Amorphous Sugar Research Articles

Characteristics of amorphous matrices composed of different types of sugars in encapsulating emulsion oil droplets during freeze-drying

The encapsulation of emulsion oil droplets by amorphous sugar matrices, formed by freeze-drying, was investigated, with a focus on the influence of the type of sugar. An oil-in-water emulsion, comprised of linoleic acid methyl ester (LME) and sucrose monolaurate (SML) as an oil phase and surfactant, respectively, were freeze-dried in the presence of different types of sugars. LME-droplet encapsulation during and after freeze-drying were evaluated by FTIR analysis. The loss of LME largely occurred in the early stage of freeze-drying. The size distribution of the encapsulated LME droplets remained unchanged before and after freeze-drying in most cases. The encapsulated fractions of LME droplets could be correlated with the glass transition temperature of the sugars in the fully hydrated state (Tg*), and the existence of an optimum Tg* value for the sugar matrix was predicted. The encapsulation ability of an amorphous sugar matrix was maximized when mono- and polysaccharide were combined so as to give a value for Tg* of approximately −50°C, although, individually, mono- and polysaccharides were quite poor for oil droplet encapsulation. These findings suggest that the structural flexibility of the amorphous sugar matrix is a major determinant in oil droplet encapsulation by an amorphous sugar matrix during freeze-drying.

Effect of Storage Relative Humidity on Physical Stability of Dried Fig

The objective of this study was to assess the effect of storage condition (relative humidity) on the structural stability of dried fig. Moisture sorption isotherms of dried fig were obtained at 5, 25 and 40C. Dried fig, like most high-sugar content materials, showed a type I isotherm and the sorption capacity of the sample decreased with increasing the temperature. The glass transition temperature (T g) and the melting enthalpy (ΔH m) of dried figs equilibrated at different relative humidities were measured using differential scanning calorimetry (DSC). The percentage of crystallization was measured using wide angle X-ray diffraction (WAXD). It was revealed that the extent of sugar crystallization increased at the intermediate relative humidity region, as implied by WAXD. The same result was observed by measuring ΔH m using DSC. The impact of different relative humidities on the sugar crystallization was explained in terms of (T − T g). Practical Applications Fig is mostly used in dried form. Low molecular weight sugars are the major component of fig solid. The physical states of these sugars play an important role in stability of dried fig during storage. Changes in water content as a function of storage condition may lead to undesired physical properties in dried fig which is of great importance for its structure and quality. Water has a great plasticization effect on this fruit and distresses its T g. Crystallization of amorphous sugars is the most important issue for physical instability of dried fig and other dried fruits with high-sugar contents during storage. The rate and extent of this phenomenon increase at intermediate relative humidities and can be described in term of T − T g. The present results showed that intermediate storage relative humidities are critical for the physical stability of dried fig during storage.

Impact of compression, physical aging, and freezing rate on the crystallization characteristics of an amorphous sugar matrix

Amorphous matrices made up of sugar molecules, are frequently used in food and pharmaceutical industries. A drawback to their use is that they are susceptible to collapse, as a result of water uptake and an increase in temperature and subsequently crystallize. Herein, the crystallization characteristics of amorphous sugar (sucrose and α-lactose) preparations were analyzed, with the purpose of obtaining knowledge that could lead to the prediction of how long the amorphous state is retained under various conditions. The impact of compression, physical aging and freezing rate on the induction period (tind) for crystallization were examined. Freeze-dried sugar samples were compressed at 74 or 443MPa (5min) and then rehumidified at specified RHs. Some freeze-dried sucrose samples were physically aged, and alternatively freeze-drying was conducted under different conditions. The isothermal crystallization of the prepared samples at different temperatures (T), the glass transition and the crystallization temperature (Tcry) were measured, using differential scanning calorimetry. The compression markedly decreased the tind, while significantly lowered the hygroscopicity. Physical aging and slower-freezing also shortened the tind. The tind was found to be correlated exclusively with (Tcry–T), regardless of rehumidification, compression, sugar type, physical aging and freezing rate in the freeze-drying process.

Glass Transition Study in Model Food Systems Prepared with Mixtures of Fructose, Glucose, and Sucrose

The glass transition temperature of model food systems prepared with several glucose/fructose/sucrose mass fractions was studied using differential scanning calorimetry (DSC). A distance-based experimental design for mixtures of 3 components was used to establish the proportion of sugars of the model systems. Thus, 32 compositions including individual sugars and sugar mixtures, both binary and ternary were prepared and analyzed. Thermograms showing the complete process of heating-cooling-reheating were used to determine the precise glass transition temperature during cooling (T(g)(c)) or reheating (T(g)(H) in amorphous sugars. The Scheffe cubic model was applied to experimental results to determine the influence of sugar composition on the glass transition temperature (P < 0.05). The final model proved to be appropriate (R(2) > 0.97, CV < 9%, model significance <0.0001) to predict the T(g) values of any dry mixture of amorphous fructose, glucose, and sucrose.

