The presentation describes mixing of solid, liquid and semisolid pharmaceutical dosage forms. It includes mechanisms of solid and liquid mixing, interparticle interactions-segregation, factors affecting mixing, applications of mixing and various equipments used for mixing of pharmaceuticals.

1. Mixing of Pharmaceuticals
Mr. A.T. Sharma
Assistant Professor
Department of Pharmaceutics
Nanded Pharmacy College, Nanded

2. Mixing
• Definition: A process that tends to result in a
randomization of dissimilar particles within a
system.
• Blending
• Cohesive and Non-cohesive solids

3. Difference Between Solid Mixing and Liquid Mixing
Liquid Mixing
• Flow currents are
responsible for transporting
unmixed material to the
mixing zone adjacent to
impeller.
• Truly homogeneous liquid
phase can be observed.
• Small sample size is
sufficient to study degree of
mixing.
• Mixing requires low power.
Solid Mixing
• Flow currents are not
possible.
• Product often consists of
two or more easily
identifiable phases.
• Large sample is required.
• Mixing requires high power.

4. Applications
• Wet mixing in granulation
• Dry mixing in direct compression
• Dry blending of powders
• Production of pellets

6. Mixing Mechanisms

7. Interparticle Interactions - Segregation
• Particle characteristics like size, size distribution,
shape and surface influence the interparticle
interactions in a powder bed.
• Inertial Forces: Tend to hold neighbouring
particles in a fixed relative position.
- van der Waals forces
- Electrostatic forces
- Surface forces
• Gravitational Forces

8. Van der Waals forces
• Weak but general attractive or repulsive forces
between neutral atoms or molecules.
• Differ from covalent or ionic bonding
Electrostatic forces
• The attractive or repulsive force between two
electrically charged objects.
Surface/ Interface forces:
• Cohesive forces – prevent intimate mixing
• Frictional forces – lumps
• Depends on SA, surface roughness, surface polarity,
surface charge, moisture
• For effective mixing, surface to surface interactions
should be minimum – surface treatment

9. Reasons of Segregation
• Poor flow properties of powder bed
• Wide differences in particle sizes
• Differences in mobilities of individual
ingredients
• Differences in particle density and shape
• Transporting stage
• Dusting stage

10. Gravitational Forces
• Tend to improve the movement of two adjacent
particles or groups of particles.
• Tumbling action promotes inter-particulate movement
due to gravitational forces.
• Motion of particles – contact with the mixer surface
or/and from contact with one other
• These motions accelerate translational and rotational
mode of single particle or group of particles
• Particle – particle collisions: Exchange of momentum
• Continuous exchange of momentum between
translational and rotational mode necessary for
effective mixing.

11. Efficiency of momentum transfer depends upon-
• Elasticity of collisions
• Coefficient of friction
• SA of contact
• Surface roughness
• Centrifugal forces

12. Factors Affecting Mixing
• Nature of the surface
• Density of the particles
• Particle size
• Particle shape
• Particle charge
• Proportion of materials

13. Twin Shell Blender/ V Cone Blender
• V shaped shell, stainless steel or transparent plastic
• Small – 20kg/ 35rpm
• Large – 1 tonne/ 15rpm
• Loading – two hatches
• Emptying – apex port
• Material loaded – 50 to 60% of volume
• Rotation - tumbling motion
• V inverted – splitting
• Splitting and dividing repeated
• High speed – dusting/ segregation
• Low speed – poor mixing

14. Double Cone Blender
• Charged and discharged – same port
• Efficient for small amount of powders
• Speed – size, shape of tumbler, nature of
material- 30-100rpm
• Method- same as V cone blender

15. Ribbon Mixer
Principle:
• Shear mixing by ribbon shaped moving blades – breaks
lumps and aggregates
• Convective mixing
Construction:
o Non-movable horizontal cylinder trough open at top
o Two helical blades, same shaft
o Blades with right and left twist – connected to fixed
speed drive
o Top loading, bottom discharge
o Lid at top

17. Sigma Blade Mixer
Principle:
• Shear mixing and kneading actions with sigma
shaped blades
• Convective mixing by cascading
Construction:
o Double trough shaped stationary bowl
o Two sigma shaped blades horizontally fitted
o Fixed speed drive
o Loading from top, unloading by tilting by rack-
and-pinion drive

19. Planetary Mixer
Principle:
• Shear between a moving blade and stationary
wall
• Blade tears mass apart
• Mixing arm moves in two ways, around own
axis and around central axis – no dead spot
• Plates in blade are sloped – powder makes
upward movement - convective mixing

20. Construction
• Vertical cylindrical shell – removable
• Mixing blade at top
• Mixing shaft driven by planetary gear train
with variable speed drive

21. Liquid Mixing
• Formation of homogeneous mass
• Agitation: Induced motion of a material in a
specified way, usually in a circulatory pattern
inside a container
• Mixing: Random distribution into one another
of two or more separate phases
• Applications: Manufacture of emulsions,
suspensions, solutions, aerosols

22. Mechanism of Liquid Mixing
• Bulk transport
• Turbulent mixing
• Laminar mixing
• Molecular diffusion

23. Mixing Devices
Impellers
o Propellers
o Turbines
o Paddles

24. Propellers
• Contains a no. of blades
• Right or left handed
• Deep tank – Push-pull propeller
• Small size
• Speed 8000rpm
• Uses:
- High mixing capacity
- Liquid of maximum viscosity of 2 pascals.second,
slurries
with 10% solids
- Gas-liquid dispersions, multivitamin elixirs, disinfectant
solutions

26. Turbines
• A circular disc with no. of short blades
• Diameter: 30-50%
• Speed: 50-200rpm
• Blades straight, curved, pitched or vertical
• Near the turbine, zone of rapid currents, high
turbulence, and intense shear
• Diffuser ring – stationary, perforated ring
surrounding turbine – reduce swirling and
vortexing

28. Paddles
• A central hub with two long flat vertical
blades
• Pitched, hemispherical with large SA
• A shaft with hub-blades rotates – 100rpm
• Radial and tangential push
• Deep tanks – several blades one above other
• Very low speed – agitation in unbaffled tank
• High speed – baffled tank

30. Pitched Blades Vortex Formation

31. Silverson Mixer - Emulsifier
Principle:
• Intense shear forces and turbulence by high
speed rotors
• Liquids pass through fine interstices of
perforated metal sheets
• Circulation through head by suction in inlet at
bottom of head
• Rapid breakdown of liquid into smaller
globules

32. Construction:
• Long supporting
columns connected to
motor – support head
• Shaft at centre – one
end to motor, other to
head
• Head has turbine
blades
• Blades surrounded by
a mesh, enclosed by a
cover with openings.

34. Working:
• Head dipped completely in
vessel containing liquids
• Motor started – shaft rotates
head and turbine blades with
very high speed
• Pressure difference created –
liquid sucked from bottom
• Intense mixing
• Centrifugal force expel contents
with great force through mesh
and openings of cover
• Intake and expulsion –
circulation – break down of
globules
Uses: Emulsions and creams of fine
particle size

35. Thank You…!!!
(Disclaimer: The images and diagrams in this
presentation have been downloaded from the google
source. I am grateful to all the publishers & the google.)