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Acetylpromazine is a phenothiazine derivative that is prone to form sub-micellar aggregates and micelles in water above pH 5. This study revisits the determination of the equilibrium constants (Avdeef et al., ADMET DMPK 4:117-178, 2016) describing the complex speciation of acetylpromazine maleate in saturated water solutions. The solubility data of Liu and Hurwitz (J Colloid Int Sci 60:410-413, 1977) were re-analyzed, with the purpose of developing an improved understanding of how activity corrections, plus the amount of added excess salt, change the value of the solubility product of the maleate salt and to what extent the sub-micellar aggregates affect the solution equilibria at levels above the critical micelle concentration (CMC). The solubility measurements below CMC in alkaline solutions were used to re-determine both the pKa and the intrinsic solubility of acetylpromazine, using a novel indirect procedure independent of the Henderson-Hasselbalch equation. The data above the CMC in the acidic pH domain were used to determine the solubility product, Ksp, of the acetylpromazine maleate salt, plus the equilibrium constants of two newly-proposed solubility-enhancing cationic sub-micellar species. To compensate for the wide variation in ionic strength, I, on the activities of species, a modified Stokes-Robinson hydration theory was used to estimate activity coefficients. Below pH 2.5, a newly proposed trimer of protonated acetylpromazine and uncharged maleic acid species, with a + 3 overall charge, rationalized the solubility profile. Also, between pH 5 and 7, a newly proposed 11-monomer acetylpromazine species (comprising eight protonated acetylpromazine, three free base components, plus two monohydrogen maleate anions, bearing a + 6 net charge) better rationalized the solubility profile in the sub-micellar zone than the previous (2016) model. It is evident that the Ksp (even when harmonized to I = 0.15 M) is not strictly constant, which can be partly explained by ion-solvent interaction activity effects. Since the pKa of maleic acid is much lower than pHmax, the alkalimetric titration of the salt releases hydrogen maleate that spontaneously dissociates. The released H+ acts as a counter-titrant, creating a titration zone where pH and solubility remain invariant beyond the point where all salt is dissolved. This phenomenon is quite different from the traditional Gibbs phase rule associated with pHmax. This study aims to provide new perspectives to aid in the analysis, interpretation, and assay design of solubility measurements of surface-active druglike molecules, that would better match the conditions found in biological media, potentially improving applications of solubility in pharmaceutical research and development, especially in early considerations of formulation strategies. Graphical Abstract