title: Novel gastroretentive controlled-release drug delivery system for amoxicillin therapy in veterinary medicine.
abstract: Beta-lactam antimicrobials, commonly used in both veterinary and human medicine, generally present short biologic half-lives, whereas their activity is enhanced as pathogen exposure is prolonged. These properties necessitate multiple-dose regimens of standard dosage forms, thereby hampering pet owner adherence, frequently resulting in therapeutic failure. This study presents a novel controlled-release gastroretentive oral drug delivery system for beta-lactams with which single-dose administration provides an effective antimicrobial course, optimizing pharmacokinetic (PK)-pharmacodynamic (PD) profiles, minimizing adverse effects and emergence of antimicrobial resistance and facilitating adherence. Our prototype sustained-delivery swelling-tablet (SDST), based on a degradable hydrophilic polymeric matrix, was designed to enable continuous input of these drugs to their absorption sites over several days. Several SDST formulations of the beta-lactam amoxicillin were evaluated in in vitro dissolution studies. Two formulations were selected for further in vivo canine studies, for determination of gastric retention and PK-PD profiling. Prolonged gastric retention times maintaining allowed for maintained effective drug concentrations against many clinically relevant pathogens for more than 48 h for one formulation and more than 5 days for the other. Both SDST formulations offer significant advantages over standard immediate-release therapy in achieving PK-PD goals and enhancing adherence. The prototypical formulations represent a novel platform which may be modified to meet various clinical requirements.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Horwitz
authors.forename: L
authors.initials: L
authors.lastname: Kagan
authors.forename: Y
authors.initials: Y
authors.lastname: Chamisha
authors.forename: I
authors.initials: I
authors.lastname: Gati
authors.forename: A
authors.initials: A
authors.lastname: Hoffman
authors.forename: M
authors.initials: M
authors.lastname: Friedman
authors.forename: E
authors.initials: E
authors.lastname: Lavy
mesh_terms: D020341:Absorbable Implants / Q000662:veterinary*; D000658:Amoxicillin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D003692:Delayed-Action Preparations; D006041:Goats / Q000097:blood* / Q000378:metabolism; D006207:Half-Life
chemical_list: D003692:Delayed-Action Preparations; D000658:Amoxicillin