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Title: Characterisation of drug loaded insoluble polymeric matrices prepared by hot melt extrusion technology for drug delivery applications
Author: Caldwell , Deborah Leigh
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2012
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In this work. polymeric matrices comprising Eudragit" RL PO were manufactured using Hot Melt Extrusion (HME) technology. The thermal, physical and chemical characteristics of Eudragit'" RL PO were investigated and suitable processing parameters defined. Above 180°C, thermal decomposition proceeded by a mechanism which caused cleavage and subsequent loss of ammonio methacrylate functional groups. Acceptable processing limits for HME of Eudragit" RL PO were defined with an optimal temperature window between 120°C and 170°C and screw speed between 100 and 150rpm. Ingress of water as a liquid and vapour changed the physical and viscoelastic properties of the material. A model water soluble drug, metformin hydrochloride (MHCI), was formulated within the Eudragit'" RL PO carrier matrix using via HME. MHCI and Eudragit" RL PO exhibited a poor interaction and MHCI displayed a low solubility in the molten polymer matrix. PXRD showed that crystalline solid dispersions formed during HME at all concentrations. Addition of Eudragit" RS PO to the hot melt formulation also caused retardation of drug release from the matrix providing a mechanism through which release of MHCI could be sustained. The effect of drug salt form on the physiochemical and drug release properties was evaluated using quinine as the free base (QB), hydrochloride (QHCI) and sulphate (QS04) forms. A significant difference in solubility in the molten polymer matrix was observed for each of the quinine forms. QB, QHCI and QS04 acted as solid-state plasticizers for Eudragit" RL PO at concentrations below saturation solubility. Salt counter ion imparted a significant influence on the solubility of drug within the polymer matrix. FT-IR and Raman spectroscopy showed that quinine exhibited multiple sites of interaction and the formation of a salt occupied a key site of interaction which rendered the salt forms less soluble in the molten polymer matrix which in turn affected the physiochemical and drug release properties from hot melt extrudates. Rheological characteri ation using capillary rheometry showed that Eudragit" RL PO exhibited non ewtonian flow behaviour. Power law index and activation energy (Ea) were calculated for the pure polymer. Shear rate did not exert a significant influence on the Eudragit" RL PO microstructre post processing and the glass transition temperature and water uptake properties of the polymer remained unchanged. Significant die swell post processing was observed and was counteracted by increasing the length of extrusion die. Addition of QB to the formulation caused an improvement in the thermal processability of the material due to solid-state plasticization of the polymer. Application of a drawing force on the drug release properties from QB loaded Eudragit" RL PO extrudates were evaluated and no significant difference in the dissolution properties were observed at any of the applied drawing forces.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available