Shelf Temperature Research Articles

Development of a Single Vial Mass Flow Rate Monitor to Assess Pharmaceutical Freeze Drying Heterogeneity.

During pharmaceutical lyophilization processes, inter-vial drying heterogeneity remains a significant obstacle. Due to differences in heat and mass transfer based on vial position within the freeze drier, edge vials freeze differently, are typically warmer and dry faster than center vials. This vial position-dependent heterogeneity within the freeze dryer leads to tradeoffs during process development. During primary drying, process developers must be careful to avoid shelf temperatures that would result in overheating of edge vials causing the product sublimation interface temperature to rise above the critical (collapse) temperature. However, at lower shelf temperatures, center vials require longer to complete primary drying, risking collapse or melt-back due to incomplete drying. Both situations may result in poor product quality affecting drug stability, activity, and reconstitution times. We present a new approach for monitoring vial location-specific water vapor mass flow based on Tunable Diode Laser Absorption Spectroscopy (TDLAS). The single vial monitor enables measurement of the gas flow velocity, water vapor temperature, and gas concentration from the sublimating ice, enabling the calculation of the mass flow rate which can be used in combination with a heat and mass transfer model to determine vial heat transfer coefficients and product resistance to drying. These parameters can in turn be used for robust and rapid process development and control.

Process Parameters as Tools to Intensify the Freeze-Drying Process and Modify the Sorption Properties of the Obtained Freeze-Dried Products

This study aimed to investigate the effect of the application of different freeze-drying conditions on the process’s kinetics and the sorption properties of dried apples. Slices of apples were frozen and subjected to a freezing-drying process with different combinations of shelf temperature (−20, 10, 20, and 30 °C) and pressure (37, 63, 103, and 165 Pa). During the freeze-drying, the temperature in the centre of the material was recorded. The moisture content in the dried material and changes in the water content in dried apples stored at a humidity of 75.3% were obtained. The Midilli et al. model was used to describe the drying kinetics of the freeze-drying with a good fit. Drying time increased from 660 (variant with a constant shelf temperature of 30 °C, pressure 63 Pa) to 1305 min (variants with temperatures −20:10:20:30 °C, pressure 63 Pa). For this reason, the most favourable experimental parameters were a temperature of 30 °C and a pressure of 63 Pa. However, applying these parameters caused higher absorption of water vapour during storage. Therefore, the selection of freeze-drying parameters should also be related to the expected properties of the final product.

Foam-Mat Freeze Drying of Kiwiberry (Actinidia arguta) Pulp: Drying Kinetics, Main Properties and Microstructure

The kiwiberry is an interesting source of bioactive compounds (micronutrients, polyphenols vitamins and pectins) and enzyme actinidine but has limited durability. The aim of this study was to determine the impact of shelf temperature (10 °C, 25 °C and 40 °C) during freeze drying on the foam-mat kiwiberry pulp drying process and the quality of the obtained material based on analyses such as moisture content, water activity, hygroscopicity, solubility, microstructure and spectral measurement using the FTIR method. The use of higher shelf temperatures during freeze drying positively influenced the drying process, reducing its duration by up to 40.7%. The shelf temperature caused changes in the dry matter content (97.2–99.6%), water activity (0.159–0.221), structure and hygroscopic properties (1.41–4.41 g water/100 g d.m.) of the kiwiberry foam mats. Foam-mat drying at 40 °C exhibited a significantly lower water activity, total porosity and hygroscopicity, providing properties favorable for good microbiological and functional stability during storage. Furthermore, this temperature applied during freeze drying resulted in an increase in the solubility of the obtained material, which indicates its possible use in the matrix of other food products.

