Thalidomide treats multiple myeloma and protracts life-span of patient, but its bioavailability is limited as it is poorly water soluble. Thalidomide nano-flakes are produced to improve the drug dissolution rate. Two nanoflake production methods are utilized for a comparative study： a supercritical antisolvent （SAS） method and a supercritical antisolvent with enhanced mass transfer （SAS-EM）. SAS-EM utilizes ultrasonication to improve dispersion upon injection within the supercritical carbon dioxide. Comparative study of SAS and SAS-EM thalidomide confirmed that the application of ultrasonication improved the micro/nano particles produced by SAS. The effects of ultrasound power on the formation of thalidomide particles are examined. The particle size and morphology were characterized by SEM. The thalidomide nano-flakes produced by SAS-EM were smaller than the particles produced by SAS. Dissolution rates of the produced particles, evaluated by HPLC, demonstrated an increase in the thalidomide dissolution rate for the SAS-EM produced particles, The polymorphs and crystallinity of thalidomide particles （flakes） were observed by FTIR and XRD. In this research, the supercritical processing significantly modified the crystal formation of thalidomide from an original state of a β-polymorph to the amorphous state α-polymorph after suoercritical orocessing.
HeyangJinMelinda HemingwayRam B. GuptaFei XiaYaping Zhao
Solubility of quinine in supercritical carbon dioxide(SCCO_2) was experimentally measured in the pressure range of 8 to 24 MPa, at three constant temperatures: 308.15 K, 318.15 K and 328.15 K. Measurement was carried out in a semi-dynamic system. Experimental data were correlated by iso-fugacity model(based on cubic equations of state, CEOS), Modified Mendez–Santiago–Teja(MST) and Modified Bartle semi-empirical models. Two cubic equations of state: Peng–Robinson(PR) and Dashtizadeh–Pazuki–Ghotbi–Taghikhani(DPTG) were adopted for calculation of equilibrium parameters in CEOS modeling. Interaction coefficients(k_(ij)& l_(ij)) of van der Waals(vdW) mixing rules were considered as the correlation parameters in CEOS-based modeling and their contribution to the accuracy of model was investigated. Average Absolute Relative Deviation(AARD) between correlated and experimental data was calculated and compared as the index of validity and accuracy for different modeling systems. In this basis it was realized that the semi-empirical equations especially Modified MST can accurately support the theoretical studies on phase equilibrium behavior of quinine–SCCO_2 media. Among the cubic equations of state DPGT within two-parametric vd W mixing rules provided the best data fitting and PR within one-parametric vd W mixing rules demonstrated the highest deviation respecting to the experimental data. Overall, in each individual modeling system the best fitting was observed on the data points attained at 318 K, which could be perhaps due to the moderate thermodynamic state of supercritical phase.
