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22/03/20173B Pharmaceuticals and Sovicell introduce a novel service offering for plasma protein binding analysis

Science & Technology

Membrane Permeability

Early rational drug candidate selection is important, since later stage preclinical and clinical development is much more costly than early stage development. The soft drug development paradigm calls for inclusion of activity, specificity and ADME/PK data in the candidate selection process. During the secondary screening and lead optimization phase it is useful to obtain such data from in vitro studies as it is nearly impossible to identify causes of unsatisfactory ADME/Tox or pharmacokinetic data from in vivo animal studies. However, this calls for relevant in vitro models, since confidence in pharmacokinetic tools decreases as their relevance to the clinical endpoint decreases.

Therefore, it is not only important to obtain any estimate of how well lead compounds permeate epithelial cell’s membranes such as the intestine’s, but to obtain meaningful and reliable estimates of membrane permeation. Our TRANSIL membrane permeability in vitro models are based on biological membranes with true phospholipid bilayers purified from in vivo sources, which are reconstituted in a highly controlled process. Moreover, all TRANSIL assay kits have an affinity measure as endpoint, which is much more robust to variations in experimental conditions and unspecific binding than rate or concentration endpoints alone. Thus, TRANSIL membrane permeability assay kits are an ideal combination of a highly meaningful in vitro model through truly biological materials, a highly reproducible test system through their production process, and a very robust endpoint. Furthermore, it is possible to determine if the permeability is pH-dependent.

In our standard product line we offer two TRANSIL membrane permeation assays. TRANSIL Intestinal Absorption is based on silica beads covered with phosphatidyl choline as a classical natural membrane bilayer model for the small intestine, while TRANSIL Brain Absorption is based on silica beads covered with porcine brain phospholipids to assess drug candidates’ ability to cross the blood brain barrier.

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