Thermostable vacuum foam dried Newcastle disease vaccine: Process optimization and pilot-scale study

Vacuum foam drying (VFD) has been shown to improve the thermostability and long-term shelf life of Newcastle Disease Virus (NDV). This study optimized the VFD process to improve the shelf life of NDV at laboratory-scale and then tested the optimized conditions at pilot-scale. The optimal NDV to T5 formulation ratio was determined to be 1:1 or 3:2. Using the 1:1 virus to formulation ratio, the optimal filling volumes were determined to be 13–17% of the vial capacity. The optimized VFD process conditions were determined to be at a shelf temperature of 25℃ with a minimum overall drying time of 44 h. The vaccine samples prepared using these optimized conditions at laboratory-scale exhibited virus titer losses of ≤ 1.0 log10 with residual moisture content (RMC) below 3%. Furthermore, these samples were transported for 97 days around China at ambient temperature without significant titer loss, thus demonstrating the thermostability of the NDV-VFD vaccine. Pilot-scale testing of the NDV-VFD vaccine at optimized conditions showed promising results for up-scaling the process as the RMC was below 3%. However, the virus titer loss was slightly above 1.0 log10 (approximately 1.1 log10). Therefore, the NDV-VFD process requires further optimization at pilot scale to obtain a titer loss of ≤ 1.0 log10. Results from this study provide important guidance for possible industrialization of NDV-VFD vaccine in the future.Key points• The process optimization and scale-up test of thermostable NDV vaccine prepared through VFD is reported for the first time in this study.• The live attenuated NDV-VFD vaccine maintained thermostability for 97 days during long distance transportation in summer without cold chain conditions.• The optimized NDV-VFD vaccine preparations evaluated at pilot-scale maintained acceptable levels of infectivity after preservation at 37℃ for 90 days, which demonstrated the feasibility of the vaccine for industrialization.

The Impact of Pulsed Electric Field Treatment and Shelf Temperature on Quality of Freeze-Dried Pumpkin

Pulsed electric field (PEF) treatment is known as a method that can intensify heat- and mass-transfer-based processes such as osmotic dehydration, drying, or freeze-drying. However, the literature about its impact on quality of freeze-dried products is limited to a few raw materials. The aim of this study was to analyze the effect of PEF on the cell disintegration index, selected bioactive compounds, and physical quality parameters of freeze-dried pumpkin. The final quality of the freeze-dried product was evaluated by residual moisture content, color analysis, total phenolic content, total carotenoid content, sugars content, and hygroscopic properties. The application of PEF treatment induced the disintegration of pumpkin cells even at low energy input (0.11 kJ/kg), and the saturation level of electroporation was reached after 4 kJ/kg. PEF treatment at 2 kJ/kg allowed 40% more total carotenoids to be retained in comparison to the untreated sample. Furthermore, all PEF-treated freeze-dried pumpkin samples exhibited lower sucrose content but had higher glucose and fructose contents in comparison to the reference samples. However, this effect was more pronounced when the shelf temperature was equal to 40 °C.

Cryogenic Pretreatment Enhances Drying Rates in Whole Berries.

The impact of cryogenic pretreatments on drying performance was studied in blueberries, seabuckthorn fruits and green grapes. The fruits were immersed in liquid nitrogen in 2 min freezing/thawing cycles (one to five). Untreated samples were used as the control. Drying experiments were carried out on treated and non-treated berries at 50 °C and 1 m/s (hot-air-drying), 50 °C and 25″ Hg vacuum (vacuum-drying), 30 mTorr total pressure and 25 °C shelf temperature (freeze-drying). The weight loss evolution of the foodstuffs was measured as a function of time. Microscopic (SEM and optical) determinations of the epicarp were performed. A visual inspection was performed and color changes and volume reductions were assessed before and after dehydration. The thickness of the berries' epicarp decreased between 20 and 50% (depending on the fruit) after 3-5 immersions in liquid N2. The drying kinetics was accelerated significantly for the three tested drying processes (i.e., drying time decreased from 48 to 16 h for blueberry freeze-drying). The best quality of dried berries was observed for pretreated blueberries after freeze-drying, keeping their volume, shape and color after the process. This work shows that "tailor-made" dried berry products with desired properties can be achieved and drying performance can be improved by the application of ultra-low temperature pretreatments.

