Quality Control Test of Tablet in Pharmaceutical Industry

Quality Control Test (Tablet Evaluation Parameter): These tests evaluate each step of formulation and the finished product to obtain good quality products. There are several tests for the evaluation of tablets.

A. Non-official test:

1. General Appearance

2. Size and shape

3. Thickness Test

4. Hardness Test

5. Friability Test

B. Official Test

6. Weight Variation 

7. Disintegration Test

8. Dissolution Test

9. Content Uniformity

1. General Appearance:

The general appearance of a tablet is its identity and "elegance," which is essential for consumer acceptance. It involves size, shape, color, odor, taste, and surface texture.

2. Size and Shape:

It depends upon the die and punches used for making tablets. Generally, they are biconvex, oval, circular, oblong, and flat.

3. Thickness:

Tablet thickness must be maintained within a ±5% range of the reference value. It is measured by an vernier caliper or screw gauge.

4. Hardness test:

Tablets must be capable of withstanding mechanical handling shocks during the manufacturing, packaging, and shipping processes and are resistant to friability. Hardness generally measures the tablet crushing strength. In general, Tablet crushing strength is measured by hardness. It's the amount of energy necessary to disintegrate a tablet. 

Why hardness of the Tablet is essential?

• It is measured to determine the need for adjustment of compression pressure. 
• If the Tablet is too hard, then it should not disintegrate easily. If the Tablet is too soft, it causes problems during coating, handling, packaging, and transportation.
• Generally, if the Tablet's hardness is too high, we first check its disintegration before rejecting the Batch.
• If the disintegration is within the limit, we accept the Batch.
• Accept the Batch if Hardness is high and disintegration is within a time.

What are the factors affecting the hardness?

• Compression of the Tablet and compressive force
• Quantity of binder used. Hardness will increase if more binder is used during the manufacturing of tablets.
• Method of granulation during tablet manufacturing. The wet granulation method gives more hardness than the direct compression method. The slugging method gives the best hardness. 

5. Friability Test:

This test aims to evaluate the tablets' physical adaptability during handling and transportation. This test is applicable for compressed tablets and uncoated tablets. This test is official according to U.S.P. but not in I.P. The Roche friabilator can be used in a laboratory to verify a tablet's friability. This is mainly composed of a plastic chamber that rotates at 25 rpm and drops the tablets into the friabilator six inches away. The friabilator is then turned on for 100 revolutions, which takes four minutes to complete. Acceptable compressed tablets lose less than 0.5 to 1.0% of their total weight.

Procedure:

• First of all, weigh the required quantity of tablets. If the total weight of a single random tablet is less than or equal to 625 mg, then take a tablet weight equal to 6.25 gm or more than 6.25 gm. If the total weight of each Tablet is more than 625 mg, then ten randomly selected whole tablets are taken. Assume this initial weight as W1.
• Now, drop the tablets in the apparatus and start until it completes 100 times the revolution.
• After completion, take out the same tablets and remove the small broken particles and dust with the help of tissue paper. Again, weigh the Tablet on the weighing balance. Assume the final weight as W2.

Calculation:

Friability %: W1-W2/W1x100

•  W1= Weight of the Tablet before friability
• W2= Weight of the tablets after friability

Acceptance Criteria: 

• The maximum loss of tablets should not be more than 1%.
• The test is not passed if all or some tablets break and friability is less than 1%.
• All the tablets are normal if the friability is more than 1%. The tests are performed three times: T1, T2, and T3. If the average of all 3 test results is less than 1%, then the test is passed. If the average of all 3 test results is more than 1%, then the test fails.

6. Weight Variation Test: Uniformity of weight:

The weight variation of tablets measured routinely helps to ensure that the Tablet contains the proper amount of the drug. The variation test is applicable when the Tablet contains 50 mg or more of the drug substance or when the dosage form unit contains 50% or more of the drug substance (weight).

Procedure:

• Take 20 tablets selected randomly and weigh them individually W1, W2, W3,.........W20.
• Calculate the average weight =(W1+W2+W3+........W20)/20
• Calculate upper and lower variation by using the given formula

Upper variation(+)=Highest wt. of tab.-Theoretical Avg. wt. of tab. x100
                                               Theoretical Avg. wt. of tablet
Lower variation (-) = Lowest wt. of tab.-Theoretical Avg. wt. of tab. x100
                                              Theoretical Avg. wt. of tablet

• Compare the individual tablet weight to the theoretical average weight. 
• The percentage error indicated should not be exceeded by more than two tablets' variation from the average weight, and no tablet differs by more than double that percentage.

Limit: Weight variation tolerance

IP Standard: 

Average Weight of Tablet	% deviation
Less than 80 or 80 mg 80 mg to 250 mg More than 250 mg	±10% ±7.5% ±5%

USP Standard:

Average Weight of Tablet	% deviation
Less than 130 or 130 mg 130 mg to 324 mg More than 324 mg	±10% ±7.5% ±5%

7. Disintegration Test:

That is the time it takes for the Tablet to disintegrate. The disintegration test calculates how long it takes for a batch of tablets to break up into smaller pieces under particular circumstances. It helps to know how long a tablet takes to disintegrate after swallowing. The time required to disintegrate the Tablet is called disintegration time. The disintegration apparatus contains a water bath and beaker filled up to mark. A basket rack holding six plastic tubes is open at the top, and the bottom is covered with a 10-mesh screen. The test requires that the Tablet break up and that every particle go through the ten mesh screen in the allowable amount of time. If any residue is left, it needs to be soft in mass. A disintegration test is not performed for controlled & sustained-release tablets.

