Procaine, a widely used local anesthetic, suffers from slow onset and rapid degradation into para-aminobenzoic acid and diethylaminoethanol, resulting in a brief half-life and short duration of action. In this study, we investigate salification in order to modify dissolution rate and permeability without altering the chemical structure or using complex formulations. Six procaine salts with carboxylic acids and four with sulfonic acids were prepared and systematically evaluated in comparison with procaine hydrochloride, focusing on their in-vitro pharmacokinetic properties in two physiological conditions at pH 4.5 and 7.4. Dissolution rate studies showed that all procaine salts achieved complete dissolution within 30 min, while procaine reached 75 % dissolution and remained partially undissolved even after 2 h. In addition, permeability studies revealed a range of permeation values among the different procaine salts, in which sulfonate anions significantly improved the permeability of procaine by approximately 40 % to 70 %. Furthermore, a correlation between permeability and lipophilicity descriptors was assessed, with particular attention to ion pair stability, the lipophilicity of the counterion and the lipophilicity of procaine in its neutral form. Notably, salts with higher permeability, primarily sulfonates, exhibited less stable ion pairs, contributing to a more effective drug diffusion and a potential for faster onset and absorption of procaine. On the other side, carboxylic acids tend to confer a higher ion pair stability, inhibiting the membrane permeation. Our findings support the canonical model of passive permeability, suggesting that the neutral form of the drug can form in response to local environmental conditions near the membrane or within the transmembrane compartment. In this context, both the neutral form and the ion pair could contribute and play a role as a part of the equilibrium of partitioning across the membrane.