Subsurface Warming of the West Antarctic Continental Shelf Linked to El Niño‐Southern Oscillation

AbstractRecent observations suggest that El Niño–Southern Oscillation (ENSO) impacts basal melting of West Antarctic ice shelves, yet sparse ocean observations limit our understanding of the associated processes. Here we investigate how ENSO events modulate subsurface West Antarctic shelf temperatures using high‐resolution global ocean‐sea ice model simulations. During El Niño, the subsurface shelf warming between 150 m and the shelf bottom can be up to 0.5°C in front of ice shelves. This warming arises from a weaker Amundsen Sea Low (ASL) and weaker coastal easterlies that reduce on‐shelf Ekman transport of cold surface waters, enabling enhanced transport of warm Circumpolar Deep Water (CDW) onto the shelf. A largely opposite response occurs during La Niña, with a stronger ASL and stronger Ekman transport that results in less cross‐shelf CDW transport and cooling in the subsurface. These findings have implications for interpreting basal melting on interannual to decadal time‐scales in West Antarctica.

Establishing a Multi-Vial Design Space for the Freeze-Drying Process by Means of Mathematical Modeling of the Primary Drying Stage

Primary drying is the most critical stage of the freeze-drying process. This work aimed to establish a design space for this process by means of mathematical modeling of the primary drying stage, capable of addressing the thermal characteristics of distinct vial suppliers. Modeling of primary drying was implemented on Microsoft Excel using steady-state heat and mass transfer equations at two extreme conditions as assessed by risk analysis, to predict product temperature and primary-drying time. The heat transfer coefficients (Kv) of four different vial suppliers were experimentally determined, both, at the center and edge of the freeze-dryer's shelf. Statistically significant differences (ANOVA p<0.05) were observed between suppliers throughout the assessed pressure range. Overall, the average Kve/Kvc (edge/center) ratio was higher than 1.6 for all suppliers due to the radiation effect. A design space for the drying process was established using mathematical modeling taking into account the Kv of the worst-case supplier, in the shelf edge. A primary drying cycle was carried out at a shelf temperature of -25 °C and a chamber pressure of 45 mTorr for 8 % sucrose and at -10 °C and 75 mTorr for 5 % NaCl. Freeze-dried products with good cosmetic appearance were obtained for the four vial suppliers both, in the shelf center and edge. The results show that it is possible to predict and establish the critical parameters for the primary drying stage, under a design space concept, considering the differences in the Kv of vial suppliers without adverse consequences on the quality of the finished freeze-dried product.

Efficient freeze-drying of foamed strawberry puree: a study on drying kinetics and physicochemical properties

The production of high-quality strawberry powder is of significant interest in the food industry. This study examines the impact of shelf temperature (10, 20, and 40 ℃) on the foaming...

Effects of Freeze-Drying on Sensory Characteristics and Nutrient Composition in Black Currant and Sea Buckthorn Berries

Fresh berries contain numerous components that can undergo complex changes during the drying process. This study aims to investigate the effect of freeze-drying on the sensory and chemical properties of black currant and sea buckthorn berries. Freeze-drying was performed at a shelf temperature of 35–55 °C with a step of 5 °C and durations of 18, 20, 22, and 24 h. Comparing the final freeze-dried berries with their fresh counterparts, it was observed that at a shelf temperature of 50 °C and a drying time of 18 to 20 h, there was a minimal loss in the content of vitamins, organic acids, and carbohydrates. However, based on organoleptic evaluations, the best results were achieved after drying for 20 h. Furthermore, the preservation of citric and malic acids in black currant berries, along with citric, tartaric acids, and sucrose in sea buckthorn berries, was only at 45.6% when the freeze-drying time was extended to 22 h. Considering the physical and chemical properties of listed freeze-dried berries, the optimal parameters were identified as a shelf temperature of 50 °C and a drying time of 20 h. The findings from this study serve as a foundation for selecting appropriate freeze-drying parameters for various types of berries.

The Freeze-Drying of Pharmaceuticals in Vials Nested in a Rack System-Part II: Primary Drying Behaviour.

