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Magnesium aluminium silicate-metformin hydrochloride complexes - The use of isothermal calorimetry in probing the understanding of clay and drug nanocomplexations

Author(s):

Ana-Maria Totea, Irina Dorin, Peter R. Laity, Barbara R. Conway, Laura Waters and Kofi Asare-Addo*  

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.

Keywords:

isothermal titration calorimetry, magnesium aluminium silicate, metformin hydrochloride, single injection mode, multiple injection mode, RSD.

Affiliation:

School of Applied Sciences, Department of Pharmacy, University of Huddersfield, Queensgate, Huddersfield, Biomolecular Formulation and Characterization Sciences, UCB, Slough SL3WE, Department of Materials Science and Engineering, University of Sheffield, Sir Robert Hadfield Building, Mappin Street, Sheffield, S1 3JD, School of Applied Sciences, Department of Pharmacy, University of Huddersfield, Queensgate, Huddersfield, School of Applied Sciences, Department of Pharmacy, University of Huddersfield, Queensgate, Huddersfield, School of Applied Sciences, Department of Pharmacy, University of Huddersfield, Queensgate, Huddersfield



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