phase diagrams were constructed by titrating a series of mixtures [lipid (miglyol 812): cosurfactant and/or surfactant (cremophor RH, imwitor 308/742, sorbitol, brij 97, crillet 3)] with water at room temperature, the phases formed visually assessed after each addition and classified as isotropic (ME), liquid crystalline (LC) or coarse emulsions (EM). Results indicate that the surfactant combination of imwitor 308 and crillet 3 proved most successful in incorporating 25 to 30% miglyol 812 into a microemulsion formulation utilizing an intermediate quantity of surfactant and maintaining homogeneity on dilution.
Agatonovic-Kustrin
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S
School of Pharmaceutical and Medical Sciences, University of South Australia, North Terrace, Adelaide 5000, Australia. nena.kustrin@unisa.edu.au
Glass
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BD
Wisch
M H
MH
D016880:Anisotropy; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry*; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D036103:Nanotechnology; D012997:Solvents; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents; D013816:Thermodynamics
D004655:Emulsions; D007202:Indicators and Reagents; D012997:Solvents; D013501:Surface-Active Agents