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Passive permeability studies of sulfonamides

Tildelt: kr 0,10 mill.





2011 - 2012

Assessment of oral bioavailability of new drugs in early drug development is of special interest since modern drug discovery have made hundreds of thousands of potential drug candidates available for high-throughput screening for activity or potency. Ther e is thus a rapidly increasing demand for the development of predictive in vitro and in silico models to assess drug absorption and disposition. Permeability screening as a mean to predict oral bioavailability has become an important issue in modern drug discovery programs both in the pharmaceutical industry and academia. One of the major problems in drug development today is that drug candidates often are suffering from poor water solubility, creating problems for permeability testing. This challenge can sometimes be overcome by the addition of solubilizers to the donor phase. The phospholipid vesicle-based barriers have earlier proved to be stabile against some relevant co-solvents and tensides, e.g. DMSO, and it thus suitable to investigate the permeab ility of poorly soluble drug.Sulfonamides (SAs) are drugs extensively used for treating certain infections caused by Gram-positive and Gram-negative microorganisms, some fungi, and certain protozoa. The poorly soluble sulfonamids is a class of drugs that has been widely studied in the applicant?s research group with point of view of their solvation/hydration characteristics in the biological relevant solvents. If it take into account that especially the solvation/hydration characteristics are the driving forces of the permeability process, thus it will be very interesting to compare/correlate to Papp values with the parameters to investigate how well permeability can be predicted based on molecular characteristics.In brief, the plan is to investigate how solubilizers (in this case DMSO) are influencing permeability of poorly soluble sulfonamides and how we can predict permeability without additives.