“Pharmaceutical Processing is the process of drug manufacturing and can be broken down into a range of unit operations such as blending, granulation, milling, coating, tablet pressing, filling and others.
“Process Automation in Pharmaceutical Industry”
SAVITRIBAI PHULE, PUNE UNIVERSITY , PUNE
PARTIAL FULFILMENT OF REQUIREMENTS FOR THE AWARD OF
MASTER OF PHARMACY
IN THE SUBJECT OF
“Pharmaceutical Manufacturing Technology”
IN THE FACULTY OF SCIENCE AND TECHNOLOGY
Bhujbal Knowledge City,
MET’s Institute of Pharmacy,
Adgaon, Nashik, 422003.
Presented By- Guided By
Dr. S.P. Ahirrao
(Dept. of PMT)
• “Pharmaceutical Processing is the process of drug
manufacturing and can be broken down into a range of
unit operations such as blending, granulation, milling,
coating, tablet pressing, filling and others.”
• “A process automation or automation system (PAS) is used
to automatically control a process such as chemical, oil
refineries, paper and pulp factories.”
• The PAS often uses a network to interconnect sensors,
controllers, operator terminals and actuators. A PAS is
often based on open standards in contrast to a DCS
(distributed control system), which is traditionally
3. Pharmaceutical Manufacturing Processes:-
• The pharmaceutical manufacturing process is typically made up of a
combination of specific unit processes choosen according to
physical and chemical characteristics of active pharmaceutical
1. Dry Granulation
2. Powder Blending
3. High Shear And Wet Granulation
4. Fluid Bed Granulation
5. Hot Melt Extrusion
7. Pharmaceutial Milling
8. Compression Of Powder Granules Into Tablets
9. Tablet Coating Equipment
10. Pharmaceutical Encapsulation
4. 1. Dry Granulation:-
Compaction of a low density powder to a granule. The
roller compation process consists of a combination of
screw feed, compaction and milling systems.
2. Powder Blending:-
In pharmaceutical industry, a wide range of excipients
may be blended together to create the final blend used
to manufacture the solid dosage form.
The uniqueness of each individual drug formulation
assures that no two blending process can be identical.
5. 3. High Shear And Wet Granulation:-
Commonly used processes for densification, to improve
flowability, content uniformity, or wettability or to improve
dispersing the qualities.
4. Fluid Bed Granulation:-
Top spray, bottom spray(wurster) and rotary(tangential spray)
are commonly used in the food and pharmaceutical
5. Hot Melt Extrusion:-
Utilised in pharmaceutical processing to enable the delievery
of drugs with poor solubility and bioavailability of a
particular interst is the use of HME to disperse active
pharmaceutical ingredients in a mattrix at the molecular
level, thus forming solid solutions.
6. 6. Drying:-
Understanding and controlling the moisture content of
powders is critical to many pharmaceutical processes.
Fluid bed or laminar flow drying conditions impact both
physical and chemical characteristics of powder and
7. Pharmaceutial Milling:-
The process of using rotary cutters in pharmaceutical
equipments machinery to remove materials from a
workplace by feeding in at an angle with the axis of the
7. 8. Compression Of Powder Granules Into Tablets:-
An efficient process for producing a solid dose
9. Tablet Coating Equipment:-
Options includes batch process coating pan off-press
continous coating at continous processing.
10. Pharmaceutical Encapsulation:-
the containment of a solid or liquid dose of a drug in a
soft shell or hard performed capsule.
The process of reducing the particle sizes of pharmaceutical
products, under very high pressure, shear, turbulance,
acceleration and impact, to make them more stable and
clinically effective. +++
8. Pharmaceutical Processing Equipment:-
• Automation refers to use of machines and
equipments for performing physical and mental
operations in the production process in place of
• Pharmaceutical automation involves mechanical
process of handling materials, distributing
medications and manufacturing and packaging
formulations in industries.
