Ipqc tests of various dosage form
Download as PPTX, PDF3 likes1,196 views
IPQC checks are carried out during the manufacturing process to monitor critical variables that can impact product quality. In-process materials are tested for identity, strength, and purity, and any rejected materials are quarantined. The objectives are quality control, process control, and ensuring final product quality through continuous monitoring and implementation of good manufacturing practices. IPQC involves establishing and documenting controls to ensure output falls within acceptable standard ranges.
Ipqc tests of various dosage form
- 1. SCHOOL OF PHARMACY AND LIFE SCIENCES, CENTURION UNIVERITY OF TECHNOLOGY AND MANAGEMENT, BHUBANESWAR
- 2. IPQC are checks that are carried out before the manufacturing process is completed. The function of in process control is monitoring and if necessary adaptation of the manufacturing process in order to comply with the specification. In process material should be tested for identity, strength and purity as appropriate and approved or rejected by the QC UNIT during the production process. Rejected in process materials should be identified and controlled under a quarantine system designed to prevent their use in manufacturing. The objective of this control is both quality and process control.
- 3. To minimize inter-batch & intra-batch variability. To ensure quality of final product. To ensure cont. monitoring of process variable which are going to affect the quality of product. To ensure implementation of GMP in mfg. To give indication of a functional Quality assurance system.
- 4. IPQC is a process of monitoring critical variables of mfg. process to ensure a Quality of the final product & give necessary instruction if any discrepancy is found. These controls are established & documented by QC & production personnel to ensure that a predictable amount of each output cycle falls within the acceptable std. Range.
- 5. Tablets 1. MOISTURE CONTENT OF DRIED GRANULATION Loss on drying(LOD) can used to determine whether or not the granulation solvent has been removed to a sufficient level during the drying operation ( Usually LT 2% moisture). 2. WEIGHT VARIATION The USP wt. Variation test is performed by weighing 20 tablets individually , calculating the avg. Wt. & comparing the individual tablet wt. to the avg. The individual wt. Should be within 5% of nominal wt. AVG. WT. OF TABLETS(USP) MAX. % DIFF. ALLOWED AVG. WT OF TABLETS(IP) 130 OR less 10 80 or less 130- 324 7.5 80- 250 More than 324 5 More than 250
- 6. 3. TABLET HARDNESS (tablet crushing strength) Tablet hardness is defined as he force required to break a tablet in a diametric compression test. Hardness tester: Monsanto, Strong cobb, Pfizer, Erweka, Schleuniger tester. Tablet hardness is determined periodically throughout the batch to ensure that tablets are robust enough for coating, packing & shipping & not too hard to affect dissolution. HARDNESS OF COMPRESSED TABLET IS 5- 8 K.G/C.M 2 Oral tablet: 4-8 k.g, chewable tablet: 3 k.g, sustained release tablet: 10-20 k.g. 4. FRAIABILITY Another measure of tablet’s strength is friability. The lab. Friability tester is known as the ROCHE FRIABILATOR. % FRIABILITY =( initial wt. – final wt./ initial wt.) x 100. It is defined as the % of wt. Loss by tab. Due to mechanical action during the test.
- 7. TEST: Contains a plastic chamber that revolves at 25 rpm, 100 revolution per min, drop tablets at a distance of 6 inches with each revolution. Tablets that lose LT 0.5- 1% of wt. are considered acceptable. 5. CONTENT UNIFORMITY : • It is defined as the degree of uniformity in the amount of the drug substance in a tablet. It is related to efficacy and for potent and narrow therapeutic index drug it is also associated with safety. TEST: done by taking 30 tablets and 10 tablets are taken individually. It will pass the test if 9 o the 10 tablet contain NLT 85% & NMT 115% and the 10th tablet contain NLT 75% & NMT 125%. The remaining 20 tablets none may fall outside range of 85- 115%.
- 8. 6. TABLET DISSOLUTION Dissolution is imp. To ensure proper drug release characteristics (in vitro availability) & batch to batch uniformity. Apparatus Type 1- Basket Type 2-paddle Type 3-Reciprocating Cylinder Methods Type 4-Flow Though Cell Methods Type 5-Paddle Over Disk Methods Type 6-Cylinder Methods Type 7-Reciprocating Disc Methods TESTS: Tablets are placed in dissolution media at 37+ 0.5 C. ACCEPTANE CRITERIA: More than 75% release in 45 min. Objectives of invitro test: Drug release is 100%. Rate of release is uniform.
