The document discusses pilot plant scale-up considerations for solid dosage forms in the pharmaceutical industry, detailing processes like blending, granulation, and drying. It emphasizes the importance of designing pilot plants to ensure consistent, economical, and reproducible large-scale production while minimizing cross-contamination. Additionally, it highlights the evaluation of laboratory studies and the necessity for thorough procedures in manufacturing chemistry to achieve product uniformity.

1. PILOT PLANT SCALE-UP CONSIDERATION
FOR SOLID DOSAGE FORM
Submitted By-
Anoothi Bain
M. Pharm 1st sem.
Department of Pharmaceutical Sciences
Dr. Harisingh Gour University, Sagar (M.P)
(a central university)

2.  Introduction
 Application of pilot plant
 Scale-up of Solid Dosage form
• Material handling
• Chemical weighing
• Blending
• Granulation
• Drying
• Reduction in particle size
• Granulation handling & Feed systems
 References
D. R. Chandravanshi

3.  Pilot Plant:-
“Defined as a part of pharmaceutical industry
where a lab scale formula is transformed into
viable product by the development of liable
practical procedure for manufacture”.
 Scale-up:-
“The art of designing of prototype using the
data obtained from the pilot plant model”.
D. R. Chandravanshi

4. Pilot Scale and Scale-Up
R & D PILOT SCALE
SCALE-UPLARGE SCALE
PRODUCTION
D. R. Chandravanshi

5.  It plays important role in technological evaluation
scale-up and transfer activities of new product.
 Evaluating the results of laboratory studies and
making product ,process corrections and
improvements.
 It is used to examine the formula to determine its
ability to withstand batch scale and process
modification.
 Evaluation and validation for process and
equipments.
 To provide master manufacturing formula with
instructions for manufacturing procedure.
D. R. Chandravanshi

7.  The primary responsibility of pilot plant is to ensure
that newly formulated dosage form should be
efficiently, economically and consistently reproducible
on a large scale production.
 The design and construction of pharmaceutical pilot
plant for product development should incorporate
necessary features to facilitate maintenance and
cleanliness.
 Pilot plant should be located on the ground floor to
expedite the delivery and shipment of supplies .
D. R. Chandravanshi

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10. Pilot plant design for
tablets
Material
handling
Chemical
weighing
Granulation
Tablet
blending
Drying
Compression
D. R. Chandravanshi

11.  Primary concerns:-Achieving reliable flow and
maintaining blend uniformity.
 Segregation leads to poor product uniformity.
 Handling system:-
 Must deliver the accurate amount of the ingredient.
 Material loss should be less.
 There should be no cross contamination
 More sophisticated methods of handling materials
such as vaccum loading systems, metring pumps ,
screw feed system.
 If a system is used to transfer materials for more than
one product steps must be taken to prevent cross
contamination. D. R. Chandravanshi

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13.  This is important step in the manufacturing process
because of possibilities for cross contamination
and misbranded products due to incorrect
quantities .
 Central weighing department is adopted by many
companies to service all the processing areas:-
 Avoidance of duplicating weighing facilities
 Lower labor cost.
D. R. Chandravanshi

14.  A chemical weighing should be designed to
provide supervision, checkers, proper weighing
equipment, lightning, dust collections, adequate
sanitation.
 Sinks and drain boards should be located to
facilitate frequent cleaning of measuring
equipments.
 High potency drugs such as steroids and alkaloids
should be weighed separately with absolute filters
to avoid cross contamination.
 Balances scales and meters should be specified and
calibrated.
D. R. Chandravanshi

15.  Powders which are to be used for granulating prior
to tableting must be blended well for proper drug
distribution.
 Inadequate blending could result in drug content
uniformity variation, especially when the tablet
and capsule is small and drug content is very low.
 Ingredients should be lumps free ,otherwise it will
cause flow problems.
 Screening and milling of the ingredients is
performed to make process more reproducible and
reliable.
D. R. Chandravanshi

16.  Equipments used for blending are:-
 V-blender
 Double cone blender
 Ribbon blender
 Bin blender
 Orbiting screw blender and high intensity mixers
 Scale up considerations
 Time of blending
 Blending load
 Size of blender
D. R. Chandravanshi

