Correlations between substituent parameters of 4-substituted benzoic acids and their in vitro dissolution and partitioning.

The in vitro dissolution and partitioning of some 4-substituted benzoic acids from nondisintegrating disks was investigated using a water-octanol system. The rates of appearance of benzoic acids in the aqueous phase differed from the rates of appearance in octanol, probably due to back-transfer from the octanol phase. The suitability of the procedure for investigating the influence of molecular modification on in vitro dissolution and partitioning is considered. Correlations among the rates of appearance in octanol, the rates of appearance in an aqueous phase, and substituent parameters of benzoic acids were investigated. The best statistical fit was obtained using molecular orbital substituent indexes.