Patel, Pinesh M.; (1999) Investigations into the surface nature of cimetidine and its salt forms. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Four new salt forms of cimetidine (maleate, malonate, fumarate and sulfamate) were prepared and characterised. The surface nature of cimetidine, cimetidine hydrochloride monohydrate and the new salt forms were compared and investigated using a variety of techniques. Using a method based on the Wilhelmy plate technique an indication of the wettability and the surface energetics of the samples was determined. The decreasing rank order of wettability determined by both the harmonic and geometric mean methods was: malonate > (fumarate/sulfamate/hydrochloride) > maleate > cimetidine. Acid-base characteristics were determined by the van Oss theory and were supported using data from water sorption and molecular modelling techniques. Water sorption studies showed that the most hydrophobic samples were cimetidine and cimetidine hydrochloride monohydrate. The new salt forms showed varying degrees of water sorption. Gravimetric and isothermal microcalorimetric techniques were used to obtain thermodynamic parameters for the sorption processes to demonstrate the differences between the samples. Various modelling techniques were used to simulate and probe the solid surface. Morphology predictions were successful for most of the samples investigated. Molecular model images of various surfaces were viewed to explain certain aspects of the contact angle data and some of the observed sorption behaviour. The polar nature of the salt forms determined by contact angle measurements was explained by the presence of favourable polar groups on the surface. The hydrophobic nature of cimetidine and cimetindine hydrochloride monohydrate was explained by the presence of non-polar groups on the crystal surface. The significant amount of water sorption observed by the maleate and malonate salt forms was demonstrated by the presence of hydrophilic channels. The disparity between the predicted and the observed morphology results explained why the modelling for the fumarate salt was unsuccessful. It was concluded that molecular modelling provided a further understanding of the surface characterisation data and also allowed greater confidence to be attached to the explanations that were proposed.

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