Background: Furosemide is a potent diuretic drug widely used for the treatment of congestive heart failure in dogs and cats, but it shows a remarkable variability in bioavailability and efficacy, when administered orally. In particular a different diuretic effect can be detected after repeated administrations of the same medicinal product in the same animal, for this reason we investigate the possible reasons of this peculiar behavior. Drug products for veterinary and for human use are compared in terms of variability of tablets splitting, in vitro dissolution profiles (in different fluids that could simulate the gastro-intestinal environment of pets) and drug distribution uniformity.
Aim the work: to study the in vitro performances of drug products in terms of variability.
Methods: 5 veterinary products and 5 products for human use, containing different furosemide doses, are characterized. Tablets splitting uniformity, in vitro dissolution profiles in different fluids that could simulate the gastro-intestinal environment of the different species and drug content distribution were tested.
Results: The in vitro dissolution profiles of the different medicines are comparable, but confirm a different dissolution rate as a function of the medium pH and volume. Many of the products considered show a wide variability in the division performances of the scored tablets and this problem could lead to the detected fluctuations in diuretic effect. The four-leaf clover shape of a veterinary product appears to give rise to more uniform fractions. A uniform distribution of the drug in the tablets and in their fractions is confirmed for all the products considered.
Conclusion: The possibility of tablets splitting allows a considerable dosage flexibility, but a non-uniform break of the tablets, to obtain the dosage suitable for the weight of the pet, can cause dangerous over-or sub-dosing, especially in critical pathologies and in small breed pets.
Key words: furosemide, veterinary drug product, tablet splitting, dissolution rate, dose variability