Dissolution calibration is one of the important procedure to ensure the dissolution testing machine is working properly or not. It's purpose is to ensure that the dissolution apparatus complies with regulatory requirements (e.g., USP, BP, EP). It helps to confirm reproducibility and accuracy in drug release testing.In this post we will know What are dissolution calibration parameters and how to calibrate it?
A. Physical Test
- Vessels structure,height, diameter,nominal capacity
- Jar Centering
- Distance between paddle or basket and inner jar
- Temperature
- Time
- RPM
- Wobbling Check
B Chemical Test
- 9. Performance verification test with prednisone tablet 10 mg
1. Vessels structure, height, diameter, capacity:
Dissolution vessels are cylindrical in shape having 160-210 mm height, 98-106 mm inside diameter, 1000 ml nominal capacity.
2. Jar Centering:
- Down the dissolution apparatus with paddle or basket.
- Take a calibrated vernier caliper and measure the distance from paddle or basket to the inner wall of jar at 4 different location equallly.
Acceptance criteria:
Difference between the largest and smallest observed readings should not be more than 2.0 mm for 360° rotation.
3. Distance between paddle or basket and inner jar:
- Fit the paddle or basket of dissolution. Click on down bottom.
- Take a calibrated depth gauge tester and measure the distance between paddle or basket to the centre of the jar.
Acceptance criteria: 25±2 mm
4. Calibration of Temperature:
Materials required are calibrated thermometer,
Measure 900 ml of pure water and fill in each jar of dissolution. There may be eight or fourteen jars. Turn on the dissolution machine and set the temperature at 37° C in the system. Allow the water to reach the set temperature. After some time take a calibrated thermometer and measure the temperature of water bath and water contained in each jars. Note down the observed temperature of the thermometer and compare with temperature displayed in the dispaly of dissolution system. Record the observed temperature in the table format.
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Observed
temperature |
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Water Bath |
37.3° C |
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Jar-01 |
37.2 |
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Jar-02 |
36.9 |
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Jar-03 |
37.0 |
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Jar-04 |
37.1 |
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Jar-05 |
37.2 |
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Jar-06 |
37.1 |
5. Calibrationn of time:
- Take a calibrated stopwatch.
- Set the time at 30 minutes in the dissolution system. Start the dissolution and stopwatch at the same time.
- Wait upto 30 minutes and record the time of both stopwatch and dissolution display. Calculate the difference of time.
- Repeat the same process at 60 monutes.
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Set time |
Observed time Dissolution
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Observed time Stopwatch
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Time difference |
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30 minutes |
30 min & 10 sec |
30 min & 20 sec |
10 seconds |
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60 minutes |
60 min & 12 sec |
60 min & 19 sec |
7 seconds |
Acceptance criteria: Difference in time should be not more than ±30 seconds
6. Calibration of RPM
- Set instrument RPM at 50 and start.
- Measure the RPM with a calibrated tachometer.
- Compare the RPM displayed in the instrument and tach ometer
- Repeat the same procedure at 100 RPM
Acceptance criteria: ±4% of set RPM.
7. Wobbling Check:
- At first set the shaft speed at 50 RPM.
- After that attach the calibrated wobble meter to the upper the paddle shaft or bottom rim of basket which wobbling should be checked. The knob of wobble meter should be properly touches the surface of shaft.
- Rotate the dial so that to coincide the needle and the dial reading to 0.
- Click on the start RPM and record the reading.
- One complete clockwise rotation of the needle indicate 1.0 mm.
- Note down the wobbling and repeat the same procedure for alll shaft.
Acceptance criteria:
For paddle & Basket: NMT ±1 mm
8. Performance verification test with prednisone tablet 10 mg:
➤Materials required are Prednisone tablet 10 mg, Prednisone IPRS, Dissolution machine, volumetric flak, measuring cylinder, beaker.
➤Prepare dissolution media:
- First of all heat the required amount of water to about 41° C. Set up 0.45 µm size filter paper in vaccum filter having stirrer. Filter the water with stirring.
- After filter completion seal the upper part of flask. Stir continue for five minutes and also vaccum.
- You can also sonicate the media to remove dissolved air from the water.
➤Meausre 500 ml prepared water media and fill in each 12 jar of dissolution.
➤Use basket as apparatus, set time as 30 minutes and tenperature 37° C±0.5° C.
➤Standard solution prepration:
- Weigh accurately 20 mg of prednisone IPRS into a 20 ml volumetric flask. Dissolve by adding 5 ml of methanol. Fill up dissolution media up to mark of volumeric flask.
- Dilute 1 ml of solution into 100 ml volumetric flaskand dilute with dissolution media up to mark.
➤Sample solution prepration:
- Place one tablet of prednisone 10 mg into each 12 jars of the dissolution. Run the machine for 30 minutes.
- Filter the sample through 0.45 µm size filter. Dilute the 10 ml of fltrate into 20 ml volumetric flask with dissolution media up to the mark.
➤Measure the absorbance in UV spectrophotometer
- Set the wavelength 242 nm in UV.
- Auto zero with dissolution media as blank.
- Take the absorbance of standard solution and sample solution
➤Calculate the percentage of dissolved prednisone.
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S.No. |
UV Absorbance |
% Dissolved |
Natural Log Scale |
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Standard |
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Sample-1 |
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Sample-2 |
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Sample-3 |
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Sample-4 |
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Sample-5 |
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Sample-6 |
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Mean (M) |
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Variance (V) |
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- Also calculate the percentage of dissolved prednisone, natural log, mean and variance of rest 6 tablets.
- Calculate the average of two mean (M) as well as two variance (V)
- Calculate geometric mean of average two mean and average two variance
- Calculate square root of above calculated geometric mean of average two variance (GMV).
- Calculate percentage of Cofficient Variance (CV)=100 x {square root of GMV-1}
- Compare the geometric mean and cofficient of variance with report of prednisone tablet that used.
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S.No. |
Obsorvation |
Acceptance Criteria |
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Geometric Mean |
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Between…..&…… |
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%CV |
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NMT…. |
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