V-blender

Most tumbling blenders are symmetrical in design this symmetry can be the greatest impediment to achieving a homogeneous mixture. The mixing rate often becomes limited by the amount of material that can cross from one side of the symmetry plane to the other (4- 8). Some blender types have been built asymmetrically (e.g., the slant cone, the offset V-blender), and show... 

Intershell flow is the slowest step in a V-blender because it is dispersive in nature while intrashell flow is convective. Both processes can be described by similar mathematics, typically using an equation such as... 

Common violations of this approach that can immediately cause problems include the attempt to scale from one geometry to another (e.g., V-blender to in-bin blender), changing fill level without concern to its effect, and keeping blending time constant while changing blender speed. 

Figure 7 Changes in segregation pattern formation in the (A) 1.9 quart and (B) 12.9 quart V-blenders.

Figure 8 A sketch of the relevant dimensions for a V-blender the actual values for the five blenders used are shown in Table 3.

Thus, as R increases. Tic decreases. This is illustrated in Figure 9, which shows the evolution of the RSD of a blending experiment in a small V-blender for three mixtures of different cohesion. Three systems were studied a low cohesion system composed of 50% Fast-Flo Lactose and 50 /o Avicel 102 a medium cohesion system composed of 50 /o Regular Lactose and 50 /o Avicel 102, and a high cohesion system composed of 50 /o Regular Lactose and 50 /o Avicel 101. In all cases, an aliquot of the system was laced with 6% micronized acetaminophen, which was used as a tracer to determine the axial mixing rate in V-blenders of different capacities (IQ, 8Q, and 28Q). 

Figure 9 (A) Relative standard deviation measured for axially segregated blends of different cohesion in a 1-quart V-blender. As cohesion increases, blending becomes slower. (B) Relative standard deviation measured for axially segregated blends of different cohesion in a 28-quart V-blender. In a large vessel, the effects of cohesion become unimportant.

Brone D, Alexander A, Muzzio FJ. Quantitative characterization of mixing of dry powders in V-blenders. AIChE J 1998 44(2) 271-278. 

Alexander AW, Shinbrot T, Muzzio FJ. Segregation patterns in V-blenders, 2001, in press. 

Carefully identify at least 10 sampling locations in the blender to represent potential areas of poor blending. For example, in tumbling blenders (such as V-blenders, double cones, or drum mixers), samples should be selected from at least two depths along the axis of the blender. For convective blenders (such as a ribbon blender), a special effort should be made to implement uniform volumetric sampling to include the corners and discharge area (at least 20 locations are recommended to adequately validate convective blenders). 

To validate both the particle velocity hypothesis and our scaling criteria, similar experiments were run in a number of different-capacity V-blenders. Vessel dimensions are shown in Table 2, along with a schematic, shown in Figure 8. 

Venting. Air that is in an otherwise empty bin, for example, must be displaced from the bin as powder fills it. If this air is forced through material in the V-blender, perhaps sealed tight in the interest of containment, this can induce fluidization segregation within the blender. To avoid this, a separate pathway or vent line to allow the air to escape without moving through the bed of material can reduce segregation. 

Development product Capsule product containing x mg of drug y ( freely water soluble ) and 1% magnesium stearate was developed using a Zanasi LZ-64 capsule-filling machine. Initial development experiments identified a causal link between blend time and dissolution rate. Capsules prepared with powders blended for 5 minutes exhibited a more rapid dissolution rate ( 95% dissolved in 10 minutes) compared to powders blended for 40 minutes ( 90% dissolved in 45 minutes). A 10-kg lot was blended for 15 minutes in a V-blender. Under these conditions the resulting capsules conformed to an in vitro dissolution acceptance criteria of Q75% in 45 minutes (in 900 mL water at 37°C, USP Basket 100 rpm). 

Scale-up product Initial trial for scale-up utilized a batch size of 570 kg, a Hoflinger Karg GFK-1500 capsule-filling machine (H K), and a V-blender, with the mixing time set to 15 minutes. Capsules resulting from this batch did not conform to the dissolution specification (only about 40% dissolved in 45 minutes). To rule out overblending with magnesium stearate, a blend time of 5 minutes in the V-blender was uti-... 

Equipment within the same class and subclass would be considered to have the same design and operating principle under SUPAC-IR and SUPAC-MR. Therefore, for example, a change from one type of diffusion mixer (e.g, V-blender from manufacturer A) to another diffusion mixer (e.g., V-blender from manufacturer B) generally would not represent a change in operating principle and would, therefore, be considered to be the same under either SUPAC-IR or SUPAC-MR. 

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