The design of experiments showed significant differences between the three extruders on all the responses studied. Overall,
the radial system produced the worst results for the drug product considered. Dome extrusion provided the best results in
terms of productivity, pellet morphology, and pellet dispersion, and the axial system provided the best results in terms of
pellets' mechanical properties. Pellet properties appeared to be linked to extrudate characteristics.
Water quantity had a favorable effect on all responses. An increase in water quantity improved the results obtained with the
least efficient extrusion system and had a smaller influence on results obtained with the more efficient system. Water quantity
had less influence on the dome and axial systems, which already yielded good results. A system that gives high-quality pellets
over a wide range of watercontent values is less sensitive to water and more robust than one which produces high-quality pellets
in a narrow range of water content. For the development of a formulation by an extrusion-spheronization process, a narrow
water-level range could cause problems, especially for the scale-up phase of development. For this reason, the axial and dome
systems are more appropriate than the radial system. The extrusion speed had no significant influence on pellet properties,
but improved extrusion productivity significantly.
This study showed the particular advantages of dome extrusion in comparison with the two other systems. The results were nevertheless
obtained for fixed spheronization conditions, which could be more appropriate for dome extrudates. It would be interesting
to compare the three extrusion systems by testing various spheronization conditions. Moreover, results were observed for a
highly soluble drug product at a fixed concentration in the formula. Testing different solubilities and concentrations of
drug substances also could give complementary information about the efficiency of the three extrusion systems. The influence
of formulation and spheronization conditions will be described in Part II of this article.
Amélie Désiré* is a doctoral student at École des Mines d'Albi-Carmaux and Centre de Recherche et de Développement Pierre Fabre, 3 ave. Hubert
Curien, 31035 Toulouse Cedex 01, France tel. +33 0 5 34 50 62 79, fax +33 0 5 34 30 32 72, email@example.com
Bruno Paillard is head of solid dosage forms, and Joël Bougaret is director of the Pharmaceutical Technology Department, both at Centre de Recherche et de Développement Pierre Fabre. Michel Baron is head of the Pharmaceutical Engineering Department at école des Mines d'Albi-Carmaux, and Guy Couarraze is head of the Pharmaceutical Physics Department at the Université Paris Sud.
*To whom all correspondence should be addressed.
Submitted: Aug. 4, 2010. Accepted: Sept. 30, 2010.
1. R. Gandhi, C.L. Kaul, and R. Panchagnula, Pharm. Sci. Technol. Today
(4), 160–170 (1999).
2. K. Umprayn, P. Chitropas, and S. Amarekajorn, Drug Dev. Ind. Pharm.
3. N.R. Trivedi et al., Critical Rev. Ther. Drug Carrier Syst.
(1), 1–40 (2007).
4. C. Vervaet, L. Baert, and J.P. Remon, Int. J. Pharm.
(2), 131–146 (1995).
5. J.J. Sousa et al., Int. J. Pharm.
(1–2), 91–106 (2002).
6. L. Baert et al., Int. J. Pharm.
(2–3), 187–192 (1992).
7. K.E. Fielden, J.M. Newton, and R.C. Rowe, Int. J. Pharm.
(2–3), 225–233 (1992).
8. J. M. Newton, S. R. Chapman, and R. C. Rowe, Int. J. Pharm.
(1), 101–109 (1995).
9. L. Baert et al., Int. J. Pharm.
(1), 7–12. (1993).
10. C. Schmidt and P. Kleinebudde, Eur. J. Pharm. Biopharm.
(2), 173–179 (1998).
11. E. Nürnberg and J. Wunderlich, Pharm. Technol. Eur.
(3), 30–34 (1999).
12. K. Thoma and I. Ziegler, Drug Dev. Ind. Pharm.
(5), 401–411 (1998).
13. K. Thoma, and I. Ziegler, Drug Dev. Ind. Pharm.
(5), 413–422 (1998).
14. E. Le Doeuff et al., 6th International Conference of Pharmaceutical Technology (Paris, 1992).
15. D. Sonaglio, B. Bataille, and M. Jacob, Pharm. Acta Helv.
(2), 69–74 (1997).