The pharmaceutical industry has for many years been interested in the formation of salts as a means of controlling the chemical/physical properties of API (active pharmaceutical ingredient) molecules. While current interest in cocrystals has led to study of their formation and phase behaviour, comparatively little data is available for salts. This work aims to come some way to redress that balance. Initial studies focussed on a single base manually ground with a number of acids (leading on from previous solution work). Salt formation was noted in a significant number of cases. The work was followed by two more detailed and contrasting case studies. These case studies are ephedrine with pimelic acid and benzoic acid.Both mono- and di-basic salts of ephedrine and pimelic acid were formed both by grinding and solution methods. Binary and aqueous ternary phase diagrams were measured to allow assessment of pure phase regions. The ideality of the systems was assessed and, while the binary phase diagram showed some relatively ideal regions, the ternary system appeared highly non-ideal.Effects on the shape and size of phase regions have been considered, especially the role ionisation plays in the ternary non-ideality. Using fundamental equations solubility has been determined as a function of pH and compared to experimental data. The pH value has also been calculated using concentrations of acid and base along the experimental liquidus of the ternary phase diagram and comparisons made with measured pH values. From these comparisons it was determined that the non-ideality and shape of the liquidus in the ephedrine/pimelic acid/water ternary phase diagram is not solely due to ionisation of the components.Some major issues that may arise in attempted salt formation studies are discussed in relation to the ephedrine and benzoic acid system. Aqueous salt formation was not successful; therefore reasons for this failure are discussed. It is concluded that while the ternary phase behaviour of a salt should be considered, it does not mean the ionisation behaviour (and hence the speciation diagram) should be ignored. These two sources of information should be assessed in conjunction with one another in order to gain the most accurate insight into a system.
Date of Award | 1 Aug 2011 |
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Original language | English |
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Awarding Institution | - The University of Manchester
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Supervisor | Roger Davey (Supervisor) |
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Phase Relationships for Molecular Salts
Cooke, C. (Author). 1 Aug 2011
Student thesis: Phd