Microwave-assisted Freeze-drying Research Articles

The influence of thermal radiation during microwave-assisted freeze-drying of pharmaceutical unit doses

New drying technologies for biologicals have recently been developed to accelerate the time-consuming batch freeze-drying (BFD) process. Among others, microwave-assisted freeze-drying (MFD) has been suggested as a faster and more effective drying technology. In this study, MFD cycles with the microwave radiation switched on and off were performed to assess the contribution of the microwave radiation to drying acceleration. It was found that thermal radiation emitted by the drying chamber walls was predominantly accelerating the drying of monodose placebos rather than microwave radiation. The combination of ultra-low chamber pressure, high thermal heat transfer and a short primary-to-secondary phase transition reduces drying times by more than 80 % compared to conventional BFD. In a second step, a design of experiment approach was used to assess the effect of thermal radiation versus microwave radiation and their combination, together with dosage properties such as fill volume and excipient concentration upon drying rate. The outcome showed the importance of high fill volume and high excipient concentration for an effective microwave contribution to the drying rate. Nevertheless, the drying acceleration for small pharmaceutical dosages with restricted solutes was mainly driven by thermal radiation rather than 2.45 GHz microwave radiation. The inability of ice to convert microwave energy into heat hampers the potential use of microwave freeze-drying for single-dose vaccines.

Process intensification of microwave-assisted freeze-drying by frequency adjustment in real-time using solid-state technology

In microwave-assisted processes, solid-state microwave technology enables control of the electromagnetic field, which can be used for process intensification. This work investigates the impact of real-time frequency adjustment on microwave-assisted freeze-drying (MFD). Frequency-based control concepts were applied in experiments with tylose gel as a food model product in a laboratory-scale plant. By applying energy-efficient resonant frequencies based on feedback related to product state, the drying time was reduced by 24.2% compared to conventional freeze-drying (CFD) due to increases in energy efficiency. Comparable temperature profiles, residual moistures, and ascorbic acid retentions to CFD were achieved. However, structural degradation occurred with MFD in up to 10.4% of the samples. The degradation could be counteracted by more refined frequency and power application. In summary, this work demonstrates the high potential of frequency-based control for MFD process intensification.

Microwave-Assisted Freeze-Drying: Impact of Microwave Radiation on the Quality of High-Concentration Antibody Formulations.

Microwave-assisted freeze-drying (MFD) offers significant time savings compared to conventional freeze-drying (CFD). While a few studies have investigated the stability of biopharmaceuticals with low protein concentrations after MFD and storage, the impact of MFD on high-concentration monoclonal antibody (mAb) formulations remains unclear. In this study, we systematically examined the effect of protein concentration in MFD and assessed protein stability following MFD, CFD, and subsequent storage using seven protein formulations with various stabilizers and concentrations. We demonstrated that microwaves directly interact with the active pharmaceutical ingredient (API), leading to decreased physical stability, specifically aggregation, in high-concentration antibody formulations. Furthermore, typically used sugar:protein ratios from CFD were insufficient for stabilizing mAbs when applying microwaves. We identified the intermediate drying phase as the most critical for particle formation, and cooling the samples provided some protection for the mAb. Our findings suggest that MFD technology may not be universally applicable to formulations well tested in CFD and could be particularly beneficial for formulations with low API concentrations requiring substantial amounts of glass-forming excipients, such as vaccines and RNA-based products.

A Time-Saving Approach to Parameter Studies in Microwave-Assisted Freeze Drying

Microwave-assisted freeze drying (MFD) is particularly suited for drying heat-sensitive materials. However, optimizing process parameters is time-consuming due to lengthy individual experiments. This study investigates the feasibility of partial MFD for parameter studies, with the process being terminated after removing 20 wt% of the water contained. The proposed approach reduces the time required for parameter evaluation by 92.0% compared to complete MFD. It also enables the evaluation of the samples’ drying homogeneity. A subsequent parameter study based on partial MFD was then conducted to evaluate the effects of chamber pressure, microwave power, and microwave frequencies on the drying kinetics and drying homogeneity. Lowering the average chamber pressure from 0.87 mbar to 0.19 mbar reduced the process duration by 18.8%. An increase in the dissipated specific microwave power from 0.048 W/g to 0.143 W/g reduced the duration by 46.7%. The targeted application of frequencies increased the average energy efficiency to as high as 92.4%, contributing to a shortened process duration of up to 51.2%. Only the application of multiple frequencies caused a notable increase in drying homogeneity. In summary, this study demonstrates the feasibility and time-saving benefits of partial drying for parameter studies in MFD and potentially different types of drying processes.

