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

Year 2018, Volume: 48 Issue: 3, 82 - 88, 01.12.2018

Diren Sarısaltık Yaşın Şükran Yılmaz Zeynep Şafak Teksin

Abstract

DOI: 10.26650/IstanbulJPharm.2018.180013

Biorelevant media are used to simulate the
physiological conditions in terms of components, pH, osmolality and buffer
capacity of the human stomach and intestine in both fasted and fed states  In this study, we aim to apply the
biorelevant media to Caco-2 cell lines to investigate the cytotoxicity effects
via the cell viability ratio and to compare the solubilizing effects of various
dissolution media on a poorly soluble model drug. Flurbiprofen
(Biopharmaceutics Classification System, BCS Class 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 lower pH values. The preparation method,
bile salts and the phospholipids did not show any additional effect on Caco-2
cell viability. In the cytotoxicity test, fed state media caused an additional
10-15% decrease in cell viability, compared to the fasted state. Similar
results were obtained when using the blank of these media which did not include
the bile salt or phospholipid. 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 least 24 h, and this ratio might be
increased by modifying the pH.

Keywords

Biorelevant media, flurbiprofen, cytotoxicity

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