Mechanical Calibration - Ministry of Public...

Bureau of Drug and Narcotic

Mechanical Calibration

Temperature control

Calibrated thermometer

37 + 0.5 ˚C

Distance between the inside bottom of the vessel

and the bottom of the basket or paddle is maintained

at 25 + 2 mm during the test use a spacing gauge or ball

USP Performance Verification Test (PVT)


• Provide experimental proof that the dissolution test

assembly is suitable for dissolution testing

• Confirms the acceptable operation of the equipment

• The result must conform to range given in the

certificate for the specification lot of reference material.

• PVT is a prerequisite for a proper performance

qualification of the dissolution assembly.


Reference Standards for PVT

Always use the current lot

Follow the instructions on the label concerning storage and handling


Prednisone USP RS

Check

• Current lot • Validity


Prednisone USP RS

Certificate

Label


Prednisone Tablets RS

Check

• Current lot • Validity



Certificate & Label



Store in a dry place.

Store at controlled room temperature Not exceeding 25 ºC



Certificate



Dissolution medium:

- Water: DI

- Preparing the medium “Deaeration”

USP Deaeration Technique - Heat water

while stirring gently

to about 41 – 45 C

-Filter under vacuum

through 0.45 um

porosity filter into

a filtering flask with

a stirring device

-Seal the flask,

continue to apply vacuum

while stirring for 5 min

-Vacuum should be

< 100 mbar

-Temperature of medium not fall below 37 C



Procedure:

499 g of deaerated water

(500 ml)

37 C

each apparatus at 50-rpm

30 minutes

uv at 242 nm

alcohol < 5% of total volume of standard solution (If used)



• Single - Stage Test • Two – Stage Test

Result:

• GM • %CV



Futility Factor


• Deaerated water

• Weight and carefully introduce dissolution medium

to the vessel 499 ml (500 g)

• Allow media in each vessel to reach 37 + 0.5 ºC

and use immediately.

• Always handle tablets with

- gloves (not cotton)

- forceps or tweezers which will not scratch or

damage the surface of the tablets

• Examine all 6 tablets, do not use chipped, cracked or

Capped tablets

• No need to weigh Tablets RS beforehand

(Weight is for information and investigation purposes)

Steps for PVT


• Prepare to drop tablets.

• For Apparatus 2 Paddle

- Drop tablets into non-rotating apparatus

- Tablets must settle to the bottom of the vessel

before rotation of the shaft begins.

• Record time

• Samples should remain at the bottom center of the vessel

• Visually inspect and record any unusual observations

• Withdraw sample at 30 minutes + 36 seconds (+2%)

and filter immediately

• Measure the amount of prednisone dissolved at

242 nm in comparison with a solution of known

concentration of USP Prednisone RS

• Calculation and conclusion

Steps for PVT


www.usp.org

Search for

PVT calculation tool

Select “Begin using the tool”

PVT Calculation Toolkit
















Data of 6 vessels

with 3 decimals



Submit data



Result & Report


Recommendations for PVT


- Designated vessels and shaft for each position

in dissolution instrument

- Rigorous mechanical calibration

- Proper deaeration of dissolution medium

- Test should be started as soon as possible

after media deaeration

- Filter samples immediately after withdrawing samples from each vessel



Tablet should be stored in original container,

according to description on label

Remove tablets from package immediately

prior to testing

Do not put tablet RS next to water bath

while waiting for bath to equilibrate

Avoid exposure to excess humidity

Prednisone Tablets RS will give low results

Do not dry Prednisone Tablets RS in an oven No need to weigh Tablets RS beforehand

Sources of factors influence dissolution


• Laboratory environment

• Medium

• Filtration

•Quantitative method

Note: instrument and analyst are qualified

Vibration


USP specification:

“ No part of the assembly, including the environment

in which the assembly is placed, contributes significant

motion, agitation, or vibration beyond that due to the

smoothly rotating stirring element.”

Source of vibration:

* Apparatus

- Tension or dirt on the drive chain or belt

- Worn parts

- Alignment of belt guide plates

- Surging of individual spindles

- Turbulence in the water bath

Laboratory Environment


Has anything changed in the lab environment?

- New equipment added to the immediate area

- Other changes (e.g. construction)

Vibration transfer

- Be careful how many testers put on the same bench

- Is bench suitable?

- What else is on the bench or nearby?

shaker, mixer, centrifuge

- consider use of vibration damping pads

Medium


Using deaerated media

- use immediately after deaeration

- transfer media carefully to minimize re-aeration

of the media

Air bubbles can attach to particles

- decreasing dissolution by reducing surface area

- Increasing dissolution by

# lifting and moving particles

# bubble clogging the meshes of the basket

and retaining particles in a zone of higher

shear stress compare to the vessel bottom

Filtration


Removal of undissolved particles

i.e. drug or excipients in the sample solution

Filtration should occur concomitantly with or

immediately after sampling

Unfiltered sample can continue drug dissolution

before filtration

Use Individual, clean syringes and filters

for sampling each vessel, each time

Filtration


Precautions:

- Prewetting may be necessary

- Adsorption of the drug onto the filter has to be

evaluated

- Chemical compatibility and extractable impurities

should be considered by the selection of

the proper (inert) filter material

- Important to perform filter check/validation

*** PVDF membrane filter is recommended for PVT

When to perform PVT ?


Installation of new apparatus

Movement or relocation of apparatus

Equipment maintenance

- Adjustment of drive mechanism

- Replacement of drive belt

- Replacement of circulator

- Replacement of vessels, baskets, paddle etc

Routine test schedule

If only one apparatus, basket or paddle, is used,

then only that apparatus needs to be tested.


Bangkok Chemart Ltd., Part.

www.bangkokchemart.com

[email protected]

02 720 9557 - 9

Where to buy USP RS ?


Date post:	17-Mar-2020
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