Molecular Properties of Ibuprofen and Its Solid Dispersions with Eudragit RL100 Studied by Solid-State Nuclear Magnetic Resonance

Abstract

A combined analysis of several high-resolution solid-state nuclear magnetic resonance experiments allowed the investigation of the structural and dynamic properties of the pure drugs and of the solid dispersions with the polymer, as well as of the degree of mixing between drug and polymer and of the chemical nature of their interaction. Such information could be related to the in vitro drug release profiles observed for the tested co-evaporates.

Detailed Characterization of the Dynamics of Ibuprofen in the Solid State by a Multi‐Technique NMR Approach

“…976 www.chemphyschem.org isobutyl group (m, n) and of four distinct signals for the tertiary aromatic carbon atoms (d-g) clearly indicates that the interconformational motions of both the isobutyl group and the aromatic ring are frozen. It has been previously shown [6] that the motion of the isobutyl group remains frozen even at higher temperatures. On the contrary, from the occurrence of peak coalescence at temperatures just below the melting point, it has been inferred that the frequency of the aromatic ring motion reaches values of the order of 200 Hz.…”

“…Signal assignments are taken from ref. [6]. 976 www.chemphyschem.org isobutyl group (m, n) and of four distinct signals for the tertiary aromatic carbon atoms (d-g) clearly indicates that the interconformational motions of both the isobutyl group and the aromatic ring are frozen.…”

“…Ibuprofen is a famous nonsteroidal anti-inflammatory drug, which in a preliminary study [6] seemed to show an interesting dynamic behavior. The motions investigated in this work include rotations of molecular fragments about single bonds and interconformational jumps, characterized by frequencies ranging from hertz to gigahertz.…”

Rapid Analysis of Organic Compounds by Proton‐Detected Heteronuclear Correlation NMR Spectroscopy with 40 kHz Magic‐Angle Spinning

“…[14][15][16] Its 1 H and 13 C resonance assignments were completed only recently with the utilization of 1 H- 13 C HETCOR experiments, which have also been proven very powerful in discerning acid and sodium forms of ibuprofen. [14] However, prolonged data acquisition from three to six days was necessary for these 13 C-detected HETCOR experiments with more than 20 mg of sample. [14] With the sensitivity gain offered by 1 H detection, we acquired a high-quality 13 C-1 H HETCOR spectrum (Figure 1 a) in 33 min on 6 mg of ibuprofen formulation containing less than 4 mg of the API.…”

“…[14] However, prolonged data acquisition from three to six days was necessary for these 13 C-detected HETCOR experiments with more than 20 mg of sample. [14] With the sensitivity gain offered by 1 H detection, we acquired a high-quality 13 C-1 H HETCOR spectrum (Figure 1 a) in 33 min on 6 mg of ibuprofen formulation containing less than 4 mg of the API. Excipients do not interfere with the API peaks, since the former are observed in the chemical shift range consistent with carbohydrates; the excipients also have a significantly longer T 1 relaxation times in this instance.…”