A quantitative study of the effect of process parameters on key granule characteristics in a high shear wet granulation process involving a two component pharmaceutical blend

Abstract

The objective of the current work was to investigate the effect of liquid to solid ratio (L/S), impeller speed and the wet massing time on the critical quality attributes of granules in a high shear wet granulation process for a two component (API and excipient) system. The parameters were evaluated for their effect on granule properties using a design of experiment based approach. Granules were characterized for their particle size distribution, content uniformity, morphology and porosity.The liquid to solid (L/S) ratio was found to have a dominant effect on the median particle size and exhibited a clear trend. The system was found to be extremely well mixed for all conditions thus implying robust composition uniformity within and between batches, independent of process parameters. The release kinetics of granules within the batch were found to be identical, independent of particle size. The granules were found to be fairly spherical as observed through a scanning electron microscope with no distinct agglomeration. The images indicate granulation by layering and consolidation. All three process parameters were found to have an effect on granule porosity, with the wet massing time having the most pronounced effect. A judicious selection of the afore mentioned process parameters will enable a balance between granule growth and porosity to be achieved without compromising on the mixing efficiency of the process thereby allowing one to build quality into the final product.