(211d) 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
flow index, dilation, compressibility, and cohesion
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.
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).
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).