This document discusses mixing in pharmaceutical manufacturing. It defines mixing as a process that randomizes particles within a system. The objectives of mixing include achieving a physical mixture, promoting chemical reactions, and heat and mass transfer. Mixing can involve solids, liquids, or semi-solids and occurs through mechanisms like convection, shear, and diffusion. Proper mixing is important to ensure a homogenous product, while segregation should be avoided. Various mixing equipment and considerations for mixer selection are also outlined.
2. • mixing is the most widely performed unit operation in pharmaceutical
manufacturing
• Definition of mixing
• mixing may be define as a unit process that tends to result in a randomization of
dissimilar particles within the system.
also, the mixing should attempt to approach this theoretical ideal will
depend on the purpose of the product and the objective of the mixing operation.
The term MIX means to put together in one mass.
the term BLENDING means to mix smoothly and inseparably together during
which a minimum energy is imparted to the bed.
The terms are very close in definition and are commonly used interchangeably in
the pharmaceutical industry.
4. • Positive Mixtures
• Are formed from materials such as gases or miscible liquid ,where irreversible
mixing would take place by diffusion, without work or force.
• Negative Mixtures
• Suspension of solid in liquid are example of negative mixtures that require work
for either formation.
• Neutral Mixtures
• Neutral mixture are static in their behavior the component having no tendency
to mix spontaneously.
• Many pharmaceutical products are example of this type ;for example ,pastes,
ointment and mixed powders.
5. • Within these main group many variation occur owing to the different physical
properties of the component of the mixture ,such factor will include;
• Viscosity (which may change during mixing ),
• The relative density of the components,
• Particle size,
• Particle shape,
• Particle charge,
• Surface tension of liquid.
• Other factors include;
• Temperature
• Mixing time
• Mixer type, volume and speed
• Proportion of materials
6. Mixing Properties
• Energy-consuming process.
• Produces a random distribution of particles.
• Mixing requires minimal energy to overcome interparticle forces.
• Mixing results are a function of time.
7. Objectives of Mixing
• To achieve a physical mixture
• To bring a physical change
• To achieve a dispersion
• To promote a chemical reaction
• Also promotion of heat and mass transfer process
8. Mixing Process
• To discuss the principles of the mixing process ,a situation will be considered
where are two compounds of the same size, shape &density that are required to
be mixed.
• For convention, mixing will be dealt within three categories: liquids, solids
(powder), and semi-solids.
9. Classification of Mixing
a. Mixing of solids
b. Mixing of liquids
c. Mixing of immiscible liquids
d. Mixing of semisolids
10. Mixing of Solids
• In the manufacture of tablets or granules normally a number of additives are
added. Therefore, mixing of powder becomes essential part of the process.
• Mixing is considered as a critical factors, especially in case of potent drugs and
low dose drugs where high amount of adjuvants are added.
• The diverse characteristics of particles such as size, shape, volume, surface area,
density, porosity, and flow charge contribute to solid mixing.
• Depending on their flow properties solids are divided into two class as; cohesive
and non cohesive.
11. • Solid particles do not have ability to move without external energy supply. There
is no mechanism like molecular diffusion. The rate of randomization of particles is
depends on the flow characteristics.
• Solid particles shows property of segregation depending on size, density and
shape.
12. Mechanisms of Solids Mixing
• The solid mixing takes place by one or a combination of two or more mechanisms
given below;
• Convective mixing (macro mixing)
• There is bulk movement of groups of particles from one part of powder bed to
another. It occurs by an inversion of the powder bed by means of blades or
paddles.
• Shear mixing
• When shear forces occurs reduces the scale of segregation by thinning of
dissimilar layers of a solid material.
13. • Diffusion mixing (micro mixing)
• It occurs when random motion of particles within a powder bed causes them to
change position relative to one another. It produced by any form of agitation of
powder.
• eg; tumbler mixers, double core blenders, V blenders, and drum blenders.
14. Perfect Mixture
It is defined as :
• as that state in which any sample removed from the mixture will have exactly the
same composition as all other samples taken from the mix.
