TY - JOUR
T1 - Thermodynamic solubility of celecoxib in organic solvents
AU - Verma, Vivek
AU - Soto, Rodrigo
AU - Bhattacharya, Shayon
AU - Thompson, Damien
AU - Ryan, Kevin M.
AU - Padrela, Luis
N1 - Publisher Copyright:
© The Royal Society of Chemistry.
PY - 2022/1/21
Y1 - 2022/1/21
N2 - The present work investigates the solubility of the stable polymorph of celecoxib (CEL) drug in a range of pure organic solvents, including methanol, isopropanol, butanol, ethyl acetate, acetonitrile and toluene, within the temperature range 278-303 K. The solid form used has been characterized by SEM, PXRD, DSC, TGA, FTIR and Raman spectroscopy. The solid form studied exhibited a melting temperature of 437.45 K, with an associated melting enthalpy of 35.93 kJ mol-1. The experimental solubility data obtained was fitted to empirical and semi-empirical models, so that the parameters obtained enable the interpolation of further solubility data within the range explored. In the studied solvents, the solubility decreases in the order: ethyl acetate > acetonitrile > methanol > isopropanol > butanol > toluene. In all the solvents used, except for in toluene, the experimental solubility values are higher than the ideal ones, indicating negative deviation with respect to Raoult's law and favourable solute-solvent interactions. The solubility order of CEL in alcohols correlated well with the solvent polarity and this finding is complemented with the CEL-solvent interactions determined by molecular dynamics simulations. The high solubility of CEL in ethyl acetate is attributed to the similar Hildebrand solubility parameter of both species.
AB - The present work investigates the solubility of the stable polymorph of celecoxib (CEL) drug in a range of pure organic solvents, including methanol, isopropanol, butanol, ethyl acetate, acetonitrile and toluene, within the temperature range 278-303 K. The solid form used has been characterized by SEM, PXRD, DSC, TGA, FTIR and Raman spectroscopy. The solid form studied exhibited a melting temperature of 437.45 K, with an associated melting enthalpy of 35.93 kJ mol-1. The experimental solubility data obtained was fitted to empirical and semi-empirical models, so that the parameters obtained enable the interpolation of further solubility data within the range explored. In the studied solvents, the solubility decreases in the order: ethyl acetate > acetonitrile > methanol > isopropanol > butanol > toluene. In all the solvents used, except for in toluene, the experimental solubility values are higher than the ideal ones, indicating negative deviation with respect to Raoult's law and favourable solute-solvent interactions. The solubility order of CEL in alcohols correlated well with the solvent polarity and this finding is complemented with the CEL-solvent interactions determined by molecular dynamics simulations. The high solubility of CEL in ethyl acetate is attributed to the similar Hildebrand solubility parameter of both species.
UR - http://www.scopus.com/inward/record.url?scp=85123365537&partnerID=8YFLogxK
U2 - 10.1039/d1ce01415c
DO - 10.1039/d1ce01415c
M3 - Article
AN - SCOPUS:85123365537
SN - 1466-8033
VL - 24
SP - 698
EP - 710
JO - CrystEngComm
JF - CrystEngComm
IS - 3
ER -