Dissolution Tester Calibration, Purpose :
Dissolution Tester Calibration, The purpose of this SOP is to describe the operation, calibration and cleaning of Dissolution Tester (Model: Electrolab, EDT 14Lx).
Dissolution Tester Calibration, Scope :
This procedure is applicable for Dissolution Tester (Model: Electrolab, EDT 14Lx), installed in the quality control laboratory at XX Pharmaceuticals Limited.
Definitions/Abbreviation:
[][]SOP: Standard Operating Procedure
[][]QC: Quality Control
[][]Dissolution test: Dissolution test is a means to monitor the rate of release of a drug substance from a dosage form to ensure consistency of manufacture and compliance with release specifications.
[][]RPM: Rotations per minute
[][]LED: Light emitting diode
[][]Concentricity: The quality of having the same center (as circles inside one another).
[][]Wobble: Move sideways or in an unsteady way.
[][]NMT: Not more than.
Responsibilities:
The roles and responsibility is as follows:
Officer/Executive/ Sr. Executive, Quality Control
[][]To ensure that the instructions of this procedure are correctly followed.
[][]To ensure cleaning of dissolution tester maintaining safety rules.
Manager, Quality Control
[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.
Head of Quality Assurance
Approval of the SOP
To ensure the overall implementation of the SOP.
Procedure:
General precautions or operational safety:
[][]Do not start the heater if there is no water in the tank.
[][]Always maintain the liquid level within the tank above the minimum level mark using purified water only.
[][]Disconnect the power supply before moving, emptying or cleaning of bath.
[][]Spillage must be cleaned up immediately after use.
[][]Do not use any aggressive material or strong solvent to clean the jar and water bath.
[][]Locate the system on a level bench without movement or distortion.
[][]Do not hold the stirrer while in operation.
[][]For lifting up the stirrer, make sure the paddles are stop.
[][]Do not disturb the sensor tube while cleaning the tank.
[][]External probe should be handled with care.
[][]Use sinkers if the dosage form unit floats. Close the vessels with the cover during Operation.
System Operation:
[][]After the System is set up, switch on the power.
[][]After Power On, the Instrument will initialize itself; the logo screen will flash for 3 seconds and then idle screen will be displayed.
[][]The idle screen displays the current status of the instrument indicating the Date, Time, RPM, Bath Temperature, External probe and loaded protocol number.
[][]Press F3 Key to login.
[][]Username and Password needs to be added.
[][]Press F1 key to enter the username & password or F3 Key to go back to the previous screen.
[][]The idle screen will be displayed.
[][]If security is disabled then the adjacent idle screen will be displayed.
ELECTROLAB
EDT 14Lx
DISSOLUTION
TEST APPARATUS
[][]Press F1 or F2 Key from front panel to enter MENU or PREPARE
[][]Menu Press F1 Key from front Panel to enter menu screen.
[][]Menu <Configure>
[][]Press 1 from alphanumeric keypad to enter configuration menu.
[][]If F3 key is pressed the previous screen will be displayed.
[][]Menu <Configure> l sampling l
[][]Press 1 from alphanumeric keypad to enter sampling menu.
[][]Menu <Configure>l sampling l [ Manual]
[][]Press 1 to select manual sampling though syringe manifold or 2 to select manual sampling though pipette.
[][]Menu <Configure>l Individual Probe l
[][]Press 2 to enter individual probe screen. Press 1 from alphanumeric keypad to select the individual probes. The number of probes can be selected either to 6/8/12/14 using up or Down arrow key, press enter to save the No. of probes and return back to configure screen.
[][]Press 2 to select option number.
[][]Press F3 key to return back to the Configure screen.
[][]Menu <Configure>l Temp Gradient l
[][]Press 3 to enter temp gradient.
[][]Set Temp gradient up to 1.5° C using increment & decrement key.
[][]Temperature Controller set.
F1 key: To ‘ON’ the temp Controller.
F2 key: To ‘OFF’ the temp Controller.
F3 key: To ‘SAVE’ & to return back to the Configure screen.
[][]Menu <Configure>l communication l
[][]Press 4 from front panel to enter Communication.
