Effects of Co-Processed and conventional excipients on content uniformity

Silicification of microcrystalline cellulose (MCC) has previously been shown to have positive effects on the powder's flowability and tabletability compared to plain MCC or physical blends of colloidal silicon dioxide (CSD) and MCC [1]. A further characteristic of silicified MCC (SMCC) is its specific surface area, which is approximately five times larger than that of plain MCC [1]. It was hypothesized, therefore, that SMCC might have beneficial effects in terms of blend and content uniformity via effects of interactive blending. This study was designed to compare the blending efficacy of silicified microcrystalline cellulose and a co-processed SMCC-based multifunctional excipient to that of physical blends comprising the same nominal components. Near infrared spectroscopy (NIRS) was used to probe blend uniformity during the blending process of the excipients and a model active pharmaceutical ingredient (API), caffeine, presenting morphological and electrostatic challenges with regard to content uniformity. In addition to NIRS, both particle size analysis and scanning electron microscopy (SEM) were used to investigate the resulting blends. Content uniformity on the tableted blends, obtained by caffeine dissolution, was used to investigate the effects of differing blend uniformity on a final oral solid dosage form. For this non-optimized formulation with a challenging API, use of SMCC and a co-processed SMCC-based multifunctional excipient yielded formulations with significant benefits over using standard MCC, or MCC blended with colloidal silicon dioxide (CSD). These benefits included a faster blend uniformity, prevention of particle attrition, and a reduced impact of blender type and materials. Additionally, use of silicified microcrystalline cellulose yielded formulations with increased tablet hardness and reduced ejection forces.