Α-lactose Monohydrate Research Articles

Structure, Morphology and Surface Properties of α-Lactose Monohydrate in Relation to its Powder Properties

The particulate properties of α-lactose monohydrate (αLMH), an excipient and carrier for pharmaceuticals, is important for the design, formulation and performance of a wide range of drug products. Here an integrated multi-scale workflow provides a detailed molecular and inter-molecular (synthonic) analysis of its crystal morphology, surface chemistry and surface energy. Predicted morphologies are validated in 3D through X-ray diffraction contrast tomography. Interestingly, from aqueous solution fastest growth is found to lie along the b-axis, i.e. the longest unit cell dimension of the αLMH crystal structure reflecting the greater opportunities for solvation on the prism compared to the capping faces leading to their slower relative growth rates. The tomahawk morphology reflects the presence of β-lactose which asymmetrically binds to the capping surfaces creating a polar morphology. The crystal lattice energy is dominated by van der Waals interactions (between lactose molecules) with electrostatic interactions contributing the remainder. Predicted total surface energies are in good agreement with those measured at high surface coverage by inverse gas chromatography, albeit their dispersive contributions are found to be higher than those measured. The calculated surface energies of crystal habit surfaces are not found to be significantly different between different crystal surfaces, consistent with αLMH's known homogeneous binding to drug molecules when formulated. Surface energies for different morphologies reveals crystals with the elongated crystal morphologies have lower surface energies compared to those with a triangular or tomahawk morphologies, correlating well with literature data that the surface energies of the lactose carriers are inversely proportional to their aerosol dispersion performance.

Investigations on the dustiness of binary acetaminophen - lactose monohydrate powder blends

In this study, binary powder blends of acetaminophen (ACAM) and α-lactose monohydrate (LM) at different mixing ratios, with fine, medium-size, and coarse particles are investigated with a new two-chamber setup (TCS) to assess dustiness. The TCS consists of an emission and a detection chamber, allowing plain diffusive or convective particle transport. The aim is to compare the diffusive transport of ACAM with binary blends of ACAM and LM at different particle sizes and similar apparent density. Fine ACAM exhibits significantly higher dust emissions compared to medium and coarse ACAM. With increasing LM portion in the blends, ACAM dust emissions decrease. The blend of fine ACAM and coarse LM shows the highest dust emission, while the blend of coarse ACAM and fine LM reveals the lowest emissions. The TCS offers precise, reproducible measurements with good repeatability, making it beneficial for laboratory and industrial applications, even with small powder quantities.

Thermal stability, preformulation, and kinetic degradation studies for gestrinone

AbstractGestrinone is an active pharmaceutical ingredient used in the treatment of endometriosis as capsules, with ongoing evaluation for intravaginal administration, while also having been studied for its potential antitumoral effects. The purpose of this study was to determine the compatibility of gestrinone with four excipients used in the development of solid pharmaceutical formulations (α-lactose monohydrate, magnesium stearate, starch, and talc) and to obtain a fully characterized thermoanalytical profile of gestrinone with the help of kinetic analysis. Preformulation studies were carried out on 1:1 mass/mass binary mixtures between gestrinone and each excipient by instrumental screening under ambient conditions using ATR-FTIR spectroscopy investigations, and later by studying the effect of thermal treatment over the samples (TG/DTG/DSC). The obtained results suggest that under ambient conditions, no chemical interactions take place between the active pharmaceutical ingredient and selected excipients, whereas under thermal stress incompatibilities are observed in all systems. The mechanism of decomposition was preliminary evaluated by the ASTM E698 and later completed by the isoconversional methods of Friedman, Kissinger–Akahira–Sunose, and Flynn–Wall–Ozawa, which suggest similar mean activation energies. The mechanism of decomposition was elucidated in the last part of the study, by employing the modified NPK method. This method suggests that gestrinone is thermally degraded by the contribution of two individual processes, both consisting of superimposed physical transformations and chemical degradations.

