The evaluation of modified microcrystalline cellulose for the preparation of pellets with high drug loading by extrusion/spheronization.

ABSTRACT

The performance of microcrystalline cellulose (MCC) which had been modified by the inclusion of various levels of sodium carboxymethylcellulose (SCMC) in the wet cake prior to drying, in terms of their ability to form pellets by a standardised extrusion/spheronization process has been assessed. Initial screening of the ability of the modified MCCs to form pellets with an 80% level of lactose as a model drug identified two potential products containing 6 or 8% of SCMC (B 6 and B 8). These two products were compared with a standard grade of MCC (Avicel PH101) in terms of their ability to produce pellets with 80% of model drugs of low (ibuprofen), intermediate (lactose) and high (ascorbic acid) water solubility when subjected to a standardised extrusion/spheronization process. Also assessed was their ability to retain water with applied pressure using a pressure membrane technique and their ability to restrict water migration during extrusion with a ram extruder. The two new types of MCC (B 6 and B 8) were able to form good quality pellets with all three model drugs, whereas Avicel PH101 could not form pellets with this high level of ibuprofen. This improved performance was related to the ability of the new types of MCC to hold higher levels of water within their structure and restrict the migration of water in the wet mass when subjected to pressure applied during the process of preparing the pellets. There is evidence to show that the two new types of MCC can function over a wider range of water contents than Avicel PH101 and that they have an improved performance if the extrusion process is rapid and if, after incorporation of the water into the powder, the sample is stored for some time before extrusion.