Elsevier

Carbohydrate Research

Volume 346, Issue 14, 18 October 2011, Pages 2193-2199
Carbohydrate Research

Characterization of the hidden glass transition of amorphous cyclomaltoheptaose

https://doi.org/10.1016/j.carres.2011.07.010Get rights and content

Abstract

An amorphous solid of cyclomaltoheptaose (β-cyclodextrin, β-CD) was formed by milling its crystalline form using a high-energy planetary mill at room temperature. The glass transition of this amorphous solid was found to occur above the thermal degradation point of the material preventing its direct observation and thus its full characterization. The corresponding glass transition temperature (Tg) and the ΔCp at Tg have, however, been estimated by extrapolation of Tg and ΔCp of closely related amorphous compounds. These compounds include methylated β-CD with different degrees of substitution and molecular alloys obtained by co-milling β-CD and methylated β-CD (DS 1.8) at different ratios. The physical characterization of the amorphous states have been performed by powder X-ray diffraction and differential scanning calorimetry, while the chemical integrity of β-CD upon milling was checked by NMR spectroscopy and mass spectrometry.

Introduction

Cyclomaltoheptaose (β-cyclodextrin, β-CD), is a cyclic oligosaccharide produced by enzymatic degradation of starch. It consists of seven d-glucose units linked by α-(1→4) glycosidic bonds.1, 2, 3 This molecule is well known for its ability to form inclusion complexes with several kinds of guest molecules,1, 2, 3 which makes it very useful in textile,4 biomedical,5, 6, 7, 8 pharmaceutic,9, 10, 11, 12 food12 and cosmetic12, 13 applications.

Up to now, the crystalline state of β-CD has been widely studied14, 15 while little is known about the physical characteristics of amorphous β-CD. Such a situation is likely to be due to the impossibility of obtaining amorphous β-CD by the usual thermal quench of the liquid phase because of the severe thermal degradation of this material that occurs before melting. Moreover there has been no investigation dedicated to the physical characterization of amorphous β-CD itself, and only scarce information can be drawn indirectly from papers investigating the complexation of β-CD with a guest molecule.16, 17, 18 In these studies the amorphization of the material arises from the freeze-drying procedure used to achieve the complexed solids. Li et al.16 were the first to propose a glass transition temperature (Tg) for amorphous β-CD. In that case, the glass transition was investigated by a thermally stimulated current, and Tg was found to be close to 50 °C. The authors also indicate that it was not possible to observe sufficient heat capacity change at Tg to characterize the glass transition by the usual differential scanning calorimetry (DSC) technique. In another study, Mazzobre et al.17 have determined the glass transition temperature of amorphous β-CD by DSC for different relative humidities ranging from 10% RH to 100% RH. The extrapolation of their data to RH = 0% leads to a Tg value located between 200 and 250 °C, which is so much higher than that previously reported by Li et al. Another investigation performed by Topchieva et al.18 localizes the Tg of amorphous β-CD between 30 and 60 °C. However, this study concerns amorphous β-CD complexed with proxanol, and until now, nothing is known concerning the influence of complexation on the glass transition of β-CD. It thus clearly appears that the glass transition temperatures (Tg) of β-CD remains loosely defined as values reported in the literature range from 30 °C up to 250 °C.16, 17, 18, 19 Moreover, nothing is known concerning the amplitude of the jump of the specific heat at TgCp(Tg)). A much better knowledge of the main physical parameters of amorphous β-CD is thus required to control this out of the equilibrium state.

In this paper, we test the possibility to amorphize β-CD by milling in order to determine the main physical characteristics of the amorphous state. Such a technique has already been applied to amorphize several pharmaceutical materials undergoing chemical degradation upon heating or undergoing chemical changes upon dissolution.20, 21, 22 Special attention will be paid to the determination of the glass transition temperature and the ΔCp(Tg). As it will appear below, this determination could not be performed directly on pure β-CD because of degradation events occurring before reaching Tg. This intrinsic difficulty will be overcome by extrapolation of the glassy characters of closely related compounds. These compounds include methylated β-CD (Me-β-CD) and Me-β-CD/β-CD molecular alloys. The mixed amorphous compounds are obtained by co-milling the pure compounds at room temperature to avoid high-temperature degradation. The milling and co-milling operations are performed with a high-energy planetary mill, and the characterization of the milled samples have been performed by Nuclear Magnetic Resonance (NMR), mass spectrometry, DSC, thermogravimetric analysis (TGA) and powder X-ray diffraction (PXRD).

Section snippets

Materials

Native β-CD and partially methylated Me-β-CD (DS 0.57) used in this work were provided by Roquette (Crysmeb®, Lestrem, France). Another partially methylated Me-β-CD (DS 1.8) was purchased from Wacker Chemie AG (Cavasol W7M®, Burghausen, Germany). Before use, the samples were systematically dried for 1 h at 90 °C. Maltodextrin (dextrose equivalent 19), a starch oligomer that presents a linear structure was used as a cyclodextrin analogue and was provided by Roquette (Glucidex®19, Lestrem, France).

Chemical characterization of milled β-CD

First, the chemical stability of β-CD under milling conditions was checked by NMR and MS analyses.

Figure 2 shows the NMR spectra of β-CD before and after milling, and maltodextrin which could potentially be produced during milling by breaking the β-CD rings. The best comparison point is provided by the 1H NMR chemical shift of anomeric carbon (C-1) hydroxyl group. For β-CD before and after milling, H-1 appears as a doublet at 4.95 ppm. In the case of maltodextrin H-1 appears as a doublet at 5.16 

Conclusion

In this paper, we have shown that β-CD undergoes a direct crystal-to-glass transformation upon mechanical milling at room temperature. This solid-state amorphization route appears to be an original alternative to the usual thermal quench of the liquid state that cannot be used in the present case since β-CD degrades totally before melting. Chemical degradation is even found to occur before the glass transition temperature of amorphous β-CD. This makes impossible the direct observation and

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