This document discusses the process of scaling up liquid oral dosage forms from a laboratory scale to a pilot plant scale. It defines key terms like plant, pilot plant, and scale-up. The objectives of pilot plant scale-up are to avoid scale-up problems, identify crucial process features, develop manufacturing procedures and instructions, evaluate equipment and costs. Common liquid dosage forms and general steps in pilot plant scale-up like personnel requirements, equipment needs, and process evaluations are covered. Specific considerations for scaling up suspensions and emulsions are also provided.

1. Prepared by:
Mr. Ashish R. Chaudhari
Asst. Professor
M.Pharm
PILOT PLANT SCALE-UP FOR LIQUID
ORALS

2.  DEFINITIONS
 INTRODUCTION
 OBJECTIVES
 LIQUID DOSAGE FORM
 STEPS INVOLVED IN PILOT PLANT
FOR ORAL LIQUIDS
 GENERAL CONSIDERATIONS
 PILOT PLANT SCALE UP FOR
SUSPENSION
 PILOT PLANT SCALE UP FOR
EMULSION
 REFERENCES
CONTENTS

3. DEFINITIONS
 Plant:- It is a place where the 3 M’s that are
Man, Material and Money are brought together for the
manufacturing of products.
 Pilot Plant:- It is 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.

5. OBJECTIVES
• To avoid the scale up problems
• To identify the crucial features of the process
• Guideline 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 and 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 monophasic 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 liquids which consist of two
phases are known as biphasic liquids.

7. STEPS INVOLVED IN PILOT PLANT FOR ORAL LIQUIDS

8. 1- Reporting Responsibilities
The goal of pilot plant scale is to facilitate the transfer of a product from the
laboratory 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.
GENERAL CONSIDERATIONS

9. 3. Space Requirements:-
Administration
and information
processing
Physical
testing area
Standard
equipment
floor space
Storage
area

10. 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
5- Raw Materials
One responsibility of pilot plant is the approval and validation of the active
ingredient and excipient raw materials used in the pharmaceutical products. The
quality of the active ingredients needs to be verified.
 Solvents
 Preservatives
 Antioxidants
 Solubilizers
 Organoleptic Agents

11. 6- Relevant Processing Equipments
 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 for are most frequently
fabricated from stainless steel
 Ease of cleaning should be considered if multiple
products are to be manufactured in the same
equipment.

12. Stages Of Operation
A Tank selection
B. Mixing
C. Filtration and clarification
D. Transfer and filling

13. 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
8-GMP Considerations
 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

14. 9- Assurance
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

15. 46
SUSPENSIONS
➢Suspensions require more attention during scale up than simple solutions
because of additional processing needs.
➢Equipments :-
* vibrating feed system and power for production scale.
* high shear mixing equipment
➢Slurries facilitate rapid and complete hydration of suspending agent
when added to large portion of the vehicle.
➢Active ingredients must be uniformly dispersed throughout the
batch.
➢Mixing at too high speed can result in entrapment of air, which may
affect physical or chemical stability of the product.

16. 47
VACUUM UNIT VERSATOR
➢Filteration – remove unwanted particles.
➢Screens of 150 mesh, having 100 microns are used.
➢Active ingredients – particle size 10 – 25 microns.
➢Transfer and filling of finished suspension should be
carefully monitored.
➢It should be constantly mixed during transfer to maintain
uniform distribution of the active ingredients.

17. 48
EMULSIONS
➢Manufacturing of liquid emulsion products entails specialized
procedures as result scale up into production equipment involves
extensive process development and validation.
➢Equipments :-
* mixing equipment
* homogenizing equipment
* screens
* pumps
* filling equipment
➢High shear mixers may lead to air entrapment, this problem can be
avoid by carrying out operation under controlled vacuum.

18. REFERENCE
1. The theory & practice of industrial pharmacy by Leon
Lachman, Herbert A. Lieberman, Joseph L. Kenig, 3rd
edition, published by Varghese Publishing house.