Irreversible thermochromic ink in the identification of over- and under-processed product segments in microwave-assisted freeze drying

The formation of over- and under-processed product regions is an inherent drawback of microwave-assisted freeze drying (MWFD) of food attributed to the inhomogeneity of microwave energy distribution. To overcome limitations in the investigation of inhomogeneity effects, the scope of this study was the development and validation of a new method using an irreversible thermochromic colour-component (ITC) with a particular colour intensity profile as a function of temperature (40–70 °C). For validation, thermal images and spatially-resolved biomarker inactivation was compared to the colour intensity pattern resulting from the temperature-induced colour reaction of ITC in MWFD. The ITC method provides advantages over existing methods, as it visualises the spatial distribution of maximum processing temperature independently of post-treatment effects and existing dryer design. This easy-to-use method has the potential to eliminate or reduce preconceptions due to poorly known inhomogeneity of microwave applications and pave the way for energy-efficient and fast MWFD of food.

Analytical solutions for the modeling, optimization, and control of microwave-assisted freeze drying

Freeze drying, aka lyophilization, is a process by which a pharmaceutical product is dried via sublimation under vacuum. An alternative to the conventional process is microwave-assisted freeze drying, which relies on microwave irradiation for drying the product, offering a reduction in the drying time by 70%–80%. This article derives exact and approximate analytical solutions to a mechanistic model for conventional, microwave-assisted, and hybrid freeze drying. The exact solution serves as a reference solution for validating numerical or approximate results due to its highest accuracy up to machine precision. The approximate solution can be computed about 4-fold faster than the numerical solutions and 200-fold faster than the exact solution with the maximum error of less than 1%, which is highly computationally efficient and accurate. Applications of the analytical solutions are demonstrated in the context of parameter estimation, optimal control, and parameter space analysis.

Accelerated Production of Biopharmaceuticals via Microwave-Assisted Freeze-Drying (MFD).

Recently, attention has been drawn to microwave-assisted freeze-drying (MFD), as it drastically reduces the typically long drying times of biopharmaceuticals in conventional freeze-drying (CFD). Nevertheless, previously described prototype machines lack important attributes such as in-chamber freezing and stoppering, not allowing for the performance of representative vial freeze-drying processes. In this study, we present a new technical MFD setup, designed with GMP processes in mind. It is based on a standard lyophilizer equipped with flat semiconductor microwave modules. The idea was to enable the retrofitting of standard freeze-dryers with a microwave option, which would reduce the hurdles of implementation. We aimed to collect process data with respect to the speed, settings, and controllability of the MFD processes. Moreover, we studied the performance of six monoclonal antibody (mAb) formulations in terms of quality after drying and stability after storage for 6 months. We found drying processes to be drastically shortened and well controllable and observed no signs of plasma discharge. The characterization of the lyophilizates revealed an elegant cake appearance and remarkably good stability in the mAb after MFD. Furthermore, overall storage stability was good, even when residual moisture was increased due to high concentrations of glass-forming excipients. A direct comparison of stability data following MFD and CFD demonstrated similar stability profiles. We conclude that the new machine design is highly advantageous, enabling the fast-drying of excipient-dominated, low-concentrated mAb formulations in compliance with modern manufacturing technology.

Microwave-Assisted Freeze-Drying with Frequency-Based Control Concepts via Solid-State Generators: A Simulative and Experimental Study

Freeze-drying is a common process to extend the shelf life of food and bioactive substances. Its main drawback is the long drying time and associated high production costs. Microwaves can be applied to significantly shorten the process. This study investigates the effects of modulating the electromagnetic field in microwave-assisted freeze-drying (MFD). Control concepts based on microwave frequency are evaluated using electromagnetic simulations. The concepts are then applied to the first part of primary drying in a laboratory-scale system with solid-state generators. Targeted frequency modulation in the electromagnetic simulations enabled an increase in energy efficiency or heating homogeneity throughout MFD while having negligible effects on the power dissipation ratio between frozen and dried product areas. The simulations predicted the qualitative effects observed in the experimental proof of concept regarding energy efficiency and drying homogeneity. Additionally, shortened drying times were observed in the experiments with a targeted application of energy-efficient frequencies. However, differences occurred in the quantitative validation of the electromagnetic models for energy efficiency in dependence on frequency. Nevertheless, the models can be used for a time-efficient investigation of the qualitative effects of the control concepts. In summary, frequency-based control of MFD represents a promising approach for process control and intensification.

