Evaluation of biorelevant media to investigate the dissolution properties on flurbiprofen and to assess cytotoxicity effects on Caco-2 cell line

Abstract

Biorelevant media are used to simulate the physiological conditions in terms of components, pH, osmolality and buffer capacityof the human stomach and intestine in both fasted and fed states In this study, we aim to apply the biorelevant mediato Caco-2 cell lines to investigate the cytotoxicity effects via the cell viability ratio and to compare the solubilizing effectsof various dissolution media on a poorly soluble model drug. Flurbiprofen (Biopharmaceutics Classification System, BCSClass 2) was selected as a model drug.In dissolution studies the pH effects were predominant at higher pH values, while bile salt effects were dominant at lowerpH values. The preparation method, bile salts and the phospholipids did not show any additional effect on Caco-2 cellviability. In the cytotoxicity test, fed state media caused an additional 10-15% decrease in cell viability, compared to thefasted state. Similar results were obtained when using the blank of these media which did not include the bile salt orphospholipid. From this, it is evident that this decrease resulted from the pH values, not the components. In conclusion,the cytotoxicity assessment showed that all the biorelevant media were compatible with 70-90% of cell viability for at least24 h, and this ratio might be increased by modifying the pH.