Mackellar, Alasdair John;
(1992)
The Controlled Crystallisation of a Model Drug.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The solubility profile of ethyl-p-hydroxybenzoate was determined in a variety of propan-2-ol / water mixtures. This study showed that it could be crystallised from a propan-2-ol / water mixture of 0.065 mole fraction propan-2-ol by the addition of water. This produced crystals of 50% undersize of 66.0 microns showing a platey habit. By varying the power input to the vessel via the stirring rate, crystal size was altered. As the stirring rate increased crystal size decreased as a result of a raised secondary nucleation rate. The supersaturation profile operating during crystallisation was varied by changing the rate of addition of water. As the rate of addition of water decreased, crystals developed an acicular habit and median crystal size was reduced. It was concluded that the reduced supersaturation caused crystal growth rates to be less. At higher growth rates crystal faces grow out of existence and this would account for the change in crystal habit when growth rates are reduced. The addition of poloxamers to the crystallisation medium also caused changes in crystal size and habit. A distinct structure / activity relationship between the hydrophillic / hydrophobic balance of the poloxamer and the effect on crystal appearance was apparent. The threshold activity concentrations of the more polar poloxamers were significantly lower than those of less polarity. At the highest concentration studied (0.23% w/w), the most hydrophilic poloxamers reduced crystal 50% undersize to 32 microns. Differential scanning calorimetry studies showed no polymorphic changes or inclusion of poloxamers into crystal lattices. Solution calorimetry indicated that poloxamer was adsorbed onto crystals and measurements of contact angles showed that crystals of an acicular habit were more polar. Using these findings a model was proposed indicating how poloxamers are adsorbed at specific crystal faces according to their structure and so change crystal size and habit.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The Controlled Crystallisation of a Model Drug |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10123392 |
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