A study of selected physico-mechanical aspects of the extrusion and spheronization processes and their relationship to the design of pelletted pharmaceutical formulations

Abstract

Pellets are becoming increasingly popular as unique delivery systems. Of the several processes available to prepare these pellets, extrusion/spheronization is better suited to produce pellets with the desired attributes such as narrow size distribution, high bulk density and low friability. The prevalent empirical approach to optimize this process warrants a complete understanding of its rheological requirements. The specific objectives are to identify and define criteria such as the plastic yield value which may govern the success of this process, and to assess the contribution of Microcrystalline cellulose (MCC) to this process. Toward this end, a twin screw extruder EXDS-60 was specially instrumented to measure screen pressure and screen temperature. In addition, techniques were developed to measure three properties of the wet mass, viz., yield value, tensile strength, and yield loci, in an attempt to relate to the qualities of ideal extrudates for spheronization. Using a model lactose/MCC system, statistically designed experiments were planned to study the relationship between formulation variables, rheological parameters of the wet mass, and quality parameters of the dried pellets. The instrumentation output provided new insights into the interplay between formulation and extrusion process variables and is further expected to assist in the design of formulations by providing objective measures of extrudability. The rheogram of the wet masses provided an important parameter in yield value. The tensile strength measurement with a specially designed split-die system provided valuable information regarding the mechanism of bonding within the wet mass. Also, the combination of yield value and weight of extrudate (as an indirect measure of tensile strength) could be used to predict the shape of the pellets. The yield loci parameters were useful in detecting over-wet granulations. Upon careful analysis of the experimental data, it was apparent that there was a critical range of rheological parameters within which pellets having optimum sphericity and narrow size distribution can be prepared. This critical range was defined as the rheological "window" within which both extrusion and spheronization can be carried out satisfactorily. Initially, MCC is perceived to be an essential "cure-all" ingredient for all extrusion/spheronization problems. Based on a consideration of the physico-chemical properties of MCC, and evidence from scanning electron microscopy, its unique contribution was attributed to its high internal porosity, and the formation of a particle network in the localized areas of the wet mass. In conclusion, the knowledge gained from this investigation facilitates the design of pelletted formulations by reducing reliance on empiricism.