International Journal of Pharmaceutics 2003-04-30

Solubility enhancement of low soluble biologically active compounds--temperature and cosolvent dependent inclusion complexation.

Helmut Viernstein, Petra Weiss-Greiler, Peter Wolschann

Index: Int. J. Pharm. 256(1-2) , 85-94, (2003)

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Abstract

The solubility enhancement of biologically active compounds was analysed in dependence on temperature, amount of cosolvents and on beta-cyclodextrin as complexing agent. The analysis was performed for the systemic fungicide triflumizole (TF), a poorly water soluble compound. All parameters lead to an improvement of the solubility, the largest effect was obtained for host-guest complexation with beta-cyclodextrin. Generally, the combination of cosolvents and beta-cyclodextrin does not increase the solubility of the compound, because cosolvents destabilize the inclusion complex. At higher cosolvent concentrations the solubility of TF is mainly determined by the solubility of the free non-complexed compound in the solvent mixtures. Raising temperature enhances the solubility in any cases. It could be shown that the temperature dependence of the solubility of TF is controlled by the solubility in the solvent mixtures and not by the inclusion reaction.