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Droplet and particle size relationship and shell thickness of inhalable lactose particles during spray drying
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2003 (English)In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 92, no 4, 900-910 p.Article in journal (Refereed) Published
Abstract [en]

To find means of controlling the size and density of particles intended for inhalation the relationship between droplet and particle size during spray drying was investigated. Lactose solutions were atomized with a two-fluid nozzle and dried in a laboratory spray drier. The effects of nozzle orifice diameter, atomization airflow and feed concentration on droplet and particle size were examined. Mass median diameter of both droplets and particles were analyzed with laser diffraction. In addition, scanning electron microscopy and transmission electron microscopy were used for studies of particle shape and morphology. It was demonstrated that nozzle orifice diameter and airflow, but not feed concentration controlled the droplet size during atomization. Increasing droplet size increased particle size but the effect was also influenced by feed concentration. Particles from solutions of a low concentration (1% w/w) were smaller than those from higher concentrations (5-20% w/w). This may be partly explained by lower yields at higher feed concentrations, but may also be related to differences in drying rate. Spray-dried lactose solutions formed hollow particles, and it was suggested that the shell thickness of the particles increased with increasing feed concentration.

Place, publisher, year, edition, pages
Wiley , 2003. Vol. 92, no 4, 900-910 p.
National Category
Medicinal Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-93362DOI: 10.1002/jps.10352OAI: oai:DiVA.org:uu-93362DiVA: diva2:166819
Available from: 2005-09-02 Created: 2005-09-02 Last updated: 2017-12-14Bibliographically 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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