Accelerated Freeze-Drying

De Luca, P. P., Klamat, M. S., Koida, C. Acceleration of freeze-drying Cycles of aqueous Solutions of Lactose and Sucrose with tertiary Buthylalcohol (tBA). Congr. Intern. Technol. Pharm. 5th Vol. 1, p. 439-447, 1989... 

Molecular imprinting is not limited to organic polymer matrices, but can also be applied to silica-based materials and even proteins. Proteins freeze-dried in the presence of a transition state analogue as template have been used successfully as catalysts, e.g., for the dehydrofluorination of a fluorobutanone. For instance, lyophilized 3-lactoglobulin imprinted in this manner with N-isopropyl-N-ni-trobenzyl-amine could accelerate the dehydrofluorination by a factor of 3.27 compared to the non-imprinted protein see Table 5 [62]. In a similar procedure, BSA was imprinted with N-methyl-N-(4-nitrobenzyl)-S-aminovaleric acid and showed an enhancement of the catalytic effect by a factor of 3.3 compared to the control protein for the same reaction see Table 5 [113]. 

In order to accelerate sample preparation, new extraction methodologies such as accelerated solvent extraction (ASE) and MAE, based on the use of elevated temperature and pressure to heat the mixture sample-solvent, have been recently developed and applied for PAH extraction from meat [695] and vegetables [696-698]. Garda Falcon et al. [699] used microwave treatment with hexane to accelerate PAH extraction from freeze-dried foods. The fat extracted in this way underwent microwave assisted saponification with ethanolic KOH. Hernandez-Borges et al. [700] combined microwave-assisted hydrolysis and extraction to isolate organic pollutants from mussels, while... 

The use of freeze-drying avoids an inherent disadvantage of spray drying, i.e., the elevated processing temperature, which accelerates the oxidation of polyunsaturated lipids. 

Barthomeuf C, Pourrat H, Pourrat A, Ibrahim H, Cottier PE. Stabilization of octastatin, a somatostatin analogue comparative accelerated stability studies of two formulations for freeze-dried products. Pharmaceutica Acta Helvetiae 1996 71 161-166. 

Nevertheless, the reliability of the assessment of the drop in titer by accelerated aging is disputable. The whole calculation principle relies on the fact that the kinetics follow laws of the Arrhenius type throughout the whole studied temperature domain. It so happens that this particular point is not that obvious if the dehydrated product contains an amorphous phase, which is quite frequently the case. As a matter of fact, a freeze-dried vaccine whose substrate contains sugars and proteins often has a vitreous transition temperature (Tg Lyo) greater than zero [12,25]. 

V. Damjanovic and D. Radulovic, Predicting the stability of freeze-dried Lactobacillus bifidus by the accelerated storage test. Cryobiology 5 101-104, 1968. 

Autoclaved rubber stoppers hold measurable amounts of water that are transferred to the freeze dried pro-duct and heating at 80° C accelerates this transfer. 

In the case of salami, starter cultures can be cultivated on meat substrate and freeze-dried, where they remain active at a large rate. The storable culture substrate is added to the salami raw mixture to start the desired ripening process. Depending on process course, it can already contain flavour or flavour-precursors which contribute to accelerating the ripening process. 

Controlled-release biodegradable PLG polymers loaded with parathyroid hormone were formulated as a freeze-dried form with particle size ranging from 27 to 47 i. The freeze-dried method did not alter the surface morphology, particle size, and parathyroid hormone content or release rate of the microspheres. The freeze-dried microspheres resuspended very rapidly and uniformly in solution. In vitro release studies indicated that except for a slight early burst ranging from 4-18%, release of parathyroid hormone from the nanoparticles was very slow over the first 14 days. At 15 days, release of parathyroid hormone accelerated rapidly. 

The plankton was collected from several ponds situated in the vicinity of the river Po. The ponds were fed by the Po water downstream to a power plant. The relatively high water temperature accelerated plankton growth, allowing the collection of the total amount necessary for the reference material within a relatively short period. The collection was done with a manually-operated net with 125 pm apertures. The wet material collected was packed in double-layer polythene bags and kept at -20 C until freeze-drying. 

P. Jameson, D. Creiff, and S. E. Crossberg, Thermal stability of freeze-dried mammalian interferons. Analysis of freeze-drying conditions and accelerated storage tests for murine interferon, Cryobiology 16, 301-314 (1979). 

Practical consequences of such metastable states and associated transitions for the freeze-drying of biopharmaceuticals are self-evident. Most damaging would be the uncontrolled release of water from a hydrate, giving rise to vial-to-vial variations in water content and water release during accelerated stability assays. Other consequences include the generation, but vial-to-vial variability, of polymorph mixtures. 

A.W. Ford and Z. Allahiary, The adverse effect of glycation of human serum albumin on its preservative activity in the freeze-drying and accelerated degradation of alkaline phosphatase, J. Pharm. Pharmacol., 1993, 45, 900-906. 

The limitations on heat transfer rates in conventionally conducted freeze drying operations have led early to the attempt to provide internal heat generation with the use of microwave power [21,22]. Theoretically, the use of microwaves should result in a very accelerated rate of drying because the heat transfer does not require internal temperature gradients and the temperature of ice could be maintained close to the maximum permissible temperature for the frozen layer without the need for excessive surface temperatures. 

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