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size distribution, greater the requirement for the sieving efforts and therefore the higher the cost for the final product. In some continuous processes for making starter pel- lets, sieving is done online, and off-size particles are directly reworked. As a result, the desired particle size comes directly from process, minimizing the amount lost to sieving loss and boosting cost effectiveness. Neutral starter pellets A variety of excipients and excipient combinations are used to make neutral starter pellets. They include: • Sugar • MCC • Polyols • Carnauba wax • Silica • Lactose-starch • Lactose-cellulose Sugar. Sugar spheres originated in the confectionery industry and entered the pharmaceutical industry more than half a century ago. Today, they are the most com- mon carrier pellet. The product comprises sucrose (maxi- mum of 92 percent), and is made into spheres by layering a sugar crystal with a sucrose-starch syrup or by applying a powder within a coating pan. While the process princi- ples and techniques have changed little over the years, today's coating pans have better controls that allow man- ufacturers to optimize production. The initial sugar crys- tal must be completely covered by the sugar-starch coat- ing for it to become a sphere, and thus the size of the crystal is of primary importance with respect to pellet sphericity. Other properties, such us friability, depend largely on the manufacturing process used to create the sugar pellet, which varies from one to another supplier. The most common method uses a coating pan, but each manufacturer can augment or adjust the basic process to achieve different results. Products include Suglets (Colorcon), Non-Pareil Seeds (JRS Pharma), and PaulOrbs (Paulaur.) With, sugar, import duties are some- times a concern. It depends on the country. In April, India increased its duties on sugar imports from 25 per- cent to 40 percent in order to protect domestic producers. Thus it often makes sense to source sugar spheres in the country or economic zone in which the drug product will be produced. MCC. This type of neutral starter pellet is 100 percent microcrystalline cellulose and is usually manufactured by extrusion-spheronization or direct pelletization. With extrusion-spheronization, the hole sizes of the extrusion plate limit the size and sphericity of the pellets. A 500- micron hole is usually the lower limit because the energy input (friction) influences the mass, which may hinder spheronization. The final sphere size of the main fraction is typically close to the hole size of the extrusion plate. Other processes use a rotor and/or fluid bed to directly pelletize MCC in a single pot, which leads to highly spherical cores of 100 to 1,400 microns. One example is Glatt's "shovel rotor" process that densifies and spheronizes the MCC using an orbital motion to create non-friable pellets suitable for drug layering. The process was described in an article last year [2]. Freund-Vector offers a conical rotor processor that directly agglomerates excipients and/or APIs; it can also apply film coats and layer powders [3]. Brand names of MCC pellets include Cellets (photo), distributed in North America by by Glatt, and Celpheres, offered by Asahi Kasei. Polyols. This class of materials includes isomalt (GalenIQ 960 from Beneo-Palatinit), xyiltol (Xylinerts from IPS), and mannitol (Mcell from Pharmatrans Sanaq). The 960 isomalt (photo) is described by Beneo- Palatinit as a free-flowing isomalt for powder blends and capsule and sachet fillings and an "excellent carrier pro- viding blend uniformity." Its particle size distribution has a D10 of 270 microns, D50 of 380 microns, and D90 of 470 microns. Xylinert pellets are sugar-free, soluble, and hygro- scopic and comprise at least 98 percent xylitol. They are available in nine particle size ranges that span 710 to 1,700 microns. Information about the process used to make them was not available. Mcell mannitol pellets are also sugar free and offer advantages similar to those of xylitol. They are manufac- tured by continuous, direct pelletization using a fluid-bed technology that creates pellets directly from a suspension or solution. The process results in robust and spherical 12 July 2015 Tablets & Capsules Six size grades of Cellets MCC starter pellets: 100 (100 to 200 microns); 200 (200 to 355 microns); 350 (350 to 500 microns); 500 (500 to 710 microns); 700 (700 to 1,000 microns); and 1000 (1,000 to 1,400 microns).