Magnesium Aluminium Silicate-Metformin Hydrochloride Complexes - The Use of Isothermal Calorimetry for Probing Clay and Drug Nanocomplexations

Author:

Totea Ana-Maria1,Dorin Irina2,Laity Peter R.3,Conway Barbara R.1,Waters Laura1,Asare-Addo Kofi1ORCID

Affiliation:

1. School of Applied Sciences, Department of Pharmacy, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH,United Kingdom

2. Biomolecular Formulation and Characterization Sciences, UCB, Slough SL3WE,United Kingdom

3. Department of Materials Science and Engineering, University of Sheffield, Sir Robert Hadfield Building, Mappin Street, Sheffield, S1 3JD,United Kingdom

Abstract

: This study reports the use of Isothermal Calorimetry (ITC) in understanding the complexation process occurring between Magnesium Aluminium Silicate (MAS) and metformin hydrochloride (MET), as a potential controlled release drug delivery system. The calorimetric results confirmed the binding between MET and MAS at various pHs (5, 7 and 9) and temperatures (25 ºC and 37 ºC). The overall change in enthalpy was found to be exothermic with a comparatively small entropic contribution to the total change in Gibbs free energy, implying that the binding was an enthalpically driven process. These findings suggest that the binding process was dominated by hydrogen bonding and electrostatic interactions. pH and temperature variation did not have a great impact on the binding, as observed from the similarity in enthalpy (ΔH), entropy (ΔS) or Gibbs free energy (ΔG), with the reaction being only slightly more exothermic at pH 5 and at 37 ºC. MAS and MET complex dispersions and particles were also formulated and analysed successfully using DSC, XRPD, ATR-FTIR, SEM/EDX, digital microscopy. 2D-SAXS. 2D-SAXS was able to differentiate between MAS particulates and MAS-MET complexes when analysed in their liquid form suggesting the importance of appropriate methodology and instrumentation used in characterisation.

Publisher

Bentham Science Publishers Ltd.

Subject

Pharmaceutical Science

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