Measurement of metoprolol solubility in supercritical carbon dioxide; Experimental and modeling study

Metoprolol is a beta-blocker agent, widely used to treat hypertension, and some heart diseases. However, due to low bioavailability and short half-life of this drug, the dose and the frequency of its daily use are high, causes to some digestive problems in patients. Designing a new drug delivery system with high efficiency and controlled drug release using a suitable supercritical method can solve these problems. To reach this goal, the solubility of Metoprolol in supercritical CO2 (scCO2) should be known. Here, solubility of Metoprolol in supercritical CO2 (scCO2) was measured at the pressure and temperature range of 120-300 bar and 308-338 K, respectively. It was determined between the mole fractions of 0.02 × 10-5 to 8.11 × 10-5. Also, obtained values were correlated via some well-known empirical models suggested through Kumar- Johnston (K-J), Sung and Shim, Adachi and Lu, Sparks, Bartle, Hozhabr, Khansary, and Jouyban. The empirical model proposed by Adachi and Lu shows the highest correlation precision, with the minimum AARD% of 13.07. Furthermore, the total mixing heat, vaporization enthalpy, and solvation enthalpy of the Metoprolol-scCO2 binary mixture were obtained as about 107.25 kJ/mol, 115.56 kJ/mol, and -8.31 kJ/mol, respectively.