Chemical Calibration Protocol for Dissolution Apparatus

INSTRUMENT	Dissolution Test Apparatus
Refer SOP No.	DQC-SOP-0531
Model No.	EDT 14 Lx
Instrument Code No.
Make	ELECTROLAB
Frequency	Half Yearly “- 15 Days”
Date of Calibration
Next Due Date

1. DISSOLUTION PERFORMANCE VERIFICATION TEST (PVT)

AS PER USP < 711 > & < 724 >

USP DISSOLUTION CALIBRATOR, DISINTEGRATING TYPE TABLET

USP Prednisone Tablets RS, Label Amount: 10 mg

Lot No. of Prednisone USP RS used ______________ Potency ___________

Lot No. of Prednisone Tablets USP used ____________

Balance ID:_________________

Valid up to: ___________

Dissolution Apparatus ID:_________________

Valid up to: ___________

UV-Visible spectrophotometer ID:_________________

Valid up to: ___________

Note:

The photocopy of the certificate of USP Prednisone Tablets is to be attached to verify the Lot number and limit.

Please conduct the calibration only after verifying the current USP certificate for the US Calibrator Tablets and the USP RS with the current USP catalogue.

Visual inspection of paddle/basket and jars is required before starting calibration.

If required make necessary changes after authorization of Head Quality.

Dissolution Medium:

Heat an adequate amount of water while stirring gently to approximately______ 45°C. Filter with the aid of vacuum through __________ 0.45 micron porosity membrane filter into a suitable filtering flask under vigorous stirring.

Seal the flask and continue to apply vacuum while stirring for an additional five minutes. The temperature of the dissolution medium should not fall below 37⁰C prior to the initiation of the test.

Standard preparation:

Prepare two independent standard preparations, a working standard and a control standard. Prepare the standards within 24 hours of use.

Working Standard preparation:

Pippete ID: _______________________

Weigh and transfer accurately about ________ 25.0 mg (22.5mg-27.5mg) of Prednisone USP RS into a _______25 ml volumetric flask. Dissolve in approximately ______10 mL _____________ (alcohol) with sonication. After cooling to ambient temperature, dilute to volume with ____________ (alcohol). Pipette out ______5 ml of this to _________500 ml volumetric flask. Dilute up to the mark with ____________________purified water and mix.

Control Standard preparation:

Pippete ID: _______________________]

Analysis Procedure:

Perform UV measurements at the wavelength of maximum absorption, for prednisone use 242 nm.

Use the dissolution medium, water as a blank.

First measure the five absorbance of prednisone from Control standard solution.

Then measure the five absorbance of prednisone from working standard solution.
Then measure the absorbance of prednisone from each filtered sample aliquots.
Bracket the absorbance of samples by taking one absorbance from same Working Standard Solution.

The maximum absorbance wavelength for both standard and sample preparation should be at 242nm.

The %RSD of the first five standards should be NMT 2.0% as well as bracketing standard.
Calculate the % dissolved by given formula against absorbance of working standard.

Single – Stage test

After transforming the % dissolved results to the natural log scale, determine the mean and variance. Convert the results to GM and %CV, and compare to the Single – Stage test acceptable ranges as per certificate. The GM must not fall outside the limits, and the %CV must not be greater than the limit. For calculation of GM and %CV, fully protected Microsoft Excel calculation sheet shall be used.

If the results satisfy both acceptance criteria, the assembly has passed the PVT

Remark: Calculation can be verified using calculation tool for PVT on www.usp.org website.

Formula for GM & % CV (expressed as Microsoft Excel worksheet functions)

x₁, x_2, …, x_nin natural log scale : Lnx₁, Lnx₂, …, Lnx_n

Single – Stage Test

Sample preparation and procedure:

For USP Apparatus 1 (Basket)

Add ________ 500ml of deaerated water as a dissolution medium to each vessel and allow them to equilibrate to ________ 37.0 ± 0.5°C. Measure the temperature of the medium in each vessel. The medium is equilibrate when the temperature has reached the set point and does not change between two successive readings made no less than three minutes apart (not more than 0.2°C change for each vessel).

Insert the shaft of basket.

Check the integrity of the tablets. Weigh and place one tablet to each of the fourteen dry baskets and attach the baskets to the shaft. Lower the position of the basket shafts to start the operation.

Immediately operate the apparatus with the conditions specified in the table below for ________ 30 minutes.

At the end of completion of time program (30min) and with rotation continuing, withdraw about 30 ml samples aliquot from zone midway of each vessel.

Filter each sample solution immediately through __________ 0.45-micron PVDF or equivalent filter; discarding first 5 ml of the filtrate to avoid adsorption of sample by membrane. A separate unused filter, cannula and clean syringe should be used for each vessel.

