High speed

mixer/granulator
 Outline
1.
2.
3.

4.
5.

6.
7.

8. GMP/PICs
9.
 1.



wet granulation

-
-
-

- 1-3
- 3-6

http://www.pms-group.net/product_pt_highspeedmixer.html
1.

http://www.comasa-sa.com/wp-content/uploads/2014/11/mic_graf_2.jpg
 1.


Vertical high speed
mixer/granulator

Vertical high speed

mixer/granulator

Horizontal high speed

mixer/granulator
Briens, Lauren, and Ryan Logan. "The Effect Of The Chopper On Granules From Wet High-Shear
Granulation Using A PMA-1 Granulator". AAPS PharmSciTech 12.4 (2011): 1358-1365.
 1.



High speed

mixer/granulator
Powder mixing

Binder addition or addition of granulating liquid

Wetting of powder and nucleation

Growth of granules and densification of the

powder
 1.

http://www.comasa-sa.com/producto/mezclador-granulador-de-alto-rendimiento/?lang=en
 High

speed mixer granulator
1.
2.
3. binder
4. - conical mixing

bowl
- impeller
- binder
- chopper
-
 High speed

mixer/granulator

https://youtu.be/p_QhQu9rido
 2.
OPEN THE CUTTING CHAMBER


jackscrew
rotor
jackscrew hopper

jackscrew hopper
cutting chamber
hopper
OPEN THECUTTING
pivot
CHAMBER center INTERLOCK
interlock actuator screw
interlock actuator screw

interlock electrical control

circuit

 2.
RELEASE THE CUTTING CHAMBER FASTENERS
hold-down clamps


hold-down clamps
cutting chamber housing
CLOSE THE CUTTING CHAMBER
jackscrew hopper
mating cutting
chamber
rotor bank out the
plunger
jackscrew hopper
 2.
FASTEN THE CUTTING CHAMBER

hold-down clamps
chamber


housing

CLOSE THE CUTTING CHAMBER SAFETY

INTERLOCK

safety interlock
actuator screw
housing
screw


interlock

motor
 2.
SCREEN CONDITION
screen
screen elongation
front-to-back


screen access information


OPEN THE SCREEN CRADLE INTERLOCK
Interlock actuator screw
chute
actuator screw

interlock

motor
 2.
REMOVE THE DISCHARGE




LOWER THE SCREEN CRADLE
wedge
screen


Gas springs cradle
RETRACT THE SCREEN CRADLE RETAINERS
screen
wedges rods
retaining knobs

mounting plates

bar handle screens

 2.
REMOVE THE SCREEN
Screen
screen
screen

screen
screen
screen rotor knives
granulator
RAISE
THE
SCREEN
screen
CRADLE
screens




CLOSE THE SCREEN CRADLE RETAINERS
screen
 2.
CLOSE THE SCREEN CRADLE INTERLOCK

interlock screw

interlock actuator screw
housing


INFEED
FLAP interlock switch
CONDITION


infeed


flaps hopper inlet

tears in the flap



flaps:


flap / mounting hardware
 2.
KNIFE SCREW TORQUE

knife hold-down screws rotor
bed knives
BEWARE KNIVES
OF ROTOR

rotor knives screen

KNIFE
BED SHARPENING




bed knife


bed knives
rotor knives rotor knives
Bed knives
fasteners

rotor knife

 2.
LUBRICATION
Motor lubrication:
motor
Rotor bearings


Grease
fittings


bearing housings

750

grease 84 lithium-based grease
NLGI grade #1.
BELT TENSION

belt tension

2
belt tension


3.



 3.



Validation Protocol of High Sheer
granulator
1. Introduction
1. FAT
2. installation qualification (IQ)
3. Operational Qualification (OQ)
4. performance Qualification (PQ)

4. Constraints (
)
 3.



1. Introduction
(URS)
-
-

-
- (Validation)
 3.



I. FAT
Test Criteria
Design Verification Check List
Deficiency & Corrective Action report
Pre installation requirements
Final report
3.

2. INSTALLATION
QUALIFICATION (IQ)
 3.



o installation qualification (IQ)

2.1
(Installation

Procedures)
commissioning (&
)




(QA)



 3.



o installation qualification (IQ)
2.2 Acceptance criteria


supplier (Purchase
Order)



 3.



o installation qualification (IQ)
2.3 Revalidation Criteria














3.

3. OPERATION QUALIFICATION
 3.



o Operational Qualification (OQ)
3.1 (Training Record )
(Qualification)


OQ
3.2 Capacity
_______ Batch per day
_________kg/hr (/day)
Maximum Volume/Capacity
required ________
Minimum Volume/Capacity
 3.
o
Operational Qualification (OQ)

3.3 Process requirements
Range ( ,
)

(
)

Binder flow rate

product limitations ( pH
)
particle size
 3.



o Operational Qualification (OQ)
3.4 process control

(Pilot
scale testing)

Solution Flowrate (____ LPM within ___LPM

range, accuracy +/-)
Impeller Speed (___ to ____ RPM, accuracy
+/-)
Chopper Speed (____ to _____ RPM, accuracy
3.



