Enhancement of dissolution rate of mitotane and warfarin prepared by using microemulsion systems

Micronization is the most effective way to enhance the dissolution rate of poorly water-soluble drugs and bioavailability in human body. Microemulsion systems were applied to micronize mitotane and warfarin by cooling method and solvent diffusion process. The triangle phase diagram of the ternary benzyl alcohol + sodium dodecyl sulfate (SDS) + water system was investigated at six different temperatures to determine an appropriate operational microemulsion regime for crystallization. The particle sizes of mitotane and warfarin re-crystallized from microemulsion systems were greatly reduced (to ∼1 μm) compared with that of the commercial ones. Consequently, the dissolution rate coefficients of re-crystallized mitotane and warfarin were significantly improved by, respectively, 7.5 and 13.3 times larger than that of the commercial ones. The crystal structures of re-crystallized mitotane and warfarin were the same as the commercial ones based on the XRD and DSC measurements. In addition, it is interesting to observe the variation of morphology of re-crystallized mitotane as a function of the composition of the SDS and the drug concentrations.

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► The triangle phase diagram of the ternary benzyl alcohol + sodium dodecyl sulfate + water system was investigated.
► The microemulsion systems were successfully applied to micronize mitotane and warfarin.
► The dissolution rate coefficients of micronized mitotane and warfarin were dramatically enhanced.
► The morphology of mitotane is subject to the SDS concentration in the microemulsion system.