Calibration of Dissolution Test Apparatus SOP

1.0 OBJECTIVE :

To describe a procedure for calibration of Dissolution Test Apparatus.

2.0 SCOPE :

The SOP is applicable for the calibration of Dissolution Test apparatus, used for carrying out Dissolution test of tablet/capsules.

3.0 RESPONSIBILITY :

Quality Control Chemist and above

4.0 ACCOUNTABILITY:

Quality Control Head

5.0 PROCEDURE :

The apparatus consists of constant temperature water bath made of transparent acrylic. The round bottom glass vessels or acrylic vessels are placed equidistant inside the bath. The jar has acrylic lids which allow passing of stirrer shaft. The shafts are suspended from the top. The stirrers are controlled by microprocessor.

The bath temperature is controlled by microprocessor based controller within + 0.1°C. Additional features of apparatus are microprocessor based digital timer. This is provided with audio alarm which operates as per pre-set time.

5.1 PRECAUTIONS

Ensure that the power supply to the instrument is switched OFF before cleaning.

Ensure that the instrument is clean and dried.

Do not start the heater if the water in the tank is less than the marked level.

Do not disturb the level of the water tank

Do not disturb the sensor tube and heater while cleaning the tank.

Do not apply the force while washing baskets.

Do not hold the stirrer while in operation.

While moving the stirrer assembly downwards/ upwards, no lids should be present on the vessel.

Paddle shaft or basket shaft should be fitted properly. Do not over tighten the shaft of (paddle/basket).

Do not lift the stirrer unit while paddles/baskets are rotating.

Always cover the dissolution vessel with acrylic lid.

Handle glass jar carefully.

Check the water level of instrument and fill the bath with water up to the marked level before placing the test vessels.

5.2 CALIBRATION

FREQUENCY

Twice in year.

PRECAUTIONS WHILE PERFORMING PERFORMANCE VERIFICATION TEST

Ensure the working area and apparatus is clean.

Prednisone tablets should not exposed to air for longer period of time.

Temperature of the medium should not drop below 37°C prior to start the test.

Sonicate baskets in purified water and dry before use. Check visually, it should be cleaned.

Ensure that vent hole of basket is cleaned by passing air through it.

Ensure that tubing of syringe manifold is cleaned and emptied before start of the test.

Basket shaft and baskets should be connected at the same time before test starting.

Medium should not get in contact with air for longer period.

After sampling, filtration should be done immediately.

Take reading after stabilizing samples at room temperature.

The following parameters of the apparatus shall be calibrated as mentioned below.

Physical Parameter of Apparatus.

Apparatus Suitability Test (Performance Verification Test).

The physical parameters of apparatus shall be calibrated by using validation kit shown in figure

Dissolution Validation Kit

Rotation per minute by using Digital Tachometer.
Vessel temperature calibration by Digital Thermometer.
Paddle/ basket wobble test by using Wobble Centering Gauge.
Distance between the bottom edge of basket/paddle to the lowest inner surface of vessel by using Depth Gauge.
Paddle / basket centering test by using Centering Device.
Calibration of timer by using Digital Stop Watch.
Apparatus suitability test is performed by dissolution calibrator tablets.

Physical Parameter of the apparatus

Rotation per minute by Digital tachometer

Paste a small piece of Metal reflection paper in Paddle / Basket Shaft, as shown in figure (b).

Set the desired RPM value and start the Stirrer.

Focus the light of Tachometer on paper by pressing side button of instrument, as shown in figure (b).

Allow the light from tachometer to fall sharply on paper and stand for one or two minutes.

Observe the readings of RPM which displayed on Tachometer. Repeat the procedure for all paddle / basket shaft.

Record the actual value in calibration protocol.

Acceptance criteria: ± 4 % of set RPM.

Vessel Temperature Calibration

Keep the calibrated digital thermometer inside the water in all vessels and observe the temperature of the water.

Actual temperature results shall be recorded in calibration protocol.

Acceptance criteria: 37.0 ± 0.5°C.

Paddle / Basket wobble Test

Ensure that the paddle or basket shaft is properly tightened with the spindle.

Lift the stirrer to a suitable level such that the top of paddle blade reaches to measuring stylus point of dial gauge as shown in figure (c).

Fix the centering device on the vessel so that the pointer is just pressed against the paddle shaft as shown in figure (d).

Start the rotation of paddle / basket shaft.

Check the maximum deviation of the pointer of device on both sides of “0” and add the reading.

Repeat the procedure for remaining paddles or basket shaft.

Record the readings in calibration protocol.

Acceptance criteria: Paddle / Basket shaft wobble: within ± 1 mm.

Distance between the bottom edges of basket/paddle to the lowest inner surface of vessel.

Empty all the vessels and keep them without lid in respective positions.

Clamp all vessel using holders provided on jar plate.

Lower the stirrer unit to the bottom most position till it stops automatically.

Insert the depth gauge inside the vessel vertically as shown in figure (e).

