Applying surface energy derived cohesive-adhesive balance model in predicting the mixing, flow and compaction behaviour of interactive mixtures

Sharad Mangal, Felix Meiser, Geoffrey Tan, Thomas Gengenbach, David A.V. Morton, Ian Larson

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)

Abstract

Objective In this study, we investigated the applicability of cohesive-adhesive balance (CAB) model to predict the interactive mixing behaviour of small excipient particles. Further, we also investigated the application of this CAB model to predict the flow and compactibility of resultant blends. Methods Excipients created by co-spraying polyvinylpyrrolidone (PVP, a model pharmaceutical binder) with various l-leucine concentrations were used for this study. Paracetamol was used as model active pharmaceutical ingredient (API). The surface energy was used to derive the work of cohesion (wco) and work of adhesion (wad) to predict the interactive mixing behaviour of the excipients with paracetamol. The blends were visualised under a scanning electron microscopy microscope to assess the interactive mixing behaviour. In addition, the flow performance and tabletting behaviour of various blends were characterised. Results The surface-energy derived work of adhesion (wad) between excipient and paracetamol particles increased, while the corresponding work of cohesion (wco) between excipient particles decreased, with increasing l-leucine concentrations. In blends for which the work of cohesion was higher than the work of adhesion (wco>wad), small excipient particles were apparent as agglomerates. For excipients with 5% and higher l-leucine concentrations, the work of adhesion between excipient and paracetamol particles was higher than or equivalent to the work of cohesion between excipient particles (wadwco) and agglomerates were less apparent. This is an indicator of formation of homogeneous interactive mixtures. At 5% (w/w) excipient proportions, blends for which wadwco demonstrated higher compactibility than other blends. Furthermore, at 10% (w/w) and higher excipient proportions, these blends also demonstrated better flow performance than other blends. Conclusion In conclusion, this is the first study to demonstrate that surface-energy derived CAB data effectively predict the interactive mixing behaviour of small excipient particles. Furthermore, at certain proportions of small excipient particles the CAB model also predicts the flow and compaction behaviour of the API/excipient blends.

Original languageEnglish
Pages (from-to)110-116
Number of pages7
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume104
DOIs
Publication statusPublished - 1 Jul 2016

Keywords

  • Cohesion-adhesion balance
  • Compactibility
  • Direct compression
  • Flow
  • High-dose API
  • l-Leucine
  • Paracetamol
  • Polyvinylpyrrolidone
  • Surface energy
  • Work of adhesion
  • Work of cohesion

Cite this

@article{c86357cbe5784467b470eee4009ec730,
title = "Applying surface energy derived cohesive-adhesive balance model in predicting the mixing, flow and compaction behaviour of interactive mixtures",
abstract = "Objective In this study, we investigated the applicability of cohesive-adhesive balance (CAB) model to predict the interactive mixing behaviour of small excipient particles. Further, we also investigated the application of this CAB model to predict the flow and compactibility of resultant blends. Methods Excipients created by co-spraying polyvinylpyrrolidone (PVP, a model pharmaceutical binder) with various l-leucine concentrations were used for this study. Paracetamol was used as model active pharmaceutical ingredient (API). The surface energy was used to derive the work of cohesion (wco) and work of adhesion (wad) to predict the interactive mixing behaviour of the excipients with paracetamol. The blends were visualised under a scanning electron microscopy microscope to assess the interactive mixing behaviour. In addition, the flow performance and tabletting behaviour of various blends were characterised. Results The surface-energy derived work of adhesion (wad) between excipient and paracetamol particles increased, while the corresponding work of cohesion (wco) between excipient particles decreased, with increasing l-leucine concentrations. In blends for which the work of cohesion was higher than the work of adhesion (wco>wad), small excipient particles were apparent as agglomerates. For excipients with 5{\%} and higher l-leucine concentrations, the work of adhesion between excipient and paracetamol particles was higher than or equivalent to the work of cohesion between excipient particles (wad≥wco) and agglomerates were less apparent. This is an indicator of formation of homogeneous interactive mixtures. At 5{\%} (w/w) excipient proportions, blends for which wad≥wco demonstrated higher compactibility than other blends. Furthermore, at 10{\%} (w/w) and higher excipient proportions, these blends also demonstrated better flow performance than other blends. Conclusion In conclusion, this is the first study to demonstrate that surface-energy derived CAB data effectively predict the interactive mixing behaviour of small excipient particles. Furthermore, at certain proportions of small excipient particles the CAB model also predicts the flow and compaction behaviour of the API/excipient blends.",
keywords = "Cohesion-adhesion balance, Compactibility, Direct compression, Flow, High-dose API, l-Leucine, Paracetamol, Polyvinylpyrrolidone, Surface energy, Work of adhesion, Work of cohesion",
author = "Sharad Mangal and Felix Meiser and Geoffrey Tan and Thomas Gengenbach and Morton, {David A.V.} and Ian Larson",
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language = "English",
volume = "104",
pages = "110--116",
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Applying surface energy derived cohesive-adhesive balance model in predicting the mixing, flow and compaction behaviour of interactive mixtures. / Mangal, Sharad; Meiser, Felix; Tan, Geoffrey; Gengenbach, Thomas; Morton, David A.V.; Larson, Ian.

