Thermodynamic modelling and experimental validation of pharmaceutical solubility in supercritical solvent

• Published in: Journal of molecular liquids 2020-12, Vol.319, p.114120, Article 114120
• Main Authors: Pishnamazi, Mahboubeh, Zabihi, Samyar, Jamshidian, Sahar, Borousan, Fatemeh, Hezave, Ali Zeinolabedini, Shirazian, Saeed
• Format: Article
• Language: English
• Subjects: Modelling; Pharmaceutics; Simulation; Thermodynamics
• ISSN: 0167-7322; 1873-3166
• DOI: 10.1016/j.molliq.2020.114120

Particle size and morphology are among the most important parameters which must be precisely controlled in pharmaceutical industries to enhance the effectiveness of the solid dosage oral formulations. One of the most interesting methods for controlling these two quality attributes is supercritical fluid based technologies by which the drug solubility in supercritical (SC) solvent, commonly carbon dioxide, dictates whether the used method is applicable for suitable particle production or not. In this work, solubility of an anti-cancer drug namely tamoxifen in supercritical CO2 was measured under different conditions. The measurements were carried out between 120 and 400 bar pressure, and 308–338 K temperature. The measurements revealed the solubility of about 1.88 × 10−5 to 9.89 × 10−4 (mole fraction basis) for tamoxifen with strong functionality to pressure and complicated functionality to temperature. In details, pressure showed to have a direct effect on solubility, while the effect of temperature depends on existence of cross-over pressure that is about 200 bar for the case of tamoxifen. It was revealed that for the pressures greater than the cross-over point, increasing temperature led to enhancement of the tamoxifen solubility due to sublimation pressure dominanacy, while for pressures lower than cross-over point, density reduction (solvating power reduction) is the dominant mechanism as the temperature enhances. Besides the experimental measurements, the possibility of correlating and extrapolating the measured solubility of tamoxifen as a function of temperature and pressure was investigated using five well-known semi-empirical density-based models including Kumar-Johnston (K-J), Garlapati-Madras, Chrastil, Mendez-Santiago and Teja (MST), and Bartle et al., among which KJ model showed the lowest average absolute relative deviation percent of about 8.26%. [Display omitted] •Measuring solubility of Tamoxifen in supercritical CO2•Mathematical modelling of drug solubility at different conditions•Studying the effect of pressure and temperature on drug solubility