Microwave-assisted freeze drying of pineapple: Kinetic, product quality, and energy consumption

Among the advanced drying methods, vacuum freeze-drying (VFD) preserves the quality of food to the greatest extent, but its biggest disadvantage is its high energy consumption. The microwave-assisted freeze drying is expected to greatly reduce the energy consumption of drying process compared to VFD. In this paper, firstly, the eutectic temperature analysis of the pineapple slices is performed using resistance method and the eutectic point of −15 °C is obtained. Secondly, the impacts of four design variables including transition moisture content, microwave power density, drying temperature, and rotational speed of turntable on the product quality and energy consumption are deeply evaluated and discussed. The results show that the higher the microwave power density, the faster the drying rate. For example, the drying process reaching the final moisture content completes in 30, 60, and 90 min under power density of 8, 6, and 4 W/g, respectively. It is observed that employing a rotating turntable and a temperature control system leads to the uniform heating of the material and improved quality of products. Moreover, the lower the transition moisture content, the better the quality of dried products. In order to maintain the appearance of the product, the transition moisture content during the drying process should be within the range of 10–30%. Finally, Taguchi method is used to analyze the trend of experimental optimization. It is found that the most obvious factor affecting the comprehensive score of microwave-assisted freeze-drying process is transition moisture content, followed by the drying temperature and rotational speed. The least affecting parameter is the microwave power density. It is concluded that the microwave-assisted freeze-drying process under the transition moisture content of 20%, drying temperature of 40 °C, turntable rotational speed of 8 rpm, and microwave power density of 6 W/g has the efficient drying performance, saving 34.5% energy consumption and 33.3% drying time compared to pure VFD.

Improving effect of disaccharides and maltodextrin on preparation of egg yolk powder by microwave-assisted freeze-drying: Functional properties, structural properties, and retention rate of active IgY

The preparation of egg yolk powder (EYP) with excellent solubility and high retention of active IgY is of great significance for increasing the added value and promoting the application of EYP. A new method of preparing EYP by microwave-assisted freeze-drying (MFD) was researched. Confocal laser scanning microscopy results demonstrated that the supplementation of excipients (sucrose, trehalose, and maltodextrin) could inhibit lipoproteins aggregation in egg yolk induced by freezing. Scanning electron microscopy indicated that drying further damaged the structure of lipoproteins in EYP, leading to lipid separation from it. FTIR and fluorescence spectra confirmed this finding, indicating that excipients enhance protein stability. Compared with conventional freeze-drying (FD), EYP prepared by MFD, particularly that containing excipients, had higher solubility (63 g/100 g), active antibody retention rate and shorter drying time. Therefore, excipients can significantly improve the solubility and stability of EYP and the retention rate of active IgY.

Valorization of turmeric (Curcuma longa L.) rhizome: Effect of different drying methods on antioxidant capacity and physical properties

Turmeric has high commercial demand internationally, owing to its high nutrient and medical value. In this research, turmeric samples were subjected to several drying methods viz. infrared freeze drying (IRFD), freeze drying (FD), and pulse-spouted microwave-assisted freeze-drying (PSMFD). Over the range of operating conditions employed in this study, IRFD of infrared radiation was showed to shorten the drying time by 21.27% relative to FD, while the retention valves of ascorbic acid, curcumin, total phenols, and total flavonoids remains at 75.61%, 94.06%, 69.00%, and 80.09%, respectively over the range of experimental parameters. IRFD significantly (P < 0.05) reduced 25.19% of the energy consumption in comparison with FD. Furthermore, the interior of IRFD samples exhibited a honeycomb porous structure, and increased hardness, lower shrinkage, apparent density compared to PSMFD. Additionally, IRFD also performed better than PSMFD and FD under vacuum freezing conditions.

Effects of freeze-drying and microwave vacuum freeze-drying on the activity of IgY: From the perspective of protein structure

Freeze-drying (FD) is often used for therapeutic proteins and other biological drugs to extend their shelf life, but it usually reduces the activity and stability of the protein and has a longer drying cycle. A microwave-assisted freeze-drying (MFD) was proposed to produce immunoglobulin of yolk (IgY) preparations. The effects of FD and MFD on the immunological activity and structure of IgY with different amounts of trehalose were investigated. Results showed that lyophilization led to a partial loss of secondary structure in IgY, which resulted in the activity loss. As the trehalose content increased from 0% to 5%, the activity retention of MFD samples increased from 20.31% to 75.57%, which was comparable to FD samples (from 23.57% to 67.78%). However, MFD had a shorter drying cycle when compared with FD. MFD can be a potential alternative to FD as a common therapeutic protein drying method.

