Evaluation of binding agents for the preparation of spherical granules by extrusion/spheronisation

A method of producing multiparticulate oral controlled release dosage forms is extrusion/spheronisation. Experimental microcrystalline cellulose (MCC) products have been assessed for the ability to provide formulations containing 80% of 3 model drugs: ibuprofen, insoluble, lactose, soluble and ascorbic acid, highly soluble drug models. The effect of the pH of the binding solution was assessed using water, pH 10 buffer and pH 2 buffer as binding fluids. It was observed that some of the MCC samples were capable of producing good quality pellets with all three drug models, therefore two of the excipients were selected for full evaluation in comparison with a standard MCC product (Avicel PH101). A ram extruder was used to determine the rheological characteristics of the formulations. The approaches of Bagley and Benbow-Bridgewater were both used to provide quantification of the rheological properties of the formulations. The ability of the mixtures to retain the fluid was assessed using the ram extruder at different extrusion speeds. The ability of the MCC samples to retain and absorb water was assessed using a pressure membrane apparatus. The angle of wall friction was determined using an annular shear cell in order to ascertain the angle of wall friction of the materials to assess if there was any association between the extent of material sticking to the spheroniser plate during spheronisation and the intercept of the yield locus. One of the MCC samples (E5666-126-4B2-8) was found to possess the greatest ability for holding the binding liquid during extrusion and there was a difference in the quantity of water required by the different MCC samples. Although there was a greater quantity of water in the MCC sample the extent of water removal from the power bed was less than with Avicel PH 101. Thus the material had a greater affinity for holding water within the powder bed. This identified with the ability of the materials to produce spherical particles with all of the model drugs