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

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.

Grantor dc:publisher.institution

University of Bradford

Year dc:date.issued

2022

Author dc:creator

• Mousa, Mohamad A.M.R.

Advisors dc:contributor.advisor

• Isreb, Mohammad
• Gough, Tim
• Timmins, Peter

• Hansen Solubility Parameters
• Solid dispersion
• Hot melt extrusion
• DMA
• Rheology
• Chain dynamics
• Phase separation
• Solid dosage forms
• Amorphous
• Poorly soluble

Statement dc:rights

• <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>.

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/10454/19855

OAI identifier oai:identifier

oai:bradscholars.brad.ac.uk:10454/19855