Physico-mechanical characterization of the extrusion-spheronization process. Part II: Rheological determinants for successful extrusion and spheronization.

Spheres are widely used as the basis for the design of multiparticulate drug delivery systems. Although the extrusion and spheronization processes are frequently used to produce such spheres, there is a lack of basic understanding of these processes and of the requisite properties of excipients and formulations. It is hypothesized that the rheological or mechanical properties of the wet mass may address the requirements of both extrusion and spheronization. The fact that certain formulations can be extruded, yet not be successfully spheronized, suggests that the two processes depend on different formulation attributes, and that there are different rheological criteria that must be met for each process to be successful. As a preliminary test of these hypotheses, methods were developed to measure the rheological behavior and mechanical properties (plastic yield value, tensile strength, yield loci) of the wet mass and/or extrudate for a model formulation system (microcrystalline cellulose, lactose, hydroxypropylmethylcellulose). The finished spheres were characterized in terms of particle size, bulk density, individual bead crushing strength, and sphericity. A Box-Behnken experimental design was employed by which the independent formulation variables could be related to the dependent rheological/mechanical properties and finished pellet characteristics. It was observed that there was a critical range of rheological/mechanical variables within which pellets having desirable criteria such as yield of 18/25 mesh cut > 60%, a shape factor > 0.85, etc., can be prepared. Screen pressure was shown to be the most critical variable affecting the yield of 18/25 mesh cut, while the yield value and tensile strength markedly influenced the shape factor. Thus, for the formulations studied, it was possible to define a "window" of rheological/mechanical properties within which both extrusion and spheronization can be successfully carried out.