CONTENTS:- DEFINITION INTRODUCTION OBJECTIVES LIQUID DOSAGE FORM STEPS INVOLVED IN PILOT PLANT FOR ORAL LIQUID GENERAL CONSIDERATION Reporting responsibility Personal requirements Space requirements Review of formula Raw materials Relevant processing equipments Process evaluation GMP consideration Assurance PILOT PLANT SCALE UP FOR SUSPENSION PILOT PLANT SCALE UP FOR EMULSION REFERENCES

1. Pilot Plant Consideration of
Liquid Dosage Form
Submitted by :-
Ashwani Tanwar
M. Pharma 1st Sem
DEPARTMENT OF PHARMACEUTICAL SCIENCE Dr. HARISINGH
GOUR VISHWAVIDYALAYA SAGAR M.P.

2. Contents-
 DEFINITION
 INTRODUCTION
 OBJECTIVES
 LIQUID DOSAGE FORM
 STEPS INVOLVED IN PILOT PLANT FOR ORAL LIQUID
 GENERAL CONSIDERATION
1. Reporting responsibility
2. Personal requirements
3. Space requirements
4. Review of formula
5. Raw materials
6. Relevant processing equipments
7. Process evaluation
8. GMP consideration
9. Assurance
 PILOT PLANT SCALE UP FOR SUSPENSION
 PILOT PLANT SCALE UP FOR EMULSION
 REFERENCES

3. Definitions
 Pilot plant:- it is a the part of the pharmaceutical
industry where a lab scale formula is transformed
into a viable product by development of liable
practical procedure of manufacturing.
 Scale up:- The art for designing of prototype using
the data obtained from the pilot plant model.

4. Introduction
 Last 25-30 year pharmaceutical research are
going on very fast speed.
 Researchars are motivated to adopt new processes
and technology.
 Scale up batches are essential for ensuring success
in the clinical testing and bioequivalence study.
 Pilot plant scale up is one of the most important
stage in the product development.

5. Objectives
 To avoid the scale -up problems.
 To identify the critical features of the process.
 Guidelines for production and process control.
 Evaluation and validation for process and
equipment.
 To provide master manufacturing formula with
instructions for manufacturing procedure.
 Update the processing equipment.
 Evaluation of time & cost factors.

6. Liquid Dosage Form
Liquid dosage forms is a pharmaceutical product, involving a
mixture of active drug components and non- drug component
(excipients) in the form in which it is marketed for use. Liquid
state form are meant for internal, parental or external use.They are
available in monohasic and biphasic forms.monophasic liquid
dosage forms are true or colloidal solution. Water is mainly used
as a solvent for majority of monophasic liquid dosage forms.
The liquid which consist of two phases are known as biphasic
liquids.

7. 1. Reporting responsibility
2. Personal requirements
3. Space requirements
4. Review of formula
5. Raw materials
6. Relevant processing equipments
7. Process evaluation
8. GMP consideration
9. Assurance

8. RAW MATERIALS WEIGHING & MEASURING
DISTILED WATER
MIXING
FILLING
PACKING
FINISHED
PRODUCT
STORAGE
QUALITY ASSURANCE

9. GENERAL CONSIDERATION
1- Reporting Responsibilities
•The goal of pilot plant scale is to facilitate the tranfer of a product from the
laborating in to production.
•The formulations continue to provide support to the production even after
the transition in to production has been completed.
•There must be good relation between pilot plant and other departments.
2- Personnel Requirement
•Have good theoretic knowledge of pharmaceutics.
•Practical experience in liquid orals manufacturing industry.
•Chemical ,physical , biochemical and medical properties of drugs.
•Have the knowledge of computer and electronics.

10. 3- Space Requirements
 Administration and information processing area
 Physical testing area
 Standard pilot plant equipment floor space
 Storage area

11. 5- Raw Materials
• One responsibility of pilot plant is the approval and validation of the active
ingredient and exicipient raw materials used in the pharmaceutical products.
• The quality of the active ingredients needs to be verified.
 Solvents
 Preservatives
 Antioxidants
 Solubilizers
 Organoleptic Agents
4- Review of Formula
•A thorough review of each and every steps of formulation is important
•The purpose of each ingredient and its contribution to the final product should be
studied
•In any modification in formula. it should be done as soon as possible in phase 3
trials. To allow time to generate meaning long term stability in a support of a
proposed new drug application

12. Solvents- Water, alcohol ,glycerol ,polyethylene glycol,
propylene glycol
Water- Compared to ordinary drinking water , purified water USP is more
free of solid impurities
•when evaporated to dryness. it must not yield greater than 0.001% of
residue
•Purified water is obtained by distillation, ion-exchange treatment, reverse
osmosis, and other relevant method.
Preservatives- preservatives are added to prevents the microbial
growth.
•Preservatives are necessary due to chance of microbial growth in raw
material, processing container and equipments the manufacturing
environments ,operations , packing materials.
•Examples- Benzoyl alcohol , chloro cresol , benzoic acid etc.

13. Antioxidants- A substance that reduces damage due to oxygen, such as
that caused by free radicals. which are capable of counteracting the
damaging effects of oxidation. Ascorbic acid ,sodium thiosulphate , sodium
metabisulphate
Organoleptic Agents- colouring agents , flavouring agents,
sweetining agent.
•Almost all formulation development work is carried out on small ,
relatively simple laboratory equipments
•The equipments that is most economic, the simplest ,the most efficient
should be selected
•Liquid pharmaceuticals processing tanks ,kettles ,pipes , mills , filter
housing and so forth are most frequently fabricated from stainless steel
•Ease of cleaning should be considered .if multiple products are to be
manufactured in the same equipment.

