Optimizing Powder Flow Properties in Capsule Filling Applications

Capsules are one of the major oral dosage forms in the pharmaceutical industry. Capsules are very effective since their contents are encapsulated in powder form not having to disintegrate in the stomach making the dosage available faster. Capsules also allow the encapsulation of materials that are not compressible or highly sensitive to the heat produced in the compaction process. The importance of encapsulating the right amount of dose is of great concern and the variability in powder filled amount from capsule to capsule and batch to batch affects the required drug concentration. The purpose of this study was to develop an effective laboratory method for characterizing powder flow properties and correlating such properties to weight variability in filled capsules. These correlations allowed to develop an approach for optimizing flow properties and minimizing weight variability in filled capsules. The methods used for powder flow characterization were bulk and tapped densities, GDR^[1] flow index, dilation^[2], compressibility, and cohesion parameters .

Capsules were filled using a Cap8^¨, a semi-automatic machine in which the powder is fed from a hopper by a rotating auger and flows into the bottom of the capsules placed in a rotary table, and a MG2, an automatic continuous machine which uses plug formation to fill the capsules. For the Cap8^¨, four different augers and three rotary speeds were used as machine parameters. While three different production speeds and variations in the bowl and piston (plug) height were used with the MG2. High drug content (>90% wt/wt) blends with micronized acetaminophen and additives such talc, magnesium stearate, and Cab-O-Sil were used to fill capsules in the Cap8^¨. Lower drug content  (<10% wt/wt) blends were used to fill capsules using the MG2. For the Cap8^¨, it was found that with increasing auger degree, the capsule weight increased with increasing compressibility and decreasing bulk and tapped densities. Blends without SiO₂ had higher average weights than blends with SiO₂. The RSD remained relatively constant for blends with SiO₂. The RSD was found to be higher for blends without SiO₂ decreasing with increasing auger degree. For the MG2, the capsule mean weight increased with increasing bulk and tapped density. The weight also increased with increasing flow factor (ffc) (decreasing cohesion parameter) measured in a shear cell and decreasing GDR flow index. Changes in capsule weight and weight variability due to blend type can be well correlated to the bulk and tapped density, compressibility, dilation, GDR flow index, the cohesion parameter and the flow factor (ffc). Powder flow properties were successfully correlated to the capsule mean weights and weight variability. The understanding and correlations found can be used to optimize capsule filling applications of these types.

1.     A.W. Alexander, B. Chaudhuri, A.M.N. Faqih, F.J. Muzzio, C. Davies, and M.S. Tomassone, Avalanching flow of cohesive powders. Powder Tech. 164, 13-21 (2006).

2.     A.M.N. Faqih, B. Chaudhuri, A.W. Alexander, S.V. Hammond, F.J. Muzzio, and M.S. Tomassone, Flow – induced dilation of cohesive granular materials. AIChE J. 52, 12, 4124-4134 (2006).