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Toward better understanding of powder avalanching and shear cell parameters of drug-excipient blends to design minimal weight variability into pharmaceutical capsules
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 1766860
Author(s) Nalluri, Venkateshwar Rao; Puchkov, Maxim; Kuentz, Martin
Author(s) at UniBasel Puchkov, Maxim
Year 2013
Title Toward better understanding of powder avalanching and shear cell parameters of drug-excipient blends to design minimal weight variability into pharmaceutical capsules
Journal International journal of pharmaceutics
Volume 442
Number 1-2
Pages / Article-Number 49-56
Keywords Binary mixtures, Critical behavior, Percolation theory, Quality by Design, Capsule filling, Mass uniformity
Abstract

Powder flow of mixtures is complex and not properly understood. The selection of drug-excipient blends with inadequate powder flow can lead to quality issues of the final dosage form. Therefore, this work aims at a better understanding of how changes in powder flow of binary blends can lead to weight variability in pharmaceutical capsule filling. We used image-analysis-based powder avalanching and shear cell testing to study blends of paracetamol and microcrystalline cellulose. A pilot-scale machine with dosator principle was employed for encapsulation. As a result, the powder flow properties improved generally with rising amounts of microcrystalline cellulose. However, a negative correlation was observed between avalanche angle and angle of internal friction. Results were discussed and percolation theory was considered to explain abrupt changes in the observed flow properties. This was particularly helpful for analysis of the capsule-filling data, since capsule weight variability displayed a threshold behavior as a function of the mixture fraction. The capsule weight variability correlated with the angle of internal friction as well as with the angle and the energy of avalanches. Based on the results we proposed a strategy of how to design minimal weight variability into powder-filled capsules.

Publisher Elsevier
ISSN/ISBN 0378-5173
edoc-URL http://edoc.unibas.ch/dok/A6124565
Full Text on edoc No
Digital Object Identifier DOI 10.1016/j.ijpharm.2012.08.010
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/22917747
ISI-Number WOS:000314690200008
Document type (ISI) Journal Article
 
   

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