Hare, C, Bonakdar, T, Ghadiri, M orcid.org/0000-0003-0479-2845 et al. (1 more author) (2018) Impact breakage of pharmaceutical tablets. International Journal of Pharmaceutics, 536 (1). pp. 370-376. ISSN 0378-5173
Abstract
Tablets are the most common solid dosage form of pharmaceutical active ingredients due to their ease of use. Their dissolution behaviour depends on the particle size distribution and physicochemical properties of the formulation, and the compression process, which need to be optimised for producing consistently robust tablets, as weaker tablets are often prone to breakage during production, transport and end use. Tablet strength is typically determined by diametric compression and friability tests. The former gives rise to propagation of a crack on a plane along the compression axis, whilst the latter, carried out in a rotating drum, incurs surface damage and produces chips and debris. These tests produce different measures of strength, neither of which have been correlated with mechanical properties that are accountable for breakage, i.e. hardness, elastic modulus and fracture toughness. We propose a new method based on single tablet impact testing, following the work of Ghadiri and Zhang, 2002, who analysed particle damage by propagation of sub-surface lateral cracks and identified the fundamental form accountable for impact surface damage to be a lumped parameter related to hardness and fracture toughness. Microindentation, carried out separately, to determine fracture toughness led to complete failure of the tablets, hence an unreliable measurement of fracture toughness and no correlation with the experimental trend. In addition, by assuming the fracture toughness to be proportional to the square root of Young's modulus, the indentation measurements do not correlate well with the impact breakage. The discrepancy between the impact and indentation methods is expected to be due to mechanical property variation across the tablet surface, and with strain rate. The impact method is a more suitable test to describe tablet propensity for attrition as it directly represents the failure mode tablets may experience during processing under well-defined conditions. In contrast, the friability test subjects tablets to a similar breakage mechanism but under less well-defined conditions, whilst the compression test represents a different failure mode that is not representative of stresses incurred during processing.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Elsevier B.V. This is an author produced version of a paper published in International Journal of Pharmaceutics. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | breakage; fracture; friability; impact; indentation; tablets |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemical & Process Engineering (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 14 Dec 2017 15:37 |
Last Modified: | 02 Dec 2018 01:38 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.ijpharm.2017.11.066 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:125163 |