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Powder Mixing – Powder mixing is an operation that serves to make two or more components uniformly distributed in the powder bed.

Mechanisms – There are three main mechanisms involved in the mixing process, related to the different kinds of particle motion.

• Convection: The large group of particles are moving together in the mixer, driven by the rotational force provide by a mixer vessel, paddle, blade, ribbon, or gas flow. The rotating flow leads to convective motion of particles and\ mainly contributes to the macroscopic mixing, rather than microscopic mixing. The mixing rate of this process is relatively high, however, to achieve a more uniform mixing, prolonged times are required, because particles within the moving group are not able to mix well.
• Shear: Shear refers to the action that one layer of powder particles moves relative to another layer of particles. Shear mixing can be caused by particles from a different powder layer, having different velocities developed in a rotary vessel or due to the compression force and extension of the powder bed. Hence, shear mixing is the movement of a layer of particles, rather than the movement of individual particles. The rate of shear mixing is intermediate and mainly causes semi microscopic mixing.
• Diffusion: Diffusion is known as the moment of individual particles, due to random motion of powder particles. When the powder bed is placed in a mixer, the volume of that powder bed increases, due to convection and shear forces, which drive the powder flowing around the mixer. Therefore, the voids between particles increase, leading to great potential for individual particles to mix with each other. The rate of diffusive mixing is relatively low, compared with convection and shear mixing; however, it contributes to the microscopic mixing.

Problems during powder mixing – Powder segregation (demixing) is the opposite process of mixing, which means the separation of the drug from the powder components. Under some circumstances, the mixing process provides the necessary situations for powder to segregate, because, during the mixing process, particles are moving relatively close to each other, and their movement may differ due to their different properties, such as size, shape, or density. Conversely, particles having similar properties tend to move together, causing that region of the powder bed to have a higher composition concentration. Some other handling processes may also cause powder segregation, such as transportation, packing, feeding, and storage. The smallest region that can measure the homogenous state in a powder mixture is called the scale of scrutiny and can be a length, area, or volume. The scale of scrutiny is a scale of the finished product. For instance, for a 100 mg tablet, the scale of scrutiny is 100 mg. When the scale of scrutiny is large or the particle size is small, which indicates a large number of particles are present in the sample, the powder mixture are relatively uniform. Segregation can never be completely avoided, so powder sampling is preferred for the final product.

Mixing equipment –

• The mortar and pestle represent one of the most commonly used small scale mixing equipment. The mortar and pestle method combines comminution and mixing in a single operation. Hence, it is very useful when some degree of particle size reduction, as well as mixing, is required. Conventional mortars include glass mortars, Wedgwood mortars, and porcelain mortars, and there is an increasing use of a newly developed mortar, called the electronic mortar and pestle (EMP), among pharmacists.
• Tumbling mixers/blenders are most commonly used for powders with similar densities. There are different types of tumbling mixers, including V-shaped, rotating cube, cylindrical, double-cone, oblique, and Y-cone mixers.
• In the ribbon mixer, spiral ribbons, paddles, or blades are mounted on a shaft, which is located in the center of the mixing equipment. Rotating of the shaft leads to the circular movement of the blades and subsequent mixing of the powder. The ribbon mixer can mix powders with poor flowability and avoid segregation as compared to tumbling mixers.

• Industrial planetary mixer – There is a mixing bowl located at the bottom of the equipment, which can move up and down. The There is a mixing bowl located at the bottom of the equipment, which can move up and down. The There is a mixing bowl located at the bottom of the equipment, which can move up and down. The bowl is used for feeding and discharging of the product. The bowl can be raised to the position of the mixing blades for the actual mixing process. The mixing blades or paddles are located off the center of the mixer. They rotate around their center and simultaneously rotate around the center of the mixer. This double rotating process can cause a more complete mixing of the entire equipment, so “dead spots” are avoided. Planetary mixers can break agglomerates easily.
• The Nautamixer is composed of a bottom discharger with a rotating screw fastened to the upper end of the rotating arm. The screw conveys the product to the top, where it can flow back to the powder feed. Hence, for this equipment, the vertical impeller and horizontal rotating arm are combined together to induce a combination of convection, shear, and diffusive mixing.
• The fluid-bed mixer is usually used for powder mixing, prior to granulation in the same bowl. Therefore, the fluid-bed mixer is part of a fluid-bed granulator system. Fluidization of the powder particles can be achieved by blowing heated and filtered air into the equipment. Efficient mixing is achieved by circulation of the fluidized powder. After mixing, granulation liquid is pumped from the liquid receiver/holder through a spray nozzle and on to the fluidized powder bed to facilitate granulation. When sufficient liquid has been sprayed to achieve appropriate granule size, the nozzle is turned off and the wet granules are dried by the fluidizing heated air.

Multiple choice questions:

1.An operation that serves to make two or more components uniformly distributed in the powder bed is called as

a)powder segregation

b)powder mixing

c)powder size reduction

d)comminution

2.How many mechanisms are involved in the mixing process of powders?

a)1

b)2

c)3

d)5

3.Which of the following mechanisms are involved in the mixing process?

a)Convection

b)Shear

c)Diffusion

d)All of these

4.In which of the following the large group of particles are moving together in the mixer, driven by the rotational force provide by a mixer vessel, paddle, blade, ribbon, or gas flow?

a)Convection

b)Shear

c)Diffusion

d)All of these

5.The mixing rate is relatively high in which of the following mechanisms?

a)Convection

b)Shear

c)Diffusion

d)All of these

6.The action that one layer of powder particles moves relative to another layer of particles is known as

a)Convection

b)Shear

c)Diffusion

d)All of these

7.Shear mixing can be caused by particles from a different powder layer, having different velocities developed in a rotary vessel or due to the compression force and extension of the powder bed.

a)true

b)false

8.The rate of shear mixing is intermediate and mainly causes _____ mixing.

a)microscopic

b)semi microscopic

c)macroscopic

d)all of these

9.The moment of individual particles, due to random motion of powder particles is called

a)Convection

b)Shear

c)Diffusion

d)All of these

10.Powder segregation is also known as

a) demixing

b)mixing

c)sticking

d)flocculation

11.Which of the following handling processes may cause powder segregation?

a)transportation

b)packing

c)feeding

d)all of these

12.The smallest region that can measure the homogenous state in a powder mixture is called

a)the scale of scrutiny

b)the scale of homogenosity

c)the graph of scrutiny

d)the scale of mixing

13.Which of the following mixing equipment’s are used in powder mixing?

a)mortar and pestle

b)ribbon mixer

c)nautamixer

d)all of these

14.The mortar and pestle method combines _____ and _____ in a single operation.

a)comminution and mixing

b)comminution and demixing

c)separation and mixing

d)sampling and mixing

15.Fluidization of the powder particles can be achieved by blowing cooled and filtered air into the equipment.

a)true

b)false

Solutions:

1. b)powder mixing
2. c)3
3. d)All of these
4. a)Convection
5. a)Convection
6. b)Shear
7. a)true
8. b)semi microscopic
9. c)Diffusion
10. a)demixing
11. d)all of these
12. a)the scale of scrutiny
13. d)all of these
14. a)comminution and mixing
15. b)false

References:

1. Remington Essentials of Pharmaceutics, 1st edition 2013, page no. 428-429.
2. Ansels Pharmaceutical dosage forms and Drug Delivery system, 10th edition, page no. 223.

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