14. A. Tank selection
B. Mixing
C. Filtration and clarification
D. Transfer and filling
A B
DC

15. Equipment qualification
Process validation
Regular process review and revalidation
Relevant written SOP
Adequate provision for training of personnel
A well defined technology transfer system
An orderly arrangement of equipments
7- Process Evaluation
Items that should be examined include the following-
•Mixing speed
•Mixing time
•Rate of addition of solvents ,solution of drugs ,slurries etc
•Heating and cooling rates
•Filter size
•Filling

16. During the scale up new product the analytic test methods
transferred to the quality department
The quality assurance staff should review the process to make
sure that the proper analysis instrumentation is available and that
personnel are trained to perform tests

17. • A Pharmaceutical suspension is a coarse
dispersion in which internal phase
(therapeutically active ingredient)is
dispersed uniformly throughout the
external phase.
Pilot plant scale up for Suspesion

18. Manufacturing process
Raw material
Weighing &
Measuring
Mixing
FillingPacking
Finished
product
storage
Quality
assurance

19. Addition and dispersion of suspending agent
 On laboratory scale, the addition of suspending agent may merely involve
sprinkling the material into the liquid vertex, but when production scale
batches are involved, it may require use of a vibrating system.
Hydration and wetting of suspending agent
 The addition of a material that tends to clump during the
process or that is difficult to disperse can also pose problems while
handling large volumes.
 This problem may be resolved by employing some spesially designed
powder feeding mechanism such as powder eductor.
 If the suspending agent is difficult to disperse, it can be successfully
incorporate by making a slurry of suspending agent with a portion of the
vehicle.
 The latter facilitates rapid and complete hydration of the suspending agent
when added to the larger portion of the vehicle.

20. Mixer equipment
 Type of mixer used are;-
 Propeller mixer.
 Turbine mixer.
 Propeller mixer;-
 It consist of number of blades, rounded,
pitched, three blade design that
produces mostly axial flow.
 Up to 0.5 meters size depending upon
the size of the tank.
 Rotate speed up to 8000rpm.

21. Type of mixer

22. Versator - To avoid air entrapment.
 The Versator’s principle of operation relies on the
spreading of thin of aerated liquid on the inside of the
rotating versator Disc under high vaccume to remove
entrapped air, foam, gas.
 The vaccume is typically 28-29”Hg and the disc speed
may range from 1200-6000rpm.

23. Filling operation
 Filling – important parameter in the transfer of liquids from
tank to tank and into containers .
 The selection of equipment depends on characteristic of liquid
such as, viscosity, type of packaging, surface tension .
 Gravimetric (specific weight).
 Volumetric (specific volume).
 Constant volume filling.

24.  An emulsion is a thermodynamically unstable
system consisting of at least two immiscible liquid
phases one of which is dispersed as globules in the
other liquid phase stabilized by a third substance
called emulsifying agent
Pilot plant scale up for emulsion

25. Formulation aspects
Purpose Agent
Particle Size Solid particles, Droplet particles
Protecting the API Buffering- systems, antioxidants,
polymers
Maintaining the appearance
Colorants, Emulsifying agents,
Penetration enhancers, gelling
agents
Taste/smell masking Sweetners, flavoring agents.

26. Layout of a pilot plant

27. Equipments
 —Tanker
 Mixer
 —Homogenizer
 —filteration assembly

28. 1.Tank selection
 Material of the tank must not
be additive to the product.
 The shape and size of
equipment must be selected
according to the batch size.
 The tanks are usually
constructed of polished
stainless steel of different
grades
 Teflon and glass lined tank.
 Adequate cleanup procedures
developed.

29. 2. Mixer
• Simple mixing is essential to
increase flow of liquids.
• If the liquid is of high viscosity,
high electrical stirrer may be
used.
• Addition of ingredients in
proper order have vital
important.
• At high viscosity there is a
chance of air entrapment.

30. Air entrapment can be minimized
• By reducing agitator speed
• By caring out the mixing procedure
in enclosed tank under vacuum
Homogenizer
• Suspensions and emulsions require considerably
greater shear forces.
• Laboratory formulation is difficult to duplicate at
large scale.
• Dispersion produced by colloidal mill or an
immersion homogenizer.
• Variety of equipment should evaluated for better
results.

31. Filtration and clarification
• Filtration procedure, requires careful evaluation to ensure that pilot scale-
ups will exhibit the same degree of clarity as their laboratory counterparts.
• During the pilot run the clarity of the filtrate should be checked periodically,
in order to establish schedule for changing pads, cake, or cartridges,
depending on the type of filtration employed.
• In filtration, filter pads are used which is made up of asbestos and cellulose.
Selection of filtration depends on
• The product viscosity
• Volumes
• Rate requirement

32. REFERENCES
 1 The theory & practice of industrial
pharmacy by Leon Lachman, Herbert A.
Lieberman, Joseph L. Kenig, 3rd edition,
published by Varghese publishing house.
 Jain N. K. Sharma S.N. A Text book of
professional pharmacy vallabh prakashan
7th edition reprint 2014.