Experimental solubility and modeling of Crizotinib (anti-cancer medication) in supercritical carbon dioxide

Abstract

Measurement of saturation solubility of drugs in a supercritical fluid is an important parameter for the implementation of supercritical technology in pharmaceutical industry. CO2 is the most sorted substance as a supercritical fluid since it has attractive properties like easily achievable critical temperature, moderate pressure. Cancer is increasingly affecting the mankind, a proper dosage while treating would help in minimizing the drug usage. The bioavailability of the drug is mainly influenced by the drug particle size. An appropriate technology is always useful in making suitable drug particles; thus, supercritical fluid technology (SFT) is considered as promising technique for the production of micro and nanoparticles. Since, particle production process through SFT needs solubility information, appropriate solubility information is necessary. In the present work, Crizotinib (anti-cancer drug) solubility in supercritical carbon dioxide (scCO2) is measured and reported, for the first time. The obtained solubilities are at temperatures 308, 318, 328,338 K and pressures 12, 15, 18, 21, 24 to 27 MPa. The measured solubilities are ranged in terms of mole fraction from (0.483 × 10−5 to 0.791 × 10−5) at 308 K, (0.315 × 10−5 to 0.958 × 10−5) at 318 K, (0.26 × 10−5 to 1.057 × 10−5) at 328 K, (0.156 × 10−5 to 1.219 × 10−5) at 338 K. The cross over region is observed at 14.5 MPa. To expand the application of the solubility data, few important solubility models and three cubic equations of sate (cubic EoS) models along with Kwak and Mansoori mixing rules are investigated. Sublimation and salvation enthalpies of Crizotinib dissolution in scCO2 are calculated.