Thermodynamics of clay – Drug complex dispersions: Isothermal titration calorimetry and high-performance liquid chromatography

Ana-Maria Totea, Juan Sabin, Irina Dorin, Karl Hemming, Peter Laity, Barbara Conway, Laura Waters, Kofi Asare-Addo

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Abstract

An understanding of the thermodynamics of the complexation process utilized in sustaining drug release in clay matrices is of great importance. Several characterisation techniques as well as isothermal calorimetry were utilized in investigating the adsorption process of a model cationic drug (diltiazem hydrochloride, DIL) onto a pharmaceutical clay system (magnesium aluminium silicate, MAS). X-ray powder diffraction (XRPD), Attenuated total reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and optical microscopy confirmed the successful formation of the DIL-MAS complexes. Drug quantification from the complexes demonstrated variable behaviour in the differing media used with DIL degrading to desacetyl diltiazem hydrochloride (DC-DIL) in the 2 M HCl media. Here also, the authors report for the first time two binding processes that occurred for DIL and MAS. A competitor binding model was thus proposed and the thermodynamics obtained suggested their binding processes to be enthalpy driven and entropically unfavourable. This information is of great importance for a formulator as care and consideration should be given with appropriate media selection as well as the nature of binding in complexes.
Original languageEnglish
JournalJournal of Pharmaceutical Analysis
Early online date5 Dec 2019
DOIs
Publication statusE-pub ahead of print - 5 Dec 2019

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Calorimetry
High performance liquid chromatography
Titration
Dispersions
Thermodynamics
Silicates
Magnesium
Clay
Diltiazem
High Pressure Liquid Chromatography
Aluminum
Pharmaceutical Preparations
Powder Diffraction
Fourier Transform Infrared Spectroscopy
Complexation
X-Ray Diffraction
X ray powder diffraction
Drug products
Adsorption
Optical microscopy

Cite this

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title = "Thermodynamics of clay – Drug complex dispersions: Isothermal titration calorimetry and high-performance liquid chromatography",
abstract = "An understanding of the thermodynamics of the complexation process utilized in sustaining drug release in clay matrices is of great importance. Several characterisation techniques as well as isothermal calorimetry were utilized in investigating the adsorption process of a model cationic drug (diltiazem hydrochloride, DIL) onto a pharmaceutical clay system (magnesium aluminium silicate, MAS). X-ray powder diffraction (XRPD), Attenuated total reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and optical microscopy confirmed the successful formation of the DIL-MAS complexes. Drug quantification from the complexes demonstrated variable behaviour in the differing media used with DIL degrading to desacetyl diltiazem hydrochloride (DC-DIL) in the 2 M HCl media. Here also, the authors report for the first time two binding processes that occurred for DIL and MAS. A competitor binding model was thus proposed and the thermodynamics obtained suggested their binding processes to be enthalpy driven and entropically unfavourable. This information is of great importance for a formulator as care and consideration should be given with appropriate media selection as well as the nature of binding in complexes.",
keywords = "Clay-drug complex dispersions, Magnesium aluminium silicate, Diltiazem hydrochloride, Isothermal titration calorimetry, High performance liquid chromatography",
author = "Ana-Maria Totea and Juan Sabin and Irina Dorin and Karl Hemming and Peter Laity and Barbara Conway and Laura Waters and Kofi Asare-Addo",
year = "2019",
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doi = "10.1016/j.jpha.2019.12.001",
language = "English",
journal = "Journal of Pharmaceutical Analysis",
issn = "2095-1779",
publisher = "Xi'an Jiaotong University",

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AU - Hemming, Karl

AU - Laity, Peter

AU - Conway, Barbara

AU - Waters, Laura

AU - Asare-Addo, Kofi

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