Production of pellets from wet masses containing olanzapine by extrusion and spheronization

In this study pellets were produced from wet masses containing olanzapine by extrusion and spheronization. This technique is used worldwide to create multiparticulate solid dosage forms. The extrudability of wet masses containing olanzapine into pellets, was tested. First pellets were manufactured containing only microcrystalline cellulose (MCC), tricalcium phosphate (TCP) and water. In the second part of the study, olanzapine was added as active pharmaceutical ingredient. In both parts of the study, pellets were manufactured with different formulations of excipients. Each formulation was extruded 2 times, immediately after mixture, and after 24 hours. The resulting pellets were tested on different properties such as density, porosity, loss on drying, size and crushing force. Finally the release of olanzapine from the pellets was tested, by a dissolution test.

When looking at the results, it can be stated that the fractions of MCC and TCP in the formulation should be balanced in order to obtain pellets with a good size between 1 and 1,4 mm. When water was added to microcrystalline cellulose, the latter tends to swell up and form a matrix structure, which can hold various substances, like olanzapine. Tricalciumphosphate has the property to interconnect the pores inside the pellets, making it more easy for olanzapine to escape from the pellets. The MCC and TCP fractions in formulations was also important for the tensile strenght of the pellets. Conclusions have been made that a formulation should contain more than 20 parts of MCC in order to resist to a crushing force. When less than 20 parts of MCC is used in a formulation, the matrix structure cannot be formed, resulting in pellets which break more easily.

When comparing the different dissolution profiles of pellets with different formulations, pellets with 20 parts MCC and 80 parts TCP have shown the largest olanzapine release. When more MCC is used in the formulation, the matrix structure is formed in that way that the olanzapine cannot be released.

The influences of excipients, such as MCC and TCP, in different fractions on the properties of pellets after extrusion and spheronization were tested in this study. Future work could examine and compare differences in these properties between MCC, TCP, and other excipients.