THE CONTROLLED CRYSTALLIZATION OF A MODEL POWDER .1. THE EFFECTS OF ALTERING THE STIRRING RATE AND THE SUPERSATURATION PROFILE, AND THE INCORPORATION OF A SURFACTANT (POLOXAMER-188)

A model drug (ethyl p-hydroxybenzoate) has been crystallised from prop anol-water mixtures by the addition of water. The effects of rate of w ater addition, stirring speed and stirrer type have all been investiga ted. By consideration of the extent of turbulence and the degree of su persaturation, the process can be assumed to be driven by secondary nu cleation mechanisms. A change in habit from plates to prismatic was ob served with changes in the rate of addition of the crystallising fluid . The effect of addition of a surfactant (poloxamer 188) was investiga ted. 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 wa s improbable that the surfactant was incorporated within the crystal l attice. By use of solution calorimetry, it was seen that a more favour able heat of solution was obtained in the presence of poloxamer. If th e crystals were washed, however, there was no difference between the h eat of solution for crystals which were prepared with or without added poloxamer. This was taken to show that the poloxamer was reversibly b ound to the crystal surface. Contact angle measurements revealed that control crystals have a greater contact angle than those produced in t he presence of poloxamer after washing of the crystals to remove rever sibly adsorbed surfactant, thus the surface remained more hydrophilic if the crystal had been formed in the presence of poloxamer. Consequen tly, it is argued that the poloxamer is adsorbing and slowing the grow th of hydrophilic surfaces of the crystal, thus making the final cryst al more hydrophilic. For this to be true, there must be a deviation fr om the standard view of poloxamers adsorbing to hydrophobic surfaces i n a largely irreversible manner. This view relates to adsorption from water, but in this work the adsorption is from a propanol-water mixtur e. High-sensitivity DSC of the solution showed that there were no phas e transitions for the surfactant in the mixed solvent (whereas there a re transitions in water). It Is proposed that this reveals fundamental information about the conformation of the surfactant in this mixed so lvent system, and that this conformational change is the reason for th e change in the adsorption profile of the surfactant onto the solid.