Theoretical and experimental study on Chloroquine drug solubility in supercritical carbon dioxide via the thermodynamic, multi-layer perceptron neural network (MLPNN), and molecular modeling

ABSTRACT

The design and development of supercritical carbon dioxide (sc-CO2) based processes for production of pharmaceutical micro/nanoparticles is one of the interesting research topics of pharmaceutical industries owing to its attractive advantages. The solubility of drugs in sc-CO2 at different temperatures and pressures is an essential parameter which should be determined for this purpose. Chloroquine as a traditional antirheumatic and antimalarial agent is approved as an effective drug for the treatment of Covid-19. Pishnamazi et al. (Pishnamazi et al., 2021) measured the solubility of this drug in sc-CO2 at the pressure range of 120-400 bar and temperature range of 308-338 K, and correlated the obtained data using some empirical models. In this work, a comprehensive computational approach was developed to more accurately study the supercritical solubility of Chloroquine. The thermodynamic models include two equations-of-state based models (Peng-Robinson and Soave-Redlich-Kowang) and two activity coefficient-based models (modified Wilson's and UNIQUAC)), as well as, a multi-layer perceptron neural network (MLPNN)) were used for this purpose. Also, molecular modeling was performed to study the electronic structure of Chloroquine and identify the potential centers of intermolecular interactions during the dissolution process. According to the obtained results, all of the theoretical models can predict Chloroquine solubility in sc-CO2 with acceptable accuracy. Among these models, the MLPNN model possesses the highest precision with the lowest average absolute relative deviation (AARD%) of 1.76% and the highest Radj value of 0.999.