A methodological evaluation and predictive in silico investigation into the multi-functionality of arginine in directly compressed tablets

Amr ElShaer, Waseem Kaialy, Noreen Akhtar, Affiong Iyrie, Tariq Hussain, Raid Alany, Afzal R. Mohammed

Research output: Contribution to journalArticle

Abstract

The acceleration of solid dosage form product development can be facilitated by the inclusion of excipients that exhibit poly-/multi-functionality with reduction of the time invested in multiple excipient optimisations. Because active pharmaceutical ingredients (APIs) and tablet excipients present diverse densification behaviours upon compaction, the involvement of these different powders during compaction makes the compaction process very complicated. The aim of this study was to assess the macrometric characteristics and distribution of surface charges of two powders: indomethacin (IND) and arginine (ARG); and evaluate their impact on the densification properties of the two powders. Response surface modelling (RSM) was employed to predict the effect of two independent variables; Compression pressure (F) and ARG percentage (R) in binary mixtures on the properties of resultant tablets. The study looked at three responses namely; porosity (P), tensile strength (S) and disintegration time (T). Micrometric studies showed that IND had a higher charge density (net charge to mass ratio) when compared to ARG; nonetheless, ARG demonstrated good compaction properties with high plasticity (Y=28.01MPa). Therefore, ARG as filler to IND tablets was associated with better mechanical properties of the tablets (tablet tensile strength (σ) increased from 0.2±0.05N/mm2 to 2.85±0.36N/mm2 upon adding ARG at molar ratio of 8:1 to IND). Moreover, tablets' disintegration time was shortened to reach few seconds in some of the formulations. RSM revealed tablet porosity to be affected by both compression pressure and ARG ratio for IND/ARG physical mixtures (PMs). Conversely, the tensile strength (σ) and disintegration time (T) for the PMs were influenced by the compression pressure, ARG ratio and their interactive term (FR); and a strong correlation was observed between the experimental results and the predicted data for tablet porosity. This work provides clear evidence of the multi-functionality of ARG as filler, binder and disintegrant for directly compressed tablets.

LanguageEnglish
Pages272–281
Number of pages10
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume96
Early online date5 Aug 2015
DOIs
Publication statusPublished - Oct 2015

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Computer Simulation
Tablets
Arginine
Indomethacin
Tensile Strength
Excipients
Porosity
Powders
Pressure
Dosage Forms
Pharmaceutical Preparations

Bibliographical note

© 2015, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

Keywords

  • indomethacin
  • arginine
  • compressibility
  • compactibility
  • tabletability
  • disintegration time
  • multifunctional excipient
  • direct compression

Cite this

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title = "A methodological evaluation and predictive in silico investigation into the multi-functionality of arginine in directly compressed tablets",
abstract = "The acceleration of solid dosage form product development can be facilitated by the inclusion of excipients that exhibit poly-/multi-functionality with reduction of the time invested in multiple excipient optimisations. Because active pharmaceutical ingredients (APIs) and tablet excipients present diverse densification behaviours upon compaction, the involvement of these different powders during compaction makes the compaction process very complicated. The aim of this study was to assess the macrometric characteristics and distribution of surface charges of two powders: indomethacin (IND) and arginine (ARG); and evaluate their impact on the densification properties of the two powders. Response surface modelling (RSM) was employed to predict the effect of two independent variables; Compression pressure (F) and ARG percentage (R) in binary mixtures on the properties of resultant tablets. The study looked at three responses namely; porosity (P), tensile strength (S) and disintegration time (T). Micrometric studies showed that IND had a higher charge density (net charge to mass ratio) when compared to ARG; nonetheless, ARG demonstrated good compaction properties with high plasticity (Y=28.01MPa). Therefore, ARG as filler to IND tablets was associated with better mechanical properties of the tablets (tablet tensile strength (σ) increased from 0.2±0.05N/mm2 to 2.85±0.36N/mm2 upon adding ARG at molar ratio of 8:1 to IND). Moreover, tablets' disintegration time was shortened to reach few seconds in some of the formulations. RSM revealed tablet porosity to be affected by both compression pressure and ARG ratio for IND/ARG physical mixtures (PMs). Conversely, the tensile strength (σ) and disintegration time (T) for the PMs were influenced by the compression pressure, ARG ratio and their interactive term (FR); and a strong correlation was observed between the experimental results and the predicted data for tablet porosity. This work provides clear evidence of the multi-functionality of ARG as filler, binder and disintegrant for directly compressed tablets.",
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A methodological evaluation and predictive in silico investigation into the multi-functionality of arginine in directly compressed tablets. / ElShaer, Amr; Kaialy, Waseem; Akhtar, Noreen; Iyrie, Affiong; Hussain, Tariq; Alany, Raid; Mohammed, Afzal R.

In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 96, 10.2015, p. 272–281.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A methodological evaluation and predictive in silico investigation into the multi-functionality of arginine in directly compressed tablets

AU - ElShaer, Amr

AU - Kaialy, Waseem

AU - Akhtar, Noreen

AU - Iyrie, Affiong

AU - Hussain, Tariq

AU - Alany, Raid

AU - Mohammed, Afzal R.

N1 - © 2015, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

PY - 2015/10

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KW - arginine

KW - compressibility

KW - compactibility

KW - tabletability

KW - disintegration time

KW - multifunctional excipient

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