Synergistic effect of polymer-drug self-assembly and hydrotropic complexation on the delivery of ibuprofen

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Journal of Pharmaceutical Research, Development and Practice,


Drug-loaded polymeric nanoconjugate is a valuable drug delivery strategy to enhance the effectiveness of poorly soluble drugs. This study investigates the synergistic effect of polymer-drug self-assembly and hydrotropic complexation, on conjugation efficiency and in vitro dissolution kinetics of ibuprofen. Ternary Ibuprofen-DEAE-Dextran-Nicotinamide nanoconjugates were prepared by hydrotropic solubilization and characterized via particle size measurement, zeta potential, conjugation efficiency, Scanning Electron Microscopy (SEM), Fourier Transform InfraRed (FTIR), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), dissolution and drug release kinetics. The formulation of ibuprofen-DEAE-Dextran conjugate reduced the size of ibuprofen (2.87 μm) significantly to 77.92 nm (272-fold) at 0.1% (2.0 x 10-3 mM) DEAE-Dextran concentration. The zeta potential values were relatively low (1.24 to +13.87 mV) indicating low repulsion stabilization. Conjugation efficiency increased to a maximum of 95.68% and particle size of nanoconjugates was in the range 77.92 ± 1.61 to 994.27 ± 91.85 nm. The surface morphologies were spherical. FTIR revealed the formation of an amide via electrostatic, hydrophobic and hydrogen bonding interaction between solubilized ibuprofen and the cationic polymer, DEAE-Dextran. DSC analysis showed that the nanoconjugates exhibited new broad and diffuse peaks. The TGA thermograms exhibited two steps degradation profile. Marked enhancement of drug release was achieved by this method. The mechanism of release was non-Fickian diffusion for lower concentrations of DEAE-Dextran, while super case II was exhibited by higher concentrations. This work shows the formulation of amorphous ibuprofen-DEAE-Dextran nanoconjugates via a combination of polymer-drug self-assembly and hydrotropic solubilization with the potential of improving the delivery of poorly soluble ibuprofen.



Ibuprofen, hydrotropic solubilization, nicotinamide, DEAE-Dextran, nanoconjugate