Evaluation, by a Statistically Designed Experiment, of an Experimental Grade of Microcrystalline Cellulose, Avicel 955, as a Technology To Aid the Production of Pellets with High Drug Loading

Abstract

A statistically designed experiment has been undertaken to evaluate an experimental grade of microcrystalline cellulose (Avicel 955) as a technology to aid the production of pellets by extrusion spheronization of formulations with high drug load. An attempt has been made to relate the properties of the drugs to the ability to produce spherical pellets which have a narrow size distribution and are round, as assessed by a 2-dimensional shape factor by the process of extrusion/spheronization. Twenty drugs were tested at a level of 80%, and in all cases pellets could be produced. In some cases in terms of either size distribution or shape they were not of the highest quality. Nevertheless, a best level of water was identified for each drug. Principal component analysis did allow structuring of the data characterizing the process and the pellets, identifying a relationship between the water content and the steady state extrusion force as one component with the median pellet size and its interquartile range as the other. When multivariate analysis was used with the whole data set, it was not possible to relate the drug properties of pKa, freezing point depression, or solubility to the water content, steady state extrusion force, median pellet diameter, its interquartile range, and its shape satisfactorily. Thus other properties of the drug must be involved in the extrusion/spheronization process. Prediction of the best water content to use in a formulation was possible for 50% of the formulations by using a nonlinear model to relate the above drug properties to the water content.