Açlik ve tokluk durumlarini taklit eden çözünme ortamlarinda yapilan çözünme hizina yönelik çalişmalar
2010
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Advisor: Yrd. Doç. Dr. Zeynep Şafak Teksin
Abstract (EN)
The Performance of In Vitro Dissolution Studies in Dissolution Media Mimicking Fast and Fed StatesNowadays, legal regulations of modern drugs consider in vitro biopharmaceutic evaluations such as drug permeability and dissolution rate. The drugs are classified considering these biopharmaceutical evaluations according to Biopharmaceutics Classification System (BCS) which is accepted the health authories.Biorelevant dissolution media, which include different amounts and compositions of bile salts and lecithin, is used to predict the in vivo performace of drugs using the in vitro dissolution tests. These media mimic the in vivo physiological conditions more than current used dissolution media.In this work, it was purposed to investigate fasted and fed state in vivo performances of levofloxacin in the BCS Class 1 (high solubility ? high permeability) and flurbiprofen in the BCS Class 2 (low solubility ? high permeability) drugs by using the in vitro tests.The solubility and the dissolution rate experiments were conducted in the conventional gastric and intestinal dissolution media (pH 1.2, pH 4.5, and pH 6.8), and the fasted state simulated intestinal fluid (FaSSIF), and fed state simulated intestinal fluid (FeSSIF), and the biorelevant media which was prepared with SIF Powder® mixture. Dissolution rate profiles and and dissolution rate data were analyzed using DDSolver kinetic program.Biorelevant dissolution media used the effect to the cell viability of Caco-2 cell cultures to determine the cytotoxicity was evaluated by MTT test.It was found that, using biorelevant media was not significant for BCS Class 1 drugs such as levofloxacin.It was determined that, flurbiprofen solubility was affected by pH value and also concentrations of sodium taurocholate and lecithin. It was seen that, the biorelevant media were convenient for solubility and dissolution studies in BCS Class 2 weak acidic drugs such as flurbiprofen. The BCS Class 2 drugs? solubility and dissolution in the absorption site are considered that the waiver criteria for in vivo bioequivalence can be applied. Finally, the weakly acidic BCS Class 2 drugs can be considered as a member of BCS Class 1 drug.
Author
Diren Sarısaltık
How to Cite
Diren Sarısaltık (Master Thesis). Açlik ve tokluk durumlarini taklit eden çözünme ortamlarinda yapilan çözünme hizina yönelik çalişmalar, 2010, Gazi University.
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