A Comparison of Three Extrusion Systems (Part II) - Pharmaceutical Technology

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A Comparison of Three Extrusion Systems (Part II)
The authors compare three systems of single-screw extrusion using binary formulations for their suitability for producing pellets of various formulations and under various spheronization conditions.


Pharmaceutical Technology
Volume 35, Issue 6, pp. 56-61

Discussion


Table II: The effect of formulation and spheronization variables on responses.
The ideal extrusion system gives the best results in terms of productivity and pellet quality, but also has the least influence on those same properties when the formula used changes (i.e., robustness), and allows pellet properties to be adjusted or improved with spheronization variables (i.e., flexibility). The extruders were analyzed as distinct designs of experiments (see Table II) to study the significant effects of other factors in order to assess which extruder presented the best robustness and flexibility.

Robustness study. A nonsignificant effect of an extrusion system when the formulation changed confirmed extruder robustness. For example, an increase in DS concentration caused an increase or decrease in pellet size for axial and dome extrusion respectively but had no significant effect for the radial system, which, therefore, is the most robust (see Table II). The influence of DS solubility and DS concentration was also extrusion system dependent. In the radial system, DS solubility had no significant effect on extrusion yield or pellet hardness, and DS concentration showed no significant effect on pellet size, circularity, yield, roughness or friability. In the dome system, DS concentration had no significant influence on pellet circularity or roughness, whereas DS solubility had significant effect on all responses. In the axial system, DS solubility had no significant influence on pellet friability, and DS concentration showed no significant effect on pellet circularity, roughness or friability. The influence of DS solubility and concentration was significant for all the other cases. The radial system, therefore, was the most robust formulation variability (particularly in terms of pellet size).

Flexibility study. A significant effect of the extrusion system when spheronization conditions changed confirmed extruder flexibility. For example, an increase in spheronization time increased pellet size in the dome system but had no significant effect in the other systems, which showed the dome system to be the most flexible (see Table II). The influence of spheronization time and speed also dependended on extrusion system. In the radial system, spheronization speed affected mechanical pellet properties (e.g., friability and hardness), whereas spheronization time influenced roundness, roughness, and true density. In the dome system, spheronization speed had a significant effect on usable yield, and spheronization time influenced pellet size, roughness and true density. In the axial system, spheronization time affected pellet roughness. Overall, the radial and dome systems were more flexible. The dome system presented good flexibility, notably on pellet size when spheronization time varied. In the axial system, changes in spheronization parameters did not compensate for bad pellets properties. Other authors have also concluded that the type of extruder influenced pellet characteristics and that axial extruders were more difficult to use because of their lower flexibility (36).


Table III: Identification of ideal extrusion system in terms of quality, robustness, and flexibility.
The conclusions of robustness and flexibility studies, combined with the quality study described previously identified the ideal extrusion system at lab scale (3, 4). The extruder systems that presented the best results for each of the three approaches are highlighted in Table III.

Regardless of spheronization parameter levels, the axial system presented the best results in terms of mechanical pellet properties and roughness, but disappointing results for process robustness and flexibility. The dome system showed the best results in terms of productivity, pellet morphology, and process flexibility, but disappointing results for process robustness. Despite the worst results in terms of process and pellet properties, the radial system presented good results for process robustness and flexibility (see Table III).

Conclusion

The objective of this study was to identify critical parameters and to select the extruder that gives the best results in terms of productivity and pellet characteristics (product quality), the one that shows the least influence on these same properties when the formulation changes (robustness), and the one that allows the adjustment of spheronization variables to improve pellet properties (flexibility).

In spite of good pellet quality results, the axial extruder seems to be the most difficult to use because of its lack of flexibility. Perfect knowledge of the initial wet mass composition and plasticity is required because its results depend on formulation. The pellet manufacturing ability of the radial extruder is not heavily influenced by the formulation, and adjustment of spheronization variables control pellet properties. For the formulations and process variables studied, the design of experiments identified the radial system as the easiest to use because of its higher robustness and flexibility—two important requirements for the development and scale-up of formulation by extrusion–spheronization. The final part of this work will validate these results at industrial scale.

Amélie Désiré* is a doctoral student at École des Mines d'Albi-Carmaux and the Centre de Recherche et de Développement Pierre Fabre, 3 ave. Hubert Curien, 31035 Toulouse Cedex 01, France tel. +33 05 34 50 62 79, fax +33 05 34 30 32 72,
. Bruno Paillard is head of solid dosage forms, and Joël Bougaret is director of the Pharmaceutical Technology Department, both at the 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: Feb. 23, 2011. Accepted: May 4, 2011


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