Enhancing Dissolution Rate of Ziprasidone via Co-grinding technique with highly Hydrophilic Carriers

Ziprasidone belongs to the class II biopharmaceutical classification system (BCS) which is characterized by a low aqueous solubility, slow dissolution and high membrane permeability. Like other drug candidates in this class this drug also has solubility limited bioavailability (60%). In order to increase the drug dissolution, its solid dispersions were prepared by the co-grinding technique using various highly hydrophilic carriers such as lactose, hydroxyprophylβ-cyclodextrin and hydroxypropylmethylcellulose. The ratios of drug to carrier were 1:1, 1:2, and 2:1. The percentage drug content for all the solid dispersion formulations was found in the range of 78.1 to 98.30. The aqueous solubility of all the coground formulations was found to increase when compared to unground pure drug. Comparison of the dissolution of the drug from its co-grounds with that of the unground pure drug revealed considerable differences. The percentage of drug dissolution of co-ground drug was 34.01 to 96.70 at the end of 1 hour whereas, for unground pure drug it was only 28. The x-ray diffraction patterns revealed that reduced crystallinity of the drug in co-ground state. The decreased crystallinity together with a reduced particle size, enhanced deaggregation and increased wettability of the drug could be accounted for the increased dissolution from the co-grounds. From the dissolution point of view, the solid dispersions prepared with all hydroxypropylemethyl cellulose were slightly superior to the all other solid dispersion formulations