Novel gastroretentive controlled-release drug delivery system for amoxicillin therapy in veterinary medicine

E. Horwitz, L. Kagan, Y. Chamisha, I. Gati, A. Hoffman, M. Friedman, Eran Lavy

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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 48h for one formulation and more than 5days 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.

Original languageEnglish (US)
Pages (from-to)487-493
Number of pages7
JournalJournal of Veterinary Pharmacology and Therapeutics
Volume34
Issue number5
DOIs
StatePublished - Oct 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • veterinary(all)

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