Towards an improved calorimetric methodology for glass transition temperature determination in amorphous sugars

Measuring glass transition temperature is necessary for predicting the state and the behavior during the processing, distribution, and storage of many amorphous sugar-rich products. Therefore, the purpose of this study was to establish an improved calorimetric methodology to assess T g in amorphous sugars. This method was created through melting crystal with differential scanning calorimetry (DSC) using the same principle proposed by Jiang, Liu, Bhandari, and Zhou (2008. Impact of caramelization on the glass transition temperature of several caramelized sugars. Part I: chemical analyses. Journal of Agricultural and Food Chemistry, 56, 5138–5147). Thermogravimetric analysis with simultaneous DSC was required to characterize the melting and thermal degradation temperatures of sugars. Thermograms showing the complete process of heating–cooling–reheating are proposed to determine the precise glass transition temperature during cooling (T gC) or reheating (Tg H), and to verify if the processed amorphous samples were created with or without thermal degradation. The melting temperature has little effect on the T g value whereas the sugar was melted without thermal degradation. Thus, using this methodology the precise T g value of amorphous sugars can be determined.

Stability and Plasticizing and Crystallization Effects of Vitamins in Amorphous Sugar Systems

Increased molecular mobility and structural changes resulting from water plasticization of glassy solids may lead to loss of the entrapped compounds from encapsulant systems. In the present study, the stability of water-soluble vitamins, vitamin B(1) (vB(1), thiamin hydrochloride) and vitamin C (vC, ascorbic acid), in freeze-dried lactose and trehalose at various water activities was studied. Water sorption of lactose-vB(1), lactose-vC, trehalose-vB(1), and trehalose-vC systems was determined gravimetrically. Glass transition and crystallization of anhydrous and plasticized sugar-vitamin systems were determined using thermal analysis. Critical water activity was calculated using water sorption and glass transition data. The retention of the vitamins was measured spectrophotometrically. The results showed that the amorphous structure protected the entrapped vitamins at low a(w). Crystallization of lactose accelerated vitamin degradation, whereas trehalose retained much higher amounts of the vitamins. Glass transition and critical water activity of solids and crystallization of component sugars should be considered in the stabilization of sensitive components.

Heterogeneity of the state and functionality of water molecules sorbed in an amorphous sugar matrix

An amorphous matrix, comprised of sugar molecules, is frequently used in the pharmaceutical industry. An amorphous sugar matrix exhibits high hygroscopicity, and it has been established that the sorbed water lowers the glass transition temperature Tg of the amorphous sugar matrix. It is naturally expected that the random allocation and configuration of sugar molecules would result in heterogeneity of states for sorbed water. However, most analyses of the behavior of water, when sorbed to an amorphous sugar matrix, have implicitly assumed that all of the sorbed water molecules are in a single state. In this study, the states of water molecules sorbed in an amorphous sugar matrix were analyzed by Fourier-transform IR spectroscopy and a Fourier self-deconvolution technique. When sorbed water molecules were classified into five states, according to the extent to which they are restricted, three of the states resulted in a lowering of Tg of an amorphous sugar matrix, while the other two were independent of the plasticization of the matrix. This finding provides an explanation for the paradoxical fact that compression at several hundreds of MPa significantly decreases the equilibrium water content at a given RH, while the Tg remains unchanged.

Effect of Sugar Additives on Stability of Human Serum Albumin during Vacuum Foam Drying and Storage

No literature on the protein stabilization of human serum albumin (HSA) by vacuum foam drying (VFD) has been reported. The purpose of this study was to investigate the effect of sugar-additive systems on the stability of HSA by VFD. For the assessment, HSA was formulated with sucrose and mannitol, respectively, alone or in combination with stabilizers, which were vacuum foam dried and stored at 25C. Protein content of the resulting dried formulations was analyzed by Lowry method. Fourier-transform infrared spectroscopy (FT-IR) analysis of the HSA secondary structure showed apparent protein structure-stabilizing effects of the amorphous sugar and phosphate combination during the VFD. In particular, sucrose-sodium phosphate monobasic mixture provide an interesting alternative to pure saccharide formulations due to their high glass transition temperatures and their increased ability to maintain a low melting transition temperature in the presence of small amounts of water. Inhibition of the sucrose crystallization in solutions under vacuum resulted in highly amorphous sucrose. Changes in the endothermic melting transition suggested reduced sucrose molecular mobility with increase in the sodium phosphate ratio. The addition of phosphate salts to sugar systems has several interesting features that merit its consideration in formulations to protect dehydrated labile biomaterials. In conclusion, our data suggest that sucrose and phosphate as additives seem to protect HSA during VFD better than lyophilized products and also maintain its stability in the VFD state during storage.

