In-process Controls in Tablet Compression and Capsule filling
Objective:
To lay down a procedure for conducting Inprocess Controls during Tablet Compression and Capsule Filling.
Scope:
This standard operating procedure is applicable to the formulation plant of a Pharmaceutical company.
Responsibility:
The production Executive / Officer shall be responsible for the implementation of this SOP.
Head-Production / designee shall be responsible for compliance with this SOP.
Accountability: Head-Production and QA shall be accountable for the compliance with this SOP.
Abbreviations and Definitions
- BMR – Batch Manufacturing Record
- SOP – Standard Operating Procedure
- QA – Quality Assurance
- mm – Millimeter
Procedure: Following parameters shall be checked during the in-process inspection of Tablets / Capsules
Description
Description of tablets:
After starting the compression collect the sample from one complete Rotation of the machine from both of the discharge ends and observe each tablet from both sides to ensure that the description shall comply with the specification mentioned in the BMR.
Description of capsules:
After starting the automatic capsule filling machine / manual capsule filling machine, collect the 20 capsule samples for the first round in case of the automatic filling machine and the first filled plate in case of manual filling. Check each capsule for specification as mentioned in BMR and record the in-process control sheet.
Lock length of capsules
Collect 20 capsules from the machine and check the lock length of the capsule one by one in mm with the help of a precalibrated digital Vernier caliper and ensure that the limits shall comply with the specification of the BMR. Record the observations in Annexure II.
Weight of the tablets.
Collect 20 tablets from each discharge chute and weigh each tablet individually as well as composite on calibrated weighing balance attached with printer, print of the same shall be attached in the BMR after review and verification by production and IPQA respectively. The weight of tablets shall be within the specified limits as specified in the BMR. Record the same in Annexure-III and Annexure-IV. If the printer is not available / out of order, in that case, the manual entry shall be done in Annexure IV. If the printout shall be attached in the BMR then there is no need to write manually in Annexure IV.
In the case of a bilayer tablet weight of the individual layer is to be recorded after every two hours.
Weight of capsules
Collect 20 capsule samples from the discharge chute of the automatic capsule filling machine / first plate of the manual capsule filling machine. The filled weight of individual capsules and composite 20 capsule weights shall be checked using calibrated weighing balance attached with a printer, print of the same shall be attached in the BMR after review and verification by production and IPQA respectively. Record the details in Annexure-III and Annexure-IV. If the printer is not available / out of order, in that case, manual entry shall be done in Annexure IV. If the printout shall be attached in the BMR then there is no need to write manually in Annexure IV.
Hardness of tablets
A precalibrated hardness tester shall be used for checking the hardness.
Collect 10 tablets from each chute of the compression machine and the minimum and maximum hardness of the tablets shall be checked and recorded in Annexure-III.
Ensure that hardness shall be within the specified limit of the BMR.
Thickness of tablets
The thickness of tablets shall be checked by a precalibrated Digital Vernier Caliper with the least count of 0.01mm.
Randomly collect 10 tablets from each chute of the compression machine.
Place the tablet between the jaws of the caliper and slide the adjustment jaw till both jaws touch the tablet.
The minimum and maximum thickness shall be displayed and recorded in Annexure III.
Friability of tablets
Precalibrated friability apparatus shall be used for calculating the friability.
Clean the drum by wiping it with the help of a clean non shredding cloth.
For the tablets with an average weight of 650 mg or less take a sample of whole tablets corresponding to about 6.5 gm and for the tablet with an average weight of more than 650 mg take a sample of 10 whole tablets.
Dedust the tablet and place the weighed tablets in the
Set the timer for 100 revolutions, normally 4 minutes (25 rpm).
Switch ‘ON’ the motor and allow the drum to rotate till the timer switch ‘OFF’ the motor.
Collect the tablets of the drum in the tray, remove the adhering powder, and reweigh the tablets. The difference between these weights (before and after) is the measure of the friability of the tablets. The percentage weight loss with respect to initial weight is the friability ie
Friability= weight before friability- weight after friability x100 / Weight before friability.
