Pharmacoscintigraphy studies to assess the feasibility of a controlled release formulation of ziprasidone

Ziprasidone, like many BCS Class II drugs with low intrinsic solubility and a strong tendency to crystallize from supersaturated solutions, presents significant technical challenges when developing an oral controlled release dosage form. In order to achieve acceptable bioavailability and prolonged exposures for once-daily dosing, good colonic absorption and a reliable controlled release (CR) technology are necessary. To this end, a novel solubilized drug form--coated crystals made by spray drying (CCSD), was formulated and progressed into human clinical studies. This report describes studies of colonic absorption for the CCSD using the Enterion™ capsule and a pharmacoscintigraphy study in which the CCSD was orally administered via a radiolabelled osmotic tablet formulation. These studies demonstrated that the probability of achieving the required drug solubilization in the colon with the CCSD concept and thereby the desired once daily pharmacokinetic profile was extremely low.