17. •Powder Segregation
Segregation is that opposite effect to mixing i.e. components tend to separate
out. this is very important in the preparation of pharmaceutical product. Because
if it occurs ,a mix may change from being random to being non-random, or a
random mix may never be achieved.
18. • Segregation Mechanisms
• Differences in the size, density, shape, and other properties of the particles of
which they are composed.
• The process of segregation occurs during mixing as well as during subsequent
handling of the completed mix, and it is most pronounced with free flowing
powders.
• Powders that are not free flowing or that exhibit high forces of cohesion or
adhesion between particles of similar or dissimilar composition are often difficult
to mix owing to agglomeration. The clumps of particles can be broken down in
such cases by the use of mixers that generate high shear forces or that subject
the powder to impact. When these powders have been mixed, however, they are
less susceptible to segregation because of the relatively high interparticulate
forces that resist interparticulate motion leading to immixing
19.
20. Ordered Mixing
It would be expected that a mix comprised of very small & much larger particles
would segregate because of size differences.
Ordered mixing probably occur to a certain extent in every pharmaceutical
powder mix, owing to interaction & cohesive/adhesive forces between
constituents.
21. Liquid Mixing
• Liquid-liquid mixtures
• a. Miscible Liquid-liquid mixture
• b. Partially miscible Liquid-liquid mixture
• c. Immiscible Liquid-liquid mixture
• Liquid-solid mixtures
• a. Homogeneous mixtures
• b. Heterogeneous mixtures
• c. Deagglomerated solids
• Some solids may wet from outside but dry from inside-tend to form lumps and
not mixed properly.
22. Liquids Mixing Mechanisms
Mixing mechanisms for liquids are classified into four categories;
• Bulk transport
• Turbulent mixing
• Laminar / streamline mixing
• Molecular diffusion
23. 1. Bulk Transport
• The movement of relatively large portion of the material being mixed from one
location in the system to another constitutes bulk transport
• to be effective it must result in a rearrangement of the various portions of the
material to be mixed. This is accomplished by means of paddles, revolving blades,
or other devices within the mixer arranged so as to move adjacent volumes of the
fluid in different directions .
24. 2. Turbulent Mixing
• Characterized by a random fluctuation of the fluid velocity at any given point
within the system
• the fluid has different instantaneous velocities at different locations at the same
instant in time.
• The velocity differences as result from turbulence within a body of fluid produce
a randomization of the fluid particles.
• For this reason turbulence is a highly effective mechanism for mixing.
25. 3. Laminar Mixing
• Stream line or laminar flow is frequently encountered when highly viscous fluids
are being processed.
• It can also occur if stirring is relatively gentle.
26. 4. Molecular Diffusion
• The primary mechanism responsible for mixing at the molecular level is diffusion
resulting from the thermal motion of the molecules
• When it occurs in conjunction with laminar flow, molecular diffusion tends to
reduce the sharp discontinuities at the interfaces between the fluid layers, and if
allowed to proceed for sufficient time, results in complete mixing.
27. Mixing Equipment
A system for batch mixing commonly consists of two primary components
• A tank or other container suitable to hold the material being mixed
• A means of supplying energy Power may be supplied to the fluid mass by means
of an impeller, air stream, or liquid jet. these also serve to direct the flow of
material within the vessel.
• Baffles, vanes, or ducts also are used to direct the bulk movement of material in
such mixers, thereby increasing their efficiency.
28. • Impellers
• On the basis of the shape and pitch of the blades. Three basic types of flow may
be produced: radial, axial and tangential. These may occur singly or in various
combinations.
• Fluid jets
• the fluids are pumped through nozzles arranged to permit good circulation of
material throughout the tank. In operation, they generate turbulent flow in the
direction of their axes.
• Baffles
• For bulk fluid flow to be most effective, an intermingling must occur
between material from remote regions in the mixer. To accomplish this, it is
frequently necessary to install auxiliary devices for directing the flow of the
fluid, usually baffle plates.
29. Mixer selection
Factors that must be taken into consideration include:
• The physical properties of the material to be mixed such as density, viscosity, and
miscibility
• Economic considerations regarding processing, e.g., time required for mixing and
the power expenditure necessary, and cost of equipment and its maintenance.
