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

Quantity Taken 100gm 1gm

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

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 5 10 15 20 25 30 Conc. From graph X dil. Factor (100) Top Middle Bottom Standard deviation

mean

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 ) Name / title / department Sign date Name / title / department Sign date Name / title / department Sign date

Author -

Checked by -

Approved by -

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