Experimental, modeling and molecular dynamics simulation of codeine phosphate dissolution in N-methyl-2-pyrrolidone + ethanol

Abstract

Background: There is only limited data for solubility of codeine phosphate in binary systems available, which comes with uncertainties about the prediction accuracy of common thermodynamic models.

Methods: This study investigated the codeine phosphate dissolution in N-methyl-2-pyrrolidone(NMP) and ethanol system using shake-flask method and mathematically described generated data by different thermodynamic models. The density as another property was also determined and fitted to the results of the Jouyban-Acree equation. The mean relative deviations were obtained to confirm the model’s accuracy. Moreover, ΔHº, ΔSº, and ΔGº of the dissolution of codeine phosphate in the NMP and ethanol system were calculated using the desired equations at Thm.

Results: The dissolution process of codeine phosphate was identified as endotherm, the solubility in the binary mixtures was best at higher mass fractions of NMP and finally, the model predictions were deemed as excellent based on a mean relative deviation that was generally below eight percent.

Conclusion: The results of this study could expand the available solubility database for codeine phosphate.