IPQC of dosage form in pharmaceutical industry

IPQC cover the entire chain of operations from the receipt of raw material in the warehouse to the release of finished products from the warehouse for distribution and or sale. IPQC is a process where quality of a product is ensured that it meets the standard according to regulatory authority guidline.

1. In-Process Quality Control Of Pharmaceutical Dosage Form Presented By : Kay Kay Shain Marma & Saad Ahmed Sami Dept. of Pharmacy University Of Chittagong Bangladesh.

2. IPQC IPQC stands for “In Process Quality Control”. It is a planned system to identify the materials, equipments, processes and operators. IPQC cover the entire chain of operations from the receipt of raw material in the warehouse to the release of finished products from the warehouse for distribution and or sale. IPQC tests are performed at regular intervals (generally each 1 hr later) during the manufacturing process. These tests are varied from dosage form to dosage form.

3. 4 R of IPQC

4. Importance of IPQC To detect the errors. To minimize the human errors. Provides accurate, specific, and definite description of the procedure to be employed. Can detect any abnormality immediately and at the same time indicate the kind of action needed to correct the problem. To enforce the flow of manufacturing and packing operations according to established rules and practices.

5. Who do IPQC Test ? Usually, the tests are carried out by- Quality compliance personnel & Production personnel. On the basis of organizational instructions and process descriptions, quality control personnel may also carry out the necessary tasks. Where to do IPQC ? In-process controls may be carried out within the production area provided they do not carry any risk for the production.”

6. Factors making IPQC effective People Training Environment Process Equipment Management Better communication

7. In Process Checks Shall Includes Following Process Controls Cleanliness of the area and line clearance Checking of the status labels on the area and process containers. Equipment/instrument: Calibration, verification and checking of the status labels. Checking and verification of material used as Material Name, Material Code, Control No. Time limits at all stages of process. Online review of batch record at every stage of process. Product attributes Like Weight, Hardness. Verification of yield at various stages of manufacturing process. Measured values obtained from the room environment like Temperature, Humidity.

8. IPQC FOR SOLID PRODUCTS

9. In-Process Quality Control tests for Tablets General appearance test Hardness Friability Disintegration time Weight variation Content uniformity Dissolution test Leakage testing for strip and blister packaging

10. General Appearance test 1.SIZE AND SHAPE : The size and shape of the tablet can be dimensionally described monitored and controlled. it is determined by the tooling during the compression process. 2.COLOR AND ODOUR : Colors used for rapid identification and consumer acceptance. but it must be uniform within a single tablet, from tablet to tablet and from lot to lot. the presence of an odor in a batch of tablets could indicate stability e.g. the characteristic odor of acetic acid in degrading aspirin tablets .Taste is important in consumer acceptance of product.

11. 3. THICKNESS : Thickness of individual tablets may be measured by a micrometer. Tablet thickness should be controlled within a ±5% variation of a standard. Thickness must be controlled to facilitate packaging. It is expressed in mm .

12. If the tablet is too hard, it may not disintegrate in the required period of time. If the tablet is too soft, it will not withstand the handling during subsequent processing such as coating or packaging. Hardness Hardness generally measures the tablet crushing strength. It is the load required to crush the tablet when placed on its edge. LIMITS : ( Take 5 tablets and avg. out) Oral tablets 4-10 kg Chewable tablets 3 kg Sustained release tablets 10-20 kg

13. Schleuniger Erweka Monsanto Strong- cobb DIFFERENT HARDNESS TESTER

14. Friability It is the tendency of tablets to powder, chip, or fragment and this can affect the Elegance appearance , consumer acceptance of tablet, and also add to tablets weight variation or content uniformity problems. It is property that is related to the hardness of the tablet.

15. Disintegration test (U.S.P.) : Disintegration test is an official test. It is the time required for the tablet to break into particles, the disintegration test is a measure only of the time required under a given set of conditions for a group of tablets to disintegrate into particles. It is performed to identify the disintegration of tablet in particular time period. Disintegration test is not performed for controlled & sustained release tablets. Disintegration test apparatus

16. Weighing 20 tablets individually calculating the average weights and comparing the individual tablet weights to the average. The value of weight variation test is expressed in percentage. • The tablet complies with the test if not more than 2 of the individual masses deviate from the average mass by more than the percentage . Weight Variation Test

17. WEIGHT VARIATION TOLERANCES FOR UNCOATED TABLETS Sr. No. Average wt. of tablet(mg) Max. % difference allowed 1 130 or less 10% 2 130-324 7.5% 3 More than 324 5% Sr. No. Average wt. of tablet(mg) Max. % difference allowed 1 84 or less 10% 2 84-250 7.5% 3 More than 250 5% IP Standards USP Standards

18. Leakage test for blister or strip packaging Vacuum Leak Method is used. It uses methylene Blue dye or another colored liquid to determine whether or not there is a leak. If there is a leak, the liquid will seep into the package, thereby giving visual proof. Vacuum leakage tester

19. IPQC OF LIQUID PRODUCTS

20. IPQC Tests FOR liquid Visual inspection Uniformity of content pH test Particle size Determination of phase Filled volume Check sealing

21. VISUAL INSPECTION Appearance should be good and patient compliant. Any bad color bad smell must be handled with care. Physical appearance of products for patient compliance is critical. So it should be good looking, elegant in appearance. DRUG CONTENT DETERMINATION Determination of drug content in suspension and syrups are important because their concentration has to be sufficient itself that it produce the pharmacological action. pH OF THE PRODUCT pH affects the stability of the product so before filling and after filling of syrups pH has to be checked out. It can be measured by pH meter.

22. DETERMINATION OF PHASE Phase separation may be observed visually or by measuring the volume of separate phases or by subjecting it to various stress conditions. PARTICLE SIZE Particle size becomes the important factor for the suitability of the product and all the particles has to be of same size and shape for proper dispersion in the solvent. Filled volume The volume should be checked with the measuring cylinder when sealing is done. Then it should be adjusted . Check Sealing Sealing should be checked by the operator to see if there are any defects .

23. IPQC of Sterile Products

24. IPQC Tests FOR STERILE PRODUCTS Some basic IPQC tests are done for sterile products such as: pH test Conductivity test Leakage test Volume test Clarity test etc. Other test like potency and sterility test is done by QC.

25. pH Test As sterile products are directly given to body cavity, so its pH must be compatible with the body fluid. The pH range for sterile products is 5.5 – 7.0 Before starting the manufacturing of the products the pH of WFI is checked. After finishing the manufacturing the pH of the product is also checked.

26. Conductivity Test As like pH the conductivity of the product must be compatible with body. The conductivity range of WFI is 0.3- 1.3 microsiemens /cm This is checked for two times. First only WFI is checked before manufacturing and then the finished product is checked. This is checked by placing the electrode into the sample as shown in figure.

27. Volume Test The volume of finished products is checked visually This test ensure the right dose Clarity Test The preparations clarity is tested visually The ampules /vials/bottles are placed under black and white background under LED light Presence of glass particle, dart or fiber is checked by this test

28. Leakage Test The test container is immersed in a dye bath. Vacuum and negative pressure is applied for some time. The container is removed from the dye bath and washed. The container is then inspected for the presence of dye visually The dye used may be of pink, blue, green, yellowish-green color.

29. Conclusion In-process control not only provides a means of controlling production. it also performs a quality assurance function . T he objective of the IPQC is to ensure the product quality by checking the processes. If any anomalies shown it is easy to correct it when a few product of a batch is manufactured. By this we can minimize material, time, cost, processes repetition. So that can it is easy to develop the quality of products. So maintaining IPQC is important and beneficial.