- 9. Dissolution testing can be interpreted in 3 stages, Cont. Testing through 3 stages unless the results confirm at either s1 or s2. The quantity q is the released labelled content of active ingredients as per a % as specified in the individual monograph; both the 5% & 15% values in the acceptance table are % of the labelled content so that these values & q are in the same terms. 7. DISINTEGRATION TEST: Disintegration of tablet means to breakdown the tablet into smaller particles after swallowing, The time required to disintegrate the tablet is called disintegration time STAG E SAMPLES TESTED ACCEPTANCE CRITERIA S1 6 Each unit is NLT q+5%. S2 6 Avg. Of 12 units (s1+s2) is equal to or GT q, & no unit is LT q-15%. S3 12 Avg. Of 24 unit (s1+s2+s3) is equal to or GT Q, NMT 2 units are LT q- 15% ; no unit is LT q- 25%.
- 10. APPARATUS: The USP device to disintegration uses 6 glass tubes that are 3 inches long, open at the top & held against a 10 mesh screen at the bottom end of the basket. The basket rack is placed in 1 L beaker of water, simulated gastric fluid, or simulated intestinal fluid at 39 or 35 C, such that the tablets remain 2.5 c.m below the surface of the liquid & not closer than 2.5 c.m from the bottom of the beaker. PROCEDURE: Place one dosage unit in each of the six tubes of the basket and if specified add a disc. Operate the apparatus using water as the immersion fluid unless another liquid is specified and maintain its temperature at 37 °C. At the end of the specified time, lift the basket from the fluid and observe the dosage units: all of the dosage units have disintegrated completely. If one or two dosage units fail to disintegrate, repeat the test on 12 additional dosage units.
- 11. • The requirements of the test are met if not less than 16 of the 18 dosage units tested are disintegrate. Table showing disintegration time, TABLET DISINTEGRATION TIME Soluble tab. 3 min. Sublingual tab. 3 min. Effervescent tab. 5 min. Uncoated tab. 15 min. Film coated tab. 30 min. Sugar coated tab. 1 hr. Enteric coated tab. 3 hr.
- 12. TABLET COATING: 1. WATER VAPOUR PREMEABILITY: If the coating is going to be used as a seal coat or to provide some physical protection for a tablet containing a water unstable drug, then it is calculated by water vapour permeability rate. 2. FILM TENSILE STRENGTH: Strips of the film are tested on a tensile strength tester by applying a known force at a cont. Rate. The elasticity and tensile strength /breaking stress of the film are evaluated. (ALL ARE SAME AS TABLET) CAPSULE: 1. UNIFORMITY OF WEIGHT: Done on 20 capsules. Limit: Not more than two of the individual weights deviate from the average weight by more than the % deviation shown on the table, none deviates
- 13. by more than twice that percentage. (All are same as tablet). AVG. WT. OF CAPSULE % DEVIATION Less than 300 mg 10% 300 mg or more 7.5% DOSAGE TYPE SUBTYPE DOSE & RATIO OF DRUG >25 mg <25 mg Hard gelatin capsule Powder or others WV CU Soft gelatin capsule Suspension, emulsion, gel CU CU Solutions WV WV
- 14. STERILE PRODUCTS: These are the products which are manufactured using sterilization or aseptic processing conditions There are two types of sterile dosage form, 1. Parenteral preparation 2. Opthalmic preparation The in-process quality control test includes the leakage and clarity testing. The quality control of finished product required the pyrogen and sterility testing. A. Leakage test: Leakage test is employed to test the package integrity. Package integrity reflects its ability to keep the product in and to keep potential contamination out. It is done by dye bath test. DYE BATH TEST The test container is immersed in a dye bath. Vacuum and pressure is applied for some time. The container is removed from the dye bath and
- 15. washed. The container is then inspected for the presence of dye either visually or by means of uv spectroscopy. The dye used may be of blue, green, yellowish-green color (Normally 1% methylene blue was used). The dye test can be optimized by use of a surfactant and or a low viscosity fluid in the dye solution to increase the capillary migration through the pores. The test is used for ampoules and vials & mainly is qualitative. B. Clarity test : Clarity testing is carried out to check the particulate matter in the sample. In this test transparent particles or white particles observed against the black background and the black or dark particles observed against the white background. Instrumental methods of evaluation of particulate matter in liquids utilizing the principles of light scattering , light absorption & electrical resistance.
- 16. C. Pyrogen testing : There are two type of test for detecting pyrogen in the formulation. LAL test: The LAL (limulus amebocyte lysate) Assay is an in vitro assay used to detect the presence and concentration of bacterial endotoxins in drugs and biological products. Endotoxins, which are a type of pyrogen, are lipopolysaccharides present in the cell walls of gram-negative bacteria. Pyrogens as a class are fever-inducing substances that can be harmful or even fatal if administered to humans above certain concentrations. This test is based upon the gelling property of an enzyme, the limulus amebocyte lysate extracted from the horse shoe crab, limulus polyphormus. The enzyme gels in the presence of bacterial endotoxin and the degree of gelling is related to the amount of endotoxin present. A no. of instrument are available for measuring the degree of gelling of enzyme. The test can be used for quantifying the amount bacterial endotoxin present.