In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 104, 01.07.2016, p. 110-116.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Applying surface energy derived cohesive-adhesive balance model in predicting the mixing, flow and compaction behaviour of interactive mixtures

AU - Mangal, Sharad

AU - Meiser, Felix

AU - Tan, Geoffrey

AU - Gengenbach, Thomas

AU - Morton, David A.V.

AU - Larson, Ian

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Objective In this study, we investigated the applicability of cohesive-adhesive balance (CAB) model to predict the interactive mixing behaviour of small excipient particles. Further, we also investigated the application of this CAB model to predict the flow and compactibility of resultant blends. Methods Excipients created by co-spraying polyvinylpyrrolidone (PVP, a model pharmaceutical binder) with various l-leucine concentrations were used for this study. Paracetamol was used as model active pharmaceutical ingredient (API). The surface energy was used to derive the work of cohesion (wco) and work of adhesion (wad) to predict the interactive mixing behaviour of the excipients with paracetamol. The blends were visualised under a scanning electron microscopy microscope to assess the interactive mixing behaviour. In addition, the flow performance and tabletting behaviour of various blends were characterised. Results The surface-energy derived work of adhesion (wad) between excipient and paracetamol particles increased, while the corresponding work of cohesion (wco) between excipient particles decreased, with increasing l-leucine concentrations. In blends for which the work of cohesion was higher than the work of adhesion (wco>wad), small excipient particles were apparent as agglomerates. For excipients with 5% and higher l-leucine concentrations, the work of adhesion between excipient and paracetamol particles was higher than or equivalent to the work of cohesion between excipient particles (wad≥wco) and agglomerates were less apparent. This is an indicator of formation of homogeneous interactive mixtures. At 5% (w/w) excipient proportions, blends for which wad≥wco demonstrated higher compactibility than other blends. Furthermore, at 10% (w/w) and higher excipient proportions, these blends also demonstrated better flow performance than other blends. Conclusion In conclusion, this is the first study to demonstrate that surface-energy derived CAB data effectively predict the interactive mixing behaviour of small excipient particles. Furthermore, at certain proportions of small excipient particles the CAB model also predicts the flow and compaction behaviour of the API/excipient blends.

AB - Objective In this study, we investigated the applicability of cohesive-adhesive balance (CAB) model to predict the interactive mixing behaviour of small excipient particles. Further, we also investigated the application of this CAB model to predict the flow and compactibility of resultant blends. Methods Excipients created by co-spraying polyvinylpyrrolidone (PVP, a model pharmaceutical binder) with various l-leucine concentrations were used for this study. Paracetamol was used as model active pharmaceutical ingredient (API). The surface energy was used to derive the work of cohesion (wco) and work of adhesion (wad) to predict the interactive mixing behaviour of the excipients with paracetamol. The blends were visualised under a scanning electron microscopy microscope to assess the interactive mixing behaviour. In addition, the flow performance and tabletting behaviour of various blends were characterised. Results The surface-energy derived work of adhesion (wad) between excipient and paracetamol particles increased, while the corresponding work of cohesion (wco) between excipient particles decreased, with increasing l-leucine concentrations. In blends for which the work of cohesion was higher than the work of adhesion (wco>wad), small excipient particles were apparent as agglomerates. For excipients with 5% and higher l-leucine concentrations, the work of adhesion between excipient and paracetamol particles was higher than or equivalent to the work of cohesion between excipient particles (wad≥wco) and agglomerates were less apparent. This is an indicator of formation of homogeneous interactive mixtures. At 5% (w/w) excipient proportions, blends for which wad≥wco demonstrated higher compactibility than other blends. Furthermore, at 10% (w/w) and higher excipient proportions, these blends also demonstrated better flow performance than other blends. Conclusion In conclusion, this is the first study to demonstrate that surface-energy derived CAB data effectively predict the interactive mixing behaviour of small excipient particles. Furthermore, at certain proportions of small excipient particles the CAB model also predicts the flow and compaction behaviour of the API/excipient blends.

KW - Cohesion-adhesion balance

KW - Compactibility

KW - Direct compression

KW - Flow

KW - High-dose API

KW - l-Leucine

KW - Paracetamol

KW - Polyvinylpyrrolidone

KW - Surface energy

KW - Work of adhesion

KW - Work of cohesion

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U2 - 10.1016/j.ejpb.2016.04.021

DO - 10.1016/j.ejpb.2016.04.021

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JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

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