The controlled crystallisation of a model powder: 2. Investigation into the mechanism of action of poloxamers in changing crystal properties

Abstract

A model drug (ethyl p-hydroxybenzoate) has been crystallised out of a propan-2-ol/water cosolvent by the addition of water. The effect of a range of concentrations of different poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymers on the size and habit of the crystals has been investigated. The surfactants resulted in decreased particle size and a change to a prismatic habit. The decrease in particle size seems to correlate with the molecular weight of the polyoxyethylene chain, if the molecular weight of the polyoxypropylene is kept constant. These effects were concentration dependent, occurring after a certain threshold concentration of surfactant had been added. The effect was also dependent upon the nature of the surfactant. The greater the molecular weight the greater the effect; this was especially true for increases in molecular weight of the polyoxyethylene. These and other data are used to propose that the polyoxyethylene is adsorbed to the surface of hydrophilic faces of the crystal in order to exert this effect on the crystal properties. It has been shown that the surfactant does not exert this effect by changes in solubility or supersaturation profiles.