The freeze-drying of biopharmaceuticals is a common strategy to extend their shelf-life and facilitate the distribution of therapeutics. The drying phase is the most demanding one in terms of energy consumption and determines the overall process time. Our previous work showed how the loading configuration can impact freezing. This paper focuses on primary drying by comparing the thermal behaviour of vials loaded in direct contact with the shelf or nested in a rack system. The overall heat transfer coefficient from the apparatus to the product was evaluated at different chamber pressures (5-30 Pa) and shelf temperatures (from -10 °C to +30 °C), and in the case of various vial positions (central, semi-border, and border vials). Because of the suspended configuration, the heat transfer coefficient was less affected by chamber pressure in vials nested in a rack system. The two loading configurations displayed comparable heat transfer efficiency below 10 Pa. For higher chamber pressure, the heat transfer coefficients of nested vials were lower than those of vials in direct contact with the shelf. Nevertheless, the rack system was beneficial for reducing the inter-vial variability as it promoted higher uniformity in the heat transfer coefficients of central vials. Eventually, thermal image analyses highlighted limited temperature differences between the vials and the rack system.

Future Response of Antarctic Continental Shelf Temperatures to Ice Shelf Basal Melting and Calving

AbstractWe investigate feedbacks between subsurface continental shelf ocean temperatures and Antarctic glacial melt using a coupled climate model. The model was forced with SSP5‐8.5 and an uncoupled projection of basal melt and calving fluxes. SSP5‐8.5 forcing with fixed pre‐industrial glacial melt warms all continental shelves, such that historically “cool” and “fresh” shelves transition to “warm.” Additional glacial melt, added at depth, cools the Eastern Ross, Amundsen, and Bellingshausen seas, suggesting a negative feedback on basal melt—a novel result for a coarse resolution coupled model. From the Weddell Sea, along East Antarctica, and into the western Ross Sea—where continental shelves transition to a “warm” state—additional glacial melt increases temperatures at the continental shelf sea floor, suggesting a positive feedback. The sign of the glacial melt–subsurface temperature feedback is critically dependent on continental shelf properties, climate state, and the vertical distribution of glacial melt inputs.

Heat Flux Analysis and Assessment of Drying Kinetics during Lyophilization of Fruits in a Pilot-Scale Freeze Dryer.

Vacuum freeze-drying as a process for achieving high product quality has attracted increasing attention in the last decade. Particularly in the pharmaceutical field and food processing industries, lyophilization can produce high-quality products compared to samples dried by conventional methods. Despite its benefits, lyophilization is a time-consuming and costly process that requires optimization of a number of process parameters, including shelf temperature, chamber pressure, freezing rate, and process time. This paper reports on the implementation of heat flux measurements that allow noninvasive real-time determination of the endpoint of the primary drying stage as an essential parameter for the effective optimization of the overall drying time. Quantitative analysis of the drying kinetics of five fruits (kiwifruit, avocado, Asian pear, persimmon, and passion fruit) was assessed by comparing the heat flux and temperature profiles of samples during the lyophilization process. For a 24 h lyophilization cycle, average heat fluxes in the primary drying phase ranged from 250 to 570 W/m2. A significant correlation was found between the temperature and heat flux distributions at the estimated endpoint of the sublimation process and the corresponding transition into the secondary drying stage. Furthermore, good agreement was also found for the freezing phase. The use of real-time heat flux measurements proved to be a cost-effective experimental method to better understand the process variables in order to reduce the lyophilization cycle time and overall energy consumption.

Determination of organoleptic indicators and vitamin c content in freezed raspberry

Due to the growing demand for functional nutrition, raspberries are of considerable interest, as they are sources of nutrients and various biologically active compounds which has high antioxidant activity. Yet, fresh berries are seasonal and perishable due to the high water content, which affects their constant availability. One of the oldest methods drying is used to remove water and ensure the stability of food during storage. Currently, one of the most advanced processing method used to expand the shelf life of berries, preserve vitamins and desired organoleptic properties is freeze-drying. The purpose of this work was to determine the organoleptic parameters and vitamin C content in freeze-dried raspberries, with respect to drying parameters. It was found that during freeze-drying of raspberries, the best organoleptic indicators and maximum preservation of vitamin C are observed at a shelf temperature of 35 0C and a duration of 18 hours. An increase in the parameters of the drying process (time and temperature) leads to a deterioration of organoleptic parameters and a decrease in vitamin C in freeze-dried berries.

