Preformulation study of the inclusion complex warfarin-?-cyclodextrin

Preformulation study of the inclusion complex warfarin-?-cyclodextrin
March 2005
By Zingone G, Rubessa F.
International Journal of Pharmaceutics, Volume 291, Issues 1-2 , 3 March 2005, Pages 3-10
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Abstract
Inclusion complex between warfarin and ?-cyclodextrin was obtained to improve the in vitro bioavailability of the drug in acidic media. Inclusion complexation in solution was studied by phase solubility technique. The apparent stability constant was influenced by the pH of the medium ranging from 633.26 M-1 (at pH 1.2, where the drug was in unionised form) to 99.81 M-1 (at pH 7.4, where the drug was in ionised form). Phase solubility study showed an AL-type diagram indicating the formation of an inclusion complex in 1:1 molar ratio. Solid binary mixtures of the drug with ?-cyclodextrin were prepared by several methods (physical mixing, kneading, co-evaporation, freeze-drying). Physicochemical characterizations were performed using differential scanning calorimetry, powder X-ray diffractometry and dissolution studies. Preparation method influenced the physicochemical properties of the binary mixtures. An inclusion complex was obtained by freeze-drying, and it showed a high solubility and drug dissolution rate. The physical stability of the complex was also studied. After one year storage in glass container at room temperature no significant changes were detected in the diffractogram, thermogram and dissolution profile of the freeze-dried product.