Analytical method development for powder characterization: Visualization of the critical drug loading affecting the processability of a formulation for direct compression

Cosima Hirschberg, Changquan Calvin Sun, Jukka Rantanen

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Characterization of particulate systems (powders) is one of the remaining scientific challenges. Evaluation of powder behaviour is often empirical and the decision-making processes are experience-based. There is a need for development of analytical instrumentation enabling more fundamental understanding of powder behaviour. Flowability and tabletability, two key factors in commercial scale manufacturing of tablets with direct compression (DC) approach, were analysed for formulations containing increasing amounts of several model active pharmaceutical ingredients (APIs). Flowability was investigated using a ring shear tester and tablets were prepared at four different compression pressures using a single punch tablet press. Thereby, a material sparing screening approach was developed to estimate the influence of APIs on behaviour of a given DC formulation. Additionally, this approach is useful for estimating the low threshold amount of API (wt%), at which the properties of an API start affecting the powder behaviour of a given formulation (API-excipient mixture). This threshold will be referred to as critical drug loading. The flowability of microcrystalline cellulose (reference grade pH 102) was used as a threshold for adequate flowability of model formulations. The threshold for tablet tensile strength was set to 2 MPa. Simultaneous visual presentation of both- flowability and tabletability were used for a fast evaluation of manufacturability of a given formulation. The results confirmed that flowability is more sensitive to drug loading than tabletability, and that the critical drug loading for a DC formulation is strongly affected by particulate properties of API. For example, decreasing the particle size of paracetamol led to rapid decrease in flowability index, whereas the tabletability was not affected.

Original languageEnglish (US)
Pages (from-to)462-468
Number of pages7
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume128
DOIs
StatePublished - Sep 5 2016

Bibliographical note

Funding Information:
We thank DFE Pharma for sponsoring some of the excipients in this study. C.C. Sun thanks Lundbeckfonden and PhRMA Foundation for partial support to his sabbatical stay at the University of Copenhagen.

Publisher Copyright:
© 2016 Elsevier B.V.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • Flowability
  • Particle shape
  • Particle size
  • Powder characterization
  • Tabletability

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