Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.743307
Title: Development of hot melt extruded solid dispersion formulation for stabilising co-amorphous compounds
Author: Wang, Hao
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2017
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Abstract:
Polypills have been proven to improve the patient compliance to multi-drug treatment. However it is still poorly understood when the drugs of a polypill formulation are manufactured as a mixture. The formations of co-amorphous mixtures are one of the possible results of blending multiple drugs in a single process. This project investigated the co-amorphous mixtures of two model drugs, felodipine and paracetamol prepared by melt-cool method. The rationale of the model drug selections is based on the high interaction potentials (hydrogen bonding) between the two drugs as both contain hydrogen donors and acceptor groups. Three molar ratios of the co-amorphous systems of paracetamol and felodipine (P-F) were prepared and their physical stabilities were studied using SEM, DSC, ATR-FTIR and PXRD. It was noted that there is no clear intermolecular interaction between felodipine and paracetamol was identified. Higher paracetamol content led to poorer physical stability of the co-amorphous system which also led to hindered release of paracetamol. The dissolution rates of felodipine from the co-amorphous systems showed no significant improvement in comparison to crystalline felodipine indicating the rapid recrystallization of felodipine during the dissolution process. However the linear nearly zero order release of paracetamol indicated the entrapment of paracetamol in the recrystallized felodipine lattice. This confirmed the formation of co-amorphous mixture without specific hydrogen bonding between the two species. Soluplus was used as the polymeric excipient with an attempt to further improve the physical stability of the co-amorphous systems. The stability of P-F 1:1 loaded Soluplus HME extrudates showed significant improvement than the co-amorphous sample. However no significant dissolution enhancement was observed. This could be partially attributed to the use of the extrudates in the rod form instead of power form in the dissolution tests. Controlled release of paracetamol and poor dissolution of felodipine were obtained from the HME samples indicating the poor solubility enhancement capability of Soluplus in this formulation. The results of this project provided further understanding of the behaviour of co-amorphous system which non-specific interactions.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.743307  DOI: Not available
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