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Inprocess 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 for formulation plant of Pharmaceutical company.
  • Responsibility:
    • Production Executive / Officer shall be responsible for implementation of this SOP.
    • Head-Production / designee shall be responsible for compliance of this SOP.
  • Accountability:Head-Production and QA shall be accountable for compliance of 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 inprocess inspection of Tablets / Capsules
  • Description
  • Description of tablets:
  • After starting the compression collect the sample from one complete Rotation of machine from both of the discharge ends and observe each tablet from both sides to ensure that the description shall comply 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 first round in case of automatic filling machine and first filled plate in case of manual filling. Check each capsule for specification as mentioned in BMR and record in inprocess control sheet.
  • Lock length of capsules
    • Collect 20 capsules form the machine and check the lock length of the capsule one by one in mm with the help of 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. 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 manually entry shall be done in Annexure IV.If the printout shall attached in the BMR then there is no need to write manually in Annexure IV.
    • In case of bilayer tablet weight of the individual layer to be recorded after every two hours.
  • Weight of capsules
    • Collect 20 capsules samples from the discharge chute of automatic capsule filling machine / first plate of manual capsule filling machine. Filled weight of individual capsule and composite 20 capsule weights shall be checked using 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. Record the details in Annexure-III and Annexure-IV. If the printer is not available / out of order, in that case manually entry shall be done in Annexure IV.If the printout shall attached in the BMR then there is no need to write manually in Annexure IV.
  • Hardness of tablets
    • Precalibrated hardness tester shall be used for checking the hardness.
    • Collect 10 tablets from each chute of the compression machine and minimum and maximum hardness of the tablets shall be checked and record in Annexure-III.
    • Ensure that hardness shall be within specified limit of the BMR.
  • Thickness of tablets
    • Thickness of tablets shall be checked by a precalibrated Digital Vernier Caliper with 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 the jaws touch the tablet.
    • The minimum and the 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 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 then 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 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 repeated twice and mean of the three test calculated, shall not be greater than 1 %.
    • If the cracked, chipped or broken tablets 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 check 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 the disc over 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 capsule are disintegrated, i.e. when no particle remains of size greater then the sieve size of the basket. Stop the apparatus and note the time taken for the disintegration the tablets/Capsule as displayed and record the same in Annexure-III.
    • If one or two tablets/capsules fail to comply the test, repeat the test with additional 12 tablets/capsules, not less than 16 of the total 18 tablets/capsules tested shall disingrate.Record the same in Annexure- III.
    • 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 stop watch for 60 minute. 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 further six tablet 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 nominal mesh aperture of 710 mm (mesh size No. 22).Record the observation in Annexure IV.
    • Frequency: – At the start of 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 case of uncoated and coated tablet inspect the tablets manually after the completion of compression /coating of the batch.
        • Visual inspection of the tablet shall be done for broken, laminated, chipped, Capped, Sticked, discolored tablets, black particle 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 case of capsule, inspect the physical appearance of capsule manually after completion of batch.
        • Visual inspection of the capsule shall be done for dented capsules, chipped, telescopic capsules, cracked capsules, opened capsules, printed on capsule shell 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 found to be more than 1.0% thorough investigation to be carried out at all stages for reasons and the findings thereof to be record in the BMR. tablets / Capsules used for in process tests shall be discarded and labeled them as ‘Rejection’.

      • Temperature and Relative humidity of areas shall be check 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
    • Bilayer tablet weight variation sheet – Annexure VI
  • Distribution:
    • Master Copy – Documentation Cell (QA)
    • Controlled Copies –  Quality Assurance, Production
  • History
Date Revision Number Reason for revision
00 New SOP

 

Annexure-1 

                        VISUAL INSPECTION RECORD TABLETS                                          

Product Name:                                     Batch Number:                            Mfg.Date:

Generic Name:                                     Batch Size:                                  Exp.Date:

 

Date Duration Inspected by  I Inspected by  II Checked by Broken Laminated Chipped Tablets Chipped Tablets Discoloured Tablet Black Particle Foreign Matter Total Rejection Checked by
From To
 

 

Note: If the rejection of tablets found to be more than 1.0% through investigation to be carried out at all stage reasons and the findings thereof to be recorded in the BMR.

