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.

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.

Real time calorimetric characterisation of clay - drug complex dispersions and particles.

Isothermal titration calorimetry (ITC) along with attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDX) and high-performance liquid chromatography (HPLC) were employed to investigate the process of adsorption of propranolol hydrochloride (PPN) onto magnesium aluminium silicate (MAS) and to characterise the MAS-PPN particles formed upon complexation. The composition of MAS was confirmed by infrared (IR) spectroscopy and a calcimeter. The calorimetric results confirmed the binding between PPN and MAS at various pHs and temperatures. The overall change in enthalpy was found to be exothermic with a comparatively small entropic contribution to the total change in Gibbs free energy. These findings suggest that the binding process was enthalpically driven and entropically unfavourable (lower affinity) suggesting hydrogen bonding and electrostatic interactions dominating the interaction. The variation of pH and temperature did not have a great impact on the thermodynamics of the binding process, as observed from the similarity in enthalpy (ΔH), entropy (ΔS) or Gibbs free energy (ΔG). A slight reduction in the binding affinity (Ka) with varing pH and temperature was however observed. SEM/EDX studies showed the occurrence of changes in the microstructural properties of MAS following complexation which may explain the potential of MAS-PPN complexes for controlled drug release promoting pharmaceutical innovation.