Low temperature fabrication of biodegradable sugar glass microneedles for transdermal drug delivery applications

Transdermal drug delivery is limited by the barrier properties of the outer skin layer. Microneedles (MNs) effectively circumvent the skin barrier to offer this route as a potential alternative to oral and parenteral delivery of therapeutics. Biodegradable microneedles offer particular advantages however processing commonly requires elevated temperatures that may adversely affect heat-labile molecules and macromolecules. In this study, solid amorphous sugar glasses containing low residual quantities of water were created by dehydration of trehalose and sucrose sugar combination solutions. Biodegradable sugar glass MNs were fabricated following optimisation of a simple and novel low temperature vacuum deposition micromoulding methodology. These had absolute morphological fidelity to silicon master structures and demonstrated sufficient structural rigidity to efficiently penetrate excised human breast skin. Sugar glass MNs incorporating a marker compound dissolved rapidly and completely in situ releasing dye into deeper skin layers. The biological activity of a model macromolecule was partially retained over extended storage following incorporation into sugar glass. This is the first demonstration that MNs created from amorphous sugar glasses can be used for incorporating and delivering molecules, and potentially biologically active macromolecules, via the transdermal route.

Synthesis and characterisation of exfoliated layered double hydroxide (LDH) / sugar nanocomposites

Abstract : In this study the preparation of layered double hydroxide (LDH)/sugar nanocomposites using an exfoliated MgAl-lactate LDH (Mg: Al = 3:1) and a sugar (sucrose and maltose) as precursors is described. The products have been characterised by powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The properties of the composite materials have been further studied using differential scanning calorimetry (DSC). The expanded interlayer spacing of the lactate LDH suggests the intercalation of lactate ions within the gallery region. Stirring of the MgAl-lactate LDH in water for 24 hours at room temperature resulted in a clear colloidal dispersion. Upon solvent evaporation, the resulting material consisted of a disorganized restacked LDH phase. The most significant evidence for the formation of nanocomposites from the exfoliated clay materials is suggested by the absence of reflections associated with the LDH in the PXRD patterns. DSC results suggest that the glass transition temperatures of the composite materials with 5%, 10% and 20% LDH loading are superior to the parent maltose. Therefore, the LDH nanolayers give the LDH filled sugar nanocomposites better thermal stability than the pristine sugar, thus these composites could be used as drug excipients in the pharmaceutical industry. Keywords : Amorphous sugar, exfoliation, layered double hydroxides, nanocomposites, thermal stability. Doi: 10.4038/jnsfsr.v39i2.3171 J.Natn.Sci.Foundation Sri Lanka 2011 39 (2): 113 - 119

Surface protein coverage and its implications on spray-drying of model sugar-rich foods: Solubility, powder production and characterisation

We have investigated the amount of protein required to produce amorphous sugar powders through spray-drying. Pea protein isolate was used as a model plant protein and sodium caseinate was used as a model dairy protein. Powder recovery in a laboratory spray dryer was used as a measure of the ease of spray drying for a given formulation. More than 80% of amorphous sucrose and fructose was produced with the addition of sodium caseinate, while the pea protein isolate was able to produce only recoveries of less than 50% of amorphous sucrose. Sensitivity of low molecular weight surfactants has been demonstrated using both ionic (sodium stearoyl lactylate) and non-ionic (polysorbate-80) surfactants. Spray-dried powders were subjected to physico-chemical characterisation and dissolution experiments. The maximum solubility of all powders was obtained after 5min of dissolution. The solubility of the sodium caseinate increased by 6–7% in the presence of fructose and low molecular weight surfactants. The solubility of the amorphous powders of sucrose–pea protein isolate was found to be lower than amorphous powders of sucrose–sodium caseinate and fructose–sodium caseinate. The addition of sucrose in water increased the solubility of the pea protein isolate from 16.84% to more than 83%. The non-ionic surfactant (Tween-80) has reduced the solubility of sucrose–pea protein isolate–Tween-80 powders significantly (p<0.05) compared to those of sucrose–pea protein isolate–sodium stearoyl lactylate powders. The solubility of sucrose–sodium caseinate powders was comparable to that of pure sodium caseinate, indicating that addition of sucrose into 0.13% sodium caseinate does not have any significant effect on the solubility of this protein at this concentration.

