Relating the characteristics of pharmaceutical powders to their prior processing, utilising Inverse Gas Chromatography

• Main Author: Merrifield, David Roy
• Published: University of Leeds 2013
• Subjects: 543.85
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.658557

This thesis sets out to evaluate the application of Inverse Gas Chromatography (lGC) in the context of being a Process Analytical Technique (PAT) for the characterisation of pharmaceutical materials. It reviews the literature as it relates to the use of chromatography to determine physico-chemical properties and discusses how this has been applied to assessing surface characteristics of powders, particularly those used for pharmaceutical purposes. The review section considers the strengths and limitations of IGC based characterisation, especially where it was intended to distinguish between batches of material that might differ only subtly. Working from this base, a study was devised that would give a better appreciation of the capability of IGC to make these distinctions. A number of materials were viewed as being suitable to study, and their selection is justified on the basis of physical and chemical properties, and the extent of their use in the pharmaceutical sector. Two approaches were used in the evaluation. Firstly, IGC was carried out on materials crystallised under carefully controlled conditions, and then following milling (size-reduction) and granulation (size-enlargement). These processes are widely used in the industry. The capability of IGC to evaluate materials thus prepared is discussed. The second approach uses a variant of molecular modelling known as systematic grid based searching. This identifies low energy locations on a crystal surface where molecules may favourably attach. This has been used to study crystal growth and appeared be analogously useful in evaluating adsorption. It is concluded that IGC is valuable in a PAT context, but mainly in a complementary role. The modelling is shown to give very good correlations between the availability of low energy sites and chromatographic retention. Recommendations are made as to how IGC can be used most effectively, and how the modelling approach can be developed further.