ABSTRACT
A supercritical fluid, such as supercritical carbon dioxide (scCO2) is increasingly used for the micronization of pharmaceuticals in the recent past. The role of scCO2 as a green solvent in supercritical fluid (SCF) process is decided by the solubility information of the pharmaceutical compound in scCO2. The commonly used SCF processes are the rapid expansion of supercritical solution (RESS) and supercritical antisolvent precipitation (SAS). To implement micronization process, solubility of pharmaceuticals in scCO2 is required. Present study is aimed at both measuring and modeling of solubilities of hydroxychloroquine sulfate (HCQS) in scCO2. Experiments were conducted at various conditions (P = 12 to 27 MPa and T = 308 to 338 K), for the first time. The measured solubilities were found to be ranging between (0.0304 × 10-4 and 0.1459 × 10-4) at 308 K, (0.0627 × 10-4 and 0.3158 × 10-4) at 318 K, (0.0982 × 10-4 and 0.4351 × 10-4) at 328 K, (0.1398 × 10-4 and 0.5515 × 10-4) at 338 K. To expand the usage of the data, various models were tested. For the modelling task existing models (Chrastil, reformulated Chrastil, Méndez-Santiago and Teja (MST), Bartle et al., Reddy-Garlapati, Sodeifian et al., models) and new set of solvate complex models were considered. Among the all models investigated Reddy-Garlapati and new solvate complex models are able to fit the data with the least error. Finally, the total and solvation enthalpies of HCQS in scCO2 were calculated with the help of model constants obtained from Chrastil, reformulated Chrastil and Bartle et al., models.
ABSTRACT
Palbociclib is a poorly water-soluble medicine which acts against metastatic breast cancer cells. Among various techniques to improve the solubility of this medicine, applying supercritical technologies to produce micro- and nano-sized particles is a possible option. For this purpose, extraction of solubility data is required. In this research, the solubility of palbociclib in supercritical carbon dioxide (ScCO2) at different equilibrium conditions was measured at temperatures between 308 and 338 K and pressures within 12-27 MPa, for the first time. The minimum and maximum solubility data were found to be 8.1 × 10-7 (at 338 K and 12 MPa) and 2.03 × 10-5 (at 338 K and 27 MPa), respectively. Thereafter, two sets of models, including ten semi-empirical equations and three Peng-Robinson (PR) based integrated models were used to correlate the experimental solubility data. Bian's model and PR equation of state using van der Waals mixing rules (PR + vdW) showed better accuracy among the examined semi-empirical and integrated models, respectively. Furthermore, the self-consistency of the obtained data was confirmed using two distinct semi-empirical models. At last, the total and vaporization enthalpies of palbociclib solubility in ScCO2 were calculated from correlation results of semi-empirical equations and estimated to be 40.41 and 52.67 kJ/mol, respectively.