Influence of freeze-drying parameters on the content of polyphenols and anthocyanins in strawberries

Strawberry berries are a valuable product rich in vitamins, anthocyanins, and polyphenolic compounds that have antioxidant effects on human health. However, due to the deterioration and seasonal availability, the issue of their long-term storage is highly relevant. Freeze-drying, a modern preservation method, preserves their properties during storage. Since the drying process can affect the appearance, nutrient content, and antioxidant activity of berries, the purpose of this study was to investigate the effects of freeze-drying parameters on the content of anthocyanins and polyphenols in Albion variety strawberries. The heating temperatures of the freeze-drying were 35°C, 40°C, 45°C, and 50°C, and the sublimation process times were 18, 20, and 22 hours. Optimal conditions were found: a shelf temperature of 45°C and 18 hours of drying. These conditions preserved both the strawberries' initial qualities and their high anthocyanin content, with only an 8.4% decrease. Similarly, polyphenol content decreased by 3.9%, while the strawberries maintained strong antioxidant activity.

Root Cause Analysis of An Inverse Relationship Between The Ice Nucleation Temperature, Process Efficiency And Quality of A Lyophilized Product

The aim of this study was to probe an unexpected relationship between the ice nucleation temperature (TIN), process efficiency and product attributes in a controlled ice nucleation (CIN) lyophilization process. An amorphous product was lyophilized with (CIN-5 °C, CIN-7 °C or CIN-10 °C) or without (NOCIN) control of ice nucleation. Process parameters and product attributes were monitored and compared using a series of advanced in-line and off-line process analytical technology (PAT) tools. Unexpectedly, an indirect relationship was observed between TIN and primary drying efficiency for the CIN processes. Further, the CIN-5 °C process was associated with higher product resistance to mass flow than corresponding CIN-7 °C and CIN-10 °C processes. Surprisingly, the air voids in some NOCIN products were larger than CIN-5 °C products but comparable to CIN-7 °C. Heat flux analysis revealed an indirect relationship between TIN and the minimum hold time required to complete solidification. The heat flux analysis also revealed all products underwent complete solidification prior to primary drying. The order of homogeneity in water activity of the products was CIN-5 °C ≥NOCIN>CIN-7 °C. The higher homogeneity in water activity of CIN-5 °C than corresponding CIN-7 °C processes indicated that the lower process efficiency of CIN-5 °C could not be attributed to unsuccessful induction of ice nucleation during CIN-5 °C. High resolution micro-CT imaging and Artificial Intelligence Image analysis revealed cake wall deformation in CIN-7 °C and NOCIN products but not in CIN-5 °C. In addition, NOCIN products had bimodal distribution in air voids with median size range of 4–5 µm and 151.9–309 µm, respectively, hence the lower process efficiency of NOCIN despite the higher D90. Thus, the observed relationship between TIN and process efficiency may be attributed to microstructural changes post freezing. This hypothesis was corroborated by visible macroscopic cake collapse in NOCIN products but not in CIN products after lyophilization at a higher shelf temperature. In conclusion, the advantages of controlling the ice nucleation temperature of a lyophilization process may only be attained through a robust process design that takes into consideration the primary and secondary drying process parameters. Further, combined use of advanced in-line and off-line PAT tools for process and product characterization may hasten the at scale adoption of advance techniques such as CIN.

Application of Quality by Design Principles to the Development of Oral Lyophilizates Containing Olanzapine.

Oral lyophilizates are intended for application to the oral cavity or for dispersing in water. The purposes of this research were: (i) to set up the quality by design approach in the development of oral lyophilizates for drug incorporation; and (ii) to evaluate the established approach by comparing its outcomes with experimentally obtained results. Within the knowledge space, properties about drugs, excipients, and the lyophilization process were acquired, followed by the determination of critical quality attributes via risk identification. Risks were assessed by failure mode and effective analysis, which recognized critical material attributes, i.e., type, concentration, particle size, solubility of drug and excipients, while as main critical process parameters, cooling rate, shelf temperature, and chamber pressure during drying were pointed out. Additionally, design space was established using the Minitab® 17 software and valued with an 88.69% coefficient of determination. A detailed comparison between the model and experimental results revealed that the proposed optimal compositions match in the total concentration of excipients (6%, w/w) in the pre-lyophilized liquid formulation, among which mannitol predominates. On the other hand, a discrepancy regarding the presence of gelatin was detected. The conclusion was that the set model represents a suitable onset toward optimization of drug-based oral lyophilizates development, preventing unnecessary investment of time and resources.