• Pharmaceutical processing equipments incudes a
wide variety of equipments for specific unit
processes, such as;
1. Higher production rates and increased
2. Efficient use of materials.
3. Better products quality.
4. Improved safety.
5. Shorter workweeks for labor.
6. Reduced factory lead times.
7. Less variability.
8. Greater control and consistency of product
1. High capital expenditure.
2. Higher level of maintenance.
3. Lower degree of flexibility.
4. Worker displacement(major demerit).
5. Emotional stress condition for workers.
6. Relocations of workers to find other work.
7. Workers become slaves of the machine.
8. Society will become dependant on automation
for its economic well being. +++
12. Pharmaceutical manufacturing of sterile Semi-solids:-
• Semisolid products have been manufactured for many years for
distribution as pharmaceutical drug products, cosmetics and health
• The semi solids category of comprised if creams, gels, ointments,
suppositories and other topical dosage forms.
Different types of semisolids are:-
2. Hydrophillic ointments
3. Water emulsifying ointments
4. Hydrophilic ointment bases
7. Hydrophobic gels
8. Hydrophilic gels
10. Paultices +++
13. Unit operation for semi solids system:-
1. Mixing of liquids
e.g.Kettle and tank filled with agitator
2. Mixing of solids
e.g.Blade mixture and tumbler
3. Mixing of semi solids
e.g.Blade mixture and tumbler
5. Milling and size reduction of slid and semi solids
e.g. End runner mill
14. PARENTERAL DOSAGE FORM:-
• Parenteral dosage forms are sterile pyrogen free
preparations intended for administration by the
injection under or through one or more layers of
skin or mucous membrane.
• There are mainly two types of parenteral dosage
A)Small Volume Parenterals (SVP):-
B)Large volume parenterals (LVP):-
15. A) SMALL VOLUME PARENTERALS(SVP):-
• These are usually ranges from 1 to 30 ml in
volume i.e. Less than 100 ml in volume.
• Mostly given as multiple doses.
• Different types of small volume parenterals are
• Ampules are sealed glass containers with an elongated
make that must be broken of our ampules
• Most of the a levels are weakest around the neck for easy
breaking, these will have a coloured band around neck.
• A 5 micron filter needle must be used when drawing
contents of ampoule into syringe, since glass particle may
have fallen inside ampoule, when top was while was snap
• In addition it is useful to wrap on alcohol wipe or small
piece of gauze around top of the ampoule before breaking
• This provides protection for fingers, if ampoule shutters and
will also reduce possibility of glass splinters become
• The drugs and other additives are packaged in vials either as
liquids or lyophilized powder.
• Made of glass or plastic and are sealed with rubber stopper.
• A needle is used to add contents to or withdraw contents
from the vial.
• Before withdrawing contents from vial and equal volume of
air is usually injected into the vial to pressurize the vial and
aid-in withdrawing contents.
• Vials may designated for single dose or multi dose use.
• Multi dose vial contents preservatives to inhibit bacterial
contamination once vial has been used.
18. Dry powders:-
• Dry powder formulation are lyophilized or freeze dried
powder must be reconstituted with some suitable
solvents to make a liquid formulation before being
withdrawn from vial.
• Some drugs are not stable in liquid form and so these
drugs put into powder form and reconstituted prior
• It consists of syringes which are prefilled with drug
• There are two varieties of prefilled syringes, namely a
cartridge type and another is glass tube type.
• After the use, all pieces are discarded.
19. B) LARGE VOLUME PARENTERAL(LVP):-
• A single dose of injection that is intended for I.V. use and
packed in containers labelled as containing more than 100
• LVPs are aq. solution usually supplied in volume of at least
100 ml with sizes of 250 ml, 500 ml, 1000 ml and 3000 ml
and 5000 ml commonly.
• The directions usually recommend that large quantities are
• Many different LVPs are commercially available.Packaged
in glass bottles or in large volume flexible containers.
• May contain greater than 100 ml to greater than 1 litre or 2
20. Examples of LVP:-
• Calcium Solution.
• Sodium Chloride Ringer Sodium Bicarbonate.
• Electrolyte Solution.
• Dextrose (Glucose) And Sugar Solution.
• Amino Acid Peptide And Protein Fractions Solutions.
• Solution Containing Combination Of Above or Sometimes with Vitamin
• Dextran And Plasma Expanders.
• Peritoneal Dialysis(LVP).
• Irrigating Solution.
• Hyperalimentation Solution(TPN) i.e. Total Parenteral Nutrition.
• Cardioplegia Solution.
• IV Admixture.
• Intermittent Solution.
• Pre-mixed I.V. Admixture.
