Molecular dynamics in amorphous double active ionic liquid developed by chemical structural modification of ibuprofen

Ibuprofen is a non-steroidal anti-inflammatory drug categorized as a Class II Biopharmaceutics Classification System (BCS) pharmaceutical with low solubility and high permeability. Though the drug and its salt form are glass-forming, but not physically stable in their amorphous state, which limits their use as amorphous drugs. In this study, a dual-active pharmaceutical ingredient, metforminium ibuprofe-nate (MtHIb), was prepared by chemical structural modification of sodium ibuprofen (NaIb) with metformin hydrochloride (MtHCl) by a stochiometric metathesis reaction. Information on translational and rotational mobility of both daughter and parents has been obtained from broadband dielectric spectroscopy (BDS) covering a wide temperature and frequency regimes in supercooled and glassy states in conjunction with quantum mechanical calculations. The temperature dependence of alpha-relaxation times was described by Vogel-Fulcher-Tammann equation. The glass transition temperature for MtHCl and MtHIb were found to be 269.45 and 227.24 K, respectively, which is in good agreement with the DSC thermogram with a slight discrepancy. The fragility index of ibuprofen is found to decrease upon the modification and attained 50.39 for MtHIb indicating its strong glass-forming nature which is well evidently supported by broad diffraction peaks in X-ray diffraction patterns of MtHIb. These results demonstrate that chemical structural modification of ILs can be considered a proven strategy for inhibit-ing the devitrification of disordered pharmaceuticals to control or bypass the secondary relaxations in the glassy state by modification of its structure. These remarkable outcomes had an impact on the fundamental understanding of amorphous pharmaceuticals on the industrial front. (c) 2022 Elsevier B.V. All rights reserved.

Automated summary

In this study, a dual-active pharmaceutical ingredient, metforminium ibuprofenate (MtHIb), was prepared by chemical structural modification. The properties of MtHIb in the glassy state were investigated using experimental and computational methods. The results demonstrate that chemical structural modification can effectively control the secondary relaxations of amorphous pharmaceuticals, which is of great significance for understanding these materials.