Powder segregation

When manufacturing a tablet formulation by direct compression, the particle size and size distribution of excipients have a significant impact on blending homogeneity, powder segregation, and flowability. This can result in unacceptable content uniformity and high tablet weight variation. In such situations, control of excipients can be critical to product quality. 

If a powder flows poorly, the vibrator can be used, but it also causes powder segregation and stratification. The addition of glidant (occasionally lubricant) in the powder mixtures can readily increase flowability at the low concerntration. Talc or fumed silicon dioxide is an example of a glidant. If this is not sufficient to improve the flow, other means of flow improvement are necessary. There are two main factors that affect powder flow particle size and particle shape. The more spherical a particle is, the better it flows. Small particles are very cohesive and hence do not flow well, but increasing the particle size will improve flow. With the aid of spray drying or spheronizers, particles become spherical. 

Segregation is a real problem in industry. Some mixers may not be able to form a random mixture of some powder mixes because of powder segregation mechanisms occurring within the mixer. Some mixers may even demix a mixture due to the dominance of segregation mechanisms acting on a particular mixer, for example, a... 

Alexander B. Roddy M. Brone D. et al. A method to quantitatively describe powder segregation during discharge from vessels. Pharm Tech Yearbook 2000 6-21. 

Most master batches are formulated from solid powders by mixing the different ingredients in a conventional (normally batch) mixer. Since considerable differences in size and shape of the individual components exist, for example between pigments and fibers and thermoplastic powders, segregation of the dry blend is a major concern. Also, the end users prefer to only re-melt the fully formulated feed and process it into parts for industrial and consumer applications. 

Gedanken and coworkers [194] exploited power ultrasound to generate in situ amorphous-carbon-activated palladium metallic clusters that proved to be a catalyst for Mizoroki-Heck reactions (without phosphine ligands) of bromobenzene and styrene (yield to an appreciable extent of 30%). The catalyst is stable in most organic solvents, without showing any palladium powder segregation, even after heating them to 400 °C. 

P/M Tool Steels. In conventionally produced high alloy tool steels (slowly cooled cast ingots), carbide tends to segregate (48). Segregated clusters of carbide persist even after hot working, and cause undesirable effects on tool fabrication and tool performance. P/M tool steels, on the other hand, provide very fine and uniform carbides in the compact, the final bar stock, and the tools. Several tool steel suppHers consoHdate gas-atomized tool steel powder by HIP to intermediate shapes, which are then hot-worked to final mill shapes. Water-atomized tool steel powder is also available (see also T OOL materials). ... 

The availabihty of spray-dried lactose, microcrystaUine cellulose, and other excipients allows for the use of granular rather than powdered phases. This eliminates some of the problems of particle segregation according to size (demixing) and even flow to the die. Direct compression eventually may be the preferred method of tablet preparation. 

Another technique is to change the particle size distribution. There are, however, disadvantages. If segregation is occurring by the sifting mechanism, the particles must be almost identical in size before sifting is prevented. Alternatively, the mean particle size can be reduced below 100 p.m, but this size reduction (qv) increases the probabiUty of segregation by the too fine powder mechanisms. 

Whenever possible a powder should be sampled when in motion and the whole of the stream of powder should be taken for many short increments of time in preference to part of the stream being taken for the whole of the time. Observance of these rules coupled with an understanding of the manner in which segregation takes place leads to the best sampling procedure. Care and skill in abstracting samples is needed and cannot be overemphasized. 

Stored Free-Flowing Material. It is practicahy impossible to representatively sample stationary free-flowing powder because of the severe segregation that has almost certainly occurred. If there is no alternative but to sample this material, several samples should be taken and analyzed separately, so that an estimate can be made of the rehabhity of the measured parameter. For free-flowing materials stored in small hoppers, dmms, cans, boxes, and... 

Powder Techniques. Highly alloyed materials made by the processes described are particularly susceptible to segregation of alloying elements during solidification both on a macro- and a microscale. Much plastic working was necessary to minimise this susceptibiUty before service appHcations. 

An ingenious method to avoid or reduce segregation of alloying elements involves preparing small spheres of material by the atomization of a Hquid stream through a nozzle to produce a powder. This powder can be compacted, often hot and triaxially by gas pressure, to form a material where, on further heating, the residual pores close by diffusion to approach 100% density. 

Creation of non-segregating blends of powder ingredients, as in sintering of fines for steel or agricultural chemical granules. 

---