Fundamental Aspects Of Solvent Effects In Crystallisation Processes

Publication Reference: 
ARR-29-09
Author Last Name: 
Davey
Authors: 
Alvin Yeoh, Roger Davey
Report Type: 
ARR - Annual Report
Research Area: 
Particle Formation
Publication Year: 
2006
Publication Month: 
11
Country: 
United Kingdom

The aim of this project is to enhance our understanding of how solvents and supersaturation affect the nucleation of polymorphic forms of compounds. Polymorphism is very important to the pharmaceutical industry as a compound’s polymorph can exhibit different physical properties, some more desirable than others. Being able to control which polymorphic form is nucleated is thus very important. In the first year of this project, the dimorphic enantiotropic compound p-aminobenzoic acid was selected as the model compound due to the availability of its solubility data and the relatively low transition temperature between its and polymorphs. The second year of the project has been focused on the precise location of the transition temperature and measuring the relative nucleation rates of and at different temperatures.

2. Background

2.1 Research background

There have been few studies of the relative nucleation rates of two polymorphic forms. Figure 1 shows a schematic phase diagram for an enantiomorphic system of Polymorphs I and II, it is characterised by a transition temperature at which the relative solubility and hence stability of forms switches. At the transition temperature