(339q) High Shear Wet Granulation Using Self-Emulsifying System: Granule Shape and Size as a Function of Some Important Process Variables

Controlling granule shape may be desirable for many reasons; among these are for example the flow properties. A spherical shape possesses a minimum surface area to volume ratio resulting in reduced cohesive forces and mechanical interlocking thereby resulting in an improved flowability of the bulk powder. Obtaining spheronisated shape is a desired prerequisite also when a subsequent coating or drug layering of the granules is necessary.

The advantage of wet granulation process in high shear mixer is that mixing, massing and granulation are performed in few minutes in the same equipment. However the high shear wet granulation (HSWG) process does not always warrant spheronisated granules. The process needs to be controlled with care as the granulation progresses so rapidly that a usable granule can be transformed very quickly into an unusable system.

The focus of this paper is therefore on the influence of process parameters on granule shape. Two different systems have been considered and results compared. Both systems include a fixed mixture of Microcrystalline Cellulose and Monohydrate Lactose as powder mass but two different binder were considered. In the first case water was considered whereas in the second case an oil-in-water emulsion was used as liquid binder in order to produce a solid self-emulsifying systems. All experiments were performed in the same vertical, bottom driven high shear granulator. The results obtained through DOE plus data statistical analysis showed that some of the process variables studied (impeller speed, granulation time, amount of initial powder and of binder) were able to induce different granule shapes. In particular a clear dependence on the binder quantity and on its nature has been observed and two main behaviours were individuated. Final structure of granules depended on structural changes which occurred during the granulation process and these were determined by the rheology of the wet bulk. Granules must be strong enough to resist the forces in the granulator, and deformable enough to generate spherical granules. Using an excess of liquid both binders produced a loss of roundness. Different surface characteristics were also observed. In particular using water, pellets resulted smaller, more rough ad with irregular shape. Composition of the second system containing an oil-in-water emulsion produced longer, more flat and smooth aggregates. These differences have been quantified using various shape factors and explained in terms of MCC granulation mechanisms where phenomena such as powder wettability, binder adsorption/desorption, intra- and inter-particle lubrication play a major role. Measures of granules strength were used in addition to corroborate our conclusions.