Hold the depth gauge vertically with both arms pressed such that the “V” bend takes the guide of the paddle shaft as shown in figure (f).

Touch the reference jaw of the depth gauge at bottom face of paddle as figure (f).

Release the arms and ensure that the lower side of the jaw touches the jar base.

Note the reading of Vernier and main scale reading as shown in figure (g) and (h).

Record the observation in calibration protocol.

Repeat the procedure for remaining vessel with paddles or basket.

Acceptance criteria: 25 ± 2 mm

Timer by stop clock

Set 30 minutes in instrument by pressing time key, start the instrument and calibrated digital stop watch simultaneously.

Record the actual value in calibration protocol.

Repeat the same procedure by setting 45 minutes and 60 minutes.

Acceptance Criteria: ± 2% of set time.

Paddle / Basket Eccentricity Test

Fix the centering device on the jar so that the pointer is just pressed against the paddle shaft.

Rotate the device with both hands around the shaft of the paddle in the jar as shown in figure (i).

Ensure that the bottom plate is not lifted from the vessel or is in contact with the jar properly.

Stop rotating when the pointer starts moving in reverse side deflection.

Ensure the correct position of reversing of the pointer by rotating the device in reverse direction.

Note down the pointer reading at this point i.e. the point of maximum deflection in one side.

Start rotating the device further with both the hands in original direction.

Note the maximum deflection of pointer.

The difference between the two deflection value divided by two gives the value of paddle / basket eccentricity.

Repeat this procedure for all remaining paddles or baskets.

Record the readings in calibration protocol.

Acceptance criteria: Paddle / Basket centering: Note more than 2.0 mm

Always basket / paddle centering with respect to vessel should be done first before doing calibration of distance between the basket/ paddle and jar.

Apparatus Suitability Test (Performance Verification Test)

This is done by using current USP dissolution calibrator.

Requirements

Prednisone Tablets USP 10 mg

Prednisone USP RS

Dissolution Medium 500 ml water

Preparation of dissolution medium: Heat a suitable amount of water, while stirring gently to about 45°C. Filter under vacuum through a 0.45 µm porosity filter into a suitable filtering flask equipped with a stirring device. Seal the flask and continue to apply vacuum while stirring for an additional five minutes. Measured vacuum should be less than 100 mbar. Other deaeration techniques validated for 37°C may be used. The temperature of the dissolution medium should not fall below 37° prior to the initiation of the test.

Standard Preparation: Transfer about 25 mg of USP Prednisone RS to a 25.0 ml volumetric flask. Dissolve in approximately 10 ml alcohol with sonication. After cooling to ambient temperature, dilute to volume with alcohol. Dilute the stock solution 5.0 ml in 500.0 ml with purified water.

Test Preparation: Put six Tablets individually in six dissolution vessels containing 500 ml of dissolution medium that has been equilibrated at 37°C and carry out dissolution. At the end of the 30 minutes, withdraw an aliquot of test solution and filter. Discard first few ml of filtrate and collect minimum 10 ml of filtrate for test preparation.

The filtering method must not cause absorptive loss of drying.

Dissolution Conditions

FOR BASKETS (TYPE–I)

RPM 50

TEMP 37°C

TIME 30 MINUTES

FOR PADDLES (TYPE–II)

RPM 50

TEMP 37°C

TIME 30 MINUTES

Procedure: Measure the absorbance of standard preparation & test preparation at 242 nm on calibrated spectrophotometer, using dissolution medium as a blank.

Calculation:

Calculate % release of Prednisone by using following formula;

Test Interpretation

Transform the percent dissolved results to the natural log scale. [Expressed as Microsoft excel work sheet function: Natural log Scale = LN (X) ]

Determine the mean and variance of natural log scale. [Expressed as Microsoft excel work sheet function: For mean = Average (LNXI)]

Calculate the average of the two means (M) and the two variances (V)

Determine a geometric mean (GM) of average of two means (M). [Expressed as Microsoft excel work sheet function: For GM = EXP (M)]

Determine a geometric mean of average of two variances (V). [Express as Microsoft excel worksheet function: GMV = Exp (v)]

Determine square root of a number of a geometric mean of average of two variances (GMV)

Determine the percent of coefficient of variation (% CV)

[Expressed as Microsoft excel worksheet function: % CV = 100 x [SQRT (GMV) – 1]

Compare the results of geometric mean (GM) and percent coefficient of variation (%CV) with the acceptance ranges given in certificate of current lot no. of Prednisone Tablet USP 10 mg which is used for calibration of Dissolution Tester.

Acceptance Criteria

The geometric mean (GM) must not fall outside the limit given in USP certificate of Prednisone Tablet.

The percent coefficient of variation (% CV) must not be greater than the limit given in USP certificate of Prednisone Tablet.

If both meet the acceptance criteria, the assembly has passed the Performance Verification Test (PVT).

6.0 ABBREVIATIONS:

Abbreviation Expanded form

mm Millimeter

cm Centimeter

0C Degree Celsius

% Percentage

RPM Rotation Per Minutes

ml Milliliter