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Aqueous two-phase systems as a formulation concept for spray-dried protein
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2005 (English)In: International Journal of Pharmaceutics, Vol. 294, no 1-2, 73-87 p.Article in journal (Refereed) Published
Abstract [en]

This study investigates to what extent an aqueous two-phase system (ATPS) can encapsulate and protect the secondary structure of a protein during spray drying. The ATPSs contained polyvinyl alcohol (PVA) and dextran solutions, in different proportions. A model protein, bovine serum albumin (BSA) and, in some experiments, trehalose were added to the ATPS prior to spray drying. Electron spectroscopy for chemical analysis (ESCA), differential scanning calorimetry (DSC), UV spectrophotometry, size exclusion high-performance liquid chromatography (SEC-HPLC) and Fourier transform infrared spectroscopy (FTIR) were used for analysis of solid and reconstituted samples. The anticipated function of the ATPS was to improve the stability of the protein by preventing interactions with the air–liquid interface during drying and by improving the encapsulation of the protein in the dried powder. BSA was found to preferentially partition to the dextran phase and in the absence of PVA, BSA dominated the powder surface. In samples containing PVA, the polymer mainly covered the powder surface, even though the dextran-rich phase was continuous, thus preventing protein surface interactions and providing improved encapsulation. However, PVA was found to cause partial loss of the native structure of BSA although the protein was well encapsulated during spray drying.

Place, publisher, year, edition, pages
Elsevier , 2005. Vol. 294, no 1-2, 73-87 p.
National Category
Medicinal Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-93365DOI: 10.1016/j.ijpharm.2005.01.015OAI: oai:DiVA.org:uu-93365DiVA: diva2:166822
Available from: 2005-09-02 Created: 2005-09-02 Last updated: 2010-07-08Bibliographically approved
In thesis
1. Spray-Dried Powders for Inhalation: Particle Formation and Formulation Concepts
Open this publication in new window or tab >>Spray-Dried Powders for Inhalation: Particle Formation and Formulation Concepts
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Spray drying is a method with a high potential in the preparation of protein particles suitable for pulmonary delivery. However, surface induced denaturation of bio-molecules during atomization and subsequent drying can be substantial and it is therefore important to develop new formulation concept for concurrent encapsulation and stabilization of proteins during spray drying. Hence, with an overall objective to increase the knowledge of the formation of particulate systems for systemic administration of proteins by spray drying, the first part of this thesis, systematically investigated the particle formation by droplet size and particle size measurements. It was described how specific properties, such as the solubility and the crystallization propensity of the solute, can affect the product, e.g. the particle size, internal structures, and possibly particle density. A new method using atomic force microscopy (AFM) for the assessment of the effective particle density of individual spray-dried particles was demonstrated. In the second part, two different formulation concepts for encapsulation of protein during spray drying were developed. Both systems used non-ionic polymers for competitive adsorption and displacement of protein from the air/water interface during spray drying. The aqueous two-phase system (ATPS) of polyvinyl alcohol (PVA) and dextran, and the surface-active polymers, hydroxypropyl methylcellulose (HPMC) and triblock co-polymer (poloxamer 188) used for in situ coating, proved efficient in encapsulation of a model protein, bovine serum albumin (BSA). Inclusion of polymeric materials in a carbohydrate matrix also influenced several particle properties, such as the particle shape and the surface morphology, and was caused by changes in the chemical composition of the particle surface and possibly the surface rheology. In addition, powder performance of pharmaceutical relevance, such as dissolution and flowability, were affected.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 78 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 15
Keyword
Pharmaceutics, Spray drying, Particle formation, Density, Protein formulation, Encapsulation, Coating, Competitive adsorption, Polymer, ESCA, AFM, FTIR, Galenisk farmaci
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-5904 (URN)91-554-6322-3 (ISBN)
Public defence
2005-09-23, B22, BMC, Husargatan 3, Uppsala, 09:15
Opponent
Supervisors
Available from: 2005-09-02 Created: 2005-09-02Bibliographically approved

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