Cinacalcet (CT) is an important drug for the treatment hyperparathyroidism. Only few studies havereported thepotential interaction between CT and other potentially coadministered drugs. In this study, the potential of invitro interaction between CT and DF sodium (DF-Na) was investigated. An ion pair salt of CT with DF was obtained by mixing the two compounds in solution; the product was fully characterized by HPLC analysis, UV, FTIR, NMR spectroscopy in addition to DSC. The solubility and partition coefficients were found to significantly decrease and increase, respectively, for the obtained ion pair salt in comparison to the parent compounds. Dissolution studies in phosphate buffer pH 6.8 revealed a significant decrease in the dissolution of an already poorly water soluble drug (decrease to ~20% of the original). Permeation studies, through Caco-2 cells monolayer, revealed a significant decrease in permeation of CT when coexisted with DF (almost to half). Apparent permeability coefficient (Papp) decreased from 3.6 × 10-6 to 1.8 × 10-6 cm/s. Interestingly, a structure for the formed CT-DF salt that could explain the above findings (increase in lipophilicity), could be proposed based on structural modelling, molecular dynamic simulations and NMR proton chemical shifts analysis.
Keywords: Cinacalcet; Diclofenac; Drug interaction; Ion pair; Molecular structure.
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