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Characterisation of smectite clay-drug complexes in polymer matrices using isothermal titration calorimetry and evaluation of drug release

Totea, Ana-Maria (2020) Characterisation of smectite clay-drug complexes in polymer matrices using isothermal titration calorimetry and evaluation of drug release. Doctoral thesis, University of Huddersfield.

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Abstract

This thesis investigated the process of adsorption of three cationic drugs having different molecular weights and therapeutic effects (propranolol hydrochloride (PPN), diltiazem hydrochloride (DIL) and metformin hydrochloride (MET)) onto a smectite clay (magnesium aluminium silicate (MAS)) and the effects of this process on extending the release of such drugs. Furthermore, two different polymers (xanthan gum (XG) and polyethylene oxide (PEO)) were used in the study in combination with the formulated clay-drug complexes.

The process of adsorption of the three drugs onto MAS was explored using 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), high-performance liquid chromatography (HPLC), microscopy and small angle X-ray scattering (SAXS). The calorimetric results confirmed the binding between MAS and the drugs at various pHs and temperatures. In all cases, an overall change in enthalpy was found to be exothermic with a comparatively small entropic contribution to the total change in Gibbs free energy. However, the binding profiles were different, one binding event being observed upon binding of PPN and MET onto MAS. The binding of DIL onto MAS exhibited two binding events and were attributed to DIL binding to montmorillonite and saponite. The findings suggest that the binding process was enthalpically driven and entropically unfavourable (lower affinity) suggesting hydrogen bonding and electrostatic interactions dominate the interaction.

The latter part of this thesis aimed to investigate the capacity of the formed MAS-PPN complexes combined with XG and PEO, compared to MAS-PPN physical mix combined with the same polymers to control the release of PPN. Bulk compaction behaviour was studied for the formulations prepared as plots of relative density vs. upper punch pressure measured during loading to 130 MPa (10 kN) and unloading. The compaction curves of all the samples tested followed roughly similar trends: the compaction behaviour was dominated by plastic recovery during the loading stage following non-reversible deformation, movement and fragmentation of the particles. Compacts were further tested for their dissolution properties in pH 1.2 hydrochloric acid and pH 6.8 buffer. Results showed that PEO was able to provide controlled PPN release in both acid and buffer at very low polymer concentrations in tablets (5% w/w), whereas burst effects were observed upon dissolution of compacts containing the same amount of XG which may be as a result of it anionic nature. Overall, a more controlled PPN release rate from the tablets containing MAS-PPN complexes compared to those containing MAS-PPN physical mixture was observed which is a result of the MAS-PPN binding and adds important benefits to drug release.

This information therefore provides a better understanding of the mechanisms of adsorption of PPN, DIL and MET onto MAS, and demonstrates the promising potential of MAS-cationic drug (drugs with short half-life) complexes as drug reservoirs in polymeric matrices to modulate drug release.

Item Type: Thesis (Doctoral)
Subjects: Q Science > QD Chemistry
Schools: School of Applied Sciences
Depositing User: Andrew Strike
Date Deposited: 23 Jun 2020 13:23
Last Modified: 23 Jun 2020 13:30
URI: http://eprints.hud.ac.uk/id/eprint/35195

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