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In situ coating: an approach for particle modification and encapsulation of proteins during spray-drying
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2006 (English)In: Internation Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 323, no 1-2, 52-63 p.Article in journal (Refereed) Published
Abstract [en]

In this paper, we present a method for in situ coating of individual protein particles in a respirable size. The aim of the coating was to influence the particle/powder properties, and to reduce or prevent surface-induced conformational changes of the protein, during spray-drying, which was the method used for simultaneously preparing and coating particles. The investigated formulations included bovine serum albumin (BSA), trehalose and either of the two non-ionic polymers, hydroxypropyl methylcellulose (HPMC) and poly(ethylene oxide)–poly(propylene oxide) triblock co-polymer (Poloxamer 188). Complete protein coating as measured by electron spectroscopy for chemical analysis (ESCA) was achieved at a polymer concentration of approximately 1% of the total solids weight, and could be predicted from the dynamic surface tension at the air/water interface, as measured by the pendant drop method. Further, particle properties such as: size, dissolution time, powder flowability, and apparent particle density, as measured by gas pycnometry, were affected by the type and concentration of the polymer. In addition, the particle surface morphology could possibly be correlated to the surface elasticity of the droplet surface during drying. Moreover, an extensive investigation (Fourier transform infrared spectroscopy, circular dichroism and size exclusion chromatography) of the structural effects of protein encapsulated in a polymeric coating suggested that in situ coating provide particulate formulations with preserved native conformation and with a high stability during rehydration.

Place, publisher, year, edition, pages
2006. Vol. 323, no 1-2, 52-63 p.
Keyword [en]
polymeric particle coating, spray-drying, competitive surface adsorption, dynamic surface tension, surface morphology
National Category
Medicinal Chemistry
URN: urn:nbn:se:uu:diva-93366DOI: 10.1016/j.ijpharm.2006.05.066ISI: 000241346400007PubMedID: 16887302OAI: oai:DiVA.org:uu-93366DiVA: diva2:166823
Available from: 2005-09-02 Created: 2005-09-02 Last updated: 2011-05-27Bibliographically 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.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 15
Pharmaceutics, Spray drying, Particle formation, Density, Protein formulation, Encapsulation, Coating, Competitive adsorption, Polymer, ESCA, AFM, FTIR, Galenisk farmaci
National Category
Pharmaceutical Sciences
urn:nbn:se:uu:diva-5904 (URN)91-554-6322-3 (ISBN)
Public defence
2005-09-23, B22, BMC, Husargatan 3, Uppsala, 09:15
Available from: 2005-09-02 Created: 2005-09-02Bibliographically approved

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