This document discusses techniques for scaling up plant and production processes in the pharmaceutical industry. It defines key terms like plant, pilot plant, and scale-up. The significance and general considerations of pilot plants are outlined. GMP, product, equipment, and personnel considerations for pilot plants are described. Specific processes for solid dosage forms like blending, granulation, drying, tablet coating, and capsule filling that must be addressed during scale-up are also summarized.

1. PLANT AND SCALE
CHNIQUES
Prepaed by :
Shubham D Ghodke
TPLANTANDSCALEUP
HNIQUES
Preparedby :
ShubhamD Ghodke

2.  CONTENTS
 Definition
 Significance
 General Consideration
 GMP Considerations
 Product Considerations
 Advantages
 Disadvantages

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 usingthe data
obtained from the pilot plant model.

4.  SIGNIFICANCE
 Permits close examination of formulae to determine its ability to withstand
batch scale and process modification.
 Review of Equipment - most compatible with theformulation & most
economical, simple and reliable in producing product
 .Raw materials - consistently meet the specifications required to produce
the product can be determined.
 Production rate adjustment after considering marketing requirements.
 Give rough idea about physical space required and of related functions.

5. GENERAL CONSIDERATIONS
Reporting
Responsibility
R &D group
with seprate
staffing
The formulator who
developed the product can
take into the production
and can provide support
even after transition into
production has been
completed.

6. 2. Personnel Requirements
 Scientists with experience in pilot plant operations as well as
in actual production area are the most preferable
 .*As they have to understand the intent of the formulator as
well as understand the perspective ofthe production
personnel.
 Engineering principles
 Knowledge of computers & electronics

7. Standard Pilot-plant Equipment Floor Space :-
 Discreet pilot plant space, where the equipment needed for manufacturing
all types of dosage form is located.
 Intermediate-sized and full scale production equipment is essential in
evaluating the effects ofscale-up of research formulations and processes.
 Equipments used should be made portable where ever possible. So that
after use it can be stored in the small store room.

8. Raw materials
 One purpose/responsibility of the pilot-plant is the approval & validation of
the active ingredient & excipients raw materials.
 Raw materials used in the small scale production cannot necessarily be
the representative for the large scale production.
 Ingredients may change in particle size, shape or morphology which result
in differences in bulk density, static charges, rate of solubility, flow
properties, color, etc.

9. Equipment
 The most economical, simplest & efficient equipment which are capable of
producing product within the proposed specifications are used.
 The size of the equipment should be such that the experimental trials run
should be relevant to the production sized batches.
 If too small the process developed will not scale up.
 If too big then the wastage of the expensive active ingredients.
 Ease of cleaning
 Time of cleaning

10. Production Rates:-
 The immediate as well as the future market trends/requirements are
considered while determining the production rates.

11. GMP CONSIDERATIONE
 equipment qualification
 Process validation
 Regularly process review & revalidation
 Relevant written standard operating procedures
 The use of competent technically qualifiedpersonnel
 Adequate provision for training of personnel
 A well-defined technology transfer system
 Validated cleaning procedures
 An orderly arrangement of equipment

12. ADVANTAGES
 Members of the production and quality control divisions can readily
observe scale up runs.
 Supplies of excipients & drugs, cleared by the quality control division, can
be drawn from the more spacious areas provided to the production
division.
 Access to engineering department personnel is provided for equipment
installation, maintenance and repair.

13. DISADVANTAGES
 The frequency of direct interaction of the formulator with the production
personnel in the manufacturing area will be reduced.
 Any problem in manufacturing will be directed towards it's own pilot-plant
personnel.

14. PRODUCT CONSIDERATIONSSOLID DOSAGE FORM
 Soliddosageform
 Material Handling
 Laboratory Scale
 Deliver accurate amount to the destination
 Large Scale*
1. Lifting drums
2. More Sophisticated Methods-
 Vacuum Loading System
 -Metering Pumps
 Prevent Cross Contamination by
 Validation Cleaning Procedures.

15. 2. Dry Blending
 Powders should be used for encapsulation or to be
 granulated prior to tabletting must be well blend
 ensure good drug distribution.
 Inadequate blending could result in drug content
 uniformity variation, especially when the tablet or capsule
 is small & the drug concentration is relatively low.
 Ingredients should be lumps free, otherwise it could cause
 flow problems.

16. 3. GranulationsReasons :-
 To improve the flow properties.
 To increase the apparent density of the powder.
 To change the particle size distribution so that the
 binding properties on compaction can be improved.

17.  Types:
a) Wet Granulation
b) Dry Granulation
c) Direct Compression Method
 A small amount potent active ingredient can be dispersed
 most effectively in a carrier granulation, when the drug is
 dissolved in granulating solution and addedduring the
 granulating process.

18. 4. Drying
 Hot air oven
1. air temperature
2. rate of air flow
3. depth of granulation on the trays
 Fluidized Bed Dryer
1. optimum loads
2. rate of airflow
3. inlet air temperature
4. humidity

19. TABLET COATING
 Equipments :-
1. conventional coating pan
2. perforated pans of fluidized-bed coating column
 Types :-
1. Sugar coating
2. Film coating
 Tablet must be sufficiently hard to withstand the the
 tumbling to which they are subjected while coating.
 Operation conditions to be established for pan or column
 operation are optimum tablet load, operating tablet, bed
 temperature, drying air flow rate, temperature, solution
 application rate.

20. CAPSULES
 To produce capsules on high-speed equipment, the
 powder blend must have,
 uniform particle size distribution
 bulk density
 formation of compact of the right size and of sufficient
 cohesiveness to be filled into capsule shells.
 Equipments:-
1. Zanasi or Mertalli - Dosator(hollow tube)
2. 2. Hoflinger - Karg - Tamping pins
3. Weight variation problem can be encountered with these two methods
4. .Overly lubricated granules - delaying disintegration.

21. THANK YOU