Evaluation of solubility and dissolution profile of itraconazole after cogrinding with various hydrophilic carriers

Abstract

The aim of this study was to improve the dissolution properties of very poorly soluble widely used antifungal drug, Itraconazole. Itraconazole were coground with cross povidone, poloxamer, polyvinyl pyrrolidone, Cremophor, sodium carboxymethylcellulose (Na CMC) high and low viscosity, citric acid and sodium butyl sulfate (SLS) by a planetary ball mill. Solubility and dissolution studies were carried out in simulated gastric fluid. Differential scanning calorimetry (DSC) was used to investigate solid interactions and crystallinity alteration of itraconazole in grinding process. All coground mixtures improved the solubility of itraconazole by affecting drug crystallinity. Cogrounds prepared with SLS and Na CMC H.V showed the highest degree of increase in solubility. Most effective carrier in improving of dissolution properties was citric acid with approximately 10 fold of improvement in dissolution efficiency. No correlation was observed between the results of solubility and dissolution. It was concluded that carrier type has a great effect on the dissolution of itraconazole from coground mixtures.