THz-TDS as a PAT tool for monitoring blend homogeneity in pharmaceutical manufacturing of solid oral dosage forms: A proof-of-concept study

The process analytical technology (PAT) framework is well established and integral to facilitate process understanding, enable a transition from batch to continuous manufacturing, and improve product quality. Near-infrared (NIR) spectroscopy has been established as a standard PAT tool for many process analytical challenges, including monitoring powder blend homogeneity. However, alternative technologies for monitoring powder blending are of interest due to the importance of the blending step in manufacturing solid oral dosage forms. Terahertz time-domain spectroscopy (THz-TDS) is therefore explored in this study as an alternative tool for monitoring blend homogeneity with the potential for endpoint control in a batch blending process. Powder blends of microcrystalline cellulose (MCC) and dibasic calcium phosphate dihydrate and blends of MCC and granulated α-lactose monohydrate were investigated non-invasively at various compositions using THz-TDS in transmission mode for acquiring spectra from samples enclosed in the blending container. It was found that attenuation- and phase-related parameters acquired with THz-TDS could reliably resolve physical changes related to the homogeneity of the blend. Further evaluations revealed that changes in the bulk density of the blend, in addition to the intrinsic optical properties of the materials, played a critical role in the observed trends for both systems. In contrast, the scattering contribution of the powder was mainly crucial for the attenuation-related parameter in blends with materials of high refractive indices. Finally, THz-TDS measurements were acquired throughout a blending process mimicking a continuous acquisition. The method could follow blending dynamics and resulted in reasonable predictive errors of the content of 0.5 – 2.5 %. Relative standard deviations for high content blends (20 %) were acceptable (3 – 7 %) whereas at low contents (5 %) significantly higher values (9 – 35 %) were found. Based on these findings, THz-TDS is a feasible PAT tool for monitoring blend homogeneity and controlling high content blend processes, although precision and accuracy is considered to improve with a more suitable interface.

Compatibility study of mirtazapine with several excipients used in pharmaceutical dosage forms employing thermal and non-thermal methods

AbstractMirtazapine is an atypical antidepressant used in the management of insomnia, post-traumatic stress disorder, anxiety or panic disorder, obsessive–compulsive disorder and migraines. It is used worldwide in pharmaceutical formulations alongside various excipients in its hemihydrate form. The objective of the study was the compatibility evaluation between MRTHH and ten pharmaceutical excipients. The presence of incompatibilities between the API and the selected excipients was evaluated using Fourier transform infrared spectroscopy performed on all pure samples and prepared mixtures at room temperature (23 ± 2 °C), as well as a complete thermal stress evaluation (TG—thermogravimetric/DTG—derivative thermogravimetric/DSC—differential scanning calorimetry). The results showed particularities for all analyzed mixtures, α-lactose monohydrate, starch, sorbitol, magnesium stearate, calcium lactate and magnesium citrate proving to be safe to use together with mirtazapine in binary mixtures at temperatures below 130 °C, while for polyvinylpyrrolidone K30 and aerosol precautions need to be considered at temperatures over 100 °C. The association of mirtazapine with D-mannitol or stearic acid proved to raise concerns even at room temperature, indicating possible interactions that may alter the chemical integrity of the active pharmaceutical ingredient and with it, its therapeutic effect. These findings should be taken into consideration during the selection of the technological procedures used in the manufacturing process of dosage forms that include mirtazapine alongside with any of these excipients so that unwanted chemical interactions could be avoided.

