Solubilization and co-solubilization of carbamazepine and nifedipine in mixed micellar systems: insights from surface tension, electronic absorption, fluorescence and HPLC measurements

Abstract

UV absorption spectral and HPLC study on the solubilization and co-solubilization behavior of antiepileptic drug Carbamazepine (CBZ) and calcium channel blocker Nifedipine (NFD), which are reported to have a synergistic potentiation, was carried out in sodium cholate based binary and ternary mixed micellar systems with non-ionic polysorbate (Tween20, Tween40) and polyoxyethylene (Brij30, Brij35, Brij56 and Brij58) surfactants. The surfactant–surfactant interactions and their effect on the aggregation number, solubility of drugs, solubilization site, surfactant–drug interactions and drug–drug interactions were evaluated and explained. Synergism in mixed micellization increases the aggregation number and decreases the polarity of palisade layer resulting in enhancement of core solubilization of drugs with concomitant decrease in palisade layer solubilization. In the C₁₂ series, CBZ shows a decrease in solubility upon surfactant mixing, indicating an appreciable solubilization in the palisade layer, whereas in the C₁₆ series an increase in its solubility was observed. For NFD, a decrease in solubility follows the trend of synergism in mixed micellization, which is more for strongly interacting surfactant systems. During co-solubilization, because CBZ occupies preferentially the palisade layer, its solubility is decreased and the solubilization of NFD, which mainly occurs within the micellar core, is favored. The magnitude of drug–drug interactions increases in mixed micelles and is more for the surfactant systems, showing more synergism in the mixed micelle formation. The mixed micellar media used in the present study, being biocompatible, are expected to be employed as solubilization and drug delivery vehicles for co-administration of these two drugs in vivo.