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

Publication date: Available online 5 December 2019Source: Journal of Pharmaceutical AnalysisAuthor(s): Ana-Maria Totea, Juan Sabin, Irina Dorin, Karl Hemming, Peter R. Laity, Barbara R. Conway, Laura Waters, Kofi Asare-AddoAbstractAn 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.Graphical abstract
Source: Journal of Pharmaceutical Analysis - Category: Drugs & Pharmacology Source Type: research