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/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.
authors.affiliation: 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.
authors.forename: Amr
authors.initials: A
authors.lastname: ElShaer
authors.affiliation: School of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK.
authors.forename: Waseem
authors.initials: W
authors.lastname: Kaialy
authors.affiliation: Aston Pharmacy School, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
authors.forename: Noreen
authors.initials: N
authors.lastname: Akhtar
authors.affiliation: Aston Pharmacy School, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
authors.forename: Affiong
authors.initials: A
authors.lastname: Iyire
authors.affiliation: The Wolfson Centre for Bulk Solids Handling Technology, Medway School of Engineering, University of Greenwich, Kent, UK.
authors.forename: Tariq
authors.initials: T
authors.lastname: Hussain
authors.affiliation: 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.
authors.forename: Raid
authors.initials: R
authors.lastname: Alany
authors.affiliation: Aston Pharmacy School, Aston University, Aston Triangle, Birmingham B4 7ET, UK. Electronic address: a.u.r.mohammed@aston.ac.uk.
authors.forename: Afzal R
authors.initials: AR
authors.lastname: Mohammed
mesh_terms: D000465:Algorithms; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry; D001120:Arginine / Q000737:chemistry*; D019245:Compressive Strength; D019295:Computational Biology / Q000379:methods*; D004339:Drug Compounding; D065546:Drug Liberation; D004548:Elasticity; D005079:Excipients / Q000737:chemistry*; D005103:Expert Systems; D007213:Indomethacin / Q000008:administration & dosage / Q000737:chemistry; D055595:Mechanical Phenomena; D008855:Microscopy, Electron, Scanning; D016062:Porosity; D011208:Powders; D055672:Static Electricity; D013223:Statistics as Topic; D013499:Surface Properties; D013607:Tablets; D013718:Tensile Strength
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D011208:Powders; D013607:Tablets; D001120:Arginine; D007213:Indomethacin
keywords: Arginine; Compactibility; Compressibility; Direct compression; Disintegration time; Indomethacin; Multifunctional excipient; Tabletability