Experimental measurement and thermodynamic modeling of Chlorothiazide solubility in supercritical carbon dioxide

Abstract

Chlorothiazide, with the brand name Diuril, is used as a diuretic as well as an antihypertensive drug. This medicine with very slight solubility in water and low permeability is categorized in the class IV of Biopharmaceutical Classification System (BCS) and possess low bioavailability. Therefore, enhancement of the drug solubility would be of great importance to reduce its dosage and consequently side effects. Decrement of Chlorothiazide particles size to micro/nano scale using a supercritical carbon dioxide (scCO2)-based method can be an efficient approach to enhance its bioavailability and therapeutic efficiency. To select and design a proper supercritical micronization/nanonization method, solubility of Chlorothiazide in scCO2 should be determined which is conducted in this work by gravimetric method. In this study, solubility of Chlorothiazide in scCO2 was obtained at various operating conditions (308–338K and 130–290 bar). It was found between 0.417 × 10−5 to 1.012 × 10−5 mol mol−1 (mole fraction) for Chlorothiazide. Moreover, the obtained values were correlated through five empirical models (Chrastil, Mendez-Santiago and Teja (MST), Kumar- Johnston (K-J), Bartle, and Garlapati-Madras), as well as SRK and PR equations of state. All of the mentioned models have shown satisfactory correlation accuracy for the drug solubility. Meanwhile, the K-J model with the minimum AARD% value of 3.15 and the PR-EoS with the mean AARD% value of 6.51 have the highest precision to fit the experimental data. Also, the extrapolative ability of the mentioned empirical models to predict the Chlorothiazide solubility outside the considered range of operating conditions was investigated.

Keywords

• Pharmaceutics
• Chlorothiazide
• Thermodynamics
• Supercritical carbon dioxide
• Solubility
• Equation of state