Advancing nanomedicine production via green thermal supercritical processing: Laboratory measurement and thermodynamic modeling

• Thermodynamic modeling of drug solubility in dense solvent. • Evaluation of Temperature and Pressure in the range 308–348 K, and 170–410 bar. • Jafari Nejad model offered the best fitting precision with the experimental data. Chlorpromazine is an antipsychotic medicine which is used to treat psychotic disorders, nausea and vomiting. Based on the Biopharmaceutical Classification System (BCS), this medicine is categorized in the IV class because of its low solubility and bioavailability. In this regard, the required dosage, and hence the consequent side effects, can be decremented by enhancing the drug solubility. The particles size reduction of Chlorpromazine by various approaches based on supercritical carbon dioxide (scCO 2 ) can efficiently enhance the bioavailability and therapeutic efficiency of the medicine. The proper design of a supercritical micronization/nanonization method requires the precise measurement of supercritical solubility of Chlorpromazine. Here, the supercritical solubility of this medicine was founded under diverse conditions (308–348 K, and 170–410 bar). The solubility of Chlorpromazine in scCO 2 varied between 3.21 × 10 -5 to 5.25 × 10 -5 mol·mole −1 (mole fraction). Also, the determined solubility values were correlated by six empirical models (Chrastil, Bartle, Sung-Shim, Jafari Nejad, Khansary, and Keshmiri). The Jafari Nejad model offered the highest fitting precision with the experimental data with an AARD% of 1.05 and R adj of 0.992. Additionally, the extrapolative capability of these models for predicting the Chlorpromazine solubility beyond the studied range was also explored.

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