Freeze drying of pharmaceuticals in vials: Influence of freezing protocol and sample configuration on ice morphology and freeze-dried cake texture

Hottot, Aurélie; Vessot, Séverine; Andrieu, Julien

doi:10.1016/j.cep.2006.09.003

Cited by 133 publications

(72 citation statements)

References 9 publications

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“…Instead, it is believed that the efficiency of latent heat removal determined the final pore size, as it has already been noted that set freezing temperatures, which are sufficiently high, can slow crystallization enough to allow annealing to occur before the end of solidification [21]. Unsurprisingly, as a clear link between annealing and increased crystal size has already been established, the largest pore size, 200 mm, occurred after the addition of an intentional thermal hold [6].…”

Section: Scaffold Structure: Influence Of Freezing Protocolmentioning

confidence: 99%

“…However, none of these thermal parameters encompasses the changes in structure owing to crystal growth and annealing, which has been shown to have a significant impact on ice [18]. Molecular movement near equilibrium has been demonstrated not only to affect crystal size, but also to contribute to phenomena such as phase separation in polymer systems [6,18,19]. To capture the effects of annealing on the crystal structure, it was necessary to define a new thermal parameter: time at equilibrium, or the time which the slurry spends in a temperature range where crystal growth is most actively occurring around the equilibrium freezing temperature.…”

Section: Defining Time At Equilibriummentioning

confidence: 99%

“…While the term annealing can commonly refer to both crystal growth effects or thermal processing steps, in this study 'annealing' refers to the rearrangement of crystal structure and 'thermal hold' refers to a step within the set freezing protocol which encourages crystal structures to rearrange. The effects of annealing become more pronounced as the length and temperature of the thermal hold increase [6,14]. As the freezing protocol influences crystal growth, changes to the freezing protocol have produced large ranges of pore sizes, ranging from 80 to 320 mm, of interest for tailoring scaffolds for diverse cell types.…”

Section: Introductionmentioning

confidence: 99%

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A design protocol for tailoring ice-templated scaffold structure

Pawelec

Husmann

Best

et al. 2014

J. R. Soc. Interface.

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ResearchCite this article: Pawelec KM, Husmann A, Best SM, Cameron RE. 2014 A design protocol for tailoring ice-templated scaffold structure. J. R. Soc. In this paper, we show, for the first time, the key link between scaffold architecture and latent heat evolution during the production of porous biomedical collagen structures using freeze-drying. Collagen scaffolds are used widely in the biomedical industry for the repair and reconstruction of skeletal tissues and organs. Freeze-drying of collagen slurries is a standard industrial process, and, until now, the literature has sought to characterize the influence of set processing parameters including the freezing protocol and weight percentage of collagen. However, we are able to demonstrate, by monitoring the local thermal events within the slurry during solidification, that nucleation, growth and annealing processes can be controlled, and therefore we are able to control the resulting scaffold architecture. Based on our correlation of thermal profile measurements with scaffold architecture, we hypothesize that there is a link between the fundamental freezing of ice and the structure of scaffolds, which suggests that this concept is applicable not only for collagen but also for ceramics and pharmaceuticals. We present a design protocol of strategies for tailoring the ice-templated scaffold structure.

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Section: Scaffold Structure: Influence Of Freezing Protocolmentioning

confidence: 99%

Section: Defining Time At Equilibriummentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A design protocol for tailoring ice-templated scaffold structure

Pawelec

Husmann

Best

et al. 2014

J. R. Soc. Interface.

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“…Previous studies using nanocapsules and albumin have shown that ice crystal size increases with increasing annealing temperature. 16,18 In this study, an annealing temperature of À108C was used to produce a large increase in growth rate while staying safely below the melting temperature of the frozen suspension. The effects of the introduction of this step and the length of the annealing time used were the focus of this study.…”

Section: Novel Freeze-drying Methods Applied To Collagen-gag Scaffoldsmentioning

confidence: 99%

“…15 Although annealing has been used to create larger ice crystals to facilitate shorter drying times for freeze-dried pharmaceuticals, the effects of annealing on the pore structure of freeze-dried scaffolds have yet to be investigated. [16][17][18] We hypothesize that annealing can be used to increase the pore size of CG scaffolds. Therefore, the specific objectives of this study were to determine (1) the effects of reducing T f to below À408C on scaffold pore size and (2) to test our hypothesis that the introduction of an annealing step during freeze-drying would lead to an increase in the pore size of CG scaffolds.…”

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confidence: 99%

Novel Freeze-Drying Methods to Produce a Range of Collagen–Glycosaminoglycan Scaffolds with Tailored Mean Pore Sizes

Haugh

Murphy

O’Brien

2010

Tissue Engineering Part C: Methods

224

196

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• to copy, distribute, display, and perform the work.• to make derivative works. Under the following conditions:• Attribution -You must give the original author credit.• Non-Commercial -You may not use this work for commercial purposes.• The pore structure of three-dimensional scaffolds used in tissue engineering has been shown to significantly influence cellular activity. As the optimal pore size is dependant on the specifics of the tissue engineering application, the ability to alter the pore size over a wide range is essential for a particular scaffold to be suitable for multiple applications. With this in mind, the aim of this study was to develop methodologies to produce a range of collagen-glycosaminoglycan (CG) scaffolds with tailored mean pore sizes. The pore size of CG scaffolds is established during the freeze-drying fabrication process. In this study, freezing temperature was varied (À108C to À708C) and an annealing step was introduced to the process to determine their effects on pore size. Annealing is an additional step in the freeze-drying cycle that involves raising the temperature of the frozen suspension to increase the rate of ice crystal growth. The results show that the pore size of the scaffolds decreased as the freezing temperature was reduced. Additionally, the introduction of an annealing step during freeze-drying was found to result in a significant increase (40%) in pore size. Taken together, these results demonstrate that the methodologies developed in this study can be used to produce a range of CG scaffolds with mean pore sizes from 85 to 325 mm. This is a substantial improvement on the range of pore sizes that were possible to produce previously (96-150 mm). The methods developed in this study provide a basis for the investigation of the effects of pore size on both in vitro and in vivo performance and for the determination of the optimal pore structure for specific tissue engineering applications.

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