Influence of rheological behaviour of particulate/polymer dispersions on liquid-filling characteristics for hard gelatin capsules.

Lactose/poloxamer dispersions were prepared by mixing under vacuum to achieve a de-aerated mix with good capsule filling properties and disperse phase uniformity at 70 degrees C. Satisfactory capsule filling of molten dispersions was achieved up to a limiting concentration of disperse phase, dependent on particle size distribution and continuous phase viscosity. Lactose/poloxamer dispersions exhibited thixotropic shear thinning behaviour with an abrupt increase in apparent viscosity above a limiting concentration of disperse phase. There was a good correlation between satisfactory filling of molten dispersions into capsules and apparent viscosity of the formulation, whereas, the pronounced increase in apparent viscosity resulted in unsatisfactory filling above a critical concentration of disperse phase. The rheological data was analysed in detail using empirical models and also used to identify capsule filling problems at extrudate shear rates for flow from hopper to pump (12 s(-1)) and from nozzle to capsule (340 s(-1)).