Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.585561
Title: Development of methods to predict and enhance the physical stability of hot melt extruded solid dispersions
Author: Yang, Ziyi
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2013
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Abstract:
The application of amorphous solid dispersions is one of the most widely used formulation strategies for the enhancement of in-vitro and in-vivo performance of poorly water-soluble drugs. However, because of their meta-stable nature, the physical stability of amorphous solid dispersions has been considered to be the main obstacle for their formulation development and commercialisation by the pharmaceutical industry. The aim of this project was to understand, predict and enhance the physical stability of amorphous solid dispersions prepared by hot melt extrusion. Four model drugs felodipine, celecoxib, fenofibrate and carbamazepine and two polymeric matrices EUDRAGIT® EPO and Kollidon® VA 64 were formulated by hot melt extrusion and spin coating into solid dispersions. A series of physicochemical characterisation techniques including MTDSC, PXRD, SEM, ATR-FTIR and AFM-LTA were used to evaluate the systems. Physical characterisation of the model drugs and polymers, prediction of drug-polymer miscibility and solubility and real-time physical stability studies under different conditions were carried out. Across the project, several key achievements were obtained. It was revealed that the physical stability of the amorphous drugs alone and the predicted processing-related apparent drugpolymer solubility were the two dominant factors controlling the physical stability of the amorphous systems. A practical method, milling, was developed to provide a more accurate prediction of processing-related apparent drug-polymer solubility. Two methods were developed to enhance the physical stability of amorphous solid dispersions: one based on formulation design, use of immiscible polymer blends and the other based on a particular type of processing, spin coating. The achievements from the project are expected to contribute to the formulation development of amorphous solid dispersions in terms of screening suitable drug candidates, selecting “safe” (physically stable) drug loadings and identification of methodologies to improve the physical stability of formulations.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.585561  DOI: Not available
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