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Novel gastroretentive controlled‐release drug delivery system for amoxicillin therapy in veterinary medicine
Author(s) -
HORWITZ E.,
KAGAN L.,
CHAMISHA Y.,
GATI I.,
HOFFMAN A.,
FRIEDMAN M.,
LAVY E.
Publication year - 2011
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.2010.01255.x
Subject(s) - amoxicillin , pharmacology , drug delivery , medicine , pharmacokinetics , bioavailability , pharmacodynamics , drug , antimicrobial , in vivo , dosage form , antibiotics , chemistry , biology , microbiology and biotechnology , biochemistry , organic chemistry
Horwitz, E., Kagan, L., Chamisha, Y., Gati, I., Hoffman, A., Friedman, M., Lavy, E. Novel gastroretentive controlled‐release drug delivery system for amoxicillin therapy in veterinary medicine. J. vet. Pharmacol. Therap. 34 , 487–493. 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.