Form fill seal technology and lyophilization technology, Mpharmacy Quality Assurance department

1. MAHATMA GANDHI VIDYAMANDIR’S
PHARMACY COLLEGE, PANCHAVATI, NASHIK-
422003
A SEMINAR ON
FORM FILL SEAL TECHNOLOGY AND LYOPHILIZATION
TECHNOLOGY
MGV’S Pharmacy College, Panchavati, Nashik
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Presented by-
Mr Kunal Anil Suryawanshi
Sub: Pharmaceutical Manufacturing Technology

2. VISION:
“TO BE A CENTRE OF PROFESSIONAL EXCELLANCE BY CONTRIBUTING
HONESTLY TO THE PHARMACIST
MOULDING PROCESS.”
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Mission:
• Impart high quality education to graduates.
• Contribute to all spheres of professional activities.
• Up hold human values and ethics.
• Nurture them into globally competent professionals.

3. CONTENT
• PROCESS AUTOMATION IN PHARMACEUTICAL INDUSTRY
• FORM FILL SEAL TECHNOLOGY (FFS)
• ADVANTAGES
• DISADVANTAGES
• APPLICATIONS
• LYOPHILIZATION TECHNOLOGY
• PRINCIPLES
• PROCESS
• EQUIPMENT
• ADVANTAGES
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4. PROCESS AUTOMATION IN PHARMACEUTICAL INDUSTRY
PROCESS AUTOMATION IN PHARMACEUTICAL INDUSTRY USING
TECHNOLOGY TO STREAMLINE AND IMPROVE THE EFFICIENCY OF
VARIOUS MANUFACTURING PROCESSES. THIS CAN INCLUDE
AUTOMATION OF TASKS SUCH AS DRUG FORMULATION, PRODUCTION,
PACKAGING, AND QUALITY CONTROL.
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5. FORM FILL SEAL TECHNOLOGY (FFS)
FORM FILL SEAL (FFS) TECHNOLOGY IS A WIDELY USED PACKAGING PROCESS IN THE
PHARMACEUTICAL INDUSTRY (AS WELLAS IN FOOD AND OTHER INDUSTRIES) FOR CREATING
PACKAGES FROM ROLLS OF FLAT, FLEXIBLE PACKAGING MATERIAL. HERE’S HOW IT WORKS:
 FORMING: THE PACKAGING MATERIAL, OFTEN A LAMINATE OF SEVERAL LAYERS FOR BARRIER
PROPERTIES AND STRENGTH, IS FED INTO THE MACHINE WHERE IT IS FORMED INTO A TUBE.
 FILLING: THE PRODUCT (IN THE PHARMACEUTICAL CONTEXT, THIS COULD BE TABLETS,
CAPSULES, POWDERS, OR LIQUIDS) IS DOSED INTO THE FORMED PACKAGING MATERIAL. THIS IS
TYPICALLY DONE WITH PRECISION TO ENSURE ACCURATE DOSING.
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6. SEALING: THE FILLED TUBE IS SEALED ALONG ITS LENGTH,
CREATING INDIVIDUAL PACKAGES.
CUTTING: THE SEALED TUBE IS THEN CUT INTO INDIVIDUAL
PACKAGES, EACH CONTAINING THE DESIRED DOSAGE OF THE
PRODUCT.
FINAL PROCESSING: DEPENDING ON THE SPECIFIC REQUIREMENTS,
THE PACKAGES MAY UNDERGO ADDITIONAL PROCESSING STEPS
SUCH AS PRINTING, LABELING OR INSPECTION BEFORE THE ARE
READY FOR DISTRIBUTION.
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7. PROCESS
• THE BASIC CONCEPT IS FORMATION, FILLING AND SEALING OF PLASTIC CONTAINER
IN ASEPTIC ENVIRONMENT.
• THE BLOW FILL PROCESS CAN BE DIVIDED INTO FOLLOWING MAIN STEPS:-
• PARISON EXTRUSION
• CONTAINER MOULDING
• CONTAINER FILLING
• CONTAINER SEALING
• CONTAINER DISCHARGE.
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Fig. Form fill seal technology

9. ADVANTAGES
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• Reduced personnel intervention.
• Saving floor space.
• The cost of material transport, storage and inventory
control is reduced.
• The code numbers and variable data such as batch no.
and expiry date can be embedded into the container
itself.

