Solubility measurement and modeling of hydroxychloroquine sulfate (antimalarial medication) in supercritical carbon dioxide

Abstract A supercritical fluid, such as supercritical carbon dioxide (scCO 2 ) is increasingly used for the micronization of pharmaceuticals in the recent past . The role of scCO 2 as a green solvent in supercritical fluid (SCF) process is decided by the solubility information of the pharmaceutical compound in scCO 2 . 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 scCO 2 is required. Present study is aimed at both measuring and modeling of solubilities of hydroxychloroquine sulfate (HCQS) in scCO 2 . 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 scCO 2 were calculated with the help of model constants obtained from Chrastil, reformulated Chrastil and Bartle et al., models.

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