Procedure:

• Take 1000 ml of disintegration beaker and fill liquid media up to mark.
• Place the beaker into the water bath and maintain the temperature at 37±2°C.
• The basket rack assembly is suspended over the beaker. Now, place one Tablet in each tube.
• The cylindrical disk made of transparent plastic is also placed over the Tablet. The disc also generates little pressure on tablets.
• Start the machine, and the assembly moves up and down at a specified rate (30 R.P.M.).
• Note down the disintegration time.

Disintegration testing conditions for different types of tablets.

Types of Tablets	Medium	Temp.	Limit
Uncoated	Water/buffer	37±2°C	NMT 15 minutes
Film-coated	Water	37±2°C	NMT 30 min
Sugar-coated (1 or 2 tabs. Fail)	Water 0.1N HCl	37±2°C	NMT 60 minutes
Dispersible	Water	20±5°C	NMT 3 minutes
Effervescent	Water	20±5°C	NMT 5 minutes
Enteric-coated	0.1M HCl/ Phosphate Buffer pH 6.8	37±2°C	2 hours in HCL: No disintegration NMT 60 minutes in buffer
Soluble	Water	20±5°C	3 minutes

U.S.P. method for uncoated tablets:

• Start the disintegration test on six tablets. 

• If one or two tablets from the six tablets fail to disintegrate entirely within 30 minutes, 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 tablets) fail to disintegrate, the Batch must be rejected.

U.S.P. method for coated tablets:

• Put the Tablet in distilled water for five minutes to remove or dissolve the coating.

• 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, it was 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 out of 18 should completely disintegrate. If more than two fail to disintegrate, the Batch must be rejected.

8. Dissolution Test:

Dissolution tests are in vitro experiments that quantify the rate and degree of pharmaceutical product substance release or dissolution from an aqueous medium—under predetermined conditions. It is a process by which a solute dissolves into a solvent or solution. It is a solid mass transfer process into a liquid medium. It mainly depends on the aqueous solubility of the drug. The aqueous solubility increases, increasing the rate of dissolution of the drug. So, this test is performed to predict the time required for a given amount of drug to be released into the solution. It also helps to determine the bioavailability of a drug. It is an official test. The size, shape, and surface area of particles have a significant impact on how quickly a drug dissolves. Dissolution is based on four processes – 1. wetting 2. Solubility 3. Swelling 4. Diffusion.

It consists of a cylindrical vessel with a hemisphere bottom and is made up of transparent glass with a 1000 ml capacity. The vessel is fitted with a cover having four holes: one for the shaft, one for the thermometer, and two for the sample.

Dissolution Apparatus According to I.P.:

According to I.P. 2018

• Apparatus I: Paddle

• Apparatus II: Basket

According to I.P. 2022

• Appratus I: Basket
• Appratus II: Paddle

Dissolution Apparatus According to U.S.P.:

Apparatus 1: Rotating Basket

Apparatus 2: Paddle assembly

Apparatus 3: Reciprocating cylinder

Apparatus 4: Flow-through cell

Apparatus 5: Paddle over disk

Apparatus 6: Cylinder

Apparatus 7: Reciprocating holder

Procedure:

• Immerse the vessel in the water bath.

• Place 1000 ml of dissolution medium into the vessel and maintain the temperature 37±0.5°C.

• Now place six tablets to type (basket or paddle)

• Set R.P.M. according to the monograph (IP/USP) and start for dissolution for a time, as mentioned in the monograph.

• After a specific interval, take 5 to 10 ml of the sample and refill the vessel with 5 to 10 ml of fresh medium.

• Now, the sample is tested by U.V. spectroscopy, HPLC, or some other suitable analytical method.

• Find the released drug amount in the sample and match it with the standard.

Acceptance Criteria:

S1 Stage: 

In the S1 stage of dissolution, six units are analyzed. The dissolved amount of each unit should not be less than (Q+5%). 

S2 Stage: 

If any of the units fall below the limit in the S1 stage, an additional six units are to be analyzed, which is the S2 stage. At this stage, the average of 12 units (S1+S2) ought to be greater than or equal to Q. No unit should be less than (Q-15%).

S3 Stage: 

If any unit falls below (Q-15%) or the average of 12 units is lower than Q. Then another 12 units are to be analyzed, which is the S3 stage. The 24-unit average (S1+S2+S3) ought to be greater than or equal to Q. No unit should be less than (Q-25%), and not more than two units should be less than (Q-15%)

Where Q= Labelled amount of dissolved substance.

9. Content Uniformity:

To determine the active ingredient by the method in the assay.

Procedure: 

• Select 30 tablets randomly, and at least ten are assayed individually.
• The Tablet passes the test if nine out of ten tablets have at least 85% and no more than 115% of the claimed label content. 
• Furthermore, the content of the tenth Tablet can be at least 75% or greater than 125% of what is labeled. 
• The remaining 20 tablets are analyzed separately if these requirements are satisfactory, and all of them may test at most 85 to 115%.

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