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Title [sv]
Upplösning av svårlösliga läkemedel under fysiologiska betingelser: effekter av föda och hjälpämnen.
Title [en]
Physiologically based dissolution profiling of poorly soluble drugs: influence of food and excipients.
Abstract [sv]
Poor drug solubility has lately become an increased obstacle in drug discovery and development. Ideally, poorly soluble compounds are identified early in the drug discovery process. Several tools have been developed for this purpose with a huge effort directed towards predictions by computational means. We have previously developed small scale screening methods for solubility assessment and used the obtained experimental data to generate predictive in silico models. Ours and work by others have so far been based on data generated in pure water. In our on-going work we now take three new steps: i) We use our knowledge of which chemical structures that result in poor solubility in our drug synthesis projects, in order to identify how to chemically steer away from poor solubility. ii) We devise new experimental models for measurement of drug solubility in in vivo like situations., and iii) We assess effects of solubility enhancing excipients on the drug solubility in physiologically relevant media. The obtained experimental results will be analyzed from a chemical and physicochemical view point. Through this approach we believe it will be possible to computationally identify compounds with a high risk of displaying poor solubility in vivo. Further, we can give guidelines on which excipients to include in formulations to enhance the solubility of compounds with solubility issues. Such rule and guidelines would improve both the drug discovery and development processes largely.
Principal InvestigatorBergström, Christel
Coordinating organisation
Uppsala University
Funder
Period
2009-01-01 － 2011-12-31
Identifiers
DiVA, id: project:3335Project, id: 2008-03777_VR

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