Physicochemical study of the interactions between Econazole and DL-α-Tocopherol with triblock copolymer aggregates in PBS media

Abstract

Solubilization enhancement of the pharmaceutical drug Econazole and vitamin E (DL-α-Tocopherol) in phosphate buffered saline aqueous media (PBS) at 298.15 K, due to the presence of aggregates of two triblock copolymers (F127 and P123), is reported. The increment in the solubility of the compounds as a function of the concentration of the triblock copolymer was determined by UV-Visible spectrophotometry. From these datum, the molar solubilization capacity, micelle–water partition coefficients and standard free energy of solubilization for each of the compounds in the different triblock copolymer solutions is reported. The effect on the thermodynamics of aggregate formation due to the incorporation of the solute into the aggregate arrangement of the triblock copolymers was investigated using differential scanning calorimetry (DSC). From our results it is evident that the presence of the solute in the triblock copolymer aggregates disrupts the original arrangement of the aggregates free of the solute, since the thermodynamic parameters associated with the aggregate formation are modified e.g. the presence of the solute lowers the enthalpy of aggregation as well as the onset temperature of aggregate formation and in general the profile of the calorimetric trace is modified. The size of the aggregates loaded with the solute was established through the determination of their hydrodynamic diameter, obtained from dynamic light scattering (DLS) measurements carried out at 283.15, 298.15 and 313.15 K. The hydrodynamic diameters of the aggregates of the triblock copolymers loaded with Econazole are very similar to the diameters obtained for the aggregates which are solute free. These results indicate that the solute most be completely engulfed by the aggregate. In the systems where the solute is DL-α-Tocopherol, the resulting hydrodynamic diameters are very different from the values obtained for the pure triblock copolymers which suggests that the solute does not sit inside the aggregate but it must be intercalated between the triblock copolymer molecules or in positions where the normal arrangement is disrupted significantly. From in vitro drug release studies of the two solutes encapsulated in the aggregates of the triblock copolymers in PBS buffer media to simulate physiological conditions we have determined that their liberation profiles can be described in terms of the Korsmeyer-Peppas and Peppas-Fassihi models.