Annexure-II

 LOCK LENGTH RECORD-CAPSULES 

Product:

Batch No.:

Generic Name:

 

Mfg. Date:

Shift :

Batch Size:

 

Exp. Date:

Operator:

M/C I.D. No.:

 

Supervisor

Date Start:

Date Finished:

Product Description:   ___________________________________________________

No. of Capsules taken: 20

Frequency: After every two hours                              Limits______________________mm to_____________________to

Date Date
S.No. Lock length (mm) S.No. Lock length (mm) S.No. Lock length (mm) S.No. Lock length (mm) S.No. Lock length (mm) Lock length (mm) Checked by Operator Name
1 5 9 13 17 Avg.=
2 6 10 14 18
3 7 11 15 19 Min.=
4 8 12 16 20 Max. =

 

 Annexure-III

IN-PROCESS CONTROL CHART (TABLET / CAPSULE)

Product Name: Batch Number: Dare started: Mfg. Date: Market: PAGE_____OF_____
Generic Name: Batch Size: Date Completed: Exp. Date: MACHINE ID No..
Date
Time
 
RHS LHS RHS LHS RHS LHS RHS LHS RHS LHS RHS LHS RHS LHS RHS LHS            Remarks
Description /Dimension
Visual defects   (OK / NOT OK) Out Put
D. T. (Limit-          ) Eq. No.
Hardnesss (Kg/Cm2) / N Limit-  Eq. No. Cummulative Out Put
Fariability / Sealing Limit- Eq. No. Rejection  Non Recoverable (Kg/Nos)
Thickness/Cap. Loc. L/ (mm) Limit- Eq. No. Machine Operator (s)
Uniformity of dosage unit Limit- Eq. No. Production
Upper Action Limit…………………………..
Av. Wt / Vol. of………………………
Lower Action Limit………………….
Signature IPQA

 

Annexure-IV

TABLETS WEIGHT / FILL WEIGHT VARIATION SHEET
Product Name:                                             Batch Numbe:                                  Mfg.Date:                                                                Generic Name:                                              Batch Size:                                        Exp. Date: M/c No……………………………………………………………………                                               Date Started……………………………………………………………                                 Dated Finished……………………………………………………….. Average Wt. / Fill Wt……………………… ……………………..                                Tolerance of individual Wt. ………………. ………………….                                               From average Wt. / Fill Wt. …………………………………..
Left Right
Date:
Time (h):
Wt: of 20Units. (g)
Av. Wt. / Fill Wt. (mg)
INDIVIDUAL WEIGHT / FILL WT. (MG) 1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Max Wt. of 20 units   (mg)
Min. Wt .of  20units   (mg)
Variation +(%)
Variation -(%)
Appearance
Contamination by  Lubricant oil
Uniformity of Dispersion
Operator
Checked by
Note: In case of capsules fill wt. or wt. of powder to be taken; Remarkes ,if any

Annnexure-V

 VISUAL INSPECTION RECORD CAPSULES                  

             

Product Name:                                     Batch Number:                                   Mfg.Date:

Generic Name:                                     Batch Size:                                         Exp.Date:

 

Date Duration Inspected by  I Inspected by  II Checked by Dented Capsules Chipped Capsules Cracked Capsules Opened Capsules Printing on capsules shells Foreign Matter Total Rejection Checked by
From To
 

 

total

Note: If the rejection of Capsules  found to be more than 1.0%  thorough  investigation to be carried out at all stage reasons and the findings thereof 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……………………………………………………………………                                               Date Started……………………………………………………………                                 Dated Finished………………………………………………………..
Tablet Layer 1
 Wt. of Tablet                                                                                      Limits(mg): Wt. of Layer 1                                                                        Limits(mg):
                                                  Date:
                                                Time (h):
LAYER WEIGHT (MG) 1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Done by
Checked by

About Pharmaceutical Guidanace

Mr. Shiv Kumar is the Author and founder of pharmaceutical guidance, he is a pharmaceutical Professional from India having more than 14 years of rich experience in pharmaceutical field. During his career, he work in quality assurance department with multinational company’s i.e Zydus Cadila Ltd, Unichem Laboratories Ltd, Indoco remedies Ltd, Panacea Biotec Ltd, Nectar life Science Ltd. During his experience, he face may regulatory Audit i.e. USFDA, MHRA, ANVISA, MCC, TGA, EU –GMP, WHO –Geneva, ISO 9001-2008 and many ROW Regularities Audit i.e.Uganda,Kenya, Tanzania, Zimbabwe. He is currently leading a regulatory pharmaceutical company as a head Quality. You can join him by Email, Facebook, Google+, Twitter and YouTube

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