[][]Select RS232 for printer/PC and ETHERNET for LAN connection using 1 or 2 numeric keys.
[][]Press F3 key to go back to configure screen.
[][]Menu <Configure>l Stirrer l
[][]Press 5 in configure screen.
[][]Press 1 to ON the Stirrer and press 2 to OFF the stirrer.
[][]Menu <Configure>l Auto Disp. l
[][]Press 7 to enter auto dispenser screen.
[][]Press 1 or 2 numeric keypad to activate auto dispenser.
[][]Menu <Configure>l Instur. No. l
[][]Press 8 to enter instrument number.10 alphanumeric character serial numbers can be entered.
[][]Press F1 keys to save the entered serial number and F3 to go back to previous screen.
[][]Menu <Protocol>
[][]Press 2 to enter protocol menu.
[][]Menu< Protocol >l Load Protocol l
[][]Press 1 to enter Load Protocol.
[][]20 Programmable protocols can be loaded
[][]Protocol No- Can be loaded using UP/Down key & to register the No. Enter key needs to be pressed.
[][]Press F1 to load next protocol and Press F2 to load previous protocol.
[][]Press F3 to go back to the protocol screen.
[][]Menu< Protocol >l Edit Protocol l
[][]Press 2 to enter Edit Protocol.
[][]Select the protocol which needs to be editing using Up/down arrow and press ‘enter’ key.
[][]The respective protocol details such as Drug name, Media name, pH value, Temperature, Media volume , Power fail, Apparatus, Time Table, Sampling Info, details need to be entered.
[][]The protocol details can be edited using alphanumeric keypad.
[][]The next parameters can be selected for editing before saving the previous parameter by pressing F3 key from front panel.
[][]To select different apparatus press enter key and select the desired apparatus using numeric keys.
[][]To edit time table parameters press Enter key. The sampling time interval, action and total number of samples (1 to 24) can be set as per user requirement using shift & alphanumeric keys.
[][]For the single time point, action table will have only one sampling option. Infinity (min) can be selected after last sample.
[][]For the multiple time point, action table will have only two sampling options media change and sample. Infinity (min) can be selected after last sample.
[][]Press F3 to save & go back to main menu screen.
[][]Menu <Settings >
[][]Press 3 to enter settings
[][]Menu <Settings > l Clock l
[][]Press 1 alphanumeric keypad to enter Clock setting screen
[][]Set Date and Time using ▲▼◄► arrow keys
[][]Press F1 from front panel to save the entered date and time, the idle screen will be displayed
[][]Press F1 from front panel to go back to the setting screen.
[][]Menu <Settings > l Wake Up l
[][]In this parameter the sleep mode time and date are set. The instrument will start automatically at the set time and date for attaining the bath temperature.
[][]Press 2 from setting screen to enter the wakeup setting screen.
[][]Wake up time and date needs to be added using Up/Down and Side arrow keys.
[][]Press F1 key to turn ON the wake up parameter, the LCD display light will be turn OFF automatically and idle screen will be displayed. Or press the F2 key to OFF the wakeup alarm.
[][]Menu <Jar Tamp >
[][]Press 6 from main menu screen to observe the jar tamp attained by individual jar.
To set RPM
[][]Press RPM key from front panel.
[][]Press numeric key to register the RPM range from 20 to 300 RPM.
[][]Press F1 key to Turn-on the motor & F2 key to Turn off.
[][]If RPM is out of range an error screen will be displayed.
[][]To Set Temperature
[][]Press Temperature key from front panel.
[][]Press numeric key to register the temperature range from 200 C to 400 C.
[][]Press F1 to turn On & F3 to turn off heater.
[][]If temperature is out of range an error screen will flash for 3 seconds.
[][]To prepare the test
[][]Load the appropriate protocol no. & press F2 key to start preparing the test.
[][]Batch No. & A.R. No. will be displayed. Using down arrow and enter key, add the batch No. & A.R No. (Lab. Control No.) up to ten digits. Press enter key to register the number.
[][]It will display checking connection where the instrument establishes link with the syringe/peristaltic pump and sample/fraction collector.
[][]After the connection between the instruments is done, sample collector will initialize & ‘Lift Not Park’ Indication will be display (If lift is not parked).
