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. 2020 May 18;5(21):12073-12080.
doi: 10.1021/acsomega.0c00277. eCollection 2020 Jun 2.

Improvement of the Solubility and Evaluation of the Physical Properties of an Inclusion Complex Formed by a New Ferulic Acid Derivative and γ-Cyclodextrin

Nao Ikeda  1 , Yutaka Inoue  1 , Yuka Ogata  1 , Isamu Murata  1 , Xuan Meiyan  2 , Jun Takayama  2 , Takeshi Sakamoto  2 , Mari Okazaki  3 , Ikuo Kanamoto  1
Affiliations

Improvement of the Solubility and Evaluation of the Physical Properties of an Inclusion Complex Formed by a New Ferulic Acid Derivative and γ-Cyclodextrin

Nao Ikeda et al. ACS Omega. .

Abstract

Ferulic acid derivative 012 (FAD012) is a ferulic acid (FA) derivative. The current study prepared a solid dispersion of FAD012 and γ-cyclodextrin (γCD) and ground it using a three-dimensional ball mill (3DGM) to prepare an inclusion complex. This study also assessed the physicochemical properties such as solubility of that complex. A Job's plot indicated that FAD012 and γCD formed an inclusion complex at a molar ratio of 1:1. Phase solubility diagrams revealed that FAD012 produced a BS diagram. According to PXRD, FAD012 produced a diffraction peak at 2θ = 7.0° and γCD produced a diffraction peak at 2θ = 9.1°. Those two peaks were not produced by the 3DGM, but new peaks (2θ = 7.3 and 16.5°) were evident. DSC patterns revealed an endothermic peak due to the melting of FAD012 at 190 °C, but no endothermic peaks were evident with the 3DGM. NIR spectra of the 3DGM indicated that the methyl group of FAD012 produced a higher peak and that the OH groups of γCD produced a higher peak. 1H-1H ROESY NMR spectra (D2O) revealed cross peaks for protons of the methyl group of FAD012 and a proton (H-3) in the cavity of γCD, so FAD012 presumably interacts with the wide opening of the γCD torus. A solubility test (25 °C) indicated that solubility improved about 5-fold for the 3DGM in comparison to the solubility of FAD012 alone (about 140 μg/mL). Based on these findings, an FAD012/γCD complex was formed by cogrinding, and its solubility improved. These observations are expected to expand the usefulness of cogrinding of FAD012 with γCD using a 3D ball mill.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Proposed Structural Images of FAD012/γCD Complexes
Figure 1
Figure 1
Job’s plot of the FAD012/γCD systems. Results were expressed as mean ± SD (n = 3).
Figure 2
Figure 2
Phase solubility diagrams of FAD012/γCD. Results were expressed as mean ± SD (n = 3).
Figure 3
Figure 3
PXRD patterns of FAD012/γCD:(a) intact FAD012, (b) intact γCD, (c) PM (FAD012/γCD = 1:1), (d) 3DGMw (FAD012/γCD = 1:1), and (e) 3DGMnw (FAD012/γCD = 1:1).
Figure 4
Figure 4
DSC curves of FAD012/γCD systems: (a) intact FAD012, (b) intact γCD, (c) PM (FAD012/γCD = 1:1), and (d) 3DGMw (FAD012/γCD = 1:1).
Figure 5
Figure 5
FT-IR spectra of FAD012/γCD systems: (a) intact FAD012, (b) intact γCD, (c) PM (FAD012/γCD = 1:1), and (d) 3DGMw (FAD012/γCD = 1:1).
Figure 6
Figure 6
(a) NIR absorption spectra of FAD012/γCD systems observed at 4000–10,000 cm–1. (b) NIR absorption spectra of FAD012/γCD systems: (X) second differential near-infrared absorption spectra of FAD012/γCD observed at 8200–8800 cm–1; (Y) second differential near-infrared absorption spectra of FAD012/γCD observed at 4600–5400 cm–1; (Z) second differential near-infrared absorption spectra of FAD012/γCD observed at 4000–4600 cm–1.
Figure 7
Figure 7
SEM morphology of FAD012/γCD systems: (a) intact FAD012, (b) intact γCD, (c) PM (FAD012/γCD = 1:1), and (d) 3DGMw (FAD012/γCD = 1:1).
Figure 8
Figure 8
1H-1H ROESY NMR spectra of FAD012/γCD systems.
Figure 9
Figure 9
Chemical structures of (a) FAD012 and (b) γCD.
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