Application of Physiologically Based Absorption Modeling for Amphetamine Salts Drug Products in Generic Drug Evaluation

• Published in: Journal of pharmaceutical sciences Vol. 104; no. 9; pp. 3170 - 3182
• Main Authors: Babiskin, Andrew H., Zhang, Xinyuan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2015; Elsevier Limited
• Subjects: absorption; Amphetamine - pharmacokinetics; bioavailability; bioequivalence; Biological Availability; Capsules - pharmacokinetics; Chemistry, Pharmaceutical - methods; clinical trial simulation; Delayed-Action Preparations - pharmacokinetics; Dextroamphetamine - pharmacokinetics; Drug Evaluation - methods; Drugs, Generic - pharmacokinetics; Humans; modified release; physiological model; Salts - pharmacokinetics; Therapeutic Equivalency; physiological model; absorption; bioavailability; bioequivalence; clinical trial simulation; modified release
• ISSN: 0022-3549; 1520-6017; 1520-6017
• DOI: 10.1002/jps.24474

Amphetamine (AMP) salts-based extended-release (ER) drug products are widely used for the treatment of attention deficit hyperactivity disorder. We developed physiologically based absorption models for mixed AMP salts ER capsules and dextroamphetamine sulfate ER capsules to address specific questions raised during generic drug postmarketing surveillance and bioequivalence (BE) guidance development. The models were verified against several data sets. Virtual BE simulations were conducted to assess BE in various populations other than normal healthy subjects where BE studies are generally conducted for approval. The models were also used to predict pharmacokinetics (PK) for hypothetical formulations having dissolution profiles falling within specification after the development of in vitro–in vivo relation. Finally, we demonstrated how to use the models to test sensitivity of PK metrics to the changes in formulation variables. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.