Determination of 3D pore network structure of freeze-dried maltodextrin

Thomik, Maximilian; Gruber, Sebastian; Foerst, Petra; Tsotsas, Evangelos; Vorhauer-Huget, Nicole

doi:10.1080/07373937.2021.1966030

Cited by 9 publications

(10 citation statements)

References 49 publications

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“…More generally, in terms of formulation for freeze-drying, though guided by general principles (Kharaghani et al, 2017), consideration must be given on a case-by-case basis to the influence of individual components on the thermal properties and final freeze-dried appearance of any given formulation. This again underlines the value of thermal analytical methods in predicting successful freeze-drying outcomes and other new analytical techniques are being introduced (Thomik et al, 2022), and their use will help avoid expensive and timeconsuming unacceptable freeze-drying runs in the development of lyophilization processes.…”

Section: Discussionmentioning

confidence: 95%

Impact of Formulation Choices on the Freeze-Drying of an Interleukin-6 Reference Material

Matejtschuk

Bird²,

Ezeajughi³

et al. 2022

Front. Mol. Biosci.

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Formulation is critical to successful delivery of lyophilized biologics. We have compared the impact of buffer choice and the addition of sodium chloride (a formulant often viewed as unfavorable for freeze-drying applications) on the outcome of trial lyophilization of an interleukin-6 reference material. While phosphate buffer was a preferred choice and yielded well-formed cakes associated with fair recovery of biological activity, the resultant residual moisture content was high (2–4% w/w). By inclusion of isotonic levels of NaCl, the freeze-dried appearance and process were not impaired, but the residual moisture delivered was considerably reduced to levels <1% w/w. We postulate that this is due to the presence of a more open-cake structure and support this with evidence from thermal analysis and scanning electron microscopy. This work illustrates the importance of wide ranging empirical investigation of formulation options in order to optimize freeze-drying outcomes for biologics.

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Section: Discussionmentioning

confidence: 95%

Impact of Formulation Choices on the Freeze-Drying of an Interleukin-6 Reference Material

Matejtschuk

Bird²,

Ezeajughi³

et al. 2022

Front. Mol. Biosci.

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“…Pore space was segmented into individual pores using watershed segmentation. As described in [ 25 ], pore diameters of all samples were calculated according to the equivalent diameter method. For the MD30 method with lamellar pores, the hydraulic diameter is a suitable alternative approach [ 17 ].…”

Section: Experimental Materials and Methodsmentioning

confidence: 99%

“…At the same time, pore scale models can assess heat and mass transfer kinetics at the front. Pore network models are a common tool to study drying processes in porous media [ 22 , 23 ], but have not yet been widely applied to study freeze-drying, except for our own work [ 24 , 25 ]. Such models can be built using realistic data for the porous material (e.g., data obtained using micro-computed X-ray tomography (µ-CT)); therefore, they can predict interesting structure–transport correlations.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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“…Only a few parameters are involved that need to be a priori defined, and these parameters concern the boundary conditions of heat and mass transfer as well as the material’s morphology. The PNM can be realized with regular lattices, e.g., as proposed in [ 20 ], or reconstructed porous domains can be implemented, e.g., [ 21 ]. The size of the domain and the incorporated physical mechanisms thereby dictate the computational effort.…”

Section: Introductionmentioning

confidence: 99%

A Non-Isothermal Pore Network Model of Primary Freeze Drying

Thomik,

Faber,

Gruber

et al. 2023

Pharmaceutics

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In this work, a non-isothermal pore network (PN) model with quasi-steady vapor transport and transient heat transfer is presented for the first time for the application of primary freeze drying. The pore-scale resolved model is physically based and allows for the investigation of correlations between spatially distributed structure and transport conditions. The studied examples were regular PN lattices with a significantly different structure, namely a spatially homogeneous PN, also denoted as monomodal PN, and a PN with significant structure variation, referred to as bimodal PN because of its bimodal pore size distribution. The material properties selected for the solid skeleton in this study are equivalent to those of maltodextrin. The temperature ranges applied here were −28 °C to −18 °C in the PN and −42 °C in the surrounding environment. The environmental vapor pressure was 10 Pa. The PNs were dried with constant temperature boundary conditions, and heat was transferred at the top side by the vapor leaving the PN. It is shown how the structural peculiarities affect the local heat and mass transfer conditions and result in a significant widening of the sublimation front in the case of the bimodal PN. The possibility of spatially and temporally resolved front structures is a unique feature of the PN model and allows the study of situations that are not yet described by classical continuum approaches, namely heterogeneous frozen porous materials. As demonstrated by the thin layers studied here, the pore-scale simulations are of particular interest for such situations, such as in lyomicroscopes or collagen scaffolds, where a length-scale separation between dry and ice-saturated regions is not possible.

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Determination of 3D pore network structure of freeze-dried maltodextrin

Cited by 9 publications

References 49 publications

Impact of Formulation Choices on the Freeze-Drying of an Interleukin-6 Reference Material

Impact of Formulation Choices on the Freeze-Drying of an Interleukin-6 Reference Material

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

A Non-Isothermal Pore Network Model of Primary Freeze Drying

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