3.5 Function

function
:Operational
Requirements

 3.



o Operational Qualification (OQ) : Function
3.5.1 (Hand-Wash)
3.5.2 Cleaning and Sanitization
3.7.1Cleaning in Place (CIP)
3.5.3 Power Failure /recovery

safe state

3.5.4 Emergency Stop
E-stop mechanism
3.5.5 Alarms /Alerts
critical alarm
3.



alarm/alerts
granulator
 3.



o Operational Qualification (OQ)
3.6 Environments
Layout

granulator ,


granulator

Vertical clearance granulator

12
3.

4. PERFORMANCE
QUALIFICATION (PQ)
 3.



o Performance Qualification (PQ)
1.critical process control variables
2. Test program acceptance criteria
3. analysis procedure
4. Acceptance Criteria
5. final report
 3.



o Performance Qualification (PQ)
1.critical process control variables

variables

 3.



o Performance Qualification (PQ)
2. Test program acceptance criteria
- Maximum , Minimum Intermediate
mixing interval

granulator maxi
-
control process parameter
 3.



o Performance Qualification (PQ)
3. analysis procedure
sample

HPLC

granulator HPMC
ose Monohydrate
slow speed
granule

granule ( 5 2 granule

granule LOD wet mass granulatio
 3.



o Performance Qualification (PQ)
4. Acceptance Criteria
granulator granule
-

- (Ampere)
granu
- granulator
 3.



o Performance Qualification (PQ)
 3.



o Performance Qualification (PQ)
5. final report summary
3.

5. CONSTRAINTS ()
 3.



o Constraints

5.1 Mechanical
5.2 Milestones and timeline
5.3 Equipment Constraints
5.4 Availibility
5.5 Procedural Constraints
 3.



o Constraint

5.1 Mechanical
Sanitary connectors
Gas purge seal
FDA approved seals and gaskets
 3.



o Constraint

5.2 Milestones and timeline

Supplier proposal ______

Supplier Functional and Design
Specifications ______


 3.



o Constraint
5.3 Equipment Constraints
1. HVAC Equipment Constraints
Indoor Temperature: ___ to ___C
Outdoor Temperature: Minimum: ___ C
Maximum: ___C

2. Climatic Conditions
Winter dry bulb _____C.
Winter wet bulb _____C.
Summer dry bulb _____C.
 3.



o Constraint

5.4 Availability
granulator ______ /
______

/
granulator


preventative maintainance ________/

 3.



o Constraint
5.5 Procedural constraints
Piping welds
welding ASME
Metals (316L Stainless Steel,
316 Stainless Steel, 304 Stainless Steel, etc.)
Noise level constraint
Labeling
wiring

label
4.
(Wet granulation)
- binder
(wet mass)

-
-

-
Content uniformity
-
-
-

-
-
4.


-
-

-
-
-

-
-
- 40c

4.

parameter


- Impeller speed
-

- Chopper speed
-
- critical parameter
- 1-3
- (Massing time)
- 3-6
- >20

4.


-
-


-

- ( )
-
-
- (
)
 5.

Chopper
Wet high-shear granulation
PMA-1 granulator


 5.

impeller

5.


300 rpm (Bumpy)

700 rpm (Roping)

1100 1500 rpm

(Roping)
5.


5.


5.


 5.

http://www.comasa-sa.com/producto/mezclador-granulador-de-
 6.

Intragranular Ingredient %
ingredients w/w
API Active 25.0
Lactose, Diluent 40.0
Monohydrate, NF
Hydroxypropyl Binder 4.0
cellulose, NF
Sodium Starch Disintegra 5.0
 6.



1. Impeller
1-3
liquid binder Impeller
2.

3. wet mass Impeller
Chopper 3-6
( /end point

2-3 )
4.
5. /
 6.




- Lodige (horizontal bowl)
- Diosna (verticle bowl)
- Garl (changeble bowl)

Diosna








 7.



Pharmaceuticals and Medical Supply (PMS)

PMS mixer

- dry mixing 1-3
- wet granulation 3-6

- stanless steel SUS 316
- conical mixing bowl
raw material

7.

High speed mixer/granulator

PMS
 7.

Changzhou Hywell Machinery

GHL

- dry mixing 2
- wet granulation 1-4

- vertical mixing bowl


7.

High speed granulator

GHL
 8. GMP/PICs




-
-
-
-

-
SOP
-




 8. GMP/PICs
-

-
-

- SOP
-

-

- critical parameter

- Carr index

- parameter
 9.
High speed mixer/granulator


-




-
Chopper-Impeller
Binder

-


- Software Hardware

 9.
validation

-
- v-shape model

-

-