Figure 7: Sticking profiles for prototype and commercially available ibuprofen formulations.
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Benchmarking sticking of a new ibuprofen formulation.
A prototype ibuprofen formulation was tested alongside three commercially available ibuprofen formulations to quantify sticking
risk before scale-up. The prototype formulation contained a 50% w/w level of ibuprofen and 5% w/w talc as the tableting lubricant.
After 100 compressions, the prototype formulation had about 1500 µg of powder adhered to the punch tip. The commercial ibuprofen
formulations had lower sticking: Albemarle had the most, followed by BASF and Advil (See Figure 7). Using Advil as the gold-standard
benchmark, the prototype formulation was deemed to be unsuitable for product scale-up without reformulation. The high level
of sticking for the prototype ibuprofen formulation was attributed to literature reports of talc as a suboptimal tableting
lubricant for sticky formulations (7, 8), in addition to ibuprofen's notorious propensity to stick. This quantitative assessment
shows the benefit of testing prototype formulations and benchmarking alongside formulations known to (or not to) exhibit sticking
behavior. Thus, unsuitable formulations can be flagged quickly during drug product design.
Conclusion
The simple method of using a removable punch tip is capable of quantitatively measuring sticking for formulations containing
various levels of tableting lubricant and various grades and concentrations of sticky ingredients. This tool can be used to
screen tableting formulations during drug-product design to optimize formulation composition, and potentially to study the
effect of sticking on tableting process parameters (e.g., tableting speed and compression force) and tooling design features
(e.g., metal composition, surface roughness, shape, curvature, and embossing).
Acknowledgments
The authors thank MDC Associates for assisting with the design and fabrication of the custom punch. They thank Gregory (Scott)
Goeken, scientist, and John Kresevic, senior principal scientist, both at Pfizer, for providing the prototype and commercial
ibuprofen formulation samples.
References
1. M. Roberts et al., J. Pharm. Pharmacol.
56 (3), 299–305 (2004).
2. T.S. McDermott et al., Powder Technol.
212 (1), 240–252 (2011).
3. D. Simmons, poster at the 12th Annual American Association of Pharmaceutical Scientists—Northeast Regional Discussion
Group (Rocky Hill, CT, 2009).
4. J.J. Wang et al., J. Pharm. Sci.
93 (2), 407–417 (2004).
5. Y. Cheng et al., Proceedings of AICHE Annual Conference (Orlando, FL, 2006), pp. 1–13.
6. F. Waimer et al., Pharm. Dev. Technol.
4 (3), 359–367 (1999).
7. M. Bose, A. Sakr, and A. Warner, Pharm. Industrie
55 (5), 519–522 (1993).
8. A. Delacourte et al., Drug Dev. Ind. Pharm.
19 (9), 1047–1060 (1993).
What would you do differently? Email your thoughts about this paper to
ptweb@advanstar.com
and we may post them on
http://PharmTech.com/.
Matthew P. Mullarney* is a principal scientist, Bruce C. MacDonald is a scientist, and Allan Hutchins is a laboratory technician, all at Pfizer, Eastern Point Road, Groton, CT 06340, tel. 860.715.4139, fax 860.441.3972, matthew.p.mullarney@pfizer.com
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