Self‐Association of Dexverapamil in Aqueous Solution

The pKaand intrinsic solubility of monomeric dexverapamil were determined from its pH–solubility profile to be 8.90 and 6.6 × 10−5M, respectively. The solubility of dexverapamil below pH 7.0 was higher than expected on the basis of the aforementioned values. This unusually high solubility is believed to be due to the self‐association of cationic dexverapamil. The apparent pKaof the self‐associated drug is estimated to be ∼7.99. The self‐association of dexverapamil hydrochloride is supported by the fact that it is surface active and that it increases the solubility of both naphthalene and anthracene in aqueous solutions. The dependence of the drug solubility on pH and the solubilization of naphthalene and anthracene as a function of ionized drug concentration suggest that the self‐associated dexverapamil is a cationic dimer.