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Effects of formulation and processin...

Badkar, Aniket V.

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Effects of formulation and processing stress on the physical stability of protein solutions.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Effects of formulation and processing stress on the physical stability of protein solutions./
作者:	Badkar, Aniket V.
面頁冊數:	141 p.
附註:	Source: Dissertation Abstracts International, Volume: 67-02, Section: B, page: 0902.
Contained By:	Dissertation Abstracts International67-02B.
標題:	Chemistry, Pharmaceutical. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3207479
ISBN:	9780542566387

Effects of formulation and processing stress on the physical stability of protein solutions.
Badkar, Aniket V.

Effects of formulation and processing stress on the physical stability of protein solutions. - 141 p.

Source: Dissertation Abstracts International, Volume: 67-02, Section: B, page: 0902.

Thesis (Ph.D.)--Mercer University, 2006.

Due to recent advances in biotechnology, several proteins and monoclonal antibodies (mAbs) are now being used as therapeutic agents. However, protein instability is an issue during protein formulation development. Protein unfolding and aggregation are one of the most common manifestations of protein instability, encountered in almost all stages of protein drug development. Biophysical and biochemical characterization of proteins is therefore important for understanding protein instability and underlying mechanisms. One of the aims of this work was to investigate the feasibility of using modulated differential scanning calorimetry (MDSC) as a novel thermal characterization technique for protein solutions. MDSC had the advantage over conventional DSC, of better resolution in separating overlapping thermal events such as unfolding and aggregation. Since unfolding and aggregation are a function of various formulation and processing conditions, the second aim of this work was to investigate the effects of solution conditions on the unfolding and aggregation behavior of IgG and its ability to form partially unfolded intermediate states. Partially unfolded intermediates have practical implications as these could act as reactive species in the aggregation pathway of proteins. It was found that even under moderate solution conditions (conditions that would generally favor stability of the native state) IgG had the propensity to undergo partial loss in its native conformation, resulting in formation of stable partially unfolded intermediates. Presence of these intermediates affected the aggregation potential of IgG solutions. The third aim was to investigate the effects of various processing stress conditions on the aggregation behavior of concentrated IgG formulations and the ability of polysorbate 80 in preventing its aggregation. It was found that aggregation of IgG was a function of the type of stress applied. Thermal stress resulted in both soluble and insoluble aggregates for IgG and the addition of polysorbate 80 did not prevent formation of these aggregates. In contrast, mechanical shaking under the conditions used caused formation of only insoluble aggregates and the addition of polysorbate 80 reduced the formation of these aggregates. Stress due to single and multiple freeze-thawing did not result in any observable aggregation of IgG solutions.

ISBN: 9780542566387Subjects--Topical Terms:

550957
Chemistry, Pharmaceutical.

Effects of formulation and processing stress on the physical stability of protein solutions.
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