High throughput lipolysis-permeation in vitro model employing the mucus-PVPA barriers to assess drug absorption from lipid-based delivery systems
In vitro lipolysis models are commonly used to assess the performance of lipid-based drug delivery systems (LbDDSs) in terms of their drug absorption potential; however, this in vitro approach has not always shown to correlate well with in vivo data. Several studies suggest that adding an absorption step to the in vitro lipolysis model would give a better estimation of absorption for drugs incorporated in LbDDSs, and thus correlate better with in vivo data. In the present work an in vitro lipolysis-permeation model was developed to assess drug absorption from LbDDSs and to predict in vivo absorption data. The in vitro model setup consisted of high throughput (HTP) lipolysis and the mucus-PVPA barriers comprising biosimilar mucus. The functionality of the mucus-PVPA barriers during lipolysis-permeation experiments was assessed, and their ability to withstand the lipolysis conditions and maintain integrity was confirmed. The model was evaluated by testing the performance of three fenofibrate containing self-nanoemulsifying drug delivery systems (SNEDDSs) (i.e. Super-SNEDDS solution 150%, SNEDDS 75% and Super-SNEDDS suspension 150%) in terms of their drug solubilization capacity and drug permeation. For the assessment of in vitro-in vivo correlation, in vivo absorption data for the same three fenofibrate-containing SNEDDSs in rats was available from a previous study. When comparing the amount of solubilized drug from the in vitro lipolysis step with the in vivo absorption data in rats, a poor in vitro-in vivo correlation was obtained. However, a satisfactory correlation (R2 > 0.9) was attained when comparing the in vitro drug permeation data after lipolysis to the in vivo absorption data in rats. Altogether, the constructed in vitro model was able to predict in vivo data and could thus potentially be used as a reliable HTP tool for further investigations of the performance of LbDDSs.
PublisherUiT Norges arktiske universitet
UiT The Arctic University of Norway
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