The Effect of Mill Type on Two Dry-Granulated Placebo Formulations - Pharmaceutical Technology

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The Effect of Mill Type on Two Dry-Granulated Placebo Formulations
The authors evaluate the effect of various mill types on particle-size distribution, flowability, tabletability, and compactibility.

Pharmaceutical Technology
Volume 32, Issue 11, pp. 72-86

The MCC–lactose formulations produced tablets of a lower crushing strength than those of the MCC–DCP formulations for all the mills evaluated. Although all the granulations performed similarly, some differences in tabletability and compactibility were evident. One noteworthy difference was a higher tablet-crushing strength for the Gerteis-milled material. Tablets had an approximately 0.5 MPa higher strength compared with the other milled lots. The authors found no definitive explanation for these results.

Although all the granulations have a flowability rating of good, the Gerteis granulation had the lowest value of 8.0, compared with the 9.1 and 9.0 for the M5A and Comill, respectively. The lower flowability value suggests a higher level of smaller particles in the granulation and correlates with the laser-diffraction data showing the Gerteis material having the smallest D10 and D50 particle-size values. However, the Gerteis material also has the highest D90 value and the greatest breadth of particle size for the three granulations. The smaller particle size and greater breadth of this granulation may contribute to the higher tabletability and compactibility observed. Also, the difference in particle size could be attributed to the ribbon properties.

Table VII: Microcrystalline cellulose–lactose compression properties.
Review of the ribbon characterization for the individual bags collected (see Table III, bag #5, 6, 7) during roller compaction suggests that the ribbons used for the three conventional mill types have identical solid fraction and thickness. The ribbon tensile strength used for the Gerteis milling, however, was the lowest of the three. It is possible that the lower strength of the ribbon contributed to the difference in granulation-particle size, thus leading to a difference in bonding properties and tablet-crushing strength.

Overall, formulation composition, not mill type, had the most significant effect on compaction properties. Compression using a high-speed rotary tablet press confirmed that differences in the formulation composition had an effect on tabletability and compactibility and that mill type did not significantly influence the tabletability and compactibility of the formulations.


The authors acknowledge Barbara Spong's active support of this study.

Thomas A. Vendola* is a scientist in solids development, and Bruno C. Hancock is a research fellow in material sciences at Pfizer, Eastern Point Rd., Groton, CT 06340, tel. 860.441.4430, fax 860.441.3972,

*To whom all correspondence should be addressed.

Submitted: Jan. 28, 2008. Accepted: Mar. 20, 2008.

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1. R.J. Lantz, "Size Reduction," in Pharmaceutical Dosage Forms: Tablets, H.A. Lieberman, L. Lachman, and J.B. Schwartz, Eds. (Marcel Dekker, New York, Vol. 2, 2nd ed., 1990), pp. 107–200.

2. B.C. Hancock et al., "The Relative Densities of Pharmaceutical Powders, Blends, Dry Granulations, and Immediate-Release Tablets," Pharm. Technol. 27 (4), 64–80 (2003).

3. A.V. Zinchuck, M.P. Mullarney, and B.C. Hancock, "Simulation of Roller Compaction Using a Laboratory Scale Compaction Simulator," Int. J. Pharm. 269, 403–415 (2004)

4. S. Behera et al., "Flowability Studies of Bulk Materials for Design of Hopper Using a Jenike Shear Cell," Powder Handling and Processing 14, 96–101 (2002)


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