Determination of interparticulate forces in ordered powder mixes

Abstract

Abstract The theory of interparticle bond formation is considered with particular reference to ordered powder mixing. A technique is described for measuring the interparticle adhesion forces between drug and excipient particles bound in ordered units. The method uses a specially constructed ultracentrifuge rotor tube insert such that fine adherent particles can be separated from coarser carrier particles in ordered mixes. The ordered units are held behind a screen in the rotor tube insert and when the forces generated by ultracentrifugation become greater than the interparticle adhesion forces the ordered units break down into their component particles. Adhesion profiles were obtained for four different ordered mixes containing drug and excipient powders by plotting force of adhesion against the cumulative percentage of fine drug particles adhering to the carrier particle surface. The adhesion profile is influenced by the quantity of drug powder adhering to the excipient carrier particle surface. Above a critical drug content, each ordered mix shows a ‘composite' adhesion profile consisting of two distinct curves linked by a lag period. The initial curve, preceding the lag period, appears to correspond to loss of large amounts of weakly bound drug particles; after the lag period only relatively strongly adhered particles are removed and this phase occurs more gradually. The critical drug concentration is related to the surface properties of the excipient and drug particles which determine the strength of adhesion forces within an ordered unit.