| dc.description.abstract | In the pharmaceutical market, approximately 50% are racemics (mixture of enantiomers); therefore, chirality becomes more and more important in drug discovery and development. In this thesis (S)-(＋)-Ibuprofen and racemic (R,S)-(±)-Ibuprofen were used as active pharmaceutical ingredients (APIs) in “initial solvent screening” and “initial salt screening” procedures respectively. In initial solvent screening, the four important properties in pharmaceutical industry such as solubility, crystal habit, crystallinity, and polymorphism of (S)-(＋)-Ibuprofen could be obtained. This approach was an easy, economical, and close to scale-up condition approach for obtaining a serious of engineering data. The “form space” constructed in this method was a material characteristic that can provide the API every opportunity to discover a new polymorph, and it could be combined with Hansen model to form a solubility sphere to predict the API solubility property in an unknown solvent.
In initial salt screening procedure, racemic (R,S)-(±)-Ibuprofen was reacted with seven bases used commonly in pharmaceutical industry to find possible salt. In this procedure only two crystallization pathways such as temperature cooling and the addition of anti-solvent were to be considered to a close-to scale-up conditions. Besides, water was used as a main solvent to avoid missing any opportunities for salt formation. Two salts: racemic (R,S)-(±)-Ibuprofen sodium dihydrate and racemic (R,S)-(±)-Ibuprofen tris(hydroxymethyl)aminomethane were produced by the method of initial salt screening. Their functional groups were identified by FTIR, and the crystal habit and thermal properties were determined by OM and DSC, TGA, respectively. Their crystal structures were determined by PXRD and SXD. They were also compared in their pH-solubility profiles, moisture sorption studies, and dissolution rate tests. Under these tests, racemic (R,S)-(±)-Ibuprofen tris(hydroxymethyl)aminomethane was considered to be stable during storage and could become a sustain-released drug. | en_US |