A molecular understanding of magnesium aluminium silicate – drug, drug - polymer, magnesium aluminium silicate - polymer nanocomposite complex interactions in modulating drug release: Towards zero order release

Ana-Maria Totea, Irina Dorin, Peter Laity, Juan Sabin, Barbara Conway, Laura Waters, Kofi Asare-Addo

Research output: Contribution to journalArticle

Abstract

This study reports the use of ITC in understanding the thermodynamics occurring for a controlled release system in which complexation has been exploited. In this study, a model drug, propranolol hydrochloride (PPN) was complexed with magnesium aluminium silicate (MAS) and these complexes were used in combination with polyethylene oxide (PEO) as a hydrophilic carrier at various concentrations to sustain the release of PPN. DSC, XRPD, ATR-FTIR and SEM/EDX were successfully used in characterising the produced complexes. 2D- SAXS data patterns for MAS and the produced complexes were shown to be symmetric and circular with the particles showing no preferred orientation at the nanometre scale. ITC studies showed differences between PPN adsorption onto MAS compared with PPN adsorption onto a MAS-PEO mixture. At both temperatures studied the binding affinity Ka was greater for the titration of PPN into the MAS-PEO mixture (5.37E+04 ± 7.54E+03 M at 25 °C and 8.63E+04 ± 6.11E+03 M at 37 °C), compared to the affinity obtained upon binding between PPN and MAS as previously reported suggesting a stronger binding with implications for the dissolution process. MAS-PPN complexes with the PEO polymer compacts displayed desired manufacturing and formulation properties for a formulator including, reduced plastic recovery therefore potentially reducing the risk of cracking/splitting and on tooling wear, controlled release of PPN at a significantly low (5 %) polymer level as well as a zero-order release profile (case II transport) using up to 50 % polymer level.
Original languageEnglish
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Early online date25 Jul 2020
DOIs
Publication statusE-pub ahead of print - 25 Jul 2020

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