10. DISADVANTAGES
• PARTICULATE CONTROL
• TEMPERATURE EFFECTS
• OXYGEN AND MOISTURE EFFECTS
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11. APPLICATIONS
• PHARMACEUTICAL:
PARENTERAL PRODUCTS
OPHTHALMIC DROPS
INHALATION SOLUTIONS(NEBULIZERS)
• BIOTECHNOLOGY PRODUCTS:
TOPICAL LIQUIDS, CREAMS, GELS, OINTMENTS
ORAL LIQUIDS
• DIAGNOSTICS:
REAGENTS IN DIAGNOSTIC PRODUCTS
• FOOD:
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12. LYOPHILIZATION TECHNOLOGY
DEFINITION: A STABILIZING PROCESS IN WHICH A SUBSTANCE IS FIRST FROZEN
AND THEN THE QUANTITY OF THE SOLVENT IS REDUCED FIRST BY SUBLIMATION
(PRIMARY DRYING STAGE) AND THEN DESORPTION (SECONDARY DRYING STAGE) TO
VALUE THAT WILL LONGER SUPPORT BIOLOGICALACTIVITY OR CHEMICAL
REACTIONS.
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14. PRINCIPLES
 LYOPHILIZATION IS CARRIED OUT USING A SIMPLE PRINCIPLE OF PHYSICS
SUBLIMATION. SUBLIMATION IS THE TRANSITION OF A SUBSTANCE FROM THE
SOLID TO THE VAPOUR STATE, WITHOUT FIRST PASSING THROUGH AN
INTERMEDIATE LIQUID PHASE.
 LYOPHILIZATION IS PERFORMED AT TEMPERATURE AND PRESSURE CONDITIONS
BELOW THE TRIPLE POINT, TO ENABLE SUBLIMATION OF ICE.
 THE ENTIRE PROCESS IS PERFORMED AT LOW TEMPERATURE AND PRESSURE BY
APPLYING VACUUM, HENCE IS SUITED FOR DRYING OF THERMOLABILE
COMPOUNDS.
 THE CONCENTRATION GRADIENT OF WATER VAPOUR BETWEEN THE DRYING
FRONT AND CONDENSER IS THE DRIVING FORCE FOR REMOVAL OF WATER DURING
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15. OBJECTIVES OF LYOPHILIZATION PROCESS
• TO PRESERVE THE BIOLOGICAL ACTIVITY OF A PRODUCT.
• TO REDUCE THE PRODUCT WEIGHT TO LOWER THE TRANSPORTATION COST.
• TO EXTEND THE SHELF LIFE OR STABILITY.
• TO DRY THERMOLABILE MATERIALS.
• TO ELIMINATE THE NEED FOR REFRIGERATED STORAGE.
• TO GET ACCURATE, STERILE DOSING INTO THE FINAL PRODUCT CONTAINER.
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18. PROCESSING
• FUNDAMENTAL PROCESS STEPS ARE:
1. FREEZING: THE PRODUCT IS FROZEN. THIS PROVIDES A NECESSARY CONDITION
FOR LOW TEMPERATURE.
2. VACCUM: AFTER FREEZING, THE PRODUCT IS PLACED UNDER VACCUM. THIS
ENABLES THE FROZEN SOLVENT IN THE PRODUCT TO VAPORIZE WITHOUT PASSING
THROUGH LIQUID PHASE, A PROCESS KNOWN AS SUBLIMATION.
3. HEAT: HEAT IS APPLIED TO THE FROZEN PRODUCT TO ACCELERATE SUBLIMATION.
4. CONDENSATION: LOW-TEMPERATURE CONDENSER PLATES REMOVE THE
VAPORIZED SOLVENT FROM THE VACCUM CHAMBER BY CONVERTING IT BACK TO
A SOLID. THIS COMPLETES THE PROCESS.
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20. FREEZE DRYING
• FREEZING THE PRODUCT SOLUTION TO A TEMPERATURE BELOW ITS EUTECTIC
TEMP.
• DECREASES THE SHELF TEMP. TO -50°C.
• LOW TEMP. AND LOW ATMOSPHERIC PRESSURE ARE MAINTAINED.
• FREONS ARE USED AS REFRIGERANT.
• FORMATION OF ICE CRYSTALS OCCURS.
• THE RATE OF ICE CRYSTALLIZATION DEFINE THE FREEZING PROCESS AND
EFFICIENCY OF PRIMARY DRYING.
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21. PRIMARY DRYING (SUBLIMATION)
• HEAT IS INTRODUCED FROM SHELF TO THE PRODUCT UNDER GRADED CONTROL
BY ELECTRICAL RESISTANCE COILS OR CIRCULATING SILICONE.
• THE TEMP. AND PRESSURE SHOULD BE BELOW THE TRIPLE POINT OF WATER I.E.,
0.0098°C AND 4.58MMHG.
• EASILY REMOVES MOISTURE UP TO 98% TO 99%.