The sample collection and filtration of all fourteen aliquots must be within ± 36 seconds.

Cool the filtered dissolution samples to ambient temperature prior to UV analysis.

For USP Apparatus 2 (Paddle)

Add ________ 500ml of deaerated water as a dissolution medium to each vessel and allow them to equilibrate to ________ 37.0 ± 0.5°C. Measure the temperature of the medium in each vessel. The medium is equilibrate when the temperature has reached the set point and does not change between two successive readings made no less than three minutes apart (not more than 0.2°C change for each vessel).

Insert the paddles.

Check the integrity of the tablets. Weigh and place one tablet to each of the fourteen jar containing 500ml of deaerated dissolution medium.

Immediately operate the apparatus with the conditions specified in the table below for ________ 30 minutes.

At the end of completion of time program (30min) and with rotation continuing, withdraw about 30 ml samples aliquot from zone midway of each vessel.

Filter each sample solution through __________0.45-micron PVDF filter or equivalent; discarding first few ml of the filtrate to avoid adsorption of sample by membrane. A separate unused filter, cannula and clean syringe should be used for each vessel.

The sample collection and filtration of all fourteen aliquots must be within ± 36 seconds.

Cool the filtered dissolution samples to ambient temperature prior to UV analysis.

Dissolution Medium	Deaerated water	Observation
Dissolution Medium Volume	500 ml
Apparatus	USP Type I
RPM	50 RPM
Temperature	37.0°C ± 0.5°C
Start Temperature	–
End Temperature	–
Start Time	–
End Time	–
Sampling time points	30 min
Filter used	0.45 µ PVDF filters
Volume withdrawn	30 ml

Dissolution Condition (USP Apparatus 2) :

Dissolution Medium	Deaerated water	Observation
Dissolution Medium Volume	500 ml
Apparatus	USP Type I
RPM	50 RPM
Temperature	37.0°C ± 0.5°C
Start Temperature	–
End Temperature	–
Start Time	–
End Time	–
Sampling time points	30 min
Filter used	0.45 µ PVDF filters
Volume withdrawn	30 ml

Space to stick the weight printouts:

Observations:

Absorbance of Control Standard:

Absorbance of Working Standard:

For USP Apparatus 1 :
Standard-1 :__________
Standard-2 :__________
Standard-3 :__________
Standard-4 :__________
Standard-5 :__________
Mean of Standards (1 to 5 ) :__________
RSD of Standards (1 to 5 ) :__________
Standard-6 :__________
Mean of Standards (1 to 6 ) :__________
RSD of Standards (1 to 6 ) :__________

For USP Apparatus 2 :
Standard-1 :__________
Standard-2 :__________
Standard-3 :__________
Standard-4 :__________
Standard-5 :__________
Mean of Standards (1 to 5 ) :__________
RSD of Standards (1 to 5 ) :__________
Standard-6 :__________
Mean of Standards (1 to 6 ) :__________
RSD of Standards (1 to 6 ) :__________

Absorbance of Working Standard:

Absorbance of Control Standard:

Difference between absorbance of Working standard and Control standard (%): for

USP Apparatus 1:__________, for USP Apparatus 2:__________ (Limit- NMT 1%)

Calculation: (Limit: 99.0% to 101.0%)

= (Absorbance of Control std / Absorbance of working std) x (Weight of working std./ Weight of control std.) x 100

Calculations:

(For USP Apparatus 1):

Calculate the % Dissolved of Prednisone after 30 min by formula given below,

% Dissolved at 30min =	Sample Absorbance x	Standard weight x	5ml x	Media Volume x	Potency x 100
	Working Standard Absorbance	25ml	500ml	Label Claim	100

(For USP Apparatus 2) :

Calculate the % Dissolved of Prednisone after 30 min by formula given below,

% Dissolved at 30min =	Sample Absorbance x	Standard weight x	5ml x	Media Volume x	Potency x 100
	Working Standard Absorbance	025ml	500ml	Label Claim	100

Results:

Sr. No.	Apparatus 1 (at 50 RPM) Absorbance	Apparatus 1 (at 50 RPM) %Dissolved	Apparatus 1 (at 50 RPM) GM	Apparatus 1 (at 50 RPM) % CV	Apparatus 2 (at 50 RPM) Absorbance	Apparatus 2 (at 50 RPM) %Dissolved	Apparatus 2 (at 50 RPM) GM	Apparatus 2 (at 50 RPM) % CV
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.

RSD	%	%
Min	%	%
Max	%	%

Mean	%	%
Limit	As per certificate	As per certificate

Done by:

Checked by:

Remark: The instrument is calibrated & qualified/ Out of calibration & not qualified for use.

Calibration: Scheduled / Not scheduled

Calibrated By

Signature/Date

Checked By

Signature/Date

Approved By

Signature/ Date