Pilot plant scale up techniques are used to transform a laboratory scale process into a viable manufacturing process. This involves evaluating results from small batches and making corrections to optimize the process and equipment for larger scale production. Critical aspects of scale up include batch size increases, equipment selection, material handling processes, mixing parameters, drying methods, compression specifications, and quality documentation. The goal is to standardize production to avoid issues during commercial manufacturing scale up.

1. Introduction to
Industrial Pharmacy
Pilot plant scale up
techniques
Ms. Ashwini U. Bhoir
Assistant Professor in
Pharmaceutics
10-08-2022 1

2. Pilot plant:
It is defined as a part of the pharmaceutical industry where a lab scale process
is transformed into a viable product by the Development of liable practical
procedure for manufacture of dosage forms.
This techniques for solid dosage form will provide guideline for the
manufacture of large scale process and this will play a pivotal role in large
scale manufacturing.
An art of designing of prototype using the data obtained from the pilot plant
model.
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3. Why conduct Pilot Plant Studies?
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4. A pilot plant can be used for
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 Evaluating the results of laboratory studies and making product and process corrections
and improvements.
 Producing small quantities of product for sensory, chemical, microbiological
evaluations, limited market testing or furnishing samples to potential customers, shelf-
live and storage stability studies.
 Determining possible salable by-products or waste stream requiring treatment before
discharge.
 Providing data that can be used in making a decision on whether or not to proceed to a
full-scale production process; and in the case of a positive decision, designing and
constructing a full-size plant or modifying an existing plant.

5. Considerations in pilot plant development :
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6. Objective of Scale up techniques:
Examination of the formula to determine it’s ability to
with stand Batch-scale and process modification.
Evaluation and Validation for process and equipment
To identify the critical features of the process
Guidelines for production and process controls.
To provide master manufacturing formula with
instructions for manufacturing procedure.
To avoid the scale-up problems
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7. Importance of Pilot plant:
Standardization of formulae.
Review of range of relevant processing equipments
The specification of raw materials
Optimization and control of production rate.
Information on infrastructure of equipments during the scale up batches physical
space required.
Identification of critical features to maintain quality of a product.
Appropriate records and reports to support GMP.
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8. Scale up techniques:
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•Scale-up is defined as the process of increasing the batch size.
•Also be viewed as a procedure for applying the same process to different output volumes.
•Batch size enlargement does not always translate into a size increase of the processing
volume.
•In mixing applications, it is indeed concerned with increasing the linear dimensions from the
laboratory to the plant size.
•In processes exist (e.g., tableting), it simply means enlarging the output by increasing the
speed. In moving from R &D to production scale, it is sometimes essential to have an
intermediate batch scale. This scale also makes possible the production of enough product for
clinical testing and samples for marketing. However, inserting an intermediate step between
R&D and production scales doesn’t in itself guarantee a smooth transition.

9. Pilot plant scale up techniques
for tablets
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10. Pilot plant scale up techniques for tablets
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 Newly formulated tablets developed by
product development personnel will prove
to be efficiently, economically, and
consistently reproducible on a production
scale.
 The design and construction of the
pharmaceutical pilot plant
 Location
 Each stage considered carefully from
experimental lab batch size to intermediate
and large scale production.
 May involve a major process change
Points to be consider
during scaling up the solid
dosage forms;
 Batch size from
intermediate to large
scale production.
 Each stage of operation.
 Different types of
equipment.
 Use of sophisticated
instruments with larger
volume load.
 Various sizes of
equipment.

11. Figure 1 Pilot plant layout
Pilot plant layout:
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12. • Handling of material is very necessary to prevent the contamination.
• The flow system should be such that it must deliver the accurate amount of ingredient.
• More sophisticated methods of handling materials are vacuum loading systems,
metering pumps, screw feed system.
Material flow
Fig no. 2: Vacuum loading machine
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13. Process and equipments:
Dry blending
• It ensure good drug distribution.
• Done by screening or milling of ingredients.
• Equipments:
 V- blender
 Double cone blender
 Ribbon blender
 Bin blender
• Scale up
considerations:
1. Time of
blending.
2. Blender
loading.
3. Size of blender Fig no. 3: Various blending machine
Granulation
• It impart good flow to the material
• Also increase the apparent density
of the powders.
• It changes the particle size
distribution.
Granulation Techniques Drying techniques
Wet granulation
Tray or fluid-bed dryer
Vacuum/gas stripping/microwave
Spray dryer
Extrusion/ Spheronization / Pelletization
Dry granulation Process
Direct compression
Slugging Mill
Roller compactor Compacts milled
Table no. 2: Various Drying techniques
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14. Wet granulation
Can be done by using machines like
Fig no. 4: Planetary mixer & Sigma blade mixer,
Drying
• Circulating hot air oven, which is heated by either
steam or electricity.
• Fluidized bed dryers (FBD) are an attractive
alternative to the circulating hot air ovens.
• Scale up considerations:
 optimum loads
 Rate of airflow
 Inlet air temperature and humidity.
Fig no. 5: Fluidized bed dryer
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15. Reduction of Particle
Size
• Mills:
 An oscillating granulator
 A hammer mill
 A mechanical sieving device
Slugging (Dry Granulation)
• Slugging process operates at
pressures of about 15 tons compared
with a normal tablet press.
Fig no. 6: A hammer mill &An oscillating granulator
Fig no.7: Schematic of slugging operation (lab)
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16. Compression
Dry Compaction
• Compressible diluents are used.
• Mainly used for few crystalline substances like NaCl, KCl that may be directly compressed.
• It is ultimate test for tablet formulation and granulation process whether the granulation can be compressed on
a high-speed tablet press.
• Process of compression:
1. Filling of empty die cavity with granules.
2. Precompression of granulation. (Optional)
3. Compression of granules.
4. Ejection of tablet from die cavity.
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17. Machines for compression of tablets
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Tablet Coating
• Equipment: conventional coating pan, perforated pans or fluidized bed coating column.
• Types: sugar coating, film coating.
• Tablets must be sufficiently hard to withstand the tumbling.
• Conditions: optimum tablet load, operation tablet, bed temperature, drying air flow rate,
temperature, solution application rate.
Fig no.8: Standard coating pan Fig no.9: Fluidized bed coating Fig no.10: Accela- cota system

