single pot processor

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