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Importance of mixing

PHC 453

 There are very few pharmaceutical products that contain

Mixing f i ibl li id
Mi i of miscible liquids and suspensions

 If, a pharmaceutical company wishes to produce a tablet

NOR KHAIZAN BINTI ANUAR, PhD

 Whenever

a product contains more than one component, a mixing or blending stage will be required in the manufacturing process.
 This is to ensure:
• an even distribution of the active component
• an even appearance
• that the dosage form releases the drug at the correct site and at the desired rate
 The unit operation of mixing is therefore involved at some stage in the production of practically every pharmaceutical preparation.

only one component.
 Generally, several ingredients are needed to ensure that

the required dosage form functions as required. dosage form containing a drug which is active at a dose of 1 mg, other components (e.g. diluent, binder, disintegrant and lubricant) will be needed both to enable the product to be manufactured and for it to be handled by the patient.

What is a unit operation?
= A basic step in a process

Various unit operation sequences in tablet manufacturing

Definition and objectives of mixing
 Mixing may be defined as a unit operation that aims to

treat two or more components, initially in an unmixed or partially mixed state, so that each unit (particle, molecule, etc.) of the components lies as nearly as possible in contact with a unit of each of the other components. OR

 List of products which utilize mixing processes:
• Mixtures of solid particles –

Tablets, capsules, sachets and dry powder inhalers.

Mixing is the process of thoroughly combining different materials to produce a homogenous product.

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• Mixtures of immiscible liquids –

• Mixtures of miscible liquids –

Emulsions and creams.

Linctuses ( a cough medicine in syrup form).

Preparation of emulsion

• Dispersions of solid particles –

 Liquids / solution:

Pastes and suspensions.

Solute
e.g. (Sugar)

 Miscible liquids:

Solution
(Sugar dissolve in water) Liquid A

Liquid C

(Water)

(Oil)

Immiscible liquids  Immiscible liquids:

Liquid A
e.g.

Solvent
(Water)

Liquid B

Miscible liquids

(Water)

(Alcohol)

(The liquid components completely dissolve in each other) e.g.

(The liquid components do not dissolve in each other)

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Physical properties of well formulated suspensions  Suspensions:

 The product must remain sufficiently homogeneous for at least the

Solid particles
e.g.

Liquid A

Suspension

(Water)

(The solid particles stay in cluster. Eventually the particles sink to the bottom to form sediment)

(Chalk)

Mixers for miscible liquids and suspensions period between shaking the container and removing the required amount.  The sediment produced on storage, if any, must be easily resuspended by moderate agitation of the container.
 The product may need to be thickened in order to reduce the settling rate of the particles.
 The resulting viscosity must not be so high that removal of the product from the container and transfer to the site of application are difficult.
 Any suspended particles should be small and uniformly sized in order to give a smooth, elegent product, free from a gritty texture. Propeller mixers

 Propeller mixers
 A propeller is a special type of fan with angles blades that

cause the circulation of the fluid in both an axial and radial direction.
 The pressure difference between the front and the rear surfaces of the blades pushes both air and fluid behind the blade.

Use of propellers in ship and aircraft

 Propeller mixer is commonly use for medium-scale fluid

mixing.
 An off-centre mounting of propeller-type stirrer in a vessel discourages the formation of a vortex, which may form when the stirrer is mounted centrally.

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 A vortex forms when the centrifugal force imparted

to the liquid by the propeller blades causes it to back up round the sides of the vessel and form a depression around the shaft.
 As the speed of rotation is increased, air may be sucked into the fluid due to the formation of a vortex. This can cause frothing and possible oxidation. Flow pattern for top-entering, off-center propeller without baffles: (a) front, (b) top, and (c) side views.

 Another method of suppressing a vortex is to fit vertical

Baffled tank

baffles into the vessel.
 These divert the rotating fluid from its circular path into the

centre of the vessel where the vortex would otherwise form.

Propeller mixer with (A) unbaffled tank and (B) baffled tank.

 The ratio of the diameter of a propeller stirrer to

the diameter of the vessel is commonly 1:10 to
1:20 and it typically operates at speeds of 1-20 rev/s.  The propeller stirrer depends for its action on a satisfactory axial and radial flow pattern which will not occur if the fluid is too viscous.
 Video:
1: Unbaffled tank
2: Baffled tank

 Other liquid mixing equipments:
 Shaker mixers

-In these mixers, the material present in the containers is agitated either by an oscillatory
(for small scale mixing) or by a rotary movement (large scale mixing). Shaker
( g
g)
mixers have limited use in industry.

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Oscillating motion

Oscillating motion is swinging from side to side, like a pendulum in a clock.

Shaker?

Shaker mixers video:

1. Shaker mixer
2. Paint mixer

Rotary motion

Rotary motion is turning round in a circle, such as a wheel turning.

Shaker Mixers

 Paddle mixers

-Some of the liquid mixers have paddles which are used as impellers which consist of flat blades attached to a vertical shaft and rotate at low speed. -The blades have a large surface area in relation to the container in which they are employed which help them to rotate close to the walls of the container and effectively mix the viscous liquids or semi-solids.
-A variety of paddle mixers having different shapes and sizes, depending on the nature and viscosity of the product are available for use in industries. 5

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Paddle Mixers

**Paddle mixer video

 Turbine mixers

-Consist of a circular disc impeller to which a number of short, straight or curved blades are attached. These mixers differ from propellers in that they are rotated at a lower speed than propellers and the ratio of the impeller and container diameter is also low.
-Turbines are effective f viscous solutions with a
T bi ff ti for i l ti ith wide range of viscosities.
-Turbines give greater shearing forces than propellers and thus they are more suitable for preparation of emulsions and creams.
-However, turbine mixers will not cope with liquids of very high viscosity since the material will not be drawn into the mixer head.

Turbine impellers

**Turbine mixers video

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