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

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

Volume: 18 Issue: 9

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

Affiliation:

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

Keywords: Isothermal titration calorimetry, magnesium aluminium silicate, metformin hydrochloride, single injection mode, multiple injection mode, RSD.

Abstract:

Background: Studying complexation between a wide variety of drugs and clay is of high importance in expanding the knowledge about controlled drug delivery and its exploitation. 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 potentially controlled release drug delivery system.

Objectives: To fully characterise and understand the complexes formed between MAS and MET and how that might impact on controlled release systems.

Methods: MAS and MET complex dispersions and particles were formulated and analysed using ITC, DSC, XRPD, ATR-FTIR, SEM/EDX, digital microscopy and 2D-SAXS.

Results: 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. 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.

Conclusion: ITC was successfully used in understanding the complexation process occurring between MAS and MET. Care and consideration however should thus be taken in the accurate determination and characterisation techniques for the formation of complexes for controlled release using MAS.

Cite this article as:

Totea Ana-Maria , Dorin Irina , Laity R. Peter , Conway R. Barbara , Waters Laura and Asare-Addo Kofi *, Magnesium Aluminium Silicate-Metformin Hydrochloride Complexes - The Use of Isothermal Calorimetry for Probing Clay and Drug Nanocomplexations, Current Drug Delivery 2021; 18 (9) . https://dx.doi.org/10.2174/1567201818666210402125244