This document discusses the scale-up considerations for producing parenteral drugs on a pilot plant scale. It describes the key unit operations in parenteral production as mixing, sterilization, filtration, filling and sealing. For each unit operation, parameters that must be considered for scale-up are identified, such as tank size and type, impeller design, membrane size, filling rate and container size. Maintaining sterility and avoiding issues like precipitation or clogging are important challenges addressed during scale-up. Quality control tests are used to evaluate the scaled processes. Proper scale-up allows efficient transition from laboratory to commercial production of injectable drug products.

1. PILOT PLANT SCALE-UP FOR
PARENTRALS
Presented By:
GANESHA K.R.
190617007
2nd Semester MPharm (Industrial Pharmacy)
Manipal College of Pharmaceutical Sciences,
Manipal.
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Under the Guidance of
Dr. MAHALAXMI RATHNANAND
Associate Professor
Department of Pharmaceutics
Manipal College of Pharmaceutical Sciences, Manipal.

2. CONTENTS
Definition
Stages of Parenteral Production
Scale Up Considerations
References
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3. Parenteral
Parenteral preparation or injectables are the sterile
solutions or suspensions of drug in aqueous or oily
vehicles meant for introduction into the body by
means of an injection under or through one or more
layers of the skin or mucous membrane.
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4. STEPS INVOLVED IN PARENTERALS
PRODUCTION
Site selection and planning
Procurement and accumulation of materials for
compounding and packaging.
Processing of parenteral products.
Packaging and labelling
Quality control of the product.
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7. UNIT OPERATIONS and Their SCALE-UP
The various unit operations included in the manufacturing
of Parenteral are as follows :
Mixing
Sterilization
Filtration
Filling and Sealing
Packing
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8. MIXING
In lab scale- mixing is achieved by magnetic stirrers or by
simple hand-shaking.
In large scale- Impellers, Air-jets, Fluid-jets and Baffle
mixers
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11. SCALE UP CONSIDERATIONS
 Tank type and size
 Tank temperature
 Impeller type and localization
 Impeller diameter
 Number of impellers
 Number of impeller blades
 Mixing speed
 Mixing duration / Processing time
 Pumps and their features
 Feeding speed
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12. Problems: Improper mixing, Contamination
IPQC Tests: Content Uniformity, Clarity Test, pH
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13. STERILIZATION & FILTERATION
Sterilization of equipment and containers:
 Dry heat sterilization : Hot air oven
 Moist heat sterilization : Autoclave
 Gas sterilization :Ethylene oxide
 Equipment like bottles , stoppering equipment , tanks , utensils , vent filters
must be sterilized before commencement of sterile operation.
 Sterilization of closures : Moist heat sterilization only
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14. FILTERATION
Two most common sizing bases for the scale-up of a sterilizing
filtration are capacity (filter area, throughput) and flowrate.
Scale Up Parameters
scale-up factor on rate (recommended value 0.8ml/min)
scale-up on actual area (recommended value 0.75–0.85 m2)
scaleup on cake discharge (recommended value 0.9cm/s).
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15.  Scale-up based on membrane capacity
 Scale-up based on flow rate
 Resistances of different filters
 Problems: precipitation, clogging of filter
 IPQC Test: Content Uniformity, Clarity Test, pH, Endotoxin residual
test
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16. FILLING AND SEALING
Selection of equipment depends on viscosity, type of packaging
& surface tension.
Lab scale- funnel & measuring cylinder
Large scale- Gravimetric filling, Volumetric filling, Constant
volume filling
Equipments for filling liquid in parenteral containers :
Piston type liquid fillers / cozzoli fillers
Rotary chemical pump filling machine
Time-pressure or time-gravity liquid filling machine
Mass flow meter
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17. Scale up Parameters
The rate and amount of fill
The volume of product delivered into the container
Size of the delivery tube
Size of the nozzle
Problems- Inaccurate filling levels, foaming & dripping
IPQC Tests: Clarity Test, leaker test, pyrogen test, net volume, drug
content, uniformity of weight.
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18. Sealing of containers
Sealing is done in aseptic area.
Sealing of ampoules : Two techniques
 Tip sealing
 Pull sealing
 Scale Up Parameters for sealing
 Heat required to seal the ampoule, vial & bottle
 Type of sealing – Primary & Secondary
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19. References
 P. Rajniak et. al, “Sterilizing filtration—Principles and practice for
successful scale-up to manufacturing”, Journal of Membrane
Science, 325 (2008),223–237.
 CVS Subramanyam and J Thimmasetty, “Industrial Pharmacy –
Selected Topics”, Page No.404-406.
 The Theory and Practice of Industrial Pharmacy: Leon Lachman,
Herbert A Lieberman, Joseph L Kanig: Section IV: Chapter 23: Pilot
Plant Scale-Up Techniques: Page No. 681 – 710
 http://www.authorstream.com/Presentation/mrmani0310-891386-
pilot-plant-scale-up-techniques-for-injectables-parenterals/
 https://www.slideshare.net/bharathpharmacist/pilot-plant-parenteal-
production
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