Experimental - Theoretical approach for determination of Metformin solubility in supercritical carbon dioxide: Thermodynamic modeling

Metformin, as an anti-hyperglycemic, is the main medicine for treating diabetes of type II. However, its daily dose is high due to its incomplete absorption and short half-life, which leads to digestive problems and patient complaints. Controlled release and increased bioavailability of this drug can be achieved using novel drug delivery systems produced with an appropriate supercritical carbon dioxide (scCO2) method. However, the solubility of Metformin in scCO2 is an essential parameter for this purpose which needs to be evaluated prior to the processing. In the current research, solubility of Metformin in scCO2 was determined at temperatures of 308, 318, 328, and 338 K, and pressures of 140, 170, 200, 230, 260, and 290 bar. It was obtained between 0.39 × 10-6 up to 1.23 × 10-6 (mole fraction). Also, the resulting values were correlated through an equation of state (Peng-Robinson (PR-EoS)) and eight well-known empirical correlations (Chrastil, Sung and Shim, Adachi and Lu, Si-Moussa, Bartle, Jafari Nejad, Keshmiri, and Jouyban). The average AARD% value of 8.24 for the PR-EoS model confirmed its satisfactory precision to predict the Metformin solubility in scCO2. Among the mentioned empirical models, the models defined by Jafari Nejad (AARD% of 4.36 and AICc of -997.07) and Keshmiri (AARD% of 4.73 and AICc of -1048.81) show the highest correlation accuracy. Moreover, the total mixing heat, the vaporization enthalpy, and the solvation enthalpies of the Metformin-scCO2 mixture were computed.