If the friability is greater than 1 %, the test is repeated twice and the mean of the three tests calculated, shall not be greater than 1 %.
If the cracked, chipped, or broken tablets are present in the sample after tumbling, the sample fails the test.
Record the activity in In-process Control Sheet as per Annexure-III.
Disintegration time:
Precalibrated disintegration apparatus shall be used for checking the disintegration time.
Remove the basket from the beaker and remove the plastic discs from each tube.
Apparatus shall be free from any kind of previous product remnants.
Place one tablet or capsule in each of the tubes and discover it.
Fill the beaker with water at 37° ±2°C up to the level marked on it, i.e. up to a level such that the wire mesh at its highest point is at least 25 mm below the surface of the liquid, and its lower point is at least 25 mm above the bottom of the beaker.
When the tablets or capsules are disintegrated, i.e. when no particle remains of size greater than the sieve size of the basket. Stop the apparatus and note the time taken for the disintegration of the tablets/Capsule as displayed and record the same in Annexure-III.
If one or two tablets/capsules fail to comply with the test, repeat the test with an additional 12 tablets/capsules, not less than 16 of the total 18 tablets/capsules tested shall disintegrate. Record the same in Annexure- III.
The water of the beaker shall be changed after every test.
Enteric-coated tablets / Capsule: If the tablet has a soluble external coating, immerse the basket at room temperature for 5 minutes. Suspend the assembly in the beaker containing 0.1M Hydrochloric acid and operate without the discs for 120 minutes. Remove the assembly from the liquid. No tablets shall show signs of cracks that would allow the escape of the contents or disintegration, apart from fragments of coating. Replace the liquid in the beaker with mixed phosphate buffer pH 6.8, add a disc to each tube, and operate the apparatus by starting the stopwatch for 60 minutes. In phosphate buffer, all the tablets shall be disintegrated. If the tablet fails to comply because of adherence to the disc, repeat the test on a further six tablets without the discs.
Dispersible and soluble tablets: Follow the above test using water at 24° C to 26°C.
Test for uniformity of Dispersion: (For dispersible tablets only). Place two tablets in 100 ml of water and stir gently until tablets are completely dispersed. A smooth dispersion is obtained which passes through a sieve/screen with a nominal mesh aperture of 710 mm (mesh size No. 22). Record the observation in Annexure IV.
Frequency: – At the start of the batch and every half an hour for composite weighing. For every two hours for individual weighing.For Disintegration time, friability, hardness, thickness, and dispersion at the start of every batch and thereafter every two hours.
Visual inspection of Tablets: In the case of uncoated and coated tablets inspect the tablets manually after the completion of compression /coating of the batch.
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- Visual inspection of the tablet shall be done for broken, laminated, chipped, Capped, Stuck, discolored tablets, black particles, and foreign matter.
- The person employed for visual inspection shall be changed after every 2 hours
- Total rejection shall be weighed and checked by the production supervisor/ officer in the attached ‘Visual Inspection Record Tablets’ (Annexure-1).
Visual inspection of Capsule: In the case of the capsule, inspect the physical appearance of the capsule manually after completion of the batch.
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- Visual inspection of the capsule shall be done for dented capsules, chipped, telescopic capsules, cracked capsules, opened capsules, printed-on capsule shells, and foreign matter.
- The person employed for visual inspection shall be changed after every 2 hours
- Total rejection shall be weighed and checked by the production supervisor/ officer in the attached “Visual Inspection Record Capsules” (Annexure-IV).
Note: If the rejection of Tablets/Capsules is found to be more than 1.0% thorough investigation is to be carried out at all stages for reasons and the findings thereof are to be recorded in the BMR. tablets / Capsules used for in-process tests shall be discarded and labeled as ‘Rejection’.
Temperature and Relative humidity of areas shall be checked as per respective SOP.
