Freeze-Drying

Kharaghani, Abdolreza; Tsotsas, Evangelos; Wolf, Carolin; Beutler, Thomas; Guttzeit, Maik; Oetjen, Georg‐Wilhelm

doi:10.1002/14356007.h12_h01.pub2

Cited by 6 publications

(8 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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 time-consuming unacceptable freeze-drying runs in the development of lyophilization processes.…”

Section: Discussionmentioning

confidence: 99%

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

Matejtschuk

Bird²,

Ezeajughi³

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Matejtschuk

Bird²,

Ezeajughi³

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

“…For comparison, in [ 37 ], a value of K [m 2 /s] = 1.349 × 10 −4 (ε/τ) d (µm) was given, assuming pressure independence of the transport coefficient and solely slip flow, which yields a value of K = 1.15 × 10 −4 assuming τ = 1. This value is almost one order of magnitude larger than our values, which could be explained by the dominance of viscous flow in our model.…”

Section: Resultsmentioning

confidence: 99%

“…The drying rates of both cases are plotted together with heat- and mass-transfer-limited freeze drying from [ 37 ] in Figure 17 . As already expected from the discussions related to Figure 16 , the monomodal PN has a higher drying rate.…”

Section: Resultsmentioning

confidence: 99%

A Non-Isothermal Pore Network Model of Primary Freeze Drying

Thomik,

Faber,

Gruber

et al. 2023

Pharmaceutics

View full text Add to dashboard Cite

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.

show abstract

“…Finding linear decreases in saturation in all samples was surprising. In most cases, a nonlinear time dependency of the ice saturation was reported in the literature [ 4 , 40 ], clearly resulting from the receding of the sublimation front into the bulk material. Only a few studies document a linear trend similar to that observed in our experiments; however, in these examples, the temperature was continuously increased during the process [ 41 , 42 ] or heat was additionally supplied by microwaves [ 11 ].…”

Section: Resultsmentioning

confidence: 99%

“…The limitation of transport kinetics generally results in long drying times and an increase in an already high energy consumption. In addition, freeze-drying, or lyophilization, is conducted at low temperatures and pressure, which further impairs drying kinetics [ 1 , 2 , 3 , 4 ] and increases energy consumption. Increasing the temperature in the freeze-dryer accelerates the process [ 5 ]; however, it also increases the risk of structural damage to the material [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Freeze-Drying

Cited by 6 publications

References 17 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

A Non-Isothermal Pore Network Model of Primary Freeze Drying

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

Contact Info

Product

Resources

About