Use this URL to cite or link to this record in EThOS:
Title: Interfacial phenomena in pharmaceutical process development
Author: Hadjittofis, Eftychios
ISNI:       0000 0004 7659 0254
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2019
Availability of Full Text:
Access from EThOS:
Access from Institution:
Interfacial phenomena are of crucial importance in both pharmaceutical process development and drug product development. Inverse Gas Chromatography (IGC), is an adsorption-based technique providing a versatile framework for the investigation of interfacial phenomena. In the light of fundamental concepts of thermodynamics, new IGC protocols have been developed enabling the accurate determination of the surface energy and the surface energy heterogeneity of crystalline materials and of the Hansen Solubility Parameter (HSP) of amorphous materials. Experimental and in silico studies are deployed to reveal the importance of sample preparation in the accuracy of IGC measurements. In this context, Monte Carlo simulations were developed to support the experimental findings. The importance of spreading pressure in IGC measurements is investigated as well. A separate chapter discusses the importance of temperature and carrier gas flow rate in the measurement of HSP, of amorphous materials. Results obtained from the three chapters, are used, alongside with the results from complimentary techniques, to investigate the facet specific interactions of copovidone solutions, with macroscopic single crystals of p-monoclinic carbamazepine. Very intriguing findings are reported, highlighting among other things, the correlation between the aggregation behaviour of the polymer and wettability. In the next chapter IGC measurements are deployed, among other techniques, to investigate the mechanism of dehydration induced concomitant polymorphism of carbamazepine dihydrate. As part of this chapter a novel bioinspired crystal growth technique has been developed, enabling the growth of macroscopic hydrates of poorly water-soluble molecules. Overall this thesis, constitutes a unique piece of work combining a plethora of characterisation techniques, with novel in silico tools to investigate interfacial phenomena, of high importance in pharmaceutical industry. It highlights the importance of fundamental notions of surface thermodynamics in the development of an in-depth understanding of interfacial phenomena and it reveals the prospects of IGC as a potential game changer in pharmaceutical process development and drug product development.
Supervisor: Heng, Jerry Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral