Sublimation Rate Research Articles

Best Practices and Guidelines (2022) for Scale-Up and Tech Transfer in Freeze-Drying Based on Case Studies. Part 1: Challenges during Scale Up and Transfer

The freeze-drying process scale-up and transfer remain a complicated and non-uniform practice. We summarized inefficient and good practices in these papers and provided some practical advice. It was demonstrated that using the same process set points/times in laboratory and commercial scale dryers may lead to loss of product quality (collapse or vial breakage). The emerging modeling approach demonstrated practical advantages. However, the upfront generation of some input parameters (vial heat transfer coefficient, minimum controllable pressure, and maximum sublimation rate) is essential for model utilization. While the primary drying step can be transferred with a high degree of confidence (e.g., using modeling), and secondary drying is usually fairly straightforward, predicting potential changes in product behavior during freezing remains challenging.Graphical

Mass Accommodation of Water on Ice at Environmentally Relevant Temperatures: Insights from Fast Scanning Calorimetry.

Using a conceptually simple, quasi-adiabatic, fast scanning calorimetry technique, we have investigated the sublimation kinetics of ice films with thicknesses ranging from 14 to 400 nm at environmentally relevant temperatures, between 223 and 268 K. The technique enables accurate determination of ice sublimation rates into vacuum under the conditions of free molecular flow during rapid yet quasistatic heating. The measured sublimation fluxes yield the vapor pressure of the ice samples, which is indistinguishable from that derived from experiments under near-equilibrium conditions. Thus, in agreement with the microscopic reversibility principle, we conclude that the mass accommodation coefficient of water by ice is unity and temperature-independent in the temperature range of the studies. We discuss these findings in the context of current computational and theoretical research into the chemistry and physics of aqueous interfaces.

Modelling of the Process of Extrusion of Dry Ice through a Single-Hole Die Using the Smoothed Particle Hydrodynamics (SPH) Method.

This article presents the outcome of research on modelling the process of the extrusion of crystalline dry ice. The purpose of this process is to densify the material and obtain pellets of several millimeters in diameter. This reduces the sublimation rate in ambient conditions of the material whose temperature in a solid state is 195 K. A lower sublimation rate means a reduction of the loss of product in its final applications, which include refrigeration and reduction of atmospheric emissions of gaseous CO2. A ram-type extruder was considered in this analysis, in which dry ice was extruded through a single-hole die of varying geometry. The article presents the results of numerical analyses of the extrusion process, using a simulation method based on the Smoothed Particle Hydrodynamics (SPH) approach. The results from simulations were verified by the experimental data in terms of the maximum force required to complete the process, in order to assess the applicability of the proposed method in further research on dry ice compression.

Cyclododecane shaping, sublimation rate and residue analysis for the extraction of painting micro-samples from resin cross-sections

Cross-section preparation of painting micro-samples is part of their routine analysis. This type of preparation can be used for several analytical techniques, such as scanning electron microscopy, Fourier-transform infrared spectroscopy, Raman spectroscopy, and optical microscopy. These techniques offer high-resolution imaging and/or elemental information, providing access to technical and material data important for the interpretation, preservation, and restoration of painted artworks. However, it also means that the material from the sample embedded in the resin becomes unreachable for further analysis, except for the polished surface of the cross-section. Degradation of the embedding medium can also occur over time, which can lead to misinterpretation, loss of information, or even complete destruction of the embedded sample. In the field of cultural heritage, cyclododecane (CDD) is commonly used for the consolidation and protection of objects, and is used in the preparation of cross-sections to prevent contamination of the sample by the embedding medium. This study enhanced the existing preparation process by shaping the CDD layer to enable extraction of the micro-sample from the resin if needed, without compromising the integrity of the sample. Moreover, the purity, the sublimation rate in a normal environment and a vacuum, and the impact of CDD on three different types of samples (historical painting on a canvas, wall painting fragment, model sample) were examined.

A Mathematical Model for Sublimation of a Thin Film in Trace Explosive Detection Problem.

