Mackellar, A.J., Buckton, G., Newton, J.M., Chowdhry, B.Z. and Orr, C.A. (1994) The controlled crystallisation of a model powder: 1. The effects of altering the stirring rate and the supersaturation profile, and the incorporation of a surfactant (poloxamer 188). International Journal of Pharmaceutics, 112 (1). pp. 65-78. 10.1016/0378-5173(94)90262-3.
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A model drug (ethyl p-hydroxybenzoate) has been crystallised from propanol-water mixtures by the addition of water. The effects of rate of water addition, stirring speed and stirrer type have all been investigated. By consideration of the extent of turbulence and the degree of supersaturation, the process can be assumed to be driven by secondary nucleation mechanisms. A change in habit from plates to prismatic was observed with changes in the rate of addition of the crystallising fluid. The effect of addition of a surfactant (poloxamer 188) was investigated. It was found that the size and habit were altered by the presence of the surfactant, in a concentration-dependent manner. Differential scanning calorimetry (DSC) studies were interpreted to show that it was improbable that the surfactant was incorporated within the crystal lattice. By use of solution calorimetry, it was seen that a more favourable heat of solution was obtained in the presence of poloxamer. If the crystals were washed, however, there was no difference between the heat of solution for crystals which were prepared with or without added poloxamer. This was taken to show that the poloxamer was reversibly bound to the crystal surface. Contact angle measurements revealed that control crystals have a greater contact angle than those produced in the presence of poloxamer after washing of the crystals to remove reversibly adsorbed surfactant, thus the surface remained more hydrophilic if the crystal had been formed in the presence of poloxamer. Consequently, it is argued that the poloxamer is adsorbing and slowing the growth of hydrophilic surfaces of the crystal, thus making the final crystal more hydrophilic. For this to be true, there must be a deviation from the standard view of poloxamers adsorbing to hydrophobic surfaces in a largely irreversible manner. This view relates to adsorption from water, but in this work the adsorption is from a propanol-water mixture. High-sensitivity DSC of the solution showed that there were no phase transitions for the surfactant in the mixed solvent (whereas there are transitions in water). It is proposed that this reveals fundamental information about the conformation of the surfactant in this mixed solvent system, and that this conformational change is the reason for the change in the adsorption profile of the surfactant onto the solid.
|Uncontrolled Keywords:||Poloxamer; Crystallization; Contact angle; Solution calorimetry; DSC; High-sensitivity DSC; Particle size; Crystal habit|
|Departments, units and centres:||Department of Pharmaceutics > Department of Pharmaceutics|
|Journal or Publication Title:||International Journal of Pharmaceutics|
|Deposited By:||Library Staff|
|Deposited On:||18 May 2012 15:43|
|Last Modified:||18 May 2012 15:43|
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