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Effect of preparation method on compactability of paracetamol granules and agglomerates
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.
2007 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 336, no 1, 148-158 p.Article in journal (Refereed) Published
Abstract [en]

The objective of this study was to investigate the effect of fracture strength of paracetamol particles on their compactability. For this purpose two series of paracetamol particles were prepared by crystal agglomeration and by granulation using different solvents. A free flowing particle size fraction of all types of particles was characterized with respect to their shape, degree of agglomeration and single fracture strength. The powders were compressed to tablets and the compression mechanism of the particles and the evolution in tablet micro-structure were assessed by compression parameters derived from the Heckel and Kawakita equations and by a tablet permeabililty coefficient. Tablet tensile strength and porosity were determined. The degree of deformation and fragmentation during compression varied between agglomerates and granules and was dependent on their failure strength. The granules varied in compactability with particle failure strength while the agglomerates showed limited variation. It is proposed that, the dominant mechanism of compression for the granules was permanent deformation while for the agglomerates it was fragmentation. It was thus found that the compression mechanism of the particles was dependent on both the degree of agglomeration and the particle failure strength.

Place, publisher, year, edition, pages
2007. Vol. 336, no 1, 148-158 p.
Keyword [en]
Wet granulation, Crystal agglomeration, Particle fracture strength, Degree of agglomeration, Tablet tensile strength
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-95421DOI: 10.1016/j.ijpharm.2006.11.046ISI: 000246491100018PubMedID: 17196775OAI: oai:DiVA.org:uu-95421DiVA: diva2:169618
Available from: 2007-02-01 Created: 2007-02-01 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Identification and Variation of some Functionality Related Characteristics of Pharmaceutically Relevant Solid Materials and their Effect on Product Performance
Open this publication in new window or tab >>Identification and Variation of some Functionality Related Characteristics of Pharmaceutically Relevant Solid Materials and their Effect on Product Performance
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this thesis was to identify some functionality related characteristics of pharmaceutically relevant solid materials and to study the effect of their variation on processing behaviour and product performance. For this purpose, particles with different characteristics were prepared under a variety of conditions by crystal agglomeration, wet granulation and spray drying. The effect of particle size distribution on the evolution of the tablet microstructure during and after compression was investigated. The compression behaviour of particles with different nominal strength and degrees of agglomeration was studied and the influence of the surfactant concentration of amorphous particles on the compression behaviour was examined. The response of the powders to compression was described with the help of various techniques characterising the microstructure and tensile strength of the tablets produced.

Furthermore, a method suitable for observing drug release from single matrix granules was developed and used to study the effect of granule porosity and compaction pressure on the drug release process.

The particle size distribution did not influence the evolution of the tablet porosity or the tensile strength during compression, but it could have an effect on the evolution of the tablet microstructure during short-term storage, depending on the instability mechanism. The compression behaviour of particles prepared by crystal agglomeration and wet granulation was dependent on their degree of agglomeration and their failure strength. For particles with similar solid state properties and compression behaviour, the surface energy appears to have an effect on the bonding strength of adsorption bonds acting at interparticulate junctions. Using the method developed to observe the drug release from single matrix granules, reproducible data was obtained enabling the drug release process to be characterised. Depending on the type of matrix and the compaction pressure, the drug release rate could be enhanced or retarded.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 92 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 47
Keyword
Pharmaceutics, Particle size distribution, Degree of agglomeration, Amorphous lactose, Matrix agglomerates, Drug release, Compactability, Tablet tensile strength, Particle fracture strength, Surfactant, Compression, Galenisk farmaci
Identifiers
urn:nbn:se:uu:diva-7462 (URN)978-91-554-6789-0 (ISBN)
Public defence
2007-02-23, B 41, BMC, Husargatan 3, Uppsala, 09:15
Opponent
Supervisors
Available from: 2007-02-01 Created: 2007-02-01Bibliographically approved

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Fichtner, FraukeAlderborn, Göran

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