Mathematical modeling and analysis of microwave-assisted freeze-drying in biopharmaceutical applications

Freeze drying is an essential unit operation for the storage of biopharmaceuticals, with its main weakness being the very long primary drying times required to sublimate all of the ice formed in the initial freezing step. This study investigates the use of microwave irradiation to reduce drying times. Mechanistic models are derived in a proposed freeze-drying process in which two energy transfer mechanisms – microwave irradiation and heat conduction – occur simultaneously. For this design, a mechanistic model derived in this article predicts an 83% reduction in primary drying time compared to conventional freeze drying. The influence of microwave power and design parameters associated with heat conduction parameters on the primary drying time are investigated and discussed. The model is implemented as open-source software in Julia and is available for engineers to use for designing such equipment.

Microwave-Assisted Freeze-Drying of Monoclonal Antibodies: Product Quality Aspects and Storage Stability.

In order to overcome the downside of long conventional freeze-drying (CFD) process times for monoclonal antibody formulations, microwave-assisted freeze-drying (MFD) was introduced. Recently, the general applicability and potential shortening of drying times were shown. However, little is known about the storage stability of MFD products compared to CFD references. Additionally, batch homogeneity issues were seen within MFD in the past. In this study, we examined four different formulations of two different monoclonal antibodies using three different glass-forming excipients: sucrose, trehalose, and arginine phosphate. These formulations were freeze-dried with two different drying protocols (CFD and MFD), stored for 24 weeks, and analyzed for solid-state and protein-related quality attributes. Moreover, a new microwave generator setup was investigated for its potential to improve batch homogeneity. In all investigated formulations, comparable stability profiles were found, although the classical magnetron generator led to inferior batch homogeneity with respect to residual moisture distribution. In contrast, the new MFD setup indicated the potential to approximate batch homogeneity to the level of CFD. However, for future applications, there is an unabated need for new machine designs to comply with pharmaceutical manufacturing requirements.

Effect of hydrocolloid addition and microwave-assisted freeze drying on the characteristics of foamed raspberry puree

Foamed fruit purees can be dried and consumed as snacks. This study compares the characteristics of foamed raspberry puree dried via microwave-assisted freeze drying and conventional freeze drying. The effect of potato protein (PP) (as a foaming agent), maltodextrin (MD) (as a foam stabilizer), and microwave power on the product characteristics was investigated. The puree contained 18%–20% higher content of anthocyanins and ascorbic acid than unprocessed raspberries. The retention of ascorbic acid and anthocyanins increased with increasing concentrations of MD and PP. Both drying methods resulted in 66%–81% retention of ascorbic acid and 53%–84% retention of total anthocyanins. The higher drying rates obtained at higher maltodextrin concentrations resulted in higher ascorbic acid and anthocyanin retention. The total color difference was significantly higher for the foam with 30% MD (w/w) at 2.0 W g−1, accounting for the formation of hot spots. Protein concentration did not have a considerable effect on product color. Increasing the maltodextrin concentration yielded a harder foam structure, while increasing the protein concentration had the opposite effect. Overall, microwave-assisted freeze drying was found to be a promising alternative to conventional freeze drying, as it offers a more efficient drying process with comparable product quality.

Impact of hydrocolloid addition and microwave processing condition on drying behavior of foamed raspberry puree

In this study, foamed raspberry puree was dried by microwave-assisted freeze drying (MWFD). The combined use of microwaves and a foamed structure was intended to accelerate the drying process, while creating an innovative product structure with intense aroma impact for consumption as a snack. The influence of potato protein as foaming agent, maltodextrin as foam stabilizer and microwave (MW) power on the drying characteristics of raspberry foams during MWFD was investigated. Conventional freeze drying (FD) experiments were performed as a reference. MD concentration was shown to significantly influence product temperature. As higher MD concentrations yielded smaller bubbles and a more uniform bubble size distribution, lower drying temperatures were needed to reach the same final moisture content.Varying MW power did not significantly influence the drying time. MWFD at 1.0 W g−1 yielded a 3–4-fold decrease in total drying time as compared to FD. The addition of 10% protein led to the most gentle drying at high MW power input due to structural changes enabling a lower resistance against water vapor mass transfer. There was a high correlation between the foam characteristics and the drying behavior. An overrun above 450% led to gentle drying at all tested microwave power input levels. Foam bubble size and bubble size distribution correlated well with drying velocity. Overall, MWFD was shown to be a much faster and more gentle alternative to FD for the production of fruit foams.

