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Application of Hansen Solubility Parameters and Thermomechanical Techniques to the Prediction of Miscibility of Amorphous Solid Dispersion. Investigating the role of cohesive energy and free volume to predict phase separation kinetics in hot-melt extruded amorphous solid dispersion using dynamic mechanical analyser, shear rheometer and solubility parameters data
Mousa, Mohamad A.M.R.
Mousa, Mohamad A.M.R.
Publication Date
2022
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The University of Bradford theses are licenced under a Creative Commons Licence.
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Accepted for publication
Institution
University of Bradford
Department
School of Pharmacy. Faculty of Life Sciences
Awarded
2022
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Abstract
Hot-melt extruded solid dispersion technique is increasingly employed to improve
the solubility of poorly water-soluble drugs. The technique relies on the enhanced
solubility of the amorphous form of the drug compared to its crystalline counterpart. These
systems however are thermodynamically unstable. This means that the drug crystallises
with time. Therefore, efforts to measure the stability of these systems over the life span
of the product are crucial.
This study focused on investigating the use of Hansen Solubility Parameters to
quantify polymer-drug interaction and to predict the stability of solid dispersions. This was
achieved through a systematic review of hot-melt extruded solid dispersion literature. The
study also investigated the use of a combined mechanical and rheological model to characterise the physicochemical and release behaviour of three solid dispersion
immediately after preparation and after storage for one month at 40oC or three months at
room temperature.
Results revealed that the total solubility parameter |ΔбT| was able to predict the
stability of the systems for more than 4 months using a cut-off point of 3 MPa-1 with a
negative predictive value of 0.9. This was followed by ΔбD with a cut-off point of 1.5 MPa-
1. Moreover, Dynamic Mechanical Analyser and shear rheometry data were shown to be
more sensitive than Differential Scanning Calorimetry, Powder X-Ray Diffraction,
Scanning Electron Microscope and Fourier Transform Infrared in detecting crystallisation
and the interaction between the drug and the polymer. The Dynamic Mechanical Analyser data were consistent with the dissolution behaviour of the samples when comparing the
freshly prepared samples with those after storage. The results highlight the need for a
unified characterisation approach and the necessity of verifying the homogeneity of
mixing during the extrusion process.
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Type
Thesis
Qualification name
PhD