Crystal size, a key character of lactose crystallization affecting microstructure, surface chemistry and reconstitution of milk powder

Lactose crystallization during storage deteriorates reconstitution performance of milk powders, but the relationship between lactose crystallization and reconstitution is inexplicit. The objective of this study is to characterize crystalline lactose in the context of formulation and elucidate the complex relationship between lactose crystallization and powder functionality. Lactose in Skim Milk Powder (SMP), Whole Milk Powder (WMP) and Fat-Filled Milk Powder (FFMP) stored under 23 %, 53 % and 75 % Relative Humidity (RH) at 25 ℃ for four months was compared. Lactose, surface chemistry and microstructure of FFMP stored at 25 ℃ and 40 ℃ at 23 % to 75 % RH for four months were also analyzed and interpreted. At the same RH, FFMP crystallized in the same pattern as WMP. At 53 % RH, FFMP and WMP differentiated from SMP in terms of lactose morphology as well as the ratio between anhydrous α-lactose and anhydrous β-lactose. Lactose remained amorphous at 23 % RH, crystallized predominantly to α/β-lactose (1:4) at 40 to 58 % RH and to α-lactose monohydrate at 75 % RH. The crystallinity index was similar for all powders containing crystalline lactose. The estimated crystallite size increased from approx. 0.1 to 20 µm with increasing RH and temperature. When amorphous lactose crystallized into crystals below approx. 0.1 µm at 25 °C and 43 % RH, the microstructure and surface lipid were comparable to that of the reference powder. This powder reconstituted into a stable suspension system comparable to that of reference (well performing) powders. These results demonstrate that crystallite size is the key property linking lactose crystallization and reconstitution. Our finding thus indicates limiting crystallite size is important for maintaining desired product quality.

Decolorization of Lactose-6-Phosphate Solutions Using Activated Carbon

Sugar phosphorylation has many applications that can be used to develop dairy and food products. During the phosphorylation process, the color of the solution turns into a dark color. The dark color causes many challenges and limitations in using phosphorylation products. The dark color could cause unpleasant color changes in the products, so it is important to remove that color. Activated carbon has been utilized for decades to remove the dark color and improve the appearance of solutions such as sugar syrup and wastewater. This methodology is cheap and environmentally friendly. The objectives of this study were to develop a method to phosphorylate α-lactose monohydrate and milk permeate and to remove the dark color of solutions. The compositional characteristics of the solution, such as pH, total solids, and color parameters (L*—lightness; a*—redness; and b*—yellowness), were examined at different stages (seven stages) of washing the solutions. α-lactose monohydrate and MPP solutions were diluted with distilled water with a ratio of 1:2.2. Activated carbon was mixed with the solutions and left for 5 min at room temperature. Subsequently, the solutions were filtered. These steps were repeated seven times until there was a transparent (colorless) solutions. The experiment was repeated using three different batches of lactose and milk permeate solutions. Both solutions’ pH and total solids decreased with an increase in the number of washings with activated carbon. The International Commission on Illumination (CIE) L*a*b* scale was studied. The L* of the initial solutions was lower than that of the final solutions. However, the a* and b* of the initial solutions were higher than the final solutions. The total color difference (∆E) was calculated for both solutions. ∆E decreased with an increase in the number of washings with activated carbon in both solutions. We conclude that activated carbon can be used to remove the dark color that results from the phosphorylation process.

Precise measurement of refractive index in the ambient environment using continuous-wave terahertz frequency-domain spectroscopy (THz-FDS)

In this paper, we present the application of THz frequency-domain spectroscopy (THz-FDS) for determining the refractive index in an ambient environment. The signal phase is extracted from the periodically oscillated photocurrent by a magnitude normalization method. The proposed method is demonstrated using experimental data of polytetrafluoroethylene and α-lactose monohydrate as reference materials collected at a relative humidity of around 17.0% ± 2.0%. A detailed comparison to the existing algorithms, including the Hilbert transform and extreme points analysis, reveals the remarkable reliability of our proposed method. This study expands the characterization capabilities of THz-FDS and furthers the development of practical terahertz spectroscopy applications.

