Laboratory determination and thermodynamic analysis of alendronate solubility in supercritical carbon dioxide

Alendronic acid, with the commercial name of Alendronate, is a bisphosphonate medicine which is generally used orally to treat the osteoporosis and Paget's disease of bones. However, its absorption is poor, and its oral bioavailability is <1%. So, development of novel delivery systems to enhance its bioavailability and reduce its side effects is essential. The design a modern drug delivery systems, through supercritical carbon dioxide (scCO₂) as a green solvent, which is known as an efficient solution to increase the drug bioavailability, reduce toxicity and side effects. Solubility of pharmaceutical substances in scCO₂ is an essential parameter that must be determined for this purpose. Here, solubility of Alendronate was experimentally studied in the span of 0.01 × 10⁻⁴ to 1.5 × 10⁻⁴ (equilibrium mole fraction), at 308–338 K and 120–300 bar. Also, obtained experimental values were correlated by two fugacity coefficient models (PR-EoS and SRK-EoS), and two activity coefficient models (modified Wilson and UNIQUAC). All these models could successfully correlate the Alderonate solubility values. Meanwhile, the solubility data obtained from the SRK-EoS (AARD% = 10.11) and modified Wilson's model (AARD% = 11.52) are more accurately fitted to the experimental data.