Effect of colloidal silica on rheological properties of common pharmaceutical excipients

Abstract

In pharmaceutical industry, the use of lubricants is mostly based on historical experiences or trial and error methods even these days. It may be demanding in terms of the material consumption and may result in sub-optimal drug composition. Powder rheology enables more accurate monitoring of the flow properties and because the measurements need only a small sample it is perfectly suitable for the rare or expensive substances. In this work, rheological properties of four common excipients (pregelatinized maize starch, microcrystalline cellulose, croscarmellose sodium and magnesium stearate) were studied by the FT4 Powder Rheometer, which was used for measuring the compressibility index by a piston and flow properties of the powders by a rotational shear cell. After an initial set of measurements, two excipients (pregelatinized maize starch and microcrystalline cellulose) were chosen and mixed, in varying amounts, with anhydrous colloidal silicon dioxide (Aerosil 200) used as a glidant. The bulk (conditioned and compressed densities, compressibility index), dynamic (basic flowability energy) and shear (friction coefficient, flow factor) properties were determined to find an optimum ratio of the glidant. Simultaneously, the particle size data were obtained using a low-angle laser light scattering (LALLS) system and scanning electron microscopy was performed in order to examine the relationship between the rheological properties and the inner structure of the materials. The optimum of flowability for the mixture composition was found, to correspond to empirical findings known from general literature. In addition the mechanism of colloidal silicone dioxide action to improve flowability was suggested and the hypothesis was confirmed by independent test. New findings represent a progress towards future application of determining the optimum concentration of glidant from the basic characteristics of the powder in the pharmaceutical research and development.