Novel inclusion complex of ibuprofen tromethamine with cyclodextrins: Physico-chemical characterization

Abstract

Guest–host interactions of ibuprofen tromethamine salt (Ibu.T) with native and modified cyclodextrins (CyDs) have been investigated using several techniques, namely phase solubility diagrams (PSDs), proton nuclear magnetic resonance ( 1H NMR), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffractometry (XRPD), scanning-electron microscopy (SEM) and molecular mechanics (MM). From the analysis of PSD data (A L-type) it is concluded that the anionic tromethamine salt of ibuprofen (p K a = 4.55) forms 1:1 soluble complexes with all CyDs investigated in buffered water at pH 7.0, while the neutral form of Ibu forms an insoluble complex with β-CyD (B S-type) in buffered water at pH 2.0. Ibu.T has a lower tendency to complex with β-CyD ( K 11 = 58 M −1 at pH 7.0) compared with the neutral Ibu ( K 11 = 4200 M −1) in water. Complex formation of Ibu.T with β-CyD (Δ G° = −20.4 kJ/mol) is enthalpy driven (Δ H° = −22.9 kJ/mol) and is accompanied by a small unfavorable entropy (Δ S° = −8.4 J/mol K) change. 1H NMR studies and MM computations revealed that, on complexation, the hydrophobic central benzene ring of Ibu.T and part of the isobutyl group reside within the β-CyD cavity leaving the peripheral groups (carboxylate, tromethamine and methyl groups) located near the hydroxyl group networks at either rim of β-CyD. PSD, 1H NMR, DSC, FT-IR, XRPD, SEM and MM studies confirmed the formation of Ibu.T/β-CyD inclusion complex in solution and the solid state.