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Ketoconazole binary and ternary solid dispersions in different macromolecular matrices

Author(s): Mohamed Abbas Ibrahim

The objective of this studywas to enhance the dissolution of Ketoconazolean imidazole antifungal agent- by solid dispersions consisting of the drug, a polymeric carrier, and a surfactant. Binary and ternary solid dispersions of Ketoconazolewere preparedwith polyvinylpyrrolidone (PVP 40000) or PEG 6000 and a non-ionic surfactant (Brij 35) using coevaporation technique. Preliminarily, themicellar solubilization ofKetoconazolewas studied in aqueous solutions of 0.1 to1%of nonionic surfactants at 37 C. It was found that Brij 35 exhibited a higher solubilizing capacity on the drug than Tween 80 and Myrj-52 and the drug exhibited a higher distribution coefficient between Brij 35 micelles. A higher dissolution rate of Ketoconazole was obtained when the drug was present in the form of solid dispersion. In addition, increasing the polymer concentration in the binary systems was accompanied by an increase in the drug dissolution rate in terms of dissolution efficiency (DE30) and relative dissolution rate (RDR30) after 30 minutes. The addition of Brij 35 to the carrier matrix led to a vast improvement of the dissolution characteristics. The powder x-ray diffraction and differential scanning calorimetry of binaryKetoconazole-PVP (1:1 and 1: 5) and Ternary Ketoconazole-PVP-Brij (1:1:0.5) solid dispersions indicated absence of drug crystalline form.

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