Studies on optimization of the bioavailability of poor water-soluble drugs

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Highly effective, specific drugs are often chiral compounds with one or more chiral centers. Since new pharmaceutical products should contain only the active enantiomer, non-active or even contradictory effective enantiomers are considered as contamination of the product. In addition, such compounds are often poor and slowly soluble in aqueous media. Such drugs are characterized by a low bioavailability since the poor water-solubility and therewith low dissolution rate is a limiting step for their absorption and biological availability.Therefore, the aim of this project is to develop methods for selective separation of the biologically active enantiomer from the racemate solution directly combined with its formulation as submicron drug in a suitable porous carrier. Alternatively, the extraction of the active enantiomer will be investigated using appropriate adsorbents. For both concepts, the bioavailability of the active ingredients is studied and evaluated by pH depended and thus targeted release.The selective enrichment of the active enantiomer covers the selection and modification of suitable carrier materials and their adaptation to the specific requirements for adsorption and separation. The carrier materials which will be used are on one hand commercial chiral adsorbents such as cyclodextrins and cyclofructanes. On the other hand inorganic carrier based on achiral silica gels and AlO(OH) will be used, which for surface modification will be further derivatised with biocompatible chiral selectors. Amino acids or chiral alcohols, which will be fixed by chemical bonds on the particle surfaces, are intended to serve as chiral selectors. A suitable characterization, e.g. studies on particle size and morphology, will help to make a selection of promising carrier systems for the separation of enantiomers. The intended systematic investigations will enable the identification of optimal process conditions and a deeper insight into the relationship between process conditions and product properties such as an optimized dissolution behavior.