SELF-ASSOCIATION OF DEXVERAPAMIL IN AQUEOUS-SOLUTION

The pK(a) and intrinsic solubility of monomeric dexverapamil were dete rmined from its pH-solubility profile to be 8.90 and 6.6 x 10(-5) M, r espectively. The solubility of dexverapamil below pH 7.0 was higher th an expected on the basis of the aforementioned values. This unusually high solubility is believed to be due to the self-association of catio nic dexverapamil. The apparent pK(a) of the self-associated drug is es timated to be similar to 7.99. The self-association of dexverapamil hy drochloride is supported by the fact that it is surface active and tha t it increases the solubility of both naphthalene and anthracene in aq ueous solutions. The dependence of the drug solubility on pH and the s olubilization of naphthalene and anthracene as a function of ionized d rug concentration suggest that the self-associated dexverapamil is a c ationic dimer.