Terahertz time-domain spectroscopy for the investigation of tablets prepared from roller compacted granules

Roller compaction before tableting is a common unit operation to increase the processability of powders. Terahertz time-domain spectroscopy (THz-TDS) has recently been introduced as a potential process analytical technology (PAT) for measuring tablet porosity based on the refractive index of the tablet. Tablet porosity is a governing parameter for tablet disintegration and dissolution. The first aim of this study was to investigate tablets prepared from roller-compacted materials with THz-TDS to explore its usefulness for particle size evaluation of granules in tablets. Secondly, the impact of roller compaction and granule size before tablet compression on the established THz-TDS based measurement of tablet porosity was investigated. Microcrystalline cellulose and α-lactose monohydrate were roller compacted separately at five specific compaction forces (2, 4, 8, 12, and 16 kN cm−1) and fractionated into three size fractions. Tablets were prepared from the fractionated and unfractionated granules at twelve tableting pressures and subjected to THz-TDS transmission measurements. It was possible to use the scattering behaviour of the tablets at terahertz frequencies to describe the granulated materials’ particle size changes during tableting. At the same time, prediction of porosity was impaired due to the deviation of the refractive index in strongly scattering samples. A correction method was introduced in which the porosity error was corrected based on the tablet’s scattering behaviour, resulting in an improved prediction of tablet porosity. In conclusion, THz-TDS is considered a promising technique for the process monitoring of tableting based on its sensitivity to porosity and particle size changes within the tablet non-destructively, with a possible application as part of an in-process control strategy of the tableting of granulated or non-granulated materials.

Tabletability and compactibility of α-lactose monohydrate powders of different particle size. II: predicted relationships

This study aimed to evaluate a material sparing method to predict tabletability and compactibility relationships. Seven α-lactose monohydrate powders with varying particle size were used as test materials. The compressibility of the powders was determined experimentally, whereas tabletability and compactibility profiles were derived both experimentally and predicted. In the prediction method, two experimental compression parameters (Kawakita and Heckel plastic stiffness) and a single tensile strength reference value were used, all necessary data obtained from a single compression experiment. For both predicted and experimental relationships, compaction and tableting parameters (performance indicators) were calculated. The correction for viscoelastic recovery was successful in generating compressibility profiles that corresponded to the series of experimental out-of-die tablet porosities. For both the tabletability and compactibility, the experimental and predicted profiles showed a high degree of similarity. Good correlations were obtained between the predicted and experimental compaction and tableting parameters. It is concluded that the hybrid prediction method is a material sparing method, which can give good approximations of tabletability and compactibility relationships. The prediction method has the potential to be included as a part of a protocol for the characterisation of the tableting performance of particulate solids.

Thermal energy and tableting effects in benznidazole product: the impacts of industrial processing

Objective The investigation of benznidazole (BZN), excipients, and tablets aims to evaluate their thermal energy and tableting effects. They aim to understand better the molecular and pharmaceutical processing techniques of the formulation. Significance The Product Quality Review, part of Good Manufacturing Practices, is essential to highlight trends and identify product and process improvements. Methods A set of technique approaches, infrared spectroscopy, X-ray diffraction, and thermal analysis with isoconversional kinetic study, were applied in the protocol. Results X-ray experiments suggest talc and α-lactose monohydrate dehydration and conversion of β-lactose to stable α-lactose upon tableting. The signal crystallization at 167 °C in the DSC curve confirmed this observation. A calorimetric study showed a decrease in the thermal stability of BZN tablets. Therefore, the temperature is a critical process parameter. The specific heat capacity (Cp) of BZN, measured by DSC, was 10.04 J/g at 25 °C and 9.06 J/g at 160 °C. Thermal decomposition required 78 kJ mol−1. Compared with the tablet (about 200 kJ mol−1), the necessary energy is two-fold lower, as observed in the kinetic study by non-isothermal TG experiment at 5; 7.5; 10; and 15 °C min−1. Conclusions These results indicate the necessity of considering the thermal energy and tableting effects of BZN manufacturing, which contributes significantly to the molecular mechanistic understanding of this drug delivery system.

