A MECHANISTIC STUDY OF FLOW AND COMPRESSION BEHAVIOR OF PHARMACEUTICAL POWDERS

Abstract

Majority of the drug substances are administered to patients in the form of oral solid dosage forms. The drug substance is mixed with excipients and the resulting powder blend is compressed into tablets. For a pharmaceutical powder to be compressed into uniform solid dosage forms, it is essential that the powder blend has good flow and compaction properties. The flow and compression properties of a pharmaceutical blend depend on the physicochemical properties of the individual components and their relative proportions in the mixture. Poor compressibility along with the poor flowable nature of most of the pharmaceutical mixtures poses tremendous challenges during the scale up and production stages. Vast majority of the tableting research was performed using single components though a typical tablet is a multi-component system. In this investigation, an attempt was made to study the flow and compression behaviors of multi-component mixtures containing several of the most commonly used pharmaceutical excipients. The effect of triboelectric charging during powder processing was also evaluated. The objectives of this study include: i) to investigate the relationship between the individual components and their mixed systems; ii) to analyze and predict the flow behavior of a mixed system from individual components using an experimental design; iii) to determine the optimum conditions for a mixture to exhibit better flow behavior; iv) to investigate the compression behavior of statistically designed multi-component mixtures using an instrumented tablet press; v) to determine the effect of mixing time, mixer type and batch size on triboelectrification of powders in a high shear mixer; and vi) to compare the antistatic effect of different lubricants/glidants on electronegative and electropositive materials. ( Lactose Anhydrous (97%w/w) blends were prepared with 3%w/w lubricant/glidant(s) in a planetary mixer as per simplex experimental design. The lubricants evaluated were: magnesium stearate, NF, stearic acid and colloidal silicon dioxide, NF (Cab-0-Sil M5). The relative amounts of lubricants/glidants were varied from 0 to 3% as per simplex design. One set of powder blends were prepared with a constant mix time of 3 minutes. Another set of powder blends were prepared with varying mix time until a relatively constant value for bulk density was achieved for specific blend. A total of ten powder blends of 500 grams each were prepared for each experiment. Response surface methodology was used to correlate the variation in lubricant/glidant(s) with the flow behavior. The powder blends and individual components were evaluated for bulk density, tapped density,