Here, we introduce an advanced mathematical model for the sublimation of thin films of explosives. The model relies on the Hertz-Knudsen-Langmuir (HKL) equation that describes the vaporization rate of an explosive and controls the mass exchange between the surface and the ambient air. The latest experimental data on sublimation and diffusion of 2,4,6-trinitrotoluene (TNT) monocrystals were factored in, as well as the data on the sublimation rate of hexogen (RDX), octogen (HMX), and picramide (TNA) traces. To advance the mathematical model we suggested previously, we took into account the structure of a substrate on which a thin explosive layer was deposited. The measurement problem of the sublimation rate and limits of an explosive arises from developing and advancing remote detection methods for explosives traces. Using mathematical modelling, we can identify a detectable quantity of a specific explosive under given conditions. We calculated the mass of the explosive in the air upon sublimation of thin explosive films from the surfaces over a wide range of the parameters in question and made conclusions regarding the application limits of the devised standoff trace explosive detection techniques.

TGA investigation of the volatilisation of fipronil at elevated temperatures

In the present work, thermogravimetric analysis (TGA) was used to study the vaporisation behaviour of fipronil in the temperature range of 150 to 230 °C, i.e., below and above the melting point of the insecticide. The sublimation and evaporation rates were measured using isothermal thermogravimetric analysis. The vapour pressure was estimated assuming that the ideal gas law holds and that the rate of mass loss can be accounted for by the variation of the evaporation rate with liquid depth within the sample crucible and the vapour diffusion coefficient for the evaporating compound into the nitrogen gas. From this, the sublimation enthalpy was determined to be 120 ± 4 kJ⋅mol−1, while the enthalpy of evaporation was 72 ± 5 kJ mol−1. Separate measurements using benzoic acid indicated that the vapour pressure predicted by the thermogravimetric method employed could be accurate to within about 12%.

Inhibiting Sublimation of Thymol by Cocrystallization

A thymol:4,4’-dipyridyl (2:1) cocrystal (Form I) is reported to suppress thymol sublimation. The cocrystal was prepared via solution-mediated phase transformation and its structure is sustained by O-H (phenol) ··· N (pyridyl) hydrogen bonds between two individual components. A cocrystal polymorph (Form II) was formed via solid state transformation or via vapor phase upon heating. Using gravimetry analysis, it was demonstrated that cocrystal Form I decreased the sublimation rate of thymol by 38-fold. This study demonstrates that cocrystallization is an effective approach to reduce vapor pressure and sublimation of solids, thus achieving odor-masking.

Evaluation of the Sublimation Process of Some Purine Derivatives: Sublimation Rate, Activation Energy, Mass Transfer Coefficients and Phenomenological Models.

Caffeine and theophylline are compounds with important applications in the pharmaceutical industry and other fields of the chemical industry. These purine derivatives have simple chemical structures, therefore, the evaluation of their sublimation process contributes to the development of mass transfer analysis methods that can later be applied to other compounds with more complex structures. With the help of thermogravimetric analysis in isothermal conditions, the kinetic study of the sublimation of caffeine and theophylline, along with the evaluation of kinetic parameters (activation energy and the pre-exponential factor), was carried out. Global mass transfer coefficients were determined, which vary for caffeine between 53 × 10−8 and 631 × 10−8 mol/s·m2·Pa, and for theophylline between 68 × 10−8 and 441 × 10−8 mol/s·m2·Pa. The dimensionless equations of the form: have been proposed, which allow the determination of individual mass transfer coefficients at temperatures between 130 and 160 °C for caffeine and between 170 and 200 °C for theophylline.