Strong coupling of localized surface plasmons and intermolecular vibration mode at terahertz frequencies

Organic molecular vibrations, typically occurring in the terahertz (THz) regime, can resonate with a metastructure. A hallmark Rabi splitting occurs when the coupling strength is sufficiently strong. In this work, we observe the strong coupling of localized surface plasmons (LSPs) and intermolecular vibration mode at THz on a metasurface spin-coated with organic molecule α-lactose monohydrate. Excited by transverse-electric THz waves, dispersive localized surface plasmons interact with nondispersive intermolecular vibrations and form two vibro-polariton modes. The angle-resolved transmission spectra of the coupled system are detected by using a terahertz time-domain spectrometer, demonstrating an anti-crossing effect with a clear Rabi splitting. By retrieving the coupling strength and Hopfield coefficients of polariton bands from the measured data, we further verify that these two bands originate from the strong coupling between LSPs and molecular vibration mode. Moreover, we show that it is possible to implement molecular concentration sensing based on this strong coupling effect. This study demonstrates a unique approach to investigate vibro-polaritons at the terahertz regime and provides a testbed for future applications of strong coupling effects in chemical detection and biosensing.

Twin-screw continuous mixing: Effect of mixing elements and processing parameters on properties of aerosol powders

Twin-screw continuous mixing was used to prepare aerosol powders containing 1% budesonide, 0.3% magnesium stearate, and 98.7% α-lactose monohydrate. The effect of mixing configuration was studied using three screw profiles containing either a combing element, 30° forward kneading element, or a 60° forward kneading element. The impact of screw speed, feed rate, and multiple passes through the mixer on powder quality was investigated. The impact of specific energy on aerosol performance was dependent on the mixing configuration, and high energy input was detrimental to FPF for the 30° kneading element. Control of content uniformity was demonstrated by varying the mixing element in the screw profile. Passing the material through the mixer multiple times improved the aerosol performance. The robust and tunable nature of twin-screw mixing makes it a process well suited for continuous manufacturing of aerosol powders.

Efficient free-space to on-chip coupling of THz-bandwidth pulses for biomolecule fingerprint sensing.

Wide bandwidth THz pulses can be used to record the distinctive spectral fingerprints related to the vibrational or rotational modes of polycrystalline biomolecules, and can be used to resolve the time-dependent dynamics of such systems. Waveguides, owing to their tight spatial confinement of the electromagnetic fields and the longer interaction distance, are promising platforms with which to study small volumes of such systems. The efficient input of sub-ps THz pulses into waveguides is challenging owing to the wide bandwidth of the THz signal. Here, we propose a sensing chip comprised of a pair of back-to-back Vivaldi antennas feeding into, and out from, a 90° bent slotline waveguide to overcome this problem. The effective operating bandwidth of the sensing chip ranges from 0.2 to 1.15 THz, and the free-space to on-chip coupling efficiency is as high as 51% at 0.44 THz. Over the entire band, the THz signal is ∼42 dB above the noise level at room temperature, with a peak of ∼73 dB above the noise. In order to demonstrate the use of the chip, we have measured the characteristic fingerprint of α-lactose monohydrate, and its sharp absorption peak at ∼0.53 THz was successfully observed, demonstrating the promise of our technique. The chip has the merits of efficient in-plane coupling, ultra-wide bandwidth, ease-of-integration, and simple fabrication. It has the potential for large-scale manufacture, and can be a strong candidate for integration into other THz light-matter interaction platforms.

