Rapid Mixer Granulator

The Rapid Mixer Granulator is a multi-purpose processor equally suitable for high speed dispersion of dry powders, aqueous or solvent granulations, and effervescent products and melt pelletization.

Blending and wet massing is accomplished by high mechanical agitation by an impeller and chopper. Mixing, densification, and agglomeration of wetted materials are achieved through shearing and compaction forces exerted by the impeller.

The primary function of chopper is to cuts lumps into smaller fragments and aids the bowl or sprayed onto the powder to achieve a more homogeneous liquid distribution.

VARIABLES :PROCESS VARIABLES :• Impeller rotation speed • Chopper rotation speed • Liquid flow rate • Load of the mixer • Liquid addition method • Wet-massing time (subsequent of liquid addition

time)

PRODUCT VARIABLES :Amount of liquid binder Characteristics of liquid binder

Surface tension Viscosity Adhesiveness

Characteristics of the feed materials Particle size and size distribution Particle specific surface area Solubility in the liquid binder Wettability

Packing properties

Mixing Bowl

VALIDATION

Validation mainly includes:

Installation qualification (IQ)Operational qualification (OQ)Performance qualification (PQ)

Equipment installation site:

Equipment is installed in the location as specified. Equipment is installed as per the supplier

instruction. Packing debris are removed As Built drawing is prepared and verified

Installation Qualification Procedure :

Test Equipment:

Spirit level For checking leveling of equipment

Multi meter For checking electrical supply

Molybdenum test kit To confirm material of construction of the Stainless Steel 316 quality

Protocol Approval :

• Objective• Critical Process control variables• Test Program and Acceptance criteria• Sampling points• Qualification results• Final Report• Report Approval

OBJECTIVE: To verify that the utility, environment, equipment and

support system produces the required output by integrating procedures, personnel, systems and materials.

To verify the performance of the Rapid Mixer Granulator - (RMG) for maximum occupancy capacity of 80%, minimum occupancy capacity 30% and intermediate occupancy capacity 55% based on 0.5 w/v bulk density, by adding lactose and Ponceau 4R supra of 1% in RMG and estimate the colour content uniformity in blend at different time intervals.

To verify the performance of Rapid Mixer Granulator - (RMG) for a specific size by granulating lactose with HPMC solution and observe amperage and granules consistency at different time intervals.

S.S.NoNo

Operation stageOperation stage Control variablesControl variables Measured parametersMeasured parameters

11 Dry MixingDry Mixing Load sizeLoad sizeMixing timeMixing time

Content uniformity Content uniformity

22 Wet MixingWet Mixing Impeller speed, chopper speedImpeller speed, chopper speedGranulation timeGranulation timeAmount of granulation fluidAmount of granulation fluid

Water content/LODWater content/LODGranules appearance Granules appearance Amperage /torqueAmperage /torque

CRITICAL PROCESS CONTROL VARIABLES:

Process control variables of dry mixing, wet mixing operations and measured parameters are identified as follows

Performance of Rapid Mixer Granulator shall be verified at different control variables such as load size, and mixing time.

Test program and acceptance criteria:

Objective: To verify the performance of the Rapid Mixer

Granulator (150 lts) for maximum, minimum and intermediate occupancy capacities and at different mixing intervals.

Granulating performance for maximum capacity at different control process parameters

Procedure (dry mixing): Add Lactose and Ponceau 4R supra (sifted through 40#) into

Rapid Mixer Granulator and mix the material for a period of 20 minutes.

Collect samples in duplicate each equivalent to 2gms using unit dose sampler from 5 different locations (shown in diagram and transfer in to individual labeled glass vials.

Collect the samples at different time intervals of 5, 10, 15 and 20 minutes

Submit the samples for analysis of colour content. Analyse the sample as per the analytical procedure. Record the results in qualification result data sheets.

Sampling points in rapid mixer granulator

4

1 2

3

5

1.Top Left2.Top Right3.Middle4.Bottom Front5.Bottom Rear

Analysis procedure:Sample preparation: Weigh sample equivalent to 10 mg of Ponceau 4 R supra and

transfer into 200ml volumetric flask add 100ml of water and sonicate for 5 minutes to dissolve completely, then dilute up to the mark with water. Filter the solution and dilute 10ml of filtrate to 50 ml with water.

Procedure: Measure the absorbance at 506nm using UV spectrophotometer.

Calculate the % of colour content using following formula.Acceptance Criteria:Colour content (assay) of all samples should be in between 90 -

110 %The average of assay results at each interval should be in between

95 -105 %Content uniformity of 5 samples RSD should not be more than 4%

Procedure (wet mixing): Add specified quantity of HPMC in purified water and dissolve

completely.Take specified quantity of Lactose monohydrate (sifted through

#40) into RMG, add above HPMC solution and granulate at slow speed till the required consistent granules formed.

Record the time of granulation at different intervals (after 5minutes and every after 2minutes till granulation completed) during granulation till appearance of granules the required consistent granules formed.

Record appearance of granules and LOD of wet mass after granulation completed.

Acceptance Criteria:RMG should be capable of producing desired granules.

Amperage reading should be increased as granulation time progresses.

Functioning of RMG should be in normal, safe and secure condition.

S.S.NoNo

Material nameMaterial nameSpecifiSpecificationcation

Quantity Quantity specifispecifi

eded(in kg)(in kg)

Quantity Quantity dispensedispense

dd(in kg)(in kg)

A.R NoA.R No

Dispensed Dispensed by by

storesstoresSign&datSign&dat

ee

Checked Checked by by QAQA

Sign&daSign&datete

11 LactoseLactose

22 Ponceau 4 R supraPonceau 4 R supra

Process parametersProcess parameters

Specification Specification Actual Actual observationobservation

Done by Done by ProductProduct

ionion

Checked by Checked by QAQA

Dry mixing Dry mixing

Mixing timeMixing time 20 minutes20 minutes

Impeller Speed Impeller Speed SlowSlow

Chopper Speed Chopper Speed --

Operational details:

LOCATIOLOCATIONN

Colour content in %Colour content in %

After 5 minutesAfter 5 minutes After 10 minutesAfter 10 minutes After 15 minutesAfter 15 minutes After 20 minutesAfter 20 minutes

11

22

33

44

55

MeanMean

RSDRSD

Sample results:

Process parametersProcess parametersSpecification Specification

Actual Actual observatioobservatio

nn

Done by Done by ProductiProducti

onon

Checked by Checked by QAQA

Dissolve HPMC in Dissolve HPMC in purified water purified water

Qty of water takenQty of water taken

Add extra quantity of Add extra quantity of water if required water if required ________kgs________kgs

--

Mixing timeMixing time Approx.15 minutesApprox.15 minutes

Impeller SlowImpeller Slow --

Chopper SlowChopper Slow --

Impeller fastImpeller fast --

Chopper fastChopper fast --

Granulation details:

Granulation Time:

Appearance of granules:

LOD of wet granules:

RSDRSD

MeanMean

Batch size: LowBatch size: Low

RSDRSD

MeanMean

Batch size: MediumBatch size: Medium

RSDRSD

MeanMean

Batch size: HighBatch size: High

After 20 minutesAfter 20 minutesAfter 15 minutesAfter 15 minutesAfter 10 minutesAfter 10 minutesAfter 5 minutesAfter 5 minutes

Colour content in %Colour content in %

Granulation Granulation timetime

LOD of wet LOD of wet granulesgranules

Wet mixing