What Do You Mean By IPQC?
IPQC is concerned with providing accurate, specific, & definite descriptions of the procedures to be employed, from, the receipt of raw materials to the release of the finished dosage forms.
In-process Quality Control
- In process Quality Control, IPQC tests are mostly performed within the production area.
- They should not carry any risk for the quality of a product.
- In-process testing enables easier identification of problems. It sometimes identifies a defective product batch that can be corrected by rework, whereas once that batch has been completed, this may not be possible.
- Failure to meet In process control specifications indicates either that procedures were not followed or some factor(S) is out of control.
Various instruments used in the IPQC department
- Analytical balance
- Friability testing apparatus
- Bulk density apparatus
- Tablet hardness tester
- Vernier Caliper
- Disintegration apparatus
- Infra-red moisture content measuring apparatus
- TLC kit
- Karl fisher Titrimeter
Official and unofficial tests for evaluation of tablets
Official Tests:
Weight variation
Disintegration
Friability Test
Non-Official Tests:
Hardness
Thickness
General Appearance:
The general appearance of a tablet, its identity and general elegance is essential for consumer acceptance, for control of lot-to-lot uniformity and tablet-to-tablet uniformity. The control of general appearance involves the measurement of size, shape, color, presence or absence of odor, taste etc.
Size & Shape:
It can be dimensionally described & controlled. The thickness of a tablet is only variable. Tablet thickness can be measured by micrometer or by other devices. Tablet thickness should be controlled within a ± 5 % variation of the standard value.
Unique identification marking:
These markings utilize some form of embossing, engraving or printing. These markings include the company name or symbol, product code, product name etc.
Organoleptic properties:
Color distribution must be uniform with no mottling. For visual color comparison compare the color of sample against standard color.
Hardness:
Tablet requires a certain amount of strength or hardness and resistance to friability to withstand mechanical shocks of handling in manufacture, packaging and shipping. Hardness generally measures the tablet crushing strength.
Hardness (crushing strength):
It is the load required to crush the tablet when placed on its edge.
Why do we measure hardness?
- To determine the need for pressure adjustments on the tableting machine.
- Hardness can affect the disintegration.
- So if the tablet is too hard, it may not disintegrate in the required period of time. And if the tablet is too soft, it will not withstand the handling during subsequent processing such as coating or packaging.
- In general, if the tablet hardness is too high, we first check its disintegration before rejecting the batch.
- If the disintegration is within limit, we accept the batch.
- If Hardness is high + disintegration is within a time accept the batch.
Factors Affecting the Hardness:
- Compression of the tablet and compressive force.
- Amount of binder. (More binder à more hardness)
- Method of granulation in preparing the tablet (wet method gives more hardness than direct method, Slugging method gives the best hardness).
Friability:
The friability of a tablet can determine in a laboratory by a friabilator. This consists of a plastic chamber that revolves at 25 rpm, dropping the tablets through a Distance of six inches in the friabilator, which is then operated for 100 revolutions. The tablets are reweighed. Compress tablets that lose less than 0.5 to 1.0 % of the Tablet weight are considered acceptable.
It is the tendency of tablets to powder, chip, or fragment and this can affect the elegant appearance, and consumer acceptance of the tablet, and also add to the tablet’s weight variation or content uniformity problems.
Friability is a property that is related to the hardness of the tablet.
An instrument called Roche friabilator is used to evaluate the ability of the tablet to withstand abrasion in packaging, handling, and shipping.
ALSO READ: Typical Interview Questions and Answer
Procedure:
- Weigh 20 tablets together = W1
- Put these tablets in the friabilator and adjust the instrument at 100 rpm (i.e. = 25 rpm for 4 min)
- Weigh the 20 tablets (only the intact ones) = W2
Friability (% loss) = W1 - W2/100
It must be less than or equal to 1 %.
Thickness test
- Thickness is an unofficial test.
- The thickness of the tablet is inversely proportional to hardness i.e. increase in hardness decreases the thickness & vice versa.
- The thickness of the tablet is measured by a Vernier caliper/screw gauge.
- It is determined for 10 tablets.
Weight variation test (uniformity of weight)
- Weigh 20 tablets selected at random, each one individually. X1, X2, X3… Xz
- Determine the average weight. X= (X1+X2 +X3+…+ Xz)/20
Limit:
Upper limit = average weight + (average weight x % error)
Lower limit = average weight - (average weight x % error)
The individual weights are compared with the upper and lower limits.
Not more than two of the tablets differ from the average weight by more than the % error listed, and no tablet differs by more than double that percentage.
Disintegration test (U.S.P.):
The 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 tablets in a particular time period. A disintegration test is not performed for controlled & sustained-release tablets.
The U.S.P. device to test disintegration uses 6 glass tubes that are 3” long; open at the top and 10 mesh screens at the bottom end. To test for disintegration time, one tablet is placed in each tube and the basket rack is positioned in a 1-L beaker of water, simulated gastric fluid or simulated intestinal fluid at 37 ± 2℃ such that the tablet remains 2.5 cm below the surface of liquid on their upward movement and not closer than 2.5 cm from the bottom of the beaker in their downward movement. Move the basket containing the tablets up and down through a distance of 5-6 cm at a frequency of 28 to 32 cycles per minute. Floating of the tablets can be prevented by placing perforated plastic discs on each tablet.
According to the test, the tablet must disintegrate and all particles must pass through the 10 mesh screen in the time specified. If any residue remains, it must have a soft mass. Liquids used in disintegration Water, Simulated gastric fluid (pH = 1.2 HCl), or Simulated intestinal fluid (pH = 7.5, KH2PO4 (phosphate buffer) + pancreatic enzyme + NaOH)
U.S.P. method for uncoated tablets:
- Start the disintegration test on 6 tablets.
- If one or two tablets from the 6 tablets fail to disintegrate completely within 30min repeat the same test on another 12 tablets. (i.e. the whole test will consume 18 tablets).
- Not less than 16 tablets disintegrate completely within the time
- if more than two tablets (from the 18) fail to disintegrate, the batch must be rejected.
For Coated tablets:
- To remove or dissolve the coat, immerse the tablet in distilled water for 5min.
- Put the tablet in the apparatus in water or HCL for 30 min at 37oC (according to the U.S.P). If not disintegrated, put in intestinal fluid.
- If one or two tablets fail to disintegrate, repeat on 12 tablets. So 16 tablets from the 18 must completely disintegrate within the time, if two or more are not disintegrated the batch is rejected.
U.S.P. and B.P Method for Enteric-coated tablets:
- Put in distilled water for five minutes to dissolve the coat.
- Then put in simulated gastric fluid (0.1M HCL) for one hour.
- Then put in simulated intestinal fluid for two hours.
- If one or two tablets fail to disintegrate, repeat this test on another 12 tablets. So 16 tablets from 18 should completely disintegrate. If more than two fail to disintegrate the Batch must be rejected.
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