title: Pharmacoscintigraphy studies to assess the feasibility of a controlled release formulation of ziprasidone.
abstract: 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.
authors.affiliation: Pfizer Inc., Center for Discovery and Development Sciences, Groton, CT 06340, USA. Electronic address: avinash.g.thombre@pfizer.com.
authors.forename: Avinash G
authors.initials: AG
authors.lastname: Thombre
authors.affiliation: Pfizer Inc., Center for Discovery and Development Sciences, Groton, CT 06340, USA.
authors.forename: Sheri L
authors.initials: SL
authors.lastname: Shamblin
authors.affiliation: Pfizer Inc., Clinical Pharmacology, New York, NY 10017, USA.
authors.forename: Bimal K
authors.initials: BK
authors.lastname: Malhotra
authors.affiliation: Quotient Clinical, Nottingham, UK.
authors.forename: Alyson L
authors.initials: AL
authors.lastname: Connor
authors.affiliation: Quotient Clinical, Nottingham, UK.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Wilding
authors.affiliation: Bend Research Inc., Bend, OR 97701, USA.
authors.forename: W Brett
authors.initials: WB
authors.lastname: Caldwell
mesh_terms: D000284:Administration, Oral; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D002214:Capsules; D003106:Colon / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000737:chemistry*; D006801:Humans; D007408:Intestinal Absorption; D010879:Piperazines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D012995:Solubility; D013844:Thiazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D014150:Antipsychotic Agents; D002214:Capsules; D003692:Delayed-Action Preparations; D010879:Piperazines; D013844:Thiazoles; C092292:ziprasidone
keywords: Controlled release; Gamma scintigraphy; Solubilization; Swellable core technology; Ziprasidone