PHYSICOMECHANICAL CHARACTERIZATION OF THE EXTRUSION-SPHERONIZATION PROCESS .2. RHEOLOGICAL DETERMINANTS FOR SUCCESSFUL EXTRUSION AND SPHERONIZATION

Spheres are widely used as the basis for the design of multiparticulat e drug delivery systems. Although the extrusion and spheronization pro cesses are frequently used to produce such spheres, there is a lack of basic understanding of these processes and of the requisite propertie s of excipients and formulations. It is hypothesized that the theologi cal or mechanical properties of the wet mass may address the requireme nts of both extrusion and spheronization. The fact that certain formul ations can be extruded, yet not be successfully sphe ronized, suggests that the two processes depend on different formulation attributes, an d that there are different theological criteria that must be met for e ach process to be successful. As a preliminary test of these hypothese s, methods were developed to measure the rheological behavior and mech anical properties (plastic yield value, tensile strength, yield loci) of the wet mass and/or extrudate for a model formulation system (micro crystalline cellulose, lactose, hydroxypropylmethylcellulose). The fin ished spheres were characterized in terms of particle size, bulk densi ty, individual bead crushing strength, and sphericity. A Box-Behnken e xperimental design was employed by which the independent formulation v ariables could be related to the dependent rheological/mechanical prop erties 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 sh own to be the most critical variable affecting the yield of 18/25 mesh cut, while the yield value and tensile strength markedly influenced t he shape factor. Thus, for the formulations studied, it was possible t o define a ''window'' of rheological/mechanical properties within whic h both extrusion and spheronization can be successfully carried out.