Possible Atmospheric Water Vapor Contribution from Martian Swiss Cheese Terrain

Mars’s south polar residual cap (SPRC) is a several-meters-thick CO2 ice cap with a variety of features, including quasi-circular depressions known as “Swiss cheese” that may expose underlying water ice. Swiss cheese pits have been suggested as a source for the observation of unusually high water vapor during the southern summer of Mars Year (MY) 8 (1969). To evaluate this hypothesis, we map the current extent of Swiss cheese pits to estimate the contribution to atmospheric water vapor from sublimation from the pits. We use data from the Mars Reconnaissance Orbiter Context Camera to map individual features and use the Mars Climate Sounder to obtain surface temperatures to estimate areas of exposed water ice to infer the amount of water vapor sublimated under typical south polar summer atmospheric conditions. We find that there is a negligible impact on atmospheric water vapor from sublimation with the current coverage and temperatures of Swiss cheese terrain (0.2% of the SPRC at an average of ∼161 K). At current typical temperatures, complete removal of residual CO2 from 99% of the SPRC would be required to sublimate enough water vapor to reproduce the MY 8 observation. However, a modest increase in temperature (∼20 K) could lead to a dramatic increase in sublimation rate, such that only water ice over 2.6% of the SPRC area would recreate the MY 8 observation. >180 K surface water ice has been observed on Mars, but such temperatures are likely transient at the south pole over the past ∼30 Mars years.

Martian and lunar sulfur concrete mechanical and chemical properties considering regolith ingredients and sublimation

• Sulfur sublimation rate at vacuum is 8000 times lower at −60 °C than at 20 °C. • Sulfur concrete permeability decreases strongly with higher sulfur content. • Sulfur concrete porosity does not change much with varying sulfur content. • The presence of alumina in sulphur concrete results in higher porosity. • Alumina and iron oxide together in sulphur concrete leads to lower porosity. Space constructions require unique materials suitable for the harsh conditions in space. Sulfur concrete (SC) is one of the most promising materials for such applications. However, the behavior of sulfur concrete in a vacuum, microgravity, and different temperature conditions and its chemical changes has not been well established yet. This study investigated the effect of vacuum, sulfur content, and compaction (trowel effect) on mechanical and hydro-mechanical properties. Moreover, this study assesses the impact of chemical reactions of aluminum and iron oxides with molten sulfur on the sulfur concrete’s mechanical properties via X-ray diffraction analysis (XRD), scanning electron microscopy (SEM-EDS), and Fourier-transform infrared spectroscopy (FTIR). The predictions from this research show that the sublimation rate under vacuum conditions at very low temperature (−60 °C) can be reduced nearly 8000 times compared with that at 20 °C according to the vapor pressure-sublimation rate relationship. In addition, mechanical experimental tests show that a slight increase in sulfur content dramatically reduces the permeability of sulfur concrete. On the other hand, the porosity is not much affected by the sulfur content. Moreover, sample compaction leads to a significant reduction and increment of the hydro-mechanical and mechanical strength, respectively, indicating the trowel's positive effect. Chemically, sulfur dioxide reacts with alumina and iron oxide via chemical adsorption, and then reaction with molecular oxygen produces S O 4 2 - confirmed by SEM-EDS, XRD, and FTIR results. The presence of alumina increases the sample porosity, although, together with iron oxide, another mineral, namely A l 2 F e 2 S O 4 6 ( H 2 O ) 12 . 6 H 2 O (Aluminocoquimbite), is formed resulting in a lower porosity. To conclude, we have shed light on sulfur concrete properties and preparation processes in unconventional environments and we have shown how different unknown parameters affect the mechanical and chemical properties of the sulfur binder.

Seasons of Ice: Water Ice Migration and Seasonal Transient Shadow at the Lunar Poles

AbstractLunar water ice can be broadly categorized as belonging to one of two populations: deep, ancient, stable deposits, and shallow, transient, recent deposits. However, a third state for lunar ice is also possible. Temporary sequestration occurs when ice is deposited into a transiently shadowed region at the lunar poles. These temporarily sequestered ice deposits are unstable over geologic time scales, but in the short term, are capable of a wide range of migration, sublimation, and retention patterns due to their thermally dependent sublimation and migration rates. We developed a model to characterize the range of possible migration and retention behaviors for temporarily sequestered ice deposits within locations with dynamic illumination conditions. We found that water ice migration, sublimation, and retention varies across the lunar polar environment, with neighboring locations experiencing different illumination and thermal conditions. We found that the residence times of temporarily sequestered ice deposits in some high latitude, non‐shadowed regions can be similar to or greater than the length of time spent above the long term stability temperature of ice during lunar winter months, leading to incomplete removal of surface or near surface ice during the day. We also found that shallowly buried, unstable ice deposits take longer to sublimate than surface deposits, leading to a temporal lag in escaping ice. This work suggests that temporary sequestration can lead to complex ice migration and retention patterns at high latitudes, with ice sublimation efficiency varying across the lunar polar environment due to local, small scale differences in illumination conditions.

