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A methodological evaluation and predictive in silico investigation into the multi-functionality of arginine in directly compressed tablets.
Eur J Pharm Biopharm. 2015 Oct; 96:272-81.EJ

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/mm(2) to 2.85±0.36N/mm(2) 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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Publisher Full Text (DOI)

Authors+Show Affiliations

ElShaer A
Drug Discovery, Delivery and Patient Care (DDDPC), School of Pharmacy and Chemistry, Kingston University London, Penrhyn Road, Kingston upon Thames, Surrey KT1 2EE, UK; Aston Pharmacy School, Aston University, Aston Triangle, Birmingham B4 7ET, UK. Electronic address: a.elshaer@kingston.ac.uk.
Kaialy W
School of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK.
Akhtar N
Aston Pharmacy School, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
Iyire A
Aston Pharmacy School, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
Hussain T
The Wolfson Centre for Bulk Solids Handling Technology, Medway School of Engineering, University of Greenwich, Kent, UK.
Alany R
Drug Discovery, Delivery and Patient Care (DDDPC), School of Pharmacy and Chemistry, Kingston University London, Penrhyn Road, Kingston upon Thames, Surrey KT1 2EE, UK; School of Pharmacy, The University of Auckland, Auckland, New Zealand.
Mohammed AR
Aston Pharmacy School, Aston University, Aston Triangle, Birmingham B4 7ET, UK. Electronic address: a.u.r.mohammed@aston.ac.uk.

MeSH

AlgorithmsAnti-Inflammatory Agents, Non-SteroidalArginineCompressive StrengthComputational BiologyDrug CompoundingDrug LiberationElasticityExcipientsExpert SystemsIndomethacinMechanical PhenomenaMicroscopy, Electron, ScanningPorosityPowdersStatic ElectricityStatistics as TopicSurface PropertiesTabletsTensile Strength

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26255158

Citation

ElShaer, Amr, et al. "A Methodological Evaluation and Predictive in Silico Investigation Into the Multi-functionality of Arginine in Directly Compressed Tablets." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 96, 2015, pp. 272-81.
ElShaer A, Kaialy W, Akhtar N, et al. A methodological evaluation and predictive in silico investigation into the multi-functionality of arginine in directly compressed tablets. Eur J Pharm Biopharm. 2015;96:272-81.
ElShaer, A., Kaialy, W., Akhtar, N., Iyire, A., Hussain, T., Alany, R., & Mohammed, A. R. (2015). A methodological evaluation and predictive in silico investigation into the multi-functionality of arginine in directly compressed tablets. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 96, 272-81. https://doi.org/10.1016/j.ejpb.2015.07.028
ElShaer A, et al. A Methodological Evaluation and Predictive in Silico Investigation Into the Multi-functionality of Arginine in Directly Compressed Tablets. Eur J Pharm Biopharm. 2015;96:272-81. PubMed PMID: 26255158.
* Article titles in AMA citation format should be in sentence-case
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 - Iyire,Affiong, AU - Hussain,Tariq, AU - Alany,Raid, AU - Mohammed,Afzal R, Y1 - 2015/08/05/ PY - 2015/03/12/received PY - 2015/07/06/revised PY - 2015/07/30/accepted PY - 2015/8/10/entrez PY - 2015/8/10/pubmed PY - 2016/8/23/medline KW - Arginine KW - Compactibility KW - Compressibility KW - Direct compression KW - Disintegration time KW - Indomethacin KW - Multifunctional excipient KW - Tabletability SP - 272 EP - 81 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 96 N2 - 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/mm(2) to 2.85±0.36N/mm(2) 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. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/26255158/A_methodological_evaluation_and_predictive_in_silico_investigation_into_the_multi_functionality_of_arginine_in_directly_compressed_tablets_ DB - PRIME DP - Unbound Medicine ER -