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Particle size and density in spray drying: effects of carbohydrate properties
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2005 (English)In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 94, no 9, 2049-2060 p.Article in journal (Refereed) Published
Abstract [en]

The purpose of this study was to examine some fundamental aspects of the particle formation during spray drying, related to particle size and density. Particles were prepared in a laboratory spray dryer from carbohydrates with different solubility and crystallization propensity, such as lactose, mannitol, and sucrose/dextran 4:1. The feed concentrations ranged from 1% w/w to saturated and the size of droplets and particles were measured by laser diffraction. Particles were also characterized by various microscopy techniques (i.e., scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and light microscopy), differential scanning calorimetry (DSC), gas adsorption, and gas pycnometry. As demonstrated larger particles could be obtained by either increasing the droplet size during atomization; increasing the concentration of the feed solution; or decreasing the solubility of the solute. The apparent particle density, measured by gas pycnometry, was found negatively correlated to the feed concentration. Due to the nonlinear relationship between the feed concentration and the particle size, it was concluded that higher solids load would cause an increase in the effective particle density and that the reduction in the apparent particle density was a result of a gradually less permeable particle surface. Further, the crystallization propensity of the carbohydrate influenced the particle formation and resulted in either hollow or porous particles.

Place, publisher, year, edition, pages
Wiley , 2005. Vol. 94, no 9, 2049-2060 p.
National Category
Medicinal Chemistry
URN: urn:nbn:se:uu:diva-93363DOI: 10.1002/jps.20418OAI: oai:DiVA.org:uu-93363DiVA: diva2:166820
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.
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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