caa a22 4500 445312580 CHVBK 20180317142635.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s11095-011-0505-7 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0505-7 Improved Ziprasidone Formulations with Enhanced Bioavailability in the Fasted State and a Reduced Food Effect [Elektronische Daten] [Avinash Thombre, Scott Herbig, Jeffrey Alderman] ABSTRACT: Purpose: To develop and characterize new formulations of ziprasidone with a reduced food effect achieved by increasing exposure in the fasted state. Methods: Formulations were developed utilizing the following solubilization technologies: inclusion complex of ziprasidone mesylate and cyclodextrin, ziprasidone free base nano-suspension, and semi-ordered ziprasidone HCl in polymer matrix. Pharmacokinetic studies were conducted with these formulations to examine the bioavailability of test formulations in fasted and fed state compared to commercial capsules (Geodon®) dosed in the fed state. Results: All formulations containing solubilized ziprasidone showed either no food effect or a reduced food effect compared to commercial capsules. Two formulations when taken in the fasted or fed state were comparable to the commercial capsules dosed in the fed state with respect to total exposure. However, peak concentrations were ~30-40% higher. Conclusions: Pharmacokinetic studies indicated solubilization technologies can be employed to successfully increase the extent of ziprasidone absorption in the fasted state, thereby reducing the food effect. Such formulations could provide simple and convenient dosing while retaining the familiar safety and efficacy profile of currently marketed capsules. Springer Science+Business Media, LLC, 2011 food effect nationallicence solubilization nationallicence ziprasidone nationallicence Thombre Avinash Worldwide Research and Development, Pfizer Inc., Eastern Point Road, 06340, Groton, Connecticut, USA aut Herbig Scott Worldwide Research and Development, Pfizer Inc., Eastern Point Road, 06340, Groton, Connecticut, USA aut Alderman Jeffrey Clinical Pharmacology, Pfizer Inc., 235 East 42nd Street, 10017, New York, New York, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3159-3170 0724-8741 28:12<3159 2011 28 11095 https://doi.org/10.1007/s11095-011-0505-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0505-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Thombre Avinash Worldwide Research and Development, Pfizer Inc., Eastern Point Road, 06340, Groton, Connecticut, USA aut NATIONALLICENCE 700 1- Herbig Scott Worldwide Research and Development, Pfizer Inc., Eastern Point Road, 06340, Groton, Connecticut, USA aut NATIONALLICENCE 700 1- Alderman Jeffrey Clinical Pharmacology, Pfizer Inc., 235 East 42nd Street, 10017, New York, New York, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3159-3170 0724-8741 28:12<3159 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer