PROLONGED-RELEASE HYDROXYPROPYL METHYLCELLULOSE MATRIX TABLETS OF FUROSEMIDE FOR ADMINISTRATION TO DOGS

Furosemide is a problematic drug in a prolonged-release product becaus e its absorption is site specific, taking place mainly in the upper pa rts of the alimentary tract. The aim of the study reported here was to develop prolonged-release furosemide formulations for dogs. The type of preparation selected was a hydroxypropyl methylcellulose (HPMC) mat rix tablet. Evaluation was based on dissolution studies, in in vivo di sintegration studies in the canine stomach and on bioavailability stud ies in Beagle dogs. The variables tested were the viscosity grade of t he polymer the amount of polymer and presence or absence of an alkalin e compound (potassium carbonate) in the formulation. When potassium ca rbonate was included, furosemide was absorbed so slowly that drug admi nistration once daily would give plateau drug plasma concentrations ev en though ther elimination half-life of furosemide is only about one h our. In vitro dissolution tests gave a wrong indication of the in vivo behaviour of the products. Thus, in vivo studies are important from t he very beginning in the development of new drug products for dogs.