Influence of compression on water sorption, glass transition, and enthalpy relaxation behavior of freeze-dried amorphous sugar matrices

An amorphous matrix comprised of sugar molecules are frequently used in the pharmaceutical industry. The compression of the amorphous sugar matrix improves the handling. Herein, the influence of compression on the water sorption of an amorphous sugar matrix was investigated. Amorphous sugar samples were prepared by freeze-drying, using several types of sugars, and compressed at 0–443MPa. The compressed amorphous sugar samples as well as uncompressed samples were rehumidified at given RHs, and the equilibrium water content and glass transition temperature (Tg) were then measured. Compression resulted in a decrease in the equilibrium water content of the matrix, the magnitude of which was more significant for smaller sized sugars. Diffusivity of water vapor in the sample was also decreased to one-hundredth by the compression. The Tg value for a given RH remained unchanged, irrespective of the compression. Accordingly, the decrease in Tg with increasing water content increased as the result of compression. The structural relaxation of the amorphous sugar matrices were also examined and found to be accelerated to the level of a non-porous amorphous sugar matrix as the result of the compression. The findings indicate that pores contained in freeze-dried sugar samples interfere with the propagation of structural relaxation.

Mobility in Amorphous Biomaterials: Microstructure, Temperature, and Interaction Among Components

Mobility in amorphous solid sugars and proteins influences the rates of chemical reactions and physical processes; we have studied the relation between mobility, structure, and rate in amorphous sugar and protein films. Phosphorescence emission and intensity decay from erythrosin B were used to monitor the temperature dependence of mobility in glucose/glycerol films. Glycerol plasticized at both low (mole ratio 1/10 glycerol/glucose) and high (mole ratio 1/2) glycerol content. The IR hydrogen bond bandwidth increased with increasing glycerol, suggesting that the strength of the bond became more widely distributed with added plasticizer. An increase with temperature in the hydrogen bond peak frequency indicated a decrease in the number of hydrogen bonds at higher temperatures. AFM images reveal no evidence for phase separation in the microstructure of films. We have also prepared thin films from zein dissolved in 70% ethanol/water by spreading and drying concentrated protein solutions on quartz slides; films contained 25 % (w/w) glycerol and different contents of the antioxidants propyl gallate and octyl gallate. The oxygen diffusion and mobility of these films were measured using phosphorescence from dispersed erythrosin B. Although both antioxidants increased the mobility of the zein matrix to about the same extent, octyl gallate, but not propyl gallate, dramatically increased the permeability of oxygen. AFM imaging indicated that propyl gallate induced aggregation of zein complexes, which could lead to more condensed film. We used a fluorescein model for photobleaching to test the performance of these antioxidants in the zein films. In this model fluorescein was used to generate singlet oxygen, which then attacks the probe to destroy fluorescence, while antioxidant clears the singlet oxygen to protect fluorescein from being destructed. Results indicate that propyl gallate provided better protection against photobleaching than octyl gallate at low concentrations.

Multiple States of Sorbed Water Molecules in Amorphous Sugar Matrix and Their Different Impacts on Physical Properties of the Matrix

Multiple States of Sorbed Water Molecules in Amorphous Sugar Matrix and Their Different Impacts on Physical Properties of the Matrix

Water Sorption Glass Transition Protein-Stabilizing Behavior of an Amorphous Sucrose Matrix Combined With Various Materials

The effects of various additives on the physical properties of an amorphous sugar matrix were compared. Amorphous, sugar-additive mixtures were prepared by freeze-drying and then rehumidified at given RHs. Sucrose and eighteen types of substances were used as the sugar and the additive, respectively, and water sorption, glass-to-rubber transition, and protein stabilization during freeze-drying for the various sucrose-additive mixtures were examined. The additives were categorized into two groups according to their effects on T(g) and water sorption. Presence of polysaccharides, cyclodextrins, and polymers (large-sized additives) resulted in a decrease in equilibrium water content from the ideal value calculated from individual water contents for sucrose and additive, and in contrast, low MW substances containing ionizable groups (small-ionized additives) resulted in an increase. The increase in T(g) by the addition of large-sized additives was significant at the additive contents >50 wt.% whereas the T(g) was markedly increased in the lower additive content by the addition of small-ionized additives. The addition of small-ionized additives enhanced the decrease in T(g) with increasing water content. The protein stabilizing effect was decreased with increasing additive content in the cases of the both groups of the additives.

