| dc.description.abstract | Racemic species involve racemic conglomerate, racemic compound, or pseudoracemate (solid solution). On the market, most racemic drugs are racemic compound (90-95%). In this thesis, we focused on the crystallization of the racemic compound drug including ibuprofen ((R/S)(±)-2-[4-isobutylphenyl)propionic acid, C13H18O2) and sodium ibuprofen dihydrate ((R/S)(±)-sodium 2-(4-isobutylphenyl) propanoate, C13H17NaO2·2H2O), and attempted to provide a series of effective engineering technology data to improve the efficiency for drug development. Two important studies in this thesis were performed.
Firstly, we were the first to use 23 solvents (water, methanol, ethanol, isopropyl alcohol (IPA), n-butyl alcohol, benzyl alcohol, acetone, acetonitrile, nitrobenzene, N,N-Dimethylformamide (DMF), dimethy sulfoxide (DMSO), methyl ethyl ketone (MEK), ethyl acetate, methyl-t- butyl ester (MTBE), n-heptane, N,N-dimethylaniline(DMA), xylene, p-xylene, toluene, benzene, 1,4 dioxane, tetrahydrofurn (THF), and chloroform.) by initial solvent-screening to collect engineering technology data including solubility, polymorphism, crystallinity, and crystal habit of racemic compound of ibuprofen, simultaneously. In this section, we are the inventors for the “form space” of the racemic compound of ibuprofen. “Form space” is the material’s characteristics. Results of this investigation were shown as the following: (1) the racemic compound of ibuprofen was practically insoluble in water, (2) the powder x-ray diffraction (PXRD) and differential scanning calorimetry (DSC) studies showed that ibuprofen was isomorphic, (3) the degree of crystallinity of racemic ibuprofen in DMF was higher than the ones given from other solvents, finally, (4) the different type of solvents (from polar to non-polar) can modify the aspect ratio of racemic compound of ibuprofen. Because the racemic compound of ibuprofen packing was formed by dimer formation in solution before the incorporation into the crystal. Hence, racemic compound of ibuprofen have a carboxylic acid group are likely to dissolve in polar solvents.
Secondly, we focused on the crystallization kinetics of racemic compound of ibuprofen. In this section, we were the first to use 0.02g of the pure enantiomer of S(-)-sodium ibuprofen dihydrate and the homochiral parent acid (S)-(+)-ibuprofen as additives. In addition, we employed electrical conductance in situ monitor the entire crystallization process and to gather thermodynamics (solubility, Gibbs free energy) and kinetics (nucleation and crystal growth) information. The fundamental nucleation and crystal growth parameters were then estimated. This investigational results were very important. Because the presence of different additives could alter the crystallization pathways to produce (1) racemic compound of sodium ibuprofen dihydrate, (2) racemic conglomerate of sodium ibuprofen dehydrate, and (3) pseudoracemic of sodium ibuprofen. | en_US |