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Self-association of dexverapamil in aqueous solution
Y Surakitbanharn1, R McCandless, J F Krzyzaniak
1Department of Pharmaceutical Sciences, College of Pharmacy, University of Arizona, Tucson 85721, USA.
Journal of Pharmaceutical Sciences
|June 1, 1995
Summary
Dexverapamil exhibits higher solubility than predicted due to self-association into cationic dimers. This aggregation behavior influences its physicochemical properties and interactions in aqueous solutions.
Area of Science:
- Physical Chemistry
- Pharmaceutical Sciences
Background:
- Understanding drug solubility and aggregation is crucial for formulation.
- Dexverapamil's physicochemical properties require detailed investigation.
Purpose of the Study:
- To determine the pKa and intrinsic solubility of monomeric dexverapamil.
- To investigate the cause of dexverapamil's unexpectedly high solubility at lower pH.
- To characterize the self-association behavior of dexverapamil.
Main Methods:
- pH-solubility profiling to determine pKa and intrinsic solubility.
- Solubility studies of naphthalene and anthracene in the presence of dexverapamil.
- Surface activity measurements.
Main Results:
- Monomeric dexverapamil has a pKa of 8.90 and intrinsic solubility of 6.6 x 10(-5) M.
- Dexverapamil exhibits higher solubility below pH 7.0 than predicted, suggesting self-association.
- Apparent pKa of self-associated dexverapamil is approximately 7.99.
- Dexverapamil is surface-active and enhances the solubility of naphthalene and anthracene.
Conclusions:
- Dexverapamil self-associates into cationic dimers below pH 7.0, explaining its enhanced solubility.
- The self-association is pH-dependent and influences drug behavior in solution.
- Cationic dimer formation is supported by surface activity and solubilization effects.