Study of the influence of the synthesis process on the sublimation of TATP and HMTD by thermal gravimetric analysis

The influence of two important parameters in the synthesis of TATP (the type of catalyst and the presence or absence of stirring during the precipitation process) on its sublimation was studied by thermal gravimetric analysis. TATP synthesised with H2SO4 as catalyst and without stirring during the precipitation process sublimates faster than the other types, due to its transformation in DADP under influence of the presence of residual acid. Between the other types of TATP, where no transformation to DADP was observed, only small differences in sublimation rate were measured. These differences are related to their different sublimation temperatures as observed during DSC experiments.The influence of the same synthesis parameters on the sublimation of HMTD was also investigated. Unlike TATP, HMTD decomposes during sublimation. This decomposition depends on the synthesis parameters. AKTS simulations show that the HMTD synthesis parameters have an influence on the temperature dependency of the kinetic parameters of the HMTD decomposition.

Dry heterometallic resist processing based on thermal sublimation deposition and development

A negative tone heterometallic ring resist (HRR) based on a supramolecular assembly [ NH2(allyl)2 ] [ Cr7NiF8(piv)16 ] with previously demonstrated resolution down to sub 10-nm lines is evaluated in terms of its flexibility to be processed either “wet” (spin cast and solvent developed) or “dry” (deposition and development by vacuum sublimation). The implemented sublimation hardware fits easily in the wafer load-lock chamber of extreme ultraviolet and electron beam exposure systems dedicated to research and development activities and allows for HRR films to be uniformly deposited or developed in the same vacuum environment. The HRR shows a sublimation rate dependence on temperature that obeys a Clausius–Clapeyron relation, with thermal stability up to 275°C. Flood exposures of the HRR show identical sensitivity between wet- and dry-deposited films, whereas contrast degradation is observed when dry development is initiated by increasing the temperature prior to system pump down. A modified sublimation setup allows for the dry development of exposed HRR samples inside the electron beam tool without breaking vacuum. In this case, nominally patterned 25 nm L/S are identically resolved at 30 keV for wet- or dry-developed HRR.

Technical transfer and commercialisation of lyophilised biopharmaceuticals — application of lyophiliser characterisation and comparability

A holistic approach was taken to characterise lyophilisers at both laboratory and commercial scale to design a focused validation strategy for commercialising parenteral drug products. Vial heat transfer coefficients (Kv) and equipment mass transfer boundaries were generated for a Lyostar II and three commercial scale IMA Lyomax lyophilisers. Kv studies were performed using gravimetric methodologies. Kv calculated for the Lyostar II was equivalent to the commercial equipment at 133 µBar however trended higher below 133 µBar and lower above 133 µBar potentially impacting primary drying product temperature during scale-up depending on the chamber pressure recipe set point. Kv profiles were consistent within and across the commercial equipment. Edge effect was most prominent at commercial scale with minimal shielding of the edge vials in contrast to the presence of a metal ring around the vial pack in the Lyostar II. Equipment capability studies for mass transfer showed commercial scale equipment could achieve lower chamber pressure and greater sublimation rates when compared to the Lyostar II. Furthermore, differences were also measured between large-scale lyophilisers based on condenser orientation (horizontal vs vertical). The results demonstrate greater equipment capability of the two-storey vertical configuration with respect to choked flow regime. Worst-case locations within a commercial lyophiliser were identified providing rationale for reduced sampling for product shelf-mapping locations. This work provides guidance on execution of commercial scale characterisation studies and application of the data to enhance scale-up, technical transfer and focused process validation strategies.

