Single crystals of V ‐amylose complexed with fatty acids and ibuprofen

Abstract

Amylose, a mostly linear homopolymer of α(1,4)‐D‐glucose extracted from native starch, has the ability to form crystalline inclusion compounds with a large variety of small molecules. In these crystallosolvates, the so‐called “V‐amylose” occurs in the form of single helices and the ligands can be located inside the helices, in‐between or both [Lourdin et al., in “Starch ‐ Metabolism and Structure"", Springer Japan, 2015, p. 61]. In this study, we have crystallized fractions of native and in vitro ‐biosynthesized amylose in the presence of various fatty acids and ibuprofen, a widely used anti‐inflammatory drug [Yang et al., Starch‐Stärke 65 (2013), 593]. The morphology, structure and stoichiometry of the resulting lamellar single crystals were characterized using TEM imaging, electron and X‐ray diffraction, and solid‐state NMR. Dilute aqueous solutions of amylose (0.1 wt%) and fatty acids were briefly heated at 160°C, then kept at 90 or 100°C for 24 h. Crystallization occurred during the slow cooling to room temperature. Depending on the type of fatty acid and crystallization conditions, hexagonal or rectangular crystals, or a combination of both, were observed. Figure 1 shows examples of such lamellar crystals prepared from native amylose in the presence of stearic acid (C18). The hexagonal platelets crystallized by cooling the solution maintained at 90°C (Figure 1a) correspond to the so‐called “V H ” structure, i.e ., the compact hexagonal packing of 6‐fold amylose single helices (Figure 1b). The aliphatic part of the fatty acid would be included inside the helices while the polar head would remain outside [Godet et al., Carbohydr. Polym. 21 (1993), 91]. When the amylose/fatty acid mixture was kept at 100°C, the lamellar crystals formed upon cooling were rectangular and generally occurred as twinned assemblies (Figure 1c). The corresponding diffraction pattern suggested an orthorhombic unit cell (Figure 1d). After drying, the rectangular crystals yielded the diffraction pattern of the V H allomorph and cracks appeared parallel to the long axis, suggesting that a loss of guest and/or water molecules by evaporation promoted an anisotropic reorganization of the helices. This effect was well documented for crystals of V‐amylose complexed with n ‐butanol [Helbert et al., Int. J. Biol. Macromol. 16 (1994), 207]. The formation of these two types of morphology and structure could be reproduced with fatty acids with different chain lengths (C10‐C18). A solution of amylose was mixed with preheated ibuprofen at 90°C and V ibuprofen crystals formed upon slow cooling. The complex grew as flower‐like aggregates of long rectangular platelets (Figure 2a). The base‐plane electron diffraction pattern (Figure 2b) is identical to that recorded from complexes of V‐amylose with isopropanol [Nishiyama et al., Macromolecules 43 (2010), 8628]. The unit cell is thus orthorhombic and would contain 7‐fold amylose single helices. Ibuprofen would be located inside and between the helices, along with a number of water molecules. This tentative model should provide a better understanding of the interaction of ibuprofen with a starch matrix as well as its controlled release.