NDLI: Formulation of Solid Dosage Forms to Overcome Gastric pH Interaction of the Factor Xa Inhibitor, BMS-561389

Content Provider	Springer Nature Link
Author	Badawy, Sherif I. Farag Gray, David B. Zhao, Fang Sun, Duxin Schuster, Alan E. Hussain, Munir A.
Copyright Year	2006
Abstract	The purpose of the study was to investigate the specific mechanism by which elevated gastric pH reduces the absorption of BMS-561389, a factor Xa inhibitor, and to develop a solid formulation strategy to overcome this gastric pH interaction.A dissolution method in an acetate buffer at pH 5.5 was used to evaluate the dissolution behavior of the tablet formulation. A precipitation model was used to screen different excipients for their potential to minimize the pH-dependent absorption of BMS-561389. Excipients that showed promise in the precipitation model were incorporated in modified tablet formulations. Dissolution rate of the modified tablets was also determined by the acetate buffer method. A canine model for pH-dependent absorption was subsequently used to evaluate the tablet formulations.Dissolution studies suggested that the reduced absorption of the original formulation was the result of the precipitation of the poorly water-soluble free base during the initial dissolution of the salt. Modified tablets containing organic acids, sulfobutylether-β-cyclodextrin, or povidone showed enhanced dissolution as compared with the original formulation. Drug absorption from the tablet containing tartaric acid was substantially independent of gastric pH in the canine model.A multitier approach was successful in identifying a solid dosage form that minimizes the pH-dependent absorption of this drug candidate.
Starting Page	989
Ending Page	996
Page Count	8
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	23
Issue Number	5
e-ISSN	1573904X
Language	English
Publisher	Springer-Verlag
Publisher Date	2006-05-02
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	absorption factor Xa free base gastric pH precipitation tablet formulation Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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