THE CONTROLLED CRYSTALLIZATION OF A MODEL POWDER .2. INVESTIGATION INTO THE MECHANISM OF ACTION OF POLOXAMERS IN CHANGING CRYSTAL PROPERTIES

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 y(oxyethylene)-poly(oxypropylene) poly(oxyethylene) block copolymers on the size and habit of the crysta ls has been investigated. The surfactants resulted in decreased partic le size and a change to a prismatic habit. The decrease in particle si ze seems to correlate with the molecular weight of the polyoxyethylene chain, if the molecular weight of the polyoxypropylene is kept consta nt. These effects were concentration dependent, occurring after a cert ain threshold concentration of surfactant had been added. The effect w as also dependent upon the nature of the surfactant. The greater the m olecular weight the greater the effect; this was especially true for i ncreases in molecular weight of the polyoxyethylene. These and other d ata are used to propose that the polyoxyethylene is adsorbed to the su rface of hydrophilic faces of the crystal in order to exert this effec t on the crystal properties. It has been shown that the surfactant doe s not exert this effect by changes in solubility or supersaturation pr ofiles.