Solutions for insoluble bioactive compounds
The multidisciplinary BIOSOL (Solvent effects on physico-chemical properties of bioactive compounds: combination of theory with experiments) project combined low-cost computational chemistry with mathematical modelling, molecular mechanics and density functional theory to optimise biomolecular solvation. Researchers worked to enhance the solubility of bioactive compounds through polymorphism, pH control and the use of co-solvents. Polymorphism is the ability of a biomolecule to exist in different solid forms based on crystal structure and other properties. Supercritical fluids technology was used to selectively crystallise specific polymorphs of bioactive molecules by varying solvent parameters. Supercritical implies a state where a substance has no distinct liquid and gas phase at certain temperature and pressure conditions. Researchers successfully obtained crystals containing specific polymorphs using supercritical carbon dioxide. Besides supercritical technology, the BIOSOL team also employed other techniques to enhance solubility. In particular, crystallisation of drug molecules with an additional molecular species proved to be highly effective. Analysis revealed far better bioactivity and solubility in comparison to the pure drug. BIOSOL members studied the solvation thermodynamics of promising bioactive molecules by combining experimental and theoretical methods with computational chemistry. They developed more efficient methods to solve integral equations and optimised their computational model. As a result, they were able to predict the hydration free energy of several bioactive molecules. This model was further extended to describe the behaviour of macromolecules in various solvents in the presence of dissolved molecular species. The BIOSOL model could prove useful for designing pharmaceutical drug carrier systems as well as shortlisting the most promising bioactive compounds. Research outcomes should help increase the bioavailability of promising bioactive compounds that were previously unsuitable for therapy due to their insolubility in biological fluids.
Keywords
Bioactive, biomolecular solvation, polymorphism, supercritical carbon dioxide, computational model, pharmaceutical drug carrier system, bioavailability