19. Pilot plant scale up techniques
for liquid
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20. Pilot plant scale up techniques for liquids
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 The physical form of a drug product that can be incorporated demonstrates
Newtonian or Pseudoplastic flow behaviour.
 It conforms to its container at room temperature.
 Liquid dosage forms may be dispersed systems or solutions.
 In dispersed systems there are two or more phases, where one phase is
distributed in another.
 A solution refers to two or more substances mixed homogeneously.

21. Steps of liquid manufacturing process
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Planning of
material
requirements.
Liquid
preparation.
Filling and
Packing.
Quality
assurance.

22. Critical aspects of liquid manufacturing
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•Physical plant
•Heating, ventilation and air controlling system.
•The effect of long processing times at suboptimal
temperatures should be considered in terms of consequences
on the physical or chemical stability of ingredients as well as
product.

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• Impeller diameter.
• Tank size (diameter).
• Number of impellers.
• Impeller type.
• Mixing capability of impeller.
• Rotational speed of the impeller.
• Height of the filled volume in the tank.
• Number of baffles.
• Transfer system.
• Clearance between Impeller Blades and
wall of the mixing tank.
• Filtration equipment
• Passivation of Stainless Steel
Points to be
consider during
scaling up the
solution

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•Points to be consider during scaling up the suspension
 Versator (To avoid air entrapment)
 Wetting of suspending agent.
 Addition and dispersion of suspending agents.
 Selection of the equipment according to batch size.
 Time and temperature required for hydration of the suspending agent.
 Mixing speeds
 Mesh size
Suspension

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Emulsion

26. Pilot plant scale up techniques
for semi solids
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27. Parameters to be consider while scaling up of semisolids
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 Mixing speed.
 Mixing equipment
 Motors
 Heating and cooling process.
 Component homogenization.
 Product transfer.
 Addition of active ingredients.
 Working temperature range.
 Shear during handling and transfer
from manufacturing to holding tank
to filling lines.
 Transfer pumps

28. Pilot plant scale up
techniques for semisolids
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•Adequate records and reporting arrangement
•An integral part
Relevant Documentation
Forms of
Documents
Earlier: Hard copy, Today: Soft copy formats, organized
way of sharing knowledge,
Configuration Management: Documentation management
and control
Types of
Documents
Permanent: Inclueds user manuals, help information,
training materials; Ex. Design specificatios, source code,
process diagrams etc.
Temporary: Internal communication; No value once the
project completed ex. Ideas, issues, control, working paper
etc.

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Structure and
Circulation of
Document
Constructed in most appropriate and structured form with
adequate indexing and controls so that it can be used as
knowledge repository. An additional advantage of
categorization of the information and documentation is
that, items can be released for review, finalization,
approval or action without waiting for other non-
dependant elements to be completed.
Helps the team members only to deal with the content
that is relevant to them. They receive it in manageable
size as parts. The complexity can be minimized

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Documents
at Start of
Scale-Up
The documentation should be constructed in most appropriate and
structured
A short and simple scale-up project- as simple as a spreadsheet
Bigger scale-up projects- use of document management toolset.
The key elements of the documents used in registration of specific
information per document includes for example, description, purpose or
objective, form and format, requirements for update, required protocols for
review and quality assurance etc.
Permanent documents: to be updated if something changes after it
finalized; temporary documentation retainas a historic record even
though something has subsequently been changed.

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Documents
Tracking
Progress
and Status
Planned date of completion, current status and effective date,
persons currently updating or reviewing the document, current
projected date of completion.
The project team members when using the document management
system must incorporate further documents as required throughout
the project;
The team member must have ability to consult previous historic
versions wherever relevant, and identify changes and determine the
reasons for those changes

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Document
during the
project
Tracking of document status by project manager and/ or project
office
Document
at the
completion
of the
project
Archival of temporary items, retention of permanent documents;
Maintenance of project repository; reuse of valuable materials for
another projects

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Reference:
1. P. Ramasubramaniyan, C. Shibin raj, P. Nagarajan, D.Sherly, L. Subramanian, P.
Solairaj, review: Pilot scale up techniques for solid dosage form- an overview for tablets.
World Journal of Pharmaceutical Research 2014; Volume 3, Issue 8, 925-931.
2. Leon Lachman, Herbert A Lieberman, Joseph L Kanig: The Theory and Practice of
Industrial Pharmacy: Section IV: Chapter 23: Pilot Plant Scale-Up Techniques: 3rd
edition, published by Varghese Publishing house, 2009; 681-710.
3. James Swarbrick, James C Boylan: Encyclopedia of Pharmaceutical Technology: Pilot
Plant Design, Volume 12 New York, 2001; 171-186.
4. Leon Lachman, Herbert A. Lieberman, Joseph B. Schwartz: Pharmaceutical dosage
forms: Tablets. Volume 3. second edition. 303-365.
5. Kamya Chaudhary, A. C. Rana, Rajni Bala, Nimrata Seth, review: scale up process of
tablet production: a prospective discussion, Int. J. of Pharm. and Bio. Sci. 2012; 2(3):
223-239