Quality control tests of tablets or Evaluation of tablets

Quality control tests of tablets or evaluation of tablets is a systematic determination of physical, chemical, mechanical, biological, or microbiological properties of tablets on the basis of in-house (Non-Pharmacopoeial), Pharmacopoeial standards such as BP, USP, Ph. Eur., Ph. Int., JP, IP, ChP, or others guidelines such as ICH etc. To design the perfect tablets and later monitor tablet production quality, quality control tests of tablets or evaluation of tablet’s physical, chemical, and bioavailability properties must essential. Bioavailability vs Bioequivalence

A variety of methods are using for evaluation of tablets or conduct quality control tests of tablets. All of the quality control tests of tablets or evaluation tests of tablets are classified into three categories:

A. Non-Pharmacopoeial or Non-Official Tests or In-House Tests of Tablet:

  1. Appearance/ Description
  2. Thickness and Diameter
  3. Hardness
  4. Organoleptic properties

B. Pharmacopoeial or Official Tests of Tablets:

  1. Identification Tests
  2. Friability
  3. Disintegration
  4. Weight Variation
  5. Uniformity of Dosage Unit
  6. Dissolution
  7. Assay
  8. Impurities

C. Specific Pharmacopoeial Tests of Tablets

  1. Microbiological Examination of tablets
  2. Acid-Neutralizing Capacity
  3. Quality test of Splitting Tablets with Functional Scoring
  4. Water content

Non-Pharmacopoeial or Non-Official Tests or In-House Tests

Choice of these tests and their specification depend on the formulator during drug product development and these tests are not restricted or specified in any pharmacopoeia.

Appearance/ Description

The appear­ance of a tablet is crucial for patient compliance and identification. The control of the appearance of a tablet includes the measurement of a number of attributes such as a tablet’s shape, surface texture, diameter, thickness, color, absence or presence of an odor, taste, physical flaws and consistency, scoreline, and legibility of any unique identification markings such as embossed or engraved with a logo or letter(s).

For example, A light blue colored, vanilla flavored, round, biconvex film-coated tablet with plain surfaces on both sides. Appearance is a non-pharmacopoeial/ unofficial/ in-house evaluation of tablets or quality control tests of tablets.

Unique Identification Markings

Unique Identification Markings of tablet: a non-pharmacopeial quality control test of tablets

Pharma­ceutical companies often use some type of unique markings such as embossed or engraved with a symbol or letters or printing on the tablet for rapid identifica­tion. The tablets may score in halves or quadrants to facilitate breaking or to make the smaller dose. Intact and clear unique identification markings on tablets are acceptable.

Thickness of tablets

The thickness of the tablet is the only dimensional variable related to the tablet compression process. Generally, it is measure with a micrometer. The thickness should control within ±5% variation of a standard value and must control for patient acceptance and make the tablet packaging easier.

Diameter and Shape of Tablets

The diameter and shape of the tablets should control by the diameter and shape of the die and punches during the compression process. USFDA recommends that the diameter of the tablet should be 8 mm or less than 8 mm and should not exceed 22 mm. Generally, tablet shapes are round, oval, oblong, caplet, cylindrical, triangular etc. The upper and lower surfaces of tablets may be flat, round, concave, or convex to various degrees. The diameter and shape of the tablet influence esophageal transit, administration techniques (i.e., use of fluids, patient position), and irrespective of patient factors. 21 Core Tablet defects

USFDA recommends that the diameter of the tablet should be 8 mm or less than 8 mm and should not exceed 22 mm.

Organoleptic properties (color, odor, and taste)

Color: Tablet color is crucial for identification and patient acceptance.

Odor: Some types of tablets such as ODT tablets, chewable tablets have an odor to make a pleasant taste and improve patient acceptance. Besides in some tablets, flavoring agents are used within coating material to mask bad odor.

Taste: Taste is important for patient acceptance especially for ODT tablets, chewable tablets, and dispersible tablets.

Tablet breaking force/Hardness of Tablets

The breaking force of tablets is commonly called “hardness” in the pharmaceutical literature; however, the use of this term is misleading according to USP. Certainly tablets require a definite amount of hardness to withstand mechanical shocks of handling in manufacture, packaging, and transportation without affecting the disintegration limit. Generally, oral tablets have a hardness of 4 to 10 kg. However, ODT tablets and chewable tablets have less hardness and often sustained-release tablets are much harder. The units of measurement of tablet hardness are Kilogram (kg), Newton (N), Kilopond (kp), Pound (lb), Strong-Cobb (SC).