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19.  Granulation is a process by which the small
particles are converted into large agglomerates
called granules.
 Reasons for granulation:-
o To impart good flow properties to the material
o To increase the apparent density of powders.
o To uniform the particle size distribution.
o Uniform dispersion of active ingredient.
 Types:-
o Wet granulation
o Dry granulation(slugging)
o Dry compaction
D. R. Chandravanshi

20.  A small amount of potent active ingredient can be
dispersed most effectively in a carrier granulation
when the drug is dissolved in granulating solution
and added during granulation process.
 Traditionally Wet granulation is carried out using:-
 Sigma blade mixer
 Heavy-duty planetary mixer
D. R. Chandravanshi

21. Planetary mixer Sigma blade mixer
D. R. Chandravanshi

22.  Now a days, for wet
granulation tumble
blenders with high
speed choppers
blades are used for
light powders ,it
ensure uniform
granule size.
D. R. Chandravanshi

23.  Use of binders:-
Binders are used in tablet formulations to make powders
more compressible and to produce tablet more resistant to
breakage during handling.
 Sometimes the binding agent imparts viscosity to the
granulating solution due to this transfer of fluid becomes
difficult ,this problem is overcome by adding granulating
agents if it occurs in scale up process.
 To avoid this problem in formulation stage, we will disperse
binding agent in the dry powder prior to granulating
 When granulating mass is having dough like
consistency then it will be subdivide into more granular
and porus mass to facilitate drying, this is performed
by passing it through a oscillating granulator or
hammer mill with large screen.
D. R. Chandravanshi

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25.  A dry powder blend that cannot be directly compressible because
of poor flow or compression properties may processed using
slugging operation.
 This is done on a tablet press designed for slugging ,which
operates at pressure of about 15 tons, compared with normal tablet
press which operates at pressure of 4 tons or less.
 Slugs range in diameter is 1inch for easily slugged material.
 After compression ,the slugs are broken down using hammer mill
or oscillating granulator to obtain uniform granule size.
 During scale –up operation ,the pilot plant scientist should pay
attention to the forces used for slugging operation, diameter of
punches , sizing and screening operation should be optimized
because it affects the particle size distribution.
D. R. Chandravanshi

26.  Dry compaction:
• It can be achieved by passing powder between two rollers that
compact the compact the material at pressure up to 10tons per
linear inch.
• Materials of very low density require compaction to achieve bulk
density sufficient to allow compression.
• Pilot plant personnel should determine whether the final API blend
could be more efficiently processed to produce a granulation with
required tableting properties.
 For slugging operation, the forces used for slugging,
punches diameter, sizing and screening operation
should be considered by pilot plant scientist to ensure
affective particle size distribution.
D. R. Chandravanshi

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28.  For drying purpose mainly two methods were used-
o Hot air oven
o Fluidized bed dryer
o Hot air oven:-
• Most conventional method of drying a granulation to
be circulating hot air oven, which is heated by either
steam or electricity in which granules are spread on a
paper-lined trays on rack track
• Tray is kept inside the oven where evaporative drying
occurs.
• Factors to be considered for scale up-
Airflow, air temperature and depth of granulation on
trays.
D. R. Chandravanshi

29. • If granulation bed is too deep or too dense then
drying will be inefficient.
• Drying time at specified temperatures and airflow
rates must be established for each product.
 Fluidized bed dryer:-
• Fluidized bed ryers is an best alternative method of
Drying.
• The important factor considered as part of scale up
fluidized bed dryer are optimum loads, rate of
airflow, inlet air temperature and humidity.
D. R. Chandravanshi

30. Fluidized bed dryer
D. R. Chandravanshi

31.  Compression factors that may be affected by the
particle size distribution are flow ability,
compressibility, uniformity of tablet weight, content
uniformity, tablet hardness and tablet color uniformity.
 First step in this process is to determine the particle
size distribution of granulation using a series of
stacked sieves of decreasing mesh openings.
 Particle size reduction of dried granulation of
production size batches can be carried out by passing
all the material through an oscillating granulator,
hammer mill, mechanical sieving device and a
screening device.
D. R. Chandravanshi

32. Oscillating granulatorHammer mill
D. R. Chandravanshi

33. Sieving euipment
D. R. Chandravanshi

34.  Lachman and liberman “The theory and practice of
industrial pharmacy ” fourth edition 2013,CBS
publisher and distributors,961-971
D. R. Chandravanshi