title: Controlled delivery of metoclopramide using an injectable semi-solid poly(ortho ester) for veterinary application.
abstract: In animal health care, current therapeutic regimens for gastrointestinal disorders require repeated oral or parenteral dosage forms of anti-emetic agents. However, fluctuations of plasma concentrations produce severe side effects. The aim of this work is to develop a subcutaneous and biodegradable controlled release system containing metoclopramide (MTC). Semi-solid poly(ortho ester)s (POE) prepared by a transesterification reaction between trimethyl orthoacetate and 1,2,6,-hexanetriol were investigated as injectable bioerodible polymers for the controlled release of MTC. MTC is present in the polymeric matrix as a solubilised form and it is released rapidly from the POE by erosion and diffusion because of its acidic character and its high hydrosolubility. If a manual injection is desired, only low molecular weight can be used. However, low molecular weight POEs release the drug rapidly. In order to extend polymer lifetime and decrease drug release rate, a sparingly water-soluble base Mg(OH)(2) was incorporated to the formulation. It was possible to produce low molecular weight POE that can be manually injected and releasing MTC over a period of several days.
authors.affiliation: Laboratory of Pharmaceutical Technique and Biopharmacy, School of Pharmacy, University of Geneva, 30, Quai Ernest-Ansermet, Switzerland.
authors.forename: Khadija
authors.initials: K
authors.lastname: Schwach-Abdellaoui
authors.forename: Marinette
authors.initials: M
authors.lastname: Moreau
authors.forename: Marc
authors.initials: M
authors.lastname: Schneider
authors.forename: Bernard
authors.initials: B
authors.lastname: Boisramć
authors.forename: Robert
authors.initials: R
authors.lastname: Gurny
mesh_terms: D000818:Animals; D004285:Dogs; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D007279:Injections, Subcutaneous; D008787:Metoclopramide / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019155:Veterinary Drugs / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D011108:Polymers; D019155:Veterinary Drugs; C401107:poly(ortho ester); D008787:Metoclopramide