PILOT PLANT SCALE UP FOR LIQUID ORALS
• Simple solutions are the easiest to scale up but requires
tanks of adequate size and mixing capability
• The equipment can have heating/ cooling capabilities for
rapid dissolution of ingredients
• Filtration equipment are required for removal of unwanted
particles
• The material used in the construction of equipment is
important
• Should be non-reactive and facilitate easy cleaning
• Fabricated stainless steel is most suitable as it is
non-reactive (expect for some acidic substances)
• This can be overcome by Passivation (pre-treating the
stainless steel with acetic acid or nitric acid solution to remove the surface
alkalinity)
• Passivation has to carried out periodic intervals
• If the batch involves preparations containing alkaline
substances, then passivation needs to be repeated before the next batch
Mixing
vessels
SCALE UP
CONSIDERATIONS- Solutions
1. Tank size (diameter)
2. Impeller type and number
3. Impeller diameter
4. Rotational speed of the impeller
5. Mixing capability of impeller
6. Clearance between Impeller Blades and wall of the mixing
tank
7. Height of the filled volume in the tank
8. Filtration equipment (should not remove active or
adjuvant ingredients)
9. Transfer system
Pilot Plant
design for Suspensions
• Suspensions require more attention during scale up because
of additional processing needs
• The addition and dispersion of suspending agents require a
vibrating feed system
• A powder eductor
can facilitate the addition of a material that tends to clump during the
process or that is difficult to disperse
• Or they can be made into a slurry with a portion of the
vehicle before addition
Powder
eductor
• If the suspending
agents are difficult to disperse, then it can be made
into a slurry
with a portion
of the vehicle
and completely dispersed using a high shear mixer
• Helps in rapid and complete hydration of the suspending
agent when added to a larger portion of the vehicle
• The time and temperature required to hydrate suspending
agents is critical.
• If the hydration process is incomplete before the other
ingredients are added, the quality of the suspension is adversely affected
High Shear
Mixer
For uniform dispersion of active ingredients; prevent wetting
difficulties and eliminate formation of dry agglomerates
1. Prepare a slurry with a wetting agent using a high shear
mixer
2. Pre-treat the hard to wet material by blending it in a
high shear powder blender with the liquid ingredients and a surfactant
• The type of mixers, pumps, mills and horse power of the
motors should be carefully selected based on the scale up performance
• The equipment should be selected according to size of the
batch and maximum viscosity of the product during the manufacturing process
E.g Size of mixer is
important
• Undersized mixers- inadequate distribution or excessive
production time
E.g Speed of mixing
• Mixing at high speed- incorporation of excessive amount of
air into the entrapped air is
difficult to remove and if left behind – can affect the physical and chemical
stability of the product and the reproducibility of the filling operation
• The entrapped air can be removed using a vacuum unit
called Versator
Versator
• The finished suspension needs to be filtered in order to
remove any unwanted particulate matter
• The mesh size of the filter should be such that it removes
only unwanted foreign particulates and not the active ingredient (since
suspension has particulate matter)
• Filters with screens of 150 mesh having aperture size of
100 microns can be used to remove unwanted suspended materials that are below
the easily visible range without retaining the suspended active ingredients
Filter
Press
SCALE UP
CONSIDERATIONS- Suspensions
1. Addition and dispersion of suspending agents
2. Hydration/Wetting of suspending agent
3. Time and temperature required for hydration of suspending
agent
4. Mixing speeds (High speed leads to air entrapment)
5. Selection of the equipment according to batch size
6. Versator (to avoid air entrapment)
7. Mesh size (the one which is chosen must be capable of
removing the unwanted foreign particulates but should not filter out any of the
active ingredients)
Pilot Plant
design for Emulsions
• Manufacturing of liquid emulsion products entails
specialized procedures and scale up into production equipment involves
extensive process development and validation
• The globule size of the internal phase affects the
physical properties of the emulsion- appearance, viscosity and physical stability
Homogenizer
SCALE UP
CONSIDERATIONS-Emulsions
1. Temperature
2. Mixing equipment
3. Homogenizing equipment
4. In process or final product filters
5. Screens, pumps and filling equipment
6. Phase volumes, viscosities and densities
Use of high shear
mixers à causes à Air entrapment
Use of high shear
mixers à Prevented by à Use of vessels that
operate under controlled vacuum
Filtration in the
final stage à causes à Affects quality of the
emulsion
Filtration in the
final stage à Prevented by à Filtration of oil and
water phases separately before emulsification
Filling
equipment
Liquid
orals filling, sealing and labeling
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