- 17. Rabbit test: The rabbit pyrogen test in an in vivo test to detect pyrogens qualitatively. Rabbits have a similar pyrogen tolerance to humans, so by observing a change in body temperature in rabbits it is possible to make a determination of the presence of pyrogens. This method can detect non-bacterial endotoxin pyrogens as well as bacterial endotoxins. It is intended to be used for liquid products that can be tolerated by the test rabbit in a dose of 10 ml per kg, injected intravenously, generally within a period of not more than 4 minutes Test animal: Use healthy, adult rabbits, preferably of the same variety. House the animals individually in an area of uniform temperature (±2 °C), possibly with uniform humidity, and free from disturbances likely to excite them. One to 3 days before using an animal that has not previously been used for a pyrogen test. Temperature recording: use an accurate thermometer graduated in 0.1 °c that has been tested to determine the time necessary to reach the maximum reading. Insert the temperature-sensing device into the rectum of the test animal to a depth of about 6 cm.
- 18. Procedure: For 2 hours before the test and during the test, withhold all food from the animals being used. Access to water may be allowed. The animals should be placed under the conditions of the test at least 1 hour before the injection. Prior to the test, 40 minutes before the injection of the test material, determine the temperature of each animal by taking 2 measurements at an interval of 30 minutes. The mean of the 2 temperatures serves as the "control temperature" of the animal. The control temperature recorded for each rabbit constitutes the temperature from which any subsequent rise following the injection of the material is calculated. Inject into a marginal vein of the ear of each of 3 rabbits 10 ml of the solution per kg of body weight . The injection should last not longer than 4 minutes, unless otherwise specified in the monograph. When the injection has been completed, record the temperature of the animal during a period of 3 hours, taking the measurements continuously or every 30 minutes. The max. Temp. recorded for each rabbit is considered to be its response; if the temp. readings taken after the injection are all below the control tem., the response is treated as a zero temp. rise.
- 19. Interpretation of result according to IP, BP, USP, PHARM ACOPEI A NO. OF RABBITS IN A GROUP PASSES IF TEMP. IS NMT ( DEGREE C) FAILS IF TEMP. IS MT (DEGREE C) IP 3 1.4 Each rabbit temp. raise should not be MT 0.6 C. 8 3.7 USP 3 _ Each rabbit temp. raise should not be MT 0.6 C. 8 3.3 BP 3 1.15 2.65 6 2.80 4.30 9 4.45 5.95 12 6.6 6.6
- 20. D. STERILITY TESTING : The test for sterility are intended for detecting the presence of viable micro organism in pharmaceutical preparation that are designed to be sterile. The test is based on the principle that if micro organism are placed in a medium that provide optimum condition of nutrition, moisture, PH, aeration, temp., they can grow and their presence will be indicated by the presence of turbidity in clear medium. Test for sterility may be carried out by one of the following two methods. 1. Membrane filtration method: Use membrane filters having a nominal pore size not greater than 0.45 μm whose effectiveness to retain microorganisms has been established. Specially adapted filters may be needed for certain products (e.g., for antibiotics). The technique described below assumes that membranes about 50 mm in diameter will be used. If filters of a different diameter are used, the volumes of the dilutions and the washings should be adjusted accordingly. The filtration apparatus and membrane are sterilized by appropriate means. The apparatus is designed so that the solution to be examined can be introduced and filtered under aseptic conditions.
- 21. it permits the aseptic removal of the membrane for transfer to the medium, or it is suitable for carrying out the incubation after adding the medium to the apparatus itself. After filtration the preparation membrane is cut into two halves. One halve is transferred in to 100 ml of culture medium meant for the growth of the bacteria and incubated at 30 to 350C. For not less than 7 days. The another halve is transferred to 100 ml of culture medium meant for fungi and incubated at 20 to 25 C for not less than 7 days. 2. Direct inoculation method: There are certain products that are not filterable or deformable. These products are normally tested using direct inoculation. In this method, the test sample is added directly into the required media, ensuring that the amount of sample is below 10%. In this method an aliquot quantity of the material being tested is drawn aseptically from the container and transferred to a vessel containing a measured quantity of a suitable culture medium. The culture is incubated at appropriate temperature for not less than 14 days. The culture medium is observed at periodic intervals during the incubation period and at the end to detect presence of any microbial growth.