Study and optimization of formulation parameters during freeze–drying cycles of model probiotic: Morphology characterization of lyophilisates by scanning electron microscopy

These experimental data are concerning the optimization of freeze-drying cycles of a model-type Casei probiotic bacteria with water based formulations using lactose and polymer polyvinylpyrrolidone (PVP) as cryo-/lyo-protectants. After a previous study devoted to the influence of the main freeze-drying parameters (freezing rates; shelf temperature; absolute pressure) on the bacteria survival ratios, this paper reports some morphological data obtained by scanning electron microscopy (SEM) with the final lyophilisates. The numerous and original SEM images realized with different formulations of water binary or ternary mixtures with fixed operating conditions proved to be very useful to explain and to understand the different bacteria survival ratios observed. Thus, with bacteria or micro-organisms systems, this powerful investigation method of characterization of lyophilisates morphology should be more largely used in the future for setting up the optimal formulations parameters (composition) and the connected operating physical parameters of freeze-drying steps (freezing rate, shelf temperature, absolute pressure).

Design of pliek-u dryer using Dafa-type solar energy

One of the food diversification strategies of coconut commodity is to process it into Pliek U. Pliek U is a typical food of the Province of Aceh, Indonesia, which in its processing stage requires a drying process. So far, Pliek U drying process is often conducted conventionally through direct drying (sun drying), so that Pliek U produced is susceptible to dust and other dirt contamination. This research aimed to design a Pliek U dryer using Dafa type solar energy. The Dafa type solar energy dryer used a turbine ventilator with a vertical axis wind turbine equipped with two solar collectors. This turbine had a simple shape and construction and was arranged like the letter S. While the two parts of the solar collector were used to collect energy from the sun directly. In the experiment, the blank test was carried out in the time range, namely from 10.20 am to 04.50 pm in sunny weather, with an interval of 30 minutes for each temperature data recording. The empty test results of the Dafa type solar energy dryer showed that the average shelf temperature was 44.21 °C, the collector temperature was 45.64 °C, and the ambient temperature was 31.14 °C. This initial test revealed that the performance ability of the tool was very effective in maintaining temperature during the drying process, so that further tests using materials for drying Pliek U may be carried out.

Experimental Study and Modelling of the Sublimation and Desorption Periods for Freeze Drying of Apple, Banana and Strawberry

Slices of fresh apple, banana and strawberry were frozen at -20 oC and freeze-dried using a shelf temperature of 40 oC. Theoretical expressions were proposed to predict vapor transfer kinetics during the primary and secondary drying stages. In the former, a model that predicts the sublimation rate as a function of time, considering the increasing dried layer thickness, was used, which improves greatly the sublimation time equation offered in several textbooks without adding much complexity. In the latter, an analytical solution of the unsteady state diffusion equation was applied. Permeabilities were determined for the primary drying model at an absolute pressure of about 30 Pa, though the relevant kinetic coefficient combines permeability and the mass of ice to sublime relative to the dry matter (sublimation kinetic coefficient). In the secondary drying stage, diffusion coefficients of vapor in the dried layer were in the order of 10−09 m2s−1 for pressures of about 3-5 Pa. In both periods, agreement of predicted and experimental values was more than satisfactory. A minimum freeze-drying time of 12, 6.8 and 8.7 h, considering a final moisture content of 4% w/w, was calculated for apple, banana and strawberry, respectively. Normalized drying curves showed a faster sublimation rate for banana, intermediate for strawberry and slowest for apple. On the other hand, desorption curves showed a faster desorption rate for apple, intermediate for banana and slower for strawberry. In each period, the ordering of the relevant kinetic coefficients (sublimation and diffusion coefficients, respectively) represented the ordering of experimental curves.