1. OBJECTIVES Based on the specific composition and manufacturing process, the modified release formulations have increased patient compliance, as well as improved safety and efficacy profiles. Several regulatory guidance are focused on the evaluation of factors susceptible to alter the in-vivo exposure profiles, after oral administration, such as food intake. In 2005, Food and Drug Administration issued an alert letter for healthcare professionals, pointing out a significant dose- dumping effect induced by ethanol consumption on controlled release capsules containing hydromorphone, leading to withdrawal of the product from the market. The in-vitro dissolution tests were adopted as an adequate surrogate to evaluate the changes in product performance, using ethanol in simulated gastric or intestinal fluid without enzymes. The current paper presents the results obtained by applying these tests to modified release formulations containing 100, 150 and 200 mg tramadol hydrochloride. The in-vitro results indicated that the tested modified release formulations containing tramadol hydrochloride were robust with respect to co-administration of ethanol. No dose-dumping effect was observed. The release rates were decreased as the amount of ethanol was increased, probably due to the presence of insoluble excipients and/or inhibited swelling process. No dose dumping effect was observed. The fractions dissolved varied from 25-37% to 17-27% as the concentration of ethanol was increased from 5 to 40%. The rank order of release rates, as well as the kinetic model adequately describing the release process (Korsmeyer-Peppas model, except for Z100 and Z150 formulations, fitted with Higuchi model), were independent on the composition of the release media. The similarity was concluded between each generic product and the reference listed drug, and for different dose strengths of the same product (qualitatively similar, according to the labeled composition). Nevertheless, it seems that increasing the quantity of ethanol in the media reduces the in-vitro differences initially observed in the simulated gastric media. A possible explanation is that several excipients present in the formulation, including macromolecular agents are insoluble in ethanol or the swelling process in inhibited, compared to the aqueous media. In-vitro screening of a potential alcohol-induced dose-dumping effect for modified release formulations containing tramadol hydrochloride Burcea Dragomiroiu George Traian Alexandru 1, Miron Dalia Simona 2, Ginghină Octav 3 *, Lupuliasa Dumitru 4, Bârcă Maria 1, Popa Daniela Elena 1, Ciobanu Anne-Marie 1, Rădulescu Flavian tefan 5 University of Medicine and Pharmacy „Carol Davila” Bucureti 1 Faculty of Pharmacy, Department of Drug Control, 6, Traian Vuia Street, 020956, Bucharest, România 2 Faculty of Pharmacy, Department of Pharmaceutical Physics and Informatics, 6, Traian Vuia Street, 020956, Bucharest, România 3 Faculty of Dental Medicine, Department of Oncological Surgery, „Sf Ioan” Hospital, 13, Vitan-Bârzeti Street, 042122, Bucharest, România 4 Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics, 6, Traian Vuia Street, 020956, Bucharest, România 5 Faculty of Pharmacy, Department of Drug Industry and Pharmaceutical Biotechnologies, 6, Traian Vuia Street, 020956, Bucharest, România Corresponding author: octavginghina@yahoo.com RESULTS AND DISCUSSION CONCLUSIONS REFERENCES Roth W., Setnik B., Zietsch M., Burst A., Breitenbach J., Sellers E., Brennan D., Ethanol effects on drug release from Verapamil Meltrex, an innovative melt extruded formulation. Int J Pharm. 2009;368(1-2):72-5. Smith A.P., Moore T.W., Westenberger B.J., Doub W.H., In vitro dissolution of oral modified-release tablets and capsules in ethanolic media. Int J Pharm. 2010;398(1-2):93-96. U.S. FDA alert for healthcare professionals. Alcohol-Palladone TM interaction. 2005. ACKNOWLEDGEMENT This work was suported by the Sectorial Operational Programme Human Resources (SOP HRD) 2007-2013, financed from the European Social Fund and by the Romanian Gouvernment under the contract number POSDRU/159/1.5/S/133377, „Program de excelenă în cercetare doctorală i postdoctorală” and by PN-II-PT-PCCA-2013-4-1903. MATERIALS AND METHODS The in-vitro dissolution tests were performed on 8 MR solid oral dosage forms using USP apparatus 2 at 50 rpm and 900 ml simulated gastric fluid containing 0, 5, 20 and 40% ethanol (v/v, degassed by filtration under vacuum). Each test was performed on three dosing units, at 37°C. Samples of 5 ml were collected every 15 min for 2 hours. The quantitative analysis of tramadol hydrochloride was performed by a spectrophotometric method (λ max =271-272 nm). 0% ethanol 5% ethanol 20% ethanol 40% ethanol