[][]‘Wait for the temperature’ indication will be display till the set temperature is achieved. User can also access MENU to cheek jar temperature.
[][]Ready indication will glow on front panel when jar temperature reach to set point & start indication will be displayed.
[][]Press START key form front panel to start the test.
[][]‘Drop the tablet and press START’ message will be displayed immediately if paddle or 45 was selected and if basket or paddle over disk was selected then ‘Press lift up, Load Apparatus’ will be displayed on screen.
[][]Press Enter to start the test, run screen will be displayed. Current status of the test and sample timing are displayed throughout the test.
[][]After completion of work, switch ‘OFF’ the instrument.
[][]Switch ‘OFF’ the mains when not required.
[][]Fill up the operation log book for Dissolution tester as per Annexure-III.
Physical Calibration
[][]Frequency: Perform mechanical calibration of the dissolution tester once in every six months or if the system has been moved, serviced or a malfunction is suspected.
Temperature Calibration:
[][]Switch on the mains.
[][]Set the temperature to 37°C by following the temperature setting procedure given in operation.
[][]Ensure that the jars are filled with water.
[][]Allow the instrument to stabilize.
[][]Measure the temperature of the water bath and of each jar with a calibrated thermometer and compare the result against the digital display on the apparatus.
[][]Record the observation as per Annexure-I.
[][]Acceptance Criteria: 37°C ± 0.5°C.
RPM Calibration:
[][]Switch on the mains.
[][]Set the RPM to 50 as per procedure given in the operation.
[][]Start the stirrer and measure the RPM by using calibrated tachometer.
[][]Record the observation as per Annexure-I.
[][]Similarly check the RPM 75, 100, and 150 and record the observations.
[][]Acceptable criteria: ± 4% of set value.
Time Calibration:
[][]Switch on the mains.
[][]Set the desired time (30 and 45 minutes) by following the temperature setting procedure given in operation.
[][]Check the time using a calibrated stop watch and record the observations as per Annexure-I.
[][]Acceptable criteria: ± 2% of set value.
Chemical Calibration (Performance Verification Testing)
[][]Frequency: Perform chemical calibration of the dissolution tester once in a year or if the system has been moved, serviced or a malfunction is suspected.
[][]For USP Dissolution Apparatus 1 (basket) and Apparatus 2 (paddle):
[][]If the instrument is outside calibration, a label of “Out of calibration” is placed.
[][]Apparatus must be calibrated with the following :
[][]Disintegrating Type – USP Prednisone Tablets 10 mg at 50 rpm
[][]Non-disintegrating Type – USP Salicylic Acid Tablets 300 mg at 100 rpm
[][]Checking Standards in the on line-USP and printing Lot-Specific Standard Certificates. Verifies Standard Lots are current within expiry.
Disintegrating Type – USP Prednisone tablets 10 mg at 50 rpm:
[][]Follow the directions for storage and use on the label of the reference standard.
[][]If drying instructions are included on the label, only dry sufficient quantity required for the test (use a clean, dry vessel when drying and not the original container).
[][]Standard solutions must be prepared on the day of use.
Prednisone standard preparation:
[][]Accurately weigh 20 mg Prednisone standard into a 100 ml volumetric flask containing 5 ml methanol.
[][]Sonicate to dissolve and dilute to volume with distilled or purified water and mix well.
[][]Further dilute 5.0 ml of this solution to 100 ml with distilled or purified water and mix well.
[][]Dissolution medium preparation and de-aeration:
[][]Filter the dissolution medium (Distilled or purified water 500 ml) with the aid of a vacuum through a 0.45 µm-porosity membrane filter into a suitable filtering flask.
Test procedure:
[][]Using a volumetric flask, measure 500 ml distilled or purified water into each of the six vessels.
[][]Allow medium to equilibrate for approximately 30 minutes before test is commenced.
[][]When dissolution bath has equilibrated, check the temperature of each vessel is 37.0°C ± 0.5°C.
[][]Carefully weigh 6 de-dusted USP Prednisone Tablets 10 mg.
