Impact of Pluronics of different structure on pharmacologically relevant properties of sulfasalazine and methotrexate

The work was focused on comprehensive evaluation and comparison of the effect of Pluronics of different architecture on the pharmacologically relevant properties of methotrexate and sulfasalazine. Solubility of drugs was measured in buffers pH = 1.6 and pH = 6.8 with variable amount of Pluronics L64, F68, F88 and F127. Solubilization capacity and micelle-water partition coefficients were estimated and analyzed. Influence of the length of poly(ethylene oxide) and poly(propylene oxide) fragments in the polymer structure on the solubilizing effect was revealed. The observed solubility increase in the presence of Pluronics follows the order F127 > F88 > F68 > L64. Interactions of methotrexate and sulfasalazine with Pluronic micelles were characterized. Binding mode and composition of micelle/drug aggregates were proposed. The effect of Pluronics on the permeability of drugs across the model barrier Permeapad (TM) was investigated. The decrease of the permeability coefficients was discussed in terms of the change of medium viscosity and interactions of the drugs with the micelles. (C) 2019 Published by Elsevier B.V.