Group contribution, the extended Hildebrand solubility (EHS) and the extended Hansen solubility approaches are utilised to estimate the solubility parameter value of trimethoprim. The solubility data in the binary solvent series showed peak solubility at the solubility parameter of solvent, 11.7 H. The regression expression on the lines of the EHS approach yielded 12.06 H. The data on the solubility of trimethoprim in individual solvents was processed as per the extended Hansen approach. The partial solubility parameters were obtained and are used to estimate the solubility parameter, 12.93 H. Extending the Flory-Huggins size correction to this approach gave a value of 10.95 H and improved the correlation coefficient by 3 percent. Partitioning of hydrogen bonding (four parameter approach) didn't improve the value.
Subrahmanyam, C. V. S., Prakash, K. R., & Rao, P. G. (1996). Estimation of the solubility parameter of trimethoprim by current methods. Pharmaceutica Acta Helvetiae, 71(3), 175-183. https://doi.org/10.1016/0031-6865(96)00015-5