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

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

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.

Acknowledgments

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.




What would you do differently? Email your thoughts about this paper to
and we may post them to the site.

References

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)


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
Which of the following business challenge poses the greatest threat to your company?
Building a sustainable pipeline of products
Attracting a skilled workforce
Obtaining/maintaining adequate financing
Regulatory compliance
Building a sustainable pipeline of products
26%
Attracting a skilled workforce
29%
Obtaining/maintaining adequate financing
14%
Regulatory compliance
31%
View Results
Eric Langer Outsourcing Outlook Eric LangerBiopharma Outsourcing Activities Update
Cynthia Challener, PhD Ingredients Insider Cynthia Challener, PhDAppropriate Process Design Critical for Commercial Manufacture of Highly Potent APIs
Jill Wechsler Regulatory Watch Jill Wechsler FDA and Manufacturers Seek a More Secure Drug Supply Chain
Sean Milmo European Regulatory WatchSean MilmoQuality by Design?Bridging the Gap between Concept and Implementation
Report: Pfizer Makes $101 Billion Offer to AstraZeneca
Medicare Payment Data Raises Questions About Drug Costs
FDA Wants You!
A New Strategy to Tackle Antibiotic Resistance
Drug-Diagnostic Development Stymied by Payer Concerns
Source: Pharmaceutical Technology,
Click here