21. Control test for SVPs and LVP:-
1) Liquor test 4) Pyrogen test
2) Sterility test 5) Particulate matter test
3) Clarity test 6) Bacterial endotoxin test
• It is done by completely submerging sealed
ampoule in a deeply coloured dye solution.
• Generally 1% methylene blue solution is used.
• The ampoule, if not sealed properly dye solution
must present outside an ampoule will enter into
ampoules and make the solution coloured.
22. 2)Clarity test:-
• The parenteral product evaluated is placed against a
white and black background with concern set in motion
in swirling action.
• It is kept in that motion until any particle becomes
visible or not.
• Care is to be taken to avoid any on the air bubbles.
• Important to check if product meets requirements of
sterility according to official books or not .
• There are two methods.
1.Direct transfer of the sample to sterile culture media
2.The membrane filtration procedure.
23. 4)Pyrogen test:-
• Samples of production batch tested in the rabbits for presence of
• There are two stages:-
I) Sham Test:-
• If animals are used for the first time in the pyrogen testing,
then condition the animal for 2-3 days by injecting 1 mg/kg
body weight of pyrogen free solution IV.
• Maintain animals like that for 18 hours in the room maintained
at the temperature of 3° Celsius.
• Record the temperature of animals. In the beginning at least 19
minutes before injection and contamination for 3 hours after
• Any animal showing variation of 0.6 °Celsius or more must not
be used in the main test.
24. II)Main test:-
• Determine control temperature of each rabbit by recording temp not more
than 30 min prior to the injection for test solution.
• Inject into air vein of each rabbit 10 ml of a test solution per kg body weight
completing each injection for 10 min after starting administration of drug.
• Test solution must warmed up to 37°±2°C.Record the temp for 1,2 and 3 hrs
subsequent to injection.
The following requirements should be passed:
1. Individual rise in temp. of 0.6°C with respect to control and some of three
individual rabbits does not exceed 1.4°C, sample passes the test
2. If anything above mentioned requirement rises, continue test with five other
3. Individual rise in temp not more than 0.6 degree Celsius and sum of all eight
does not exceed 3.7°C the sample passes the test.
25. Monitoring of pharmaceutical manufacturing technology:-
1.Visual method 3.Filtration method
2.Coulter counter method 4.Light blockage method
1. Visual method:-
Field containers are examined against strong illuminated screen by
holding the neck and rotating it slowly or inverted to give foreign matter
2. Coulter counter method:-
It is used for detection of particles less than 0.1 micrometre in diameter.
3. Filtration method:-
Materials are collected on filters and evaluated under microscope
4. Light blockage test:-
It is the technique used for hydraulic oils.
26. Cleaning in place(CIP):-
• Cleaning in place is a method of automated cleaning interior surface
of pipes, vessels, equipments, filters and associated fittings without
• CIP is commonly used for equipment as piping tanks and filters.CIP
employs turbulent flow through piping or sprayballs of large
surfaces.In some cases CIP can also be accomplished with fill, soak
• The benefit to industries is that cleaning done is very faster, labour
intensive and more repeatable and posses less chemical exposure
• CIP started as manual practice working, involving a balance
tank,centrifugal pump and connection to the system being cleaned.
• Since 1950, CIP has involved to include fully automated system with
programmable logic controllers, multiple balance tanks, sensors
valves, and heat exchangers also data acquisition and specially
designated spray nozzle system.
• Simple and manually operated CIP system still found in use today.
27. Sterilization in place (SIP):-
• Sterilization in place refers to sterilization of production equipment without
• Sterilization is usually carried out by means of superheated system
• SIP system where used in areas where germ reduction plays a decisive role.
• Examples are han biotechnology or or in food industry.
Process of sterilization in place:-
Sterilization is carried out with steam at 120 degrees celsius and to
bar over a period of about 60 to 70 minutes
The duration where is according to application and system types
Challenges of sterilisation with superheated system:-
Displacement of air present in production plant
Increasing temperature in the entire system to require sterilization
Avoiding temperature process and condensate formation
28. Checklist for handling after sterilization:-
• For the safer handling of system many details
• they help to maintain sterility of Process plant
after the sterilization
• Slight over pressure in system all time prevents
imgress of air.
• On developing product sterile use, distilled or
sterilizd water as control rising or decrease in