Sublimation and Diffusion Kinetics of 2,4,6-Trinitrotoluene (TNT) Single Crystals by Atomic Force Microscopy (AFM).

In this article, we report the in-situ nanoscale experimental measurement of sublimation rates, activation energy of sublimation, and diffusion coefficients of 2,4,6-trinitrotoluene (TNT) single crystals in air using atomic force microscopy (AFM). The crystals were prepared by slow evaporation at 5 °C using acetone-dissolved TNT. The mass loss was calculated by monitoring the shrinkage of the surface area of layered islands formed on the surface of the TNT crystals due to sublimation upon isothermal heating at temperatures below the melting point. The results suggest the sublimation process occurs via two-dimensional detachment of TNT molecules from the non-prominent facets on the crystal surface which imitates the nucleation and crystal growth process. Sublimation rates are one order of magnitude smaller than previously reported values. However, the calculated activation energy (112.15 ± 3.2 kJ/mol) and temperature-dependent sublimation rates agree well with the reported values for TNT thin films and microcrystals determined by UV-vis absorbance spectroscopy and quartz crystal microscopy (QCM) (90–141 kJ/mol). The average diffusion coefficient is (4.35 × 10–6 m2/s) which is within the range of the reported theoretical values with an average of 5.59 × 10–6 m2/s, and about 25% less than that determined using thermogravimetric analysis for powder TNT.

Pressure‐Dependent Chemical Decomposition of an HMX‐Based PBX During Low‐Velocity Impacts

AbstractHMX decomposition kinetics are usually calibrated in the temperature range around 200 °C. This leads to an underestimation of several orders of magnitude of the thermal explosion times during impacts compared to measurements collected in Henson and Smilowitz, in Non‐shock initiation of explosives, Shock wave science and technology reference library, 2010. It highlights the incomplete physics used in the single‐ or multi‐stage decomposition kinetics to model the solid‐to‐gas transformation of HMX. The experimental device proposed in this work allows the observation of sample pressure and size during heating tests and thus allows the phase transition and thermal explosion of the samples to be observed in real time. The Henson and Smilowitz model is revisited by integrating (1) the mechanical resistance of the molecular network to the phase change and (2) a dependence of the vaporization and sublimation rates on the pressure. The latter describes the pressure‐dependence on the virtual melting mechanism and consequently on the presence or absence of δ‐HMX in the solid and liquid states. Good correlations between the numerical results and data are obtained. The modified model is then extrapolated to the low velocity impact range.

Temperature and Heat Transfer Control During Freeze Drying. Effect of Vial Holders and Influence of Pressure

ObjectiveA common issue of freeze drying is the inhomogeneity between samples, both in regards to water content and structure. The purpose of this study is to address this issue, and try to understand the cause of inhomogeneity in the heat transfer and sample temperature.MethodsThe temperature and the heat transfer was measured using different setups, both with and without vial holders at various positions at different shelf temperature and chamber pressures. By comparing sublimation rate measurements (water sample) with temperature equilibrium measurements with a non-evaporating liquid (oil sample), the heat transfer contribution from radiation and conduction could be separated and investigated individually.ResultsThe oil sample temperature increases each time the pressure is decreased; the increase is highest at lower shelf temperatures. Using vial holder reduces the deviation between the samples but have limited effect on the temperature increase. The sublimation rate for water sample is pressure dependent and samples close to the walls have a higher sublimation rate than vials in the center. The sublimation rate increases slightly when using a vial holder but the deviation between vials becomes more random.ConclusionsThe heat transfer consists of conduction through rectified vapor and radiation from surrounding walls, about 65–75% of the heat is transferred by conduction and 25–35% by radiation under normal operational conditions. As the vial holder is also influenced by the radiation, the vial inside the holder is indirectly affected by the surrounding radiation.

