Ingham, Andrew James; (2005) Technological enhancements in freeze drying. Doctoral thesis (Ph.D.), University College London.

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Abstract

The aims of this thesis are to tackle some of the newer areas of lyophilisation protection including enhancing technology to better determine the primary drying length of a freeze drying cycle. An attempt has been made to focus research from the perspective of a research freeze-dryer when used for scale up studies. It is hoped that the data gathered due to this approach can be applied across a broad range of formulations. Control of the freeze drying cycle is examined, relating a formulation's physical change induced during a freeze-drying cycle to both the freezing and drying stages. Changes occuring to the size of a liposome population with narrow polydispersity using laser light scattering are used to examine the effects of freezing rate, low temperature processing and rehydration; aggregation during both conventional and non-conventional freeze- drying cycles is also investigated. The relationship between protein protection and sucrose recrystalisation was determined with a combination of modelling and sequence analysis. Sucrose recrystalisation in the dry state was examined with a variety of enzymes, unifying existing research by allowing the prediction of losses in enzyme activity by examination of the amino acid sequence. Enzymes studied included: catalase, lactate dehydrogenase, lysozyme, asparaginase, adenosine deaminase, β-galactosidase, fructose-6-phosphate kinase (phosphofructokinase), β-amylase, glucose oxidase, ascorbate oxidase and ribonuclease.

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