Experimental study and modeling of letrozole (anticancer drug) solubility in subcritical water: Production of nanoparticles using subcritical water precipitation method

Abstract

A green solvent anti-solvent precipitation was applied, for the first time, to precipitate nanoparticles of letrozole (LTZ) using subcritical water solutions. In this novel technology, subcritical water (SW) and cold water at ambient conditions used as solvent and anti-solvent, respectively, to improve the bioavailability of LTZ as a poorly water-soluble drug. The solubility of LTZ in SW was first measured at different temperatures (298.15–383.15 K) and at the constant pressure of 5 MPa using a static method. Furthermore, two semi-empirical models, including the linear and Apelblat models, were applied to correlate the drug solubility. The statistical result showed the superior performance of the Apelblat model. Then, the influence of procedure parameters, including SW temperature (363.15–383.15 K), polyethylene glycol concentration (0.01–0.03 wt%), and anti-solvent temperature (273.15–293.15 K) were studied on the size and the morphology of the precipitated drug nanoparticles. According to the results, excellent size reduction of the precipitated particles of LTZ from 20 μm (unprocessed drug) to about 79 nm was achieved using green technology with no need for organic solvents and post-processing purification stages.