Significant Drying Time Reduction Using Microwave-Assisted Freeze-Drying for a Monoclonal Antibody

Microwave-assisted freeze-drying (MFD) is a rapid drying process well known in food technology. However, little is known about its application to biologicals. In this study, we investigated the applicability and feasibility of this technology to different monoclonal antibody formulations and the influence on the resulting product properties. Moreover, one of our main objectives was to study if significant reductions in drying times could be achieved. In addition, the effect of the drying process on the accelerated stability of a sucrose-based antibody formulation at 40°C and 25°C over 12 weeks was investigated. MFD resulted in drying time reduction >75%. For all model formulations, cake appearance and solid state properties were found to be comparable to standard lyophilized products. These formulations covered a wider range of lyophilization excipients comprising sucrose and trehalose, semi-crystalline forming solids like mannitol:sucrose mixtures and others like arginine phosphate and a mixture of 2-hydroxypropyl-β-cyclodextrin with sucrose. Moreover, comparable low changes in relative monomer content, the relative amount of soluble aggregates and cumulative particles ≥1 μm per mL were observed over 12 weeks of storage, regardless of the drying technology. This makes MFD a promising innovative alternative for the rapid production of freeze-dried biologicals while maintaining product quality.

Physicochemical and nutritional properties of wasabi (Eutrema yunnanense)dried by four different drying methods

ABSTRACTWasabi (Eutrema yunnaense) is a popular, commonly known as a specially health and a very precious flavoring food, which is served together with other foods, such as sushi and sashimi throughout the world. Isothiocyanate is the major flavor substance of wasabi which is extremely volatile, thus affecting the quality of wasabi products. The aim of this study was to obtain wasabi with the highest isothiocyanate content as well as other physicochemical and nutritional characteristics. Wasabi samples were dried by four different drying methods including, hot air-drying (HD), radio frequency-assisted hot air-drying (RFD), pulse-spouted microwave-assisted freeze-drying (PSMFD), and freeze-drying (FD). After drying, color, odor, taste, volume shrinkage, sensorial analysis, water content, and distribution as well as chlorophyll, ascorbic acid (vitamin C), and isothiocyanate content of the final dried products were measured. The drying time of each drying method was also measured. Highest contents of vitamin C, chlorophyll, and isothiocyanate of wasabi were obtained by FD followed by PSMFD. The volume shrinkage of wasabi dried by FD was the largest, followed by PSMFD, RFD, and HD, which is 0.992, 0.988, 0.894, and 0.882, respectively. The best color, highest sensorial scores, and small discrepancy (difference) of odor and taste substances from fresh samples of drying wasabi were obtained by freeze-drying which were close to PSMFD samples. As for drying time, RFD lasted 4.5 h compared to HD which lasted 9.5 h. PSMFD took 4.5 h less than FD (9 h).

Comparison of three microwave‐assisted drying methods on the physiochemical, nutritional and sensory qualities of re‐structured purple‐fleshed sweet potato granules

SummaryPurple‐fleshed sweet potato (PFSP) with high anthocyanin level was attractive to health concern. Three drying methods, namely microwave‐assisted freeze‐drying (MWFD), microwave‐assisted vacuum drying (MWVD) and microwave‐assisted spouted bed drying (MWSBD), were compared in the drying of PFSP granules. Product’s texture, colour, anthocyanin level and energy consumption were investigated. Drying periods varied among drying methods. MWSBD needed the least time to finish the drying process. Different drying methods had a significant effect (P &lt; 0.05) on texture and anthocyanin level. Maximum penetration force of MWSBD treated sample was lowest (14.99 N). Anthocyanin level of MWSBD products was not as high as that of MWFD products, but colour and appearance were fine. MWFD products owned good crispness through sensory evaluation. Energy consumption of MWFD was about two times higher than that of MWVD. Final results indicated that MWSBD may be an alternative way to MWFD with measurements to maintain the anthocyanin level.

Studies on different combined microwave drying of carrot pieces

SummaryThree different combined microwave (MW) drying methods were compared, namely microwave‐assisted vacuum drying (MWVD), microwave‐assisted freeze drying (MWFD), microwave‐enhanced spouted bed drying (MWSD), in terms of drying rate, drying uniformity, product colour, rehydration ratio, retention of β‐carotene and vitamin C, and energy consumption. The drying rate of MWVD and MWSD were much faster than that of MWFD. The largest drying rate was obtained in MWSD with 3.5 W g−1. In general, the colour of MWSD products was very uniform. Rehydration ratio of MWFD carrot pieces was almost the same as the freeze‐dried (FD) products and better than MWVD and MWSD products. In addition, the highest retention of carotene and vitamin C was observed in MWFD carrot pieces. No significant differences were observed in carotene and vitamin C between MWVD and MWSD products. However, the energy consumption in MWFD was the highest.