Metal detector challenge test shall be checked as per respective SOP.
Forms and Records
- Visual Inspection Record – Tablets – Annexure-I
- Lock Length Record – Capsules – Annexure-II
- In Process Control Sheet – Annexure-III
- Tablet Weight / Fill Weight Variation Sheet – Annexure-IV
- Visual Inspection Record – Capsules – Annexure-V
Distribution:
- Master Copy – Documentation Cell (QA)
- Controlled Copies – Quality Assurance, Production
History
Annexure-1
VISUAL INSPECTION RECORDS TABLETS
Product Name :_______Batch Number:_______________Mfg.Date:
Generic Name:________Batch Size:___________Exp.Date:
- Date
- Duration
- Inspected by
- Checked by
- Broken Laminated
- Chipped Tablets
- Chipped Tablets
- Discolored Tablet
- Black Particle
- From___To____
- Foreign Matter
- Total Rejection
- Checked by
Note: If the rejection of tablets is found to be more than 1.0% investigation is to be carried out at all stages reasons and the findings thereof are to be recorded in the BMR.
Annexure-II
LOCK LENGTH RECORD-CAPSULES
Product Description: _________No. of Capsules taken: 20
Frequency: After every two hours, Limits__________mm to_________to
- S.No.
- Lock length (mm)
- Checked by
- Operator Name
- Avg.=
- Min.=
- Max. =
Annexure-III
IN-PROCESS CONTROL CHART (TABLET / CAPSULE)
Product Name:
Batch Number:
Dare started:
Mfg. Date:
Market:
Generic Name:
Batch Size:
Date Completed:
Exp. Date:
- Date
- Time
- Description /Dimension
- Visual defects(OK / NOT OK)
- D. T. (Limit-__________) Eq. No.
- Hardness (Kg/Cm2) / N Limit- Eq. No.
- Variability / Sealing Limit- Eq. No.
- Thickness/Cap. Loc. L/ (mm) Limit- Eq. No.
- Uniformity of dosage unit Limit- Eq. No.
- Upper Action Limit…………………………..
- Av. Wt / Vol. of………………………
- Lower Action Limit………………….
- Signature
- Out Put
- Cumulative Out Put
- Rejection Non Recoverable (Kg/Nos)
- Machine Operator (s)
Annexure-IV
TABLETS WEIGHT / FILL WEIGHT VARIATION SHEET
Product Name :______Batch Number: _______Mfg.Date: ___________Generic Name:______
Batch Size:____________Exp. Date:
M/c No………………………Started……………………Dated Finished…………………………
Date:
Time (h):
Wt: of 20Units. (g)
Av. Wt. / Fill Wt. (mg)
INDIVIDUAL WEIGHT / FILL WT. (MG)
- Max Wt. of 20 units (mg)
- Min. Wt .of 20units (mg)
- Variation +(%)
- Variation -(%)
- Appearance
- Contamination by Lubricant oil
- Uniformity of Dispersion
- Note: In case of capsules fill wt. or wt. of powder to be taken; Remarks ,if any
Annexure-V
VISUAL INSPECTION RECORD CAPSULES
Product Name :_______Batch Number:_________Mfg.Date:
Generic Name: _________Batch Size:____________Exp.Date:
- Date
- Duration
- Inspected by
- Checked by
- Dented Capsules
- Chipped Capsules
- Cracked Capsules
- Opened Capsules
- Printing on capsules shells
- Foreign Matter
- From _____To_____
- Total Rejection
Note: If the rejection of Capsules is found to be more than 1.0% thorough investigation is to be carried out at all stages reasons and the findings thereof are to be recorded in the BMR.
Annexure-VI
BILAYER TABLETS WEIGHT VARIATION SHEET
Product Name:
Batch Number:
Mfg.Date:
Generic Name:
Batch Size:
Exp. Date:
M/c No……………Started………………Finished………………………………
Wt. of Tablet
