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

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

Journal

Current drug delivery
ISSN: 1875-5704
Titre abrégé: Curr Drug Deliv
Pays: United Arab Emirates
ID NLM: 101208455

Informations de publication

Date de publication:
2021
Historique:
received: 22 09 2020
revised: 11 12 2020
accepted: 26 02 2021
pubmed: 3 4 2021
medline: 14 1 2022
entrez: 2 4 2021
Statut: ppublish

Résumé

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. To fully characterise and understand the complexes formed between MAS and MET and how that might impact on controlled release systems. MAS and MET complex dispersions and particles were formulated and analysed using ITC, DSC, XRPD, ATR-FTIR, SEM/EDX, digital microscopy and 2D-SAXS. 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. 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.

Sections du résumé

BACKGROUND 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 OBJECTIVE
To fully characterise and understand the complexes formed between MAS and MET and how that might impact on controlled release systems.
METHODS 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 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 CONCLUSIONS
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.

Identifiants

pubmed: 33797383
pii: CDD-EPUB-115158
doi: 10.2174/1567201818666210402125244
doi:

Substances chimiques

Aluminum Compounds 0
Magnesium Compounds 0
Pharmaceutical Preparations 0
Silicates 0
aluminum magnesium silicate 6M3P64V0NC
Metformin 9100L32L2N
Magnesium I38ZP9992A
Clay T1FAD4SS2M

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1280-1291

Informations de copyright

Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Auteurs

Ana-Maria Totea (AM)

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

Irina Dorin (I)

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

Peter R Laity (PR)

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

Barbara R Conway (BR)

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

Laura Waters (L)

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

Kofi Asare-Addo (K)

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

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Classifications MeSH