The use of dynamic vapour sorption methods for the characterisation of water uptake in amorphous trehalose

Water uptake by amorphous sugars is an issue of high importance for the food and pharmaceutical industries. However, while the processes associated with sorption-induced crystallisation have been widely studied, little is known regarding the uptake mechanisms associated with pre-crystallisation water levels. In the present investigation we use dynamic vapour sorption to study the water uptake mechanisms associated with amorphous trehalose. More specifically, we have prepared spray-dried amorphous trehalose with three initial water contents and studied water uptake as a function of time and relative humidity. We model the data obtained prior to crystallisation and suggest two mechanisms that are based on Type II diffusion (using the Peleg equation), which predominates under high humidity conditions (50% RH and above), while we use a Type I Fickian diffusion expression to model uptake under low relative humidity conditions (40% RH and below). The model allows prediction of equilibrium sorption values which correlate well with previously published data calculated from equilibrium vapour pressure data. We also note that the water content following recrystallisation is greater than that predicted by the stoichiometric ratio. A novel model is suggested whereby recrystallisation onset times may be estimated from the vapour sorption data. In conclusion the study has demonstrated that pre-crystallisation water sorption may be associated with two mechanisms depending on the humidity conditions and that such modelling allows insights into both the mechanisms of uptake and the storage behaviour of amorphous sugar samples.

The Effect of Molecular Size on Molecular Mobility in Amorphous Oligosaccharides

The physical properties and especially the molecular mobility of amorphous carbohydrate matrixes directly influence the stability of foods, feeds, and pharmaceuticals and the dessication tolerance of animals and plants during anhydrobiosis. Phosphorescence of the sodium salt of erythrosin B was used to investigate the local molecular mobility in pure amorphous solids of a homologous series of malto-oligosaccharides (maltose, G2; maltotriose, G3; maltotetraose, G4; maltopentaose, G5; maltohexaose, G6; and maltoheptaose, G7); sucrose and maltodextrin DE18 (a hydrolytic fraction of starch) were investigated for comparison. Measurements of the temperature-dependence of the phosphorescence emission energy, an indicator of the extent of local dipolar relaxation, and the phosphorescence emission lifetime, an indicator of the rate of collisional quenching of the excited state by matrix molecules, demonstrate that the local matrix molecular mobility increases with molecular size, and thus, with an increase in T g, in these glucose oligosaccharides. Master curves of the spectroscopic measures of matrix mobility for each oligosaccharide, plotted against T–T g, were not superimposable, suggesting that local properties of the amorphous sugar matrixes, rather than T g per se, influence local matrix mobility. Indicators of spectral heterogeneity also varied with molecular size, indicating that dynamic site heterogeneity also increased with molecular size and thus, T g. These results emphasize the importance of additional research in developing appropriate “molecular rules” for designing amorphous matrix systems with better long-term stability for foods, feeds, or pharmaceuticals.

A Review of A Molecular Dynamics Simulation Study Concerning Thermal Stabilization of Proteins by Amorphous Sugars

A Review of A Molecular Dynamics Simulation Study Concerning Thermal Stabilization of Proteins by Amorphous Sugars

Development of Rapidly Disintegrating Oral Tablets Using Crystalline Transition of Amorphous Sugar

Development of Rapidly Disintegrating Oral Tablets Using Crystalline Transition of Amorphous Sugar

Temperature scanning FTIR analysis of secondary structures of proteins embedded in amorphous sugar matrix

Heat-induced changes in secondary structures of five proteins (bovine serum albumin, BSA; human serum albumin, HSA; myoglobin; ribonuclease A, RNase A; and, β-lactoglobulin, β-Lg) in an amorphous sugar matrix were analyzed by temperature-scanning Fourier transform infrared spectroscopy to elucidate the mechanism of heat-induced conformational change of solid-phase proteins. Three sugars, trehalose, maltose, and dextran (MW 6000), were used. Loss of α-helices due to increasing temperature was observed for BSA, HSA, and myoglobin, which are rich in α-helices. RNase A showed a marked decrease in predominant secondary structural components (β-sheet) with increasing temperature. However, no noticeable changes in the content of secondary structures, except for a slight loss of α-helices, were observed for β-Lg, which is also β-sheet-rich. These heat-induced conformational changes were significant at temperatures above the glass transition temperature. The heat-induced conformational change in BSA dried with sugar appeared time-independent and was clearly different from that due to dehydration and from the thermal conformational change for a solution of BSA. In particular, differences in secondary structural components that increased due to loss of α-helices were noted. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3088–3098, 2009