IN VITRO SCREENING OF ALCOHOL-INDUCED DOSE DUMPING PHENOMENA FOR CONTROLLED RELEASE TRAMADOL TABLETS

The aim of the study was to evaluate the influence of ethanol content in acidic media on the in vitro release of tramadol hydrochloride from controlled release tablets. The selected products represented both hydrophilic and lipid-based monolithic systems, covering a wide range of dose strengths with various similarity degrees of the qualitative composition. The results confirmed the inhibition of release by gradually increasing the ethanol proportion up to 40% (v/v). The reduced hydration of the macromolecular agents and consequent increased diffusional resistance were suggested as the leading causes of this phenomenon. In vitro release similarity was observed between the different strengths of the same product, as well as between reference listed drug and generics, for the same media. The critical conditions simulated by the upper level of alcohol content minimized the impact of composition and manufacturing variables. Irrespective of media composition, strength and hydrolipophilic nature of the matrix, the kinetic model adequately describing the experimental data was preserved.