single pot processor
TRANSCRIPT
Single Pot ProcessorPrinciple, benefits and Characteristics
Girish S SonarCipla Ltd.,Pharma R&DVikhroli (W), Mumbai
Date: 19.03.2013
Disclaimer
All material on this presentation, including text and
images, is of presenter's opinion only and does not
represent that of any vendor or promoting any
machine/equipment nor employee's view.
• What is ‘Single Pot Processor’?• SPP Vs RMG• Design features and Benefits• Application• Working Principle • Case Study• Post-approval changes
Outline
• What is ‘Single Pot Processor’?• RMG Vs SPP• Design features and Benefits• Application• Working Principle • Case Study• Post-approval changes
Outline
• A high-shear-mixer-granulator-dryer, combining the steps of mixing, granulation and drying in oral solid dosage form production
• Thus, single pot processing (SPP) is the
production of pharmaceutical granules using a wet granulation process in which dry mixing, liquid addition, wet granulation, drying and sizing of the granules is done in one machine.
What is ‘Single Pot Processor’
SPP = RMG + FBE + Mill
SPP = RMG FBE Mill
=
• What is ‘Single Pot Processor’?• SPP Vs RMG• Design features and Benefits• Application• Working Principle • Case Study• Post-approval changes
SPP Vs RMGFeatures SPP RMGFunction Granulation + Drying +
Milling + BlendingGranulation
Jacket temp Specific control No specific control available
Impeller position Top driven At Bottom Alignment Tilt up to 70° FixBinder addition mechanism
Pressure difference/ peristaltic pump
Peristaltic pump
Drying mechanism
Combination of heating, tilting the bowl, vacuum, microwaves, Transflow
No drying
• What is ‘Single Pot Processor’?• RMG Vs SPP• Design features and Benefits• Application• Working Principle • Case Study• Post-approval changes
Flexibility: Single Pot Processing: mixing, granulation and drying in
1 machine - number of material handling steps is decreased
Drying technique : Vacuum-drying, microwaves, Transflow and swinging bowl – improvement of the granule characteristics and a reduction in drying time
Explosion proof design
Containment: Perfect GMP-design, easy to clean, CIP system Dust-free loading
Design features and Benefits (1)
Swinging Bowl: better granulate quality and faster drying User friendly: operator-machine interaction (Video
monitoring) Top driven mixer and chopper: easy cleaning, GMP accepted Process parameters are independent of atmospheric
conditions High yield Reduced use of cleaning liquids Solvent recovery systems Change over in less than 2 hours Compact technology – reduce space requirement
Design features and Benefits (2)
• What is ‘Single Pot Processor’?• RMG Vs SPP• Design features and Benefits• Application• Working Principle • Case Study• Post-approval changes
1. Wet granulation - Water based, solvent based2. Vacuum drying3. Effervescent products – to control fusion
reaction 4. Oncology drugs, hormonal products or highly
potent compounds- special care require to avoid exposure of the operators
5. Hot melt granulation6. Pelletizing7. Coating
Application
• What is ‘Single Pot Processor’?• RMG Vs SPP• Design features and Benefits• Application• Working Principle • Case Study• Post-approval changes
‘Top Driven’ advantage
Shaft seals are not in direct contact with the product : No risk for cross contamination
Easy to clean and inspect : full accessibility with open bowl
No need for hoist to remove the impeller blade
Liquid addition system
Granulation endpoint determination NIR and FBRM (Focused Beam Reflectance Measurement) : Measurement of moisture content, homogeneity of the mix and particle distribution Visual observation through camera Torque measurement of Impeller and Chopper
Drying mechanism
Vacuum Drying - Principle • The boiling point of liquids is lower at lower pressures• By applying vacuum in the bowl, the boiling point of the granulation
liquid used is significantly decreased.
Characteristics of Vacuum Drying System• Highly efficient vacuum system (roots bower + Vacuum pump)• Energy supply through heated jacket of lid and bowl• Liquid recovery unit ( 1 or 2 condensers)
Schematic Diagram of Technical Area
TRANSFLOTM Drying
Microwave Drying - Advantage • Energy supply independent from
vessel wall; wall temperature can be controlled in order to avoid caking
• No risk of wet lumps (drying inside to outside)
• Significantly reduced drying time• Scale up of drying time is linear
(linear to installed μ-wave power) ; similar drying time small and large batch size
Drying Techniques Compared
Swinging bowl
SPP – Control System
SPP – Containment Buck Valve/ Hicoflex technology for loading and discharging Isolated boxes for higher toxic compounds Contained sampling valve Oxygen sensor provided to ensure the level is below the explosion limits Oxygen replaced by Nitrogen gas in a automatic cycle
Buck Valve Hicoflex Valve Oxygen Sensor Isolated Box
Cleaning system (1)
• Through the wall design, small area to clean
• Numerous improvements to avoid gaps and dead space inside the bowl in order to make WIP/CIP easier
• No permanent cabling and piping around the machine
Cleaning system (2)
• What is ‘Single Pot Processor’?• RMG Vs SPP• Design features and Benefits• Application• Working Principle • Case Study• Post-approval changes
Case Study : Effervescent Product (1)
Ingredient Qty/batch (in Kg)Active 45.00Anhydrous Acid 115.50Alkali 98.30Binder 4.50Sweetner 0.45Purified water 1.60
C6H8O7 + 3 NaHCO3 Na3C6H5O7 + 3 H2O + 3 CO2 + Heat Citric acid Sodium bicarbonate Sodium Citrate
Predetermined Targets: Control the reaction Max yield Efficient drying
Case Study : Effervescent Product (2)
33
Case Study : Effervescent Product (3)
Is it ‘scalable process’?
25L 600L/1200L
• What is ‘Single Pot Processor’?• RMG Vs SPP• Design features and Benefits• Application• Working Principle • Case Study• Post-approval changes
Post approval changes (SUPAC): Manufacturing Equipment Changes
Level Definition Existing process Changed process
Filing Documentation
I 1. Change from non automated or non mechanical equipment to automated or mechanical equipment to move ingredients and
2. Change to alternative equipment of the same design and operating principles of the same or of a different capacity.
Granulation: RMGDrying: Tray dryer
Granulation: SPPDrying: SPP
Annual report
II Change in equipment to a different design and different operating principles.
Granulation: RMGDrying: FBE
Granulation: SPPDrying: SPP
Prior approval supplement with justification for change
Ref: SUPAC-IR: Immediate Release Solid Oral Dosage Forms, November 1995 SUPAC-MR: Modified Release Solid Oral Dosage Forms, September 1997
http://www.gea-ps.com/npsportal/cmsdoc.nsf/WebDoc/webb8eta36
Thanks for attention !
Any Question ?
Girish S SonarCipla Ltd.,Pharma R&DVikhroli (W), Mumbai