PRACTICAL PROTOCOL

Roll no- 23

Pages -

Aim :- To prepare validation protocol of a mixer and perform its validation of mixing
performance with respect to low dose drug.
Purpose :1) Reduction of quality cost.
2) Process validation.
3) Assurance of quality and safety.
References :1) Lackman. L , Liberman The theory and practice of industrial pharmacy ,
Varghese publication page no. 1-20.
2) Potdar A.M Pharmaceutical Quality Assurance , 2007 Nirali publication
page no. 8.42.
3) Haider S.I Validation standard operating procedure ,second edition page no
353-355.
Requirements :1) ChemicalsSr. No
Name of Chemical
1
Calcium carbonate (CaCo3)
2
Potassium paramagnet (KmNo4)
3
Crystal violet

2) Glasswares Sr . No
Name Of Glassware
1
Vials
2
Stirrer
3
Beaker
4
Volumetric flask
5
Volumetric flask

Quantity Taken
100gm
1gm

Capacity
10 ml
----100ml
100ml
10ml

Quantity
10
01
02
01
05

3) Instruments
Sr. No Name of Instrument
1
Colourimeter
2
Double cone blender

Model
Photocal -652

Make
Equip-tronics

Theory : Validation :A documented programmed which provides a high degree of assurance that specific
processes will consistency produce a product meeting its predetermined specification
and quality attributes.
Importance of validation
1) Reduction of quality cost.
2) Process validation.
3) Assurance of quality and safety.
Mixing :A process that tends to result in a randomization of dissimilar particles , within a
system or to put together in one mass or assemblage with more or less through
diffusion of the constituent elements among one another.
Mechanisms of mixing
1) Diffusion :- random action of individual particles in the mixer.
2) Convection :- transfer of adjacent particles groups in the mixture .
3) Shear :- configuration change through slip planes.
A) Equipments used for mixing :- (powder)
Tumbler mixer
Double cone blender
Agitated powder mixer
Air mixer
B) Equipments used for mixing :- (liquids)
Propeller mixer
Turbine mixer
Paddle mixer
C) Equipments used for mixing :- (semisolid)
Triple roller mill
Agitator mixer
Planetary mixer

 Double cone blender :It is developed in an attempt to overcome some of the shortcoming of rotating
mixer. The mixing of powder in double cone blender is due to tumbling and
shearing action with blade . The efficiency of blender depends mainly on speed of
rotation .
The rate of rotation should be optimum which depends upon the size and shape of
tumbler as well as nature of material. The common range is 30-100 rpm.
The material to be blended is loaded approximately 50-60% of the total capacity
of blender . As the blender rotates the material undergoes tumbling motion and mixes
the material.
The double cone blender is an efficient design for mixing powder of difference
densities and is used mainly for small quantity of powder.

Procedure:- ( Calibration curve of crystal violet )

1) Dissolve 10mg of crystal violet in 1 M H2SO4 to produce 100ml . Heat the
solution for 5-10min (until boil).
2) Cool the beaker solution at room temp. and filter with the help of cotton plug
in funnel.
3) Prepare dilution from the above stock solution 100mg/ml to produce conc.
10 g/ml and also prepare the 2,4,6,8,10 g/ml using 1M H2SO4.
4) Measure the absorbance on colorimeter.

Observation Table:Concentration
2
4
6
8
10

Absorbance

Procedure :1) Weigh 100gm of CaCo3 and 1gm of crystal violet and pass them through
sieve no 60.
2) Load those powder in double cone blender and note down the rpm of double
cone blender.

3) Take the samples from top, middle, and bottom. Dissolve them in 10ml 1M
H2SO4 in vials.
4) Filter it and measure the absorbance using colorimeter.
5) Determine the conc. Using calibration curve and calculate the std. deviation
of each five interval, predict the optimum time of mixing.

Observation table ( I ) :Sr. no

1
2
3
4
5
6

Time
5
10
15
20
25
30

Top

Middle

Bottom

Observation table ( II ) :Sr. no Time

1
2
3
4
5
6

Conc. From graph X dil. Factor (100)

Top
Middle
Bottom

mean

Standard
deviation

5
10
15
20
25
30

Result :Mixing of crystal violet with CaCO3 was carried out and validation parameter of
mixing were as below
Sr. no Parameter
1
2
3

i)
CaCO3
ii)
Crystal violet
Optimum mixing time
Conc. of optimum time

Mixing method ( double

cone blender)
100gm
1gm

SOP NO -123

Effective date- dd/mm/yy

Approved by- Mr.abc

Title

Blender ( double cone )

Author -

Name / title / department

Sign date

Checked by -

Name / title / department

Sign date

Approved by -

Name / title / department

Sign date

Revisions :Sr. no

Section

Pages

Initials / date

SOP NO -124

Effective date- dd/mm/yy

Approved by- Mr.abc

Subject :- Blender ( double cone )

Purpose:To describe the procedure for validation of blender to ensure that it meets
installation, operational, and performance qualification requirements.
Responsibility :It is the responsibility of the production manager and technical services manager to
follow the procedure. The quality assurance manager is responsible for SOP
compliance.
Procedure :1. Verify approved purchase order
2. Verify invoice
3. Check manufacturer and supplier
4. Verify model number and serial number
5. Check for any physical damage
6. Confirm location and installation requirements per recommendation of
manufacturer.
7. Verify that the required utilities are available
8. Installation shall be conducted per instruction provided in the manual.
9. Ensure that all relevant documentation is received
i)
ii)
iii)
iv)
v)

User manual
Maintenance manual
List of change parts
Electrical drawing
Mechanical drawing