Thermal characteristics of crystalline and amorphous 2′-fucosyllactose, a human milk oligosaccharide

The thermal characteristics of crystalline and amorphous forms of a human milk oligosaccharide, 2ʹ-fucosyllactose (2ʹ-FL), were investigated by differential scanning calorimetry and thermogravimetric analysis, and compared with the two forms of α-lactose monohydrate. Crystalline 2ʹ-FL (87.48% crystallinity according to X-ray diffraction) showed dehydration at 143.4 °C (close to lactose) and melting at 230.6 °C (the same as β-lactose crystal). Amorphous 2ʹ-FL showed glass transition at 127.6 °C and crystallisation at 192.8 °C, which were much higher than the corresponding temperatures for amorphous lactose. 2ʹ-FL showed thermal decomposition at temperatures about 10 °C higher (210–212 °C) than lactose, indicating the higher thermal stability of 2ʹ-FL. Amorphous 2ʹ-FL showed sharp decreases in glass transition (127.6 °C to 36.5 °C) and crystallisation (192.8 °C to 103.4 °C) temperatures with increasing water activity (aw) from 0 to 0.53, above which no glass transition or crystallisation was observed.

Quantitative analysis of aqueous biomolecular mixtures by THz spectroscopy based on high-power LiNbO3 radiation source

The rapid and accurate identification of the types and contents of early pathological markers by THz technology are of particular importance for the prevention and treatment of major diseases. Nevertheless, these markers usually contain interference from water and other non-target molecules, resulting in low signal-to-noise ratio (SNR) and making identification and quantitative analysis difficult. Here, based on THz spectroscopy from a high-power THz source radiated by LiNbO3, we perform quantitative and real-time THz detection of mixtures (α-lactose monohydrate and 4-aminobenzoic acid) in liquids. The results demonstrate that the absorption spectra of the aqueous biomolecular mixtures exhibit an accumulation of THz features of each pure product, i.e., the amplitude of the absorption peaks is proportional to the mixing ratio, while the corresponding absorption baseline increases with decreasing concentration. Furthermore, the content of the target substance can be calculated from the linear relationship between the absorption spectra of pure and mixed samples. This technology will support the future application of THz-TDS in early disease diagnosis under complex states and environments.

The Optimisation of Carrier Selection in Dry Powder Inhaler Formulation and the Role of Surface Energetics

This review examines the effects of particle properties on drug-carrier interactions in the preparation of a dry powder inhaler (DPI) formulation, including appropriate mixing technology. The interactive effects of carrier properties on DPI formulation performance make it difficult to establish a direct cause-and-effect relationship between any one carrier property and its effect on the performance of a DPI formulation. Alpha lactose monohydrate remains the most widely used carrier for DPI formulations. The physicochemical properties of α-lactose monohydrate particles, such as particle size, shape and solid form, are profoundly influenced by the method of production. Therefore, wide variations in these properties are inevitable. In this review, the role of surface energetics in the optimisation of dry powder inhaler formulations is considered in lactose carrier selection. Several useful lactose particle modification methods are discussed as well as the use of fine lactose and force control agents in formulation development. It is concluded that where these have been investigated, the empirical nature of the studies does not permit early formulation prediction of product performance, rather they only allow the evaluation of final formulation quality. The potential to leverage particle interaction dynamics through the use of an experimental design utilising quantifiable lactose particle properties and critical quality attributes, e.g., surface energetics, is explored, particularly with respect to when a Quality-by-Design approach has been used in optimisation.

Evaluating Spatially Offset Low-Frequency Anti-Stokes Raman Spectroscopy (SOLFARS) for Detecting Subsurface Composition below an Emissive Layer: A Proof of Principle Study Using a Model Bilayer System.