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22. SECONDARY DRYING (DESORPTION)
• THE TEMP. IS RAISED TO 50°C TO 60°C AND VACCUM IS LOWERED ABOUT 50MM
HG.
• BOUND WATER IS REMOVED.
• RATE OF DRYING IS LOW.
• IT TAKES ABOUT 10-20 HRS.
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23. PACKING
• AFTER DRYING THE VACCUM IS REPLACED BY FILTERED DRY AIR OR NITROGEN
TO ESTABLISH ATMOSPHERIC PRESSURE.
• AMPOULE ARE SEALED BY EITHER TIP SEALING OR PULL SEALING METHOD.
• VIALS AND BOTTLES ARE SEALED WITH RUBBER CLOSURES AND ALUMINIUM
CAPS.
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24. EQUIPMENT
THE EQUIPMENT USED IN LYOPHILIZATION TYPICALLY INCLUDES:
1. FREEZE DRYER: THIS IS THE MAIN EQUIPMENT USED IN THE LYOPHILIZATION
PROCESS. IT CONSISTS OF A VACCUM CHAMBER, SHELVES TO HOLD THE PRODUCT,
A CONDENSER TO COLLECT MOISTURE, AND A REFRIGERATION SYSTEM. FREEZE
DRYERS COME IN VARIOUS SIZES AND CONFIGURATIONS DEPENDING ON THE
SCALE OF PRODUCTION.
2. VACUUM SYSTEM: A VACUUM PUMP IS USED TO CREATE AND MAINTAIN THE LOW-
PRESSURE ENVIRONMENT INSIDE THE FREEZE DRYER. THIS IS ESSENTIAL FOR THE
SUBLIMATION OF ICE AND THE REMOVAL OF MOISTURE FORM THE PRODUCT.
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25. 3. REFRIGERATION SYSTEM: FREEZE DRYERS ARE EQUIPPED WITH A
REFRIGERATION SYSTEM TO COOL THE SHELVES AND CONDENSER TO
THE PRODUCT AT A LOW TEMPERATURE THROUGHOUT THE PROCESS.
4. CONTROL SYSTEM: MODERN LYOPHILIZERS ARE EQUIPPED WITH
ADVANCED CONTROL SYSTEMS TO MONITOR AND CONTROL VARIOUS
PARAMETERS SUCH AS TEMPERATURE, PRESSURE, AND TIME. THIS
SYSTEMS ENSURE THE PROCESS IS CARRIED OUT EFFICIENTLY AND
ACCURATELY.
5. PRODUCT CHAMBERS: THESE ARE THE COMPARTMENTS WHERE THE
PRODUCT IS PLACED FOR LYOPHILIZATION. THEY ARE USUALLY
EQUIPPED WITH SHELVES TO HOLD THE PRODUCT CONTAINERS.
6. CONDENSER: THE CONDENSER IS USED TO COLLECT THE MOISTURE THAT
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26. ADVANTAGES
• REMOVAL OF WATER AT LOW TEMPERATURE.
• THERMOLABILE MATERIALS CAN BE DRIED.
• COMPATIBLE WITH ASEPTIC OPERATIONS.
• MORE PRECISE FILL WEIGHT CONTROL.
• STERILITY CAN BE MAINTAINED.
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27. DISADVANTAGES
• MANY BIOLOGICAL MOLECULES ARE DAMAGED BY THE STRESS ASSOCIATE WITH FREEZING ,
FREEZE DRYING, OR BOTH.
• THE PRODUCT IS PRONE TO OXIDATION, DUE TO HIGH POROSITYAND LARGE SURFACE AREA.
THEREFORE THE PRODUCT SHOULD BE PACKED IN VACCUM OR USING INERT GAS OR IN A
CONTAINER IMPERVIOUS TO GASES.
• COST MAY BE AN ISSUE, DEPENDING ON THE PRODUCT.
• LONG TIME PROCESS.
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28. REFERENCES
1. THE LYOPHILIZATION OF PHARMACEUTICALS: A REVIEW BY N.A. WILLIAMS AND G.P. POLLI. JOURNAL OF
PHARMACEUTICAL SCIENCE AND TECHNOLOGY.
2. PHARMACEUTICAL ENGINEERING- PRINCIPLES AND PRACTICES BY C.V.S. SUBRAMANYAM, J. THIMMA
SETTY, SARASIJA SURESH AND V. KUSUM DEVI. PG 401-405.
3. THE THEORY AND PRACTICE OF INDUSTRIAL PHARMACY BY LEON LACHMANN, HERBERT. A. LIEBERMAN
AND JOSEPH I. KANIG, 1991. PG 62-64, 672-674.
4. AULTON’S PHARMACEUTICS – THE DESIGN AND MANUFACTURE OF MEDICINES BY MICHEAL E. AULTON,
2009. PG 195.
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29. THANK YOU !!!
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