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An atomic force microscopy approach for assessment of particle density applied to single spray-dried carbohydrate particles
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2007 (English)In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 96, no 4, 905-912 p.Article in journal (Refereed) Published
Abstract [en]

To evaluate an atomic force microscopy (AFM) approach for effective density analysis of single spray dried carbohydrate particles in order to investigate the internal structure of the particles. In addition, the AFM method was compared to an established technique, that is gas pycnometry. Resonant frequency AFM analysis was employed for determination of the mass of individual particles of spray-dried lactose, mannitol, and a mixture of sucrose/dextran (4:1). The effective particle density was calculated using the diameter of the spherical particles obtained from light microscopy. The apparent particle density was further analyzed with gas pycnometry. It was observed by microscopy that particles appeared either solid or hollow. A solid appearance applied to an effective particle density close to the true density of the material, whereas a density around 1 g/cm3 corresponded to a hollow appearance. However, carbohydrates, which crystallized during spray drying, for example, mannitol appeared solid but the average effective particle density was 0.95 g/cm3, indicating a continuous but porous structure. AFM measurements of effective particle density corroborate the suggestion of differences in particle structure caused by the varying propensity of carbohydrates to crystallize during spray drying, resulting in mainly either amorphous hollow or crystalline porous particles.

Place, publisher, year, edition, pages
2007. Vol. 96, no 4, 905-912 p.
Keyword [en]
Amorphous, Atomic force microscopy (AFM), Crystallization, Gas pycnometry, Microparticles, Morphology, Particle density, Spray drying
National Category
Pharmaceutical Sciences
URN: urn:nbn:se:uu:diva-93364DOI: 10.1002/jps.20795ISI: 000245426900016PubMedID: 17094123OAI: oai:DiVA.org:uu-93364DiVA: diva2:166821
Available from: 2005-09-02 Created: 2005-09-02 Last updated: 2011-02-08Bibliographically 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.
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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