The V-blender has been one of the most common tumbling blenders used to mix granular materials in the pharmaceutical industry (e.g. Alexander et al., 2004). However, it has been observed recently that there is a growing trend in this industry to rely on bin-blenders when developing new mixing processes. V-blenders have also been replaced by bin-blenders at the scale-up stage or even in existing processes since these blenders are considered equivalent from the regulatory point of view of SUPAC (Scale-Up and Post Approval Changes) (FDA, 1995). One of the advantages of the bin-blender, also known as intermediate bulk container (IBC), is that it is known to reduce material handling by the operators as well as material contamination. Indeed, bin-blenders are movable and closed-contained. Despite these advantages, switching from a V-blender to a bin-blender may have an impact on the powder blend or end-use properties since these two mixing systems exhibit different flow behaviors that can lead to segregation or incomplete mixing.

The objective of this work consists of investigating granular mixing in a bin-blender and a V-blender in order to better understand how the flow dynamics differs in these two types of blenders. This comparative work aims at assessing the impact of varying process parameters such as the particle size, the fill level and the rotational speed on the mixing behavior. The two blenders that are considered are custom-made 8-qt scaled-down versions of industrial V- and conical bin-blenders. The material consists of cohesionless monodisperse granules that contain spheronized microcrystalline cellulose PH101 (Avicel) and hydroxypropyl methylcellulose (HMPC). Red iron oxide is also present in the case of colored particles. Mixing behavior in both blenders will be discussed on the basis of RSD curves and mixing times, all obtained using thief probes and image analysis techniques.

As a complement to the experimental work, numerical simulation results of the granular flow in both blenders with the discrete element method (DEM) will be presented. DEM-based modeling allows obtaining information that is difficult to measure experimentally such as, for instance, the particle velocity field. The simulations involve a large number of particles over large spans of time, which is needed when one wants to gain insight into mixing phenomena that have been observed experimentally to manifest themselves very slowly (Lemieux et al., 2005).

Alexander A., Shinbrot T., Johnson B. and Muzzio F., V-blender segregation patterns for free-flowing materials: effects of blender capacity and fill level, International Journal of Pharmaceutics, 269, 19-28, 2004.

Department of Health and Human Services, Food and Drug Administration. Guidance for Industry : Immediate Release Solid Oral Dosage Forms; scale-up and post approval changes: chemistry, manufacturing, and controls, in vitro dissolution testing, and in vivo bioequivalence documentation. U.S., November 1995.

Lemieux M., Léonard G., Doucet J., Leclaire L.-A., Viens F., Bertrand F. and Chaouki J., Large-scale numerical investigation of solids mixing in a V-Blender using the discrete element method, submitted to Powder Technology, 2005.