This work explores the potential use of spatially offset low-frequency anti-Stokes Raman spectroscopy (SOLFARS) to detect subsurface composition below an emissive surface. A range of bilayer tablets were used to evaluate this approach. Bilayer tablets differed in both the underlying layer composition (active pharmaceutical ingredient to excipient ratio, celecoxib: α-lactose monohydrate) and the upper layer thickness of the fluorescent coating (polyvinylpyrrolidone mixture with sunset yellow FCF dye). Two low- (<300 cm-1) plus mid- (300 to 1800 cm-1) frequency Raman instrumental setups, with lateral displacements for spatial analysis of solid dosage forms, using different excitation wavelengths were explored. The 532 nm system was used to illustrate how the low-frequency anti-Stokes Raman approach works with samples exhibiting extreme fluorescence/background emission interference, and the 785 nm system was used to demonstrate the performance when less extreme fluorescence/emission is present. Qualitative and quantitative chemometric analyses were performed to evaluate the performance of individual spectral domains and their combinations for the determination of the composition of the subsurface layer as well as the coating layer thickness. Overall, the commonly used midfrequency region (300-1800 cm-1) proved superior when using 785 nm incident laser for quantifying the coating thickness (amorphous materials), whereas a combined Stokes and anti-Stokes low-frequency region was found to be superior for quantifying underlying crystalline materials. When exploring individual spectral regions for subsurface composition using spatially offset measurements, the anti-Stokes LFR spectral window performed best. The anti-Stokes low-frequency range also demonstrated an advantage for models composed of data exhibiting high levels of fluorescence (e.g., data collected using 532 nm incident laser), as the Stokes scattering was masked by fluorescence. Transmission measurements were also explored for comparison and showed the best applicability for both upper and lower layer analysis, attributed to the inherently larger bulk sampling volume of this setup. From a practical perspective, these results highlight the potential adjustments that can be made to already existing (in-line) Raman setups to facilitate similar analysis in pharmaceutical industry-based settings.

Lactose crystallization and Maillard reaction in simulated milk powder based on the change in water activity.

Maillard reaction (MR) and lactose crystallization (LC) are important reactions in the storage of milk powder. In this study, three models with different proteins based on skimmed milk powder were established to investigate the relationship between MR and LC at different water activities (aw ). Moisture sorption isotherm, glass transition temperature (Tg ), and glycation products were evaluated, and the protein structure and lactose crystallinity were determined. The results indicated that MR product content, browning, and LC subsequently enhanced with the increase in aw . The Tg value dropped lower than 0 at aw 0.43 in whey protein isolate-lactose (WP-Lac) model and at aw 0.54 in casein-whey protein isolate-lactose (CN-WP-Lac) model and casein-lactose (CN-Lac) model. The crystallinity of α-lactose monohydrate and anhydrous β-lactose in WP-Lac model was more significant than CN-WP-Lac and CN-Lac models (p<0.05). The molecular band of whey protein gradually blurred in the Sodium dodecyl-sulfate polyacrylamide gel electrophoresis image, and the content of α-helix of WP-Lac model increased by 45.15% from aw 0.33 to 0.53 (p<0.05), while that of CN-WP-Lac model increased by only 3.95% (p<0.05). With the increase in aw , WP-Lac model formed more browning and crystallization products than CN-WP-Lac model, indicating that the presence of micelle macromolecules and the interaction between casein and whey proteins limited the browning and crystallization in CN-WP-Lac model. Practical Application Maillard reaction and lactose crystallization are important reactions in the storage of milk powder, and the result will provide theoretical guidance for the development of milk powder in the food industry.

Dissociation and Recombination Processes in Lactose Monohydrate Detected by THz Time-Domain Spectroscopy

The terahertz (THz) region has much appeal for differentiating between hydrate systems and for physically characterizing pharmaceutical drug materials. The present study employs THz absorption spectroscopy to investigate the effect of heating on dehydration and hydration in α-lactose monohydrate. Distinctive THz absorption spectra were observed following various heating durations. The THz absorption spectra for α-lactose monohydrate and anhydrous α-lactose exhibit clear differences. Pure α-lactose monohydrate displays clear absorption peaks at 0.53, 1.05, 1.11, 1.33, and 1.56 THz. The complete dehydration of α-lactose monohydrate takes only 15 mins at 145°C (418 K). Moreover, the THz refractive index of α-lactose monohydrate decreases during dehydration. The dehydration of α-lactose monohydrate was also studied using Beer–Lambert law to compare THz absorption spectra as functions of the heating time. The absorption coefficient spectra recorded at 0.53 and 1.35 THz for α-lactose monohydrate after different dehydration times vary linearly with the remaining water content.