Experimental Study of the Impact of Pore Structure on Drying Kinetics and Sublimation Front Patterns

Freeze-drying frozen maltodextrin solutions with solid contents of 5% and 30% (w/w) was experimentally investigated using neutron imaging at PSI Villigen/Switzerland. Different solid contents, as well as annealing at −5 °C for 11 h, were used to modify the porous structure of the samples, which was quantified using X-ray computed tomography. Annealing of the 5% (w/w) sample, with a pore size distribution (PSD) of 23.7 ± 11.1 µm, yielded a very open pore space with high porosity (ε = 0.96) and a PSD of 33.0 ± 27.0 µm. In contrast, the higher solid content resulted in small, lamellar, narrow pores with high anisotropy and a porosity of ε = 0.65, as well as a PSD of 13.5 ± 4 µm. In operando neutron imaging was used to show the impact of the structure of frozen maltodextrin on the overall drying kinetics and shape of the sublimation front during freeze-drying. For this purpose, a freeze-drying stage was employed, which allowed a novel approach to time- and space-resolved monitoring of the ice phase. The sublimation front propagation was quantitatively analyzed based on ice saturation profiles and sublimation rates. The dependence of drying velocity on structure is nicely demonstrated by the data. In addition, it is shown that the sublimation front widened during freeze-drying, resulting in either rather concave or convex shape depending on morphological parameters.

Development of a Nondestructive Monitoring Technique for Vial Freeze-Drying Process using Microwave Resonance Spectroscopy

In this study, we developed a nondestructive monitoring technique for the drying progress of products in vials during the freeze-drying process using microwave resonance spectroscopy. An aqueous mannitol solution, commonly used as an excipient for injectable drugs, was used as the model material. The drying progress was determined using a mathematical model (i.e., Rp−Kv model), in which the parameters of mass and heat transfer were experimentally determined while considering the variation of the drying progress and position of the product on the drying shelf. A strong correlation was found between the extent of drying and changes in the microwave resonance spectrum. The simulation results were regressed against the changes in the resonance peak frequency and resonance intensity. Using this regression equation, the extent of drying could be predicted from the acquired spectral data. In this way, we were able to estimate the design space (the relationship between the operating conditions, internal temperature of the product, and sublimation rate), which changed with the extent of drying from the spectrum obtained inline, showing that it is possible to set the appropriate operating conditions based on the spectra.

Cosmogenic nuclide dating of two stacked ice masses: Ong Valley, Antarctica

Abstract. We collected a debris-rich ice core from a buried ice mass in Ong Valley, located in the Transantarctic Mountains in Antarctica. We measured cosmogenic nuclide concentrations in quartz obtained from the ice core to determine the age of the buried ice mass and infer the processes responsible for the emplacement of the debris currently overlaying the ice. Such ice masses are valuable archives of paleoclimate proxies; however, the preservation of ice beyond 800 kyr is rare, and therefore much effort has been recently focused on finding ice that is older than 1 Myr. In Ong Valley, the large, buried ice mass has been previously dated at > 1.1 Ma. Here we provide a forward model that predicts the accumulation of the cosmic-ray-produced nuclides 10Be, 21Ne, and 26Al in quartz in the englacial and supraglacial debris and compare the model predictions to measured nuclide concentrations in order to further constrain the age. Large downcore variation in measured cosmogenic nuclide concentrations suggests that the englacial debris is sourced both from subglacially derived material and recycled paleo-surface debris that has experienced surface exposure prior to entrainment. We find that the upper section of the ice core is 2.95 + 0.18 / −0.22 Myr old. The average ice sublimation rate during this time period is 22.86 + 0.10 / −0.09 m Myr−1, and the surface erosion rate of the debris is 0.206 + 0.013 / −0.017 m Myr−1. Burial dating of the recycled paleo-surface debris suggests that the lower section of the ice core belongs to a separate, older ice mass which we estimate to be 4.3–5.1 Myr old. The ages of these two stacked, separate ice masses can be directly related to glacial advances of the Antarctic ice sheet and potentially coincide with two major global glaciations during the early and late Pliocene epoch when global temperatures and CO2 were higher than present. These ancient ice masses represent new opportunities for gathering ancient climate information.