A mechanistic study of flow and compression behavior of pharmaceutical powders

The objectives of current study include: (i) analysis and prediction of the flow behavior of a mixture from individual components, (ii) investigation of the compression behavior of multi-component mixtures using an instrumented rotary tablet press and (iii) evaluation of various additives for antistatic effect on pharmaceutical powders. Lactose anhydrous blends were prepared with magnesium stearate, stearic acid and/or Cab-O-Sil as per simplex design. Blends were prepared with a constant mix time and variable mix times to achieve maximum bulk density. The blends and individual components were evaluated for Carr\u27s indices, moisture content and particle size distribution. The relationship for powder properties between the mixture and its components appears to be non-linear. Addition of Cab-O-Sil and mixing time had significant effect on the improvement of flow behavior of blends. The model predicted that lactose anhydrous would show optimum flow behavior with 0.25%w/w magnesium stearate, 1.48%w/w stearic acid and 1.27%w/w Cab-O-Sil. The mixtures of anhydrous lactose, Avicel PH101, Starch 1500 and magnesium stearate were prepared as per simplex design and were compressed using an instrumented Piccola tablet press. Mixtures and tablets were characterized and the compression force-time curves were analyzed. Contour plots were generated to study the effect of formulation composition on tablet and compaction parameters. Tablet weight variation, thickness and porosity increased with an increase in Starch 1500. The compressibility and tablet hardness increased with an increase in Avicel PH101. The ejection force increased with an increase in lactose. Heckel plots provided useful information on densification and deformation behavior of multi-component mixtures under pressure. Magnesium stearate, stearic acid, Cab-O-Sil and Pruv were evaluated for their antistatic effect on triboelectrification of Starch 1500, Avicel PH101 and cimetidine formulation during high shear mixing. The charges were measured using a Faraday Cup connected to NanoCoulomb Electrometer after 0, 5, 10, 11, 12 and 13 minutes of mixing. Magnesium stearate was more effective in reducing charges on electronegative materials such as Avicel PH101 whereas Cab-O-Sil was more effective with electropositive materials such as cimetidine. Mixing time had an adverse effect on antistatic efficiency of additives. Mixer type and batch size also affected the triboelectrification of powders