Pharmacopoeial or Official Tests

These tests are specified either in individual product monograph or general monographs.

Identification Tests of Tablets

The identification test is specified in a product monograph as an aid to confirm that the tablet contains the labeled drug substance by providing positive identification of the active substance(s) and identification of specific excipient(s), such as preservatives in a drug product.

Generally, one method of confirming the identity is to compare the retention time of the sample with that obtained for the standard injections in a chromatographic assay procedure by HPLC. Other methods also used to orthogonally confirm the identity of the active ingredient are: Thin-Layer Chromatographic Identification Test, Spectroscopic Identification Tests, Nuclear Magnetic Resonance Spectroscopy, Near-Infrared Spectroscopy as well as Raman Spectroscopy among others [2]. It is a pharmacopoeial test for the evaluation of tablets or quality control tests of tablets.

Friability test of uncoated tablets

Friability testing is used to test the durability of tablets during transit (packing, transportation). Measurement of tablet friability supplements other physical strength measurements, such as tablet breaking force. It is a pharmacopoeial test for the evaluation of tablets or quality control tests of tablets. You may also read the Friability test of tablets, Granules, Spheroids.

For ≤ 650 mg weight of tablets, take 6.5 g tablets or as near as possible to 6.5 g. For tablets with more than 650 mg weight, take 10 tablets. The tablets must be carefully dedusted prior to testing. Friability may calculate from the following equation:

Friability test: evaluation test of Tablets

Limit: A maximum weight loss (obtained from a single test or from the mean of three tests) of not more than 1.0% is considered acceptable [2, 3]. Moreover, effervescent tablets and chewable tablets may have different specifications as far as friability is concerned.

Disintegration Time test

Disintegration is the process by which a solid oral dosages form such as tablet breaks down into smaller particles or granules. The tablets must disintegrate and all particles must pass through the 10-mesh screen in the time specified. Complete disintegration is that state in which any residue of the unit (tablet or capsule or granules) except fragments of insoluble coating or capsule shell, remaining on the screen of the disintegration apparatus or adhering to the lower surface of the disk if used, is a soft mass having no palpably firm core. Disintegration is provided to determine whether tablets, capsules, or granules disintegrate within the prescribed time when placed in a suitable liquid medium in a 1000 ml beaker at 37°C ± 2°C. It is a pharmacopoeial test for the evaluation of tablets or quality control tests of tablets.

Disintegration Time of Tablets as per USP

Types of TabletImmersion Fluid/ MediumTemp.Limit
*Uncoated or Plain-coated tabletsWater or specified medium as the immersion fluid.37 ± 2°CAs specified in the individual product monograph.
Delayed-Release Tablets or Acid-Resistant or Enteric-Coated Tablet0.1 M Hydrochloric acid, or Simulated Gastric Fluid as specified in the monograph.37 ± 2°CAfter 1 hour no evidence of disintegration, cracking or softening.
pH 6.8 phosphate buffer, or Simulated Intestinal Fluid as specified in the product monograph.37 ± 2°CAs specified in the individual product monograph.5 mins or as specified in the individual product monograph.
Effervescent Tablets200 ml of water in 250–400 ml beaker.37 ± 2°C5 mins or as specified in the individual product monograph.
Effervescent GranulesPlace 1 dose in 200 ml of water in 250–400 ml beaker.37 ± 2°C5 mins or as specified in the individual product monograph.
Buccal, Sublingual Tablets, Orally Disintegrating Tablets, Chewable TabletsWater or specified medium as the immersion fluid.37 ± 2°CAs specified in the individual product monograph.
Tablets for Oral Suspension or Oral Solution or Topical solutionWater or specified medium as the immersion fluid.37 ± 2°CAs specified in the individual product monograph.
* If 1 or 2 tablets fail to disintegrate completely, repeat the test on 12 additional tablets.

Disintegration Time of Tablets as per BP

Types Of TabletsImmersion Fluid/ MediumTemp.LimitRemarks
Uncoated TabletsWater37 ± 2°C15 MinutesIf fail to comply repeat the test on a further 6 tablets, omitting the discs.
Film Coated TabletsWater37 ± 2°C30 MinutesIf fail to comply repeat the test on a further 6 tablets, omitting the discs.
Coated Tablets other than Film-Coated Tablets / Sugar Coated TabletsWater37 ± 2°C60 MinutesIf fail to comply repeat the test on a