[][]Drop one previously de-dusted tablet into each of the vessels via the sample holes in the lids, raising the stirrer shaft fully before dropping the tablet into the vessel, and pushing the shaft fully down when the tablet has reached the bottom.
[][]Operate the apparatus at 50 rpm for 30 minutes.
[][]After 30 minutes withdraw approximately 50 ml midway between the surface of the dissolution medium and the top of the blade, not less than 1cm from the vessel wall.
[][]Filter through a Whatman Number 1 filter paper, discarding the first few ml of filtrate.
[][]Scan the standard from 300-200 nm to obtain the maximum absorbance at the optimum wavelength (approximately 242 nm).
[][]Determine the absorbance of the six samples at that wavelength in fixed mode.
Calculate the percentage prednisone dissolved for all 12 stations using the following calculations:
% Dissolved =
Absorbance of Sample x Standard Concentration (mg/l) x Standard Potency x 100 DIVIDED BY
Absorbance of Standard x Sample Concentration if 100% dissolved (C100)
Acceptance Criteria:
[][]Check the percentage released limit of USP dissolution calibration tablets (Disintegration type: Prednisone tablets) from the respective batch certificate provided by USP.
[][]If any one station is outside of specification, place an “Instrument out of calibration, DO NOT USE” label on the instrument.
[][]Inform In-charge, QC; if the results do not meet the criteria.
Test interpretation:
The apparatus shall be suitable if the individual calculated values at each indicated speed are within the range specified in the tablet obtained with the each lot of tablets.
Note: An amount of alcohol not to exceed 5% of the total volume of the standard solution may be used to bring the prednisone standard into solution prior to dilution with dissolution medium.
Recording of Results:
[][]All relevant information on the calibration must be completed on Annexure-II.
[][]When all the results have been checked affix a Calibration label to the instrument.
Cleaning procedure
[][]Lift the stirrer unit by using “lift UP” key.
[][]Immerse the replenishment tubes in a vessel of the instrument or a beaker outside of the instrument containing purified water.
[][]Press F1 Key [Menu] from front panel.
[][]Press 5 from alphanumeric keypad to enter Run.
[][]Again press 2 for cleaning cycle.
[][]Iterations of cleaning cycle will be displayed, press F3 to save the command.
[][]Batch No.:, A. R. No.:, User Name: will be displayed. Press Enter 3 times.
[][]Display will be showed Press UP to edit/Press Enter to proceed, again press Enter.
[][]It will display checking connection where the instrument establishes link with the syringe/peristaltic pump and sample/fraction collector. At that time wait for few seconds.
[][]Press START
[][]ABORT STOP will be displayed on the LED screen.
[][]To start the cleaning cycle, press Start.
[][]After completion of cleaning cycle display will show checking connection Press START
[][]ABORT STOP
[][]Press F3 to stop the cleaning cycle and start the empty tube cleaning.
[][]Before start the empty tube cleaning, the replenishment tube should be placed in the open air from vessel or beaker.
[][]Remove the test vessels from their place and discard the medium.
[][]Wash each vessel with purified water and then set them inside the dissolution bath number wise.
[][]Remove basket/ paddle apparatus from the dissolution tester. Wash them with purified water and dry with tissue paper and keep at dedicated place.
[][]Clean and replace the water from dissolution bath fortnightly (once in every two weeks) or if necessary.
[][]Remove all vessels from the dissolution bath.
[][]Remove the basket/ paddle apparatus from the stirrer unit.
[][]Remove the circulating pipe which is provided at the right rare side of the dissolution bath.
[][]Start the circulation pump from the option menu and drain the dirty water in a waste water bucket.
[][]Insert the circulating pump in its proper place.
[][]Wash the dissolution bath with raw water, detergent solution and then again with raw water sequentially until no foam of detergent remains in the bath.
[][]Wash the bath finally with purified water and fill the bath with the same up to the level mark.
[][]De-dust the outer surface of the instrument with a clean dry cloth every day.
Annexure: Dissolution Tester Calibration
Annexure-I: Physical Calibration Information Sheet for Dissolution Tester
Annexure-II: Chemical Calibration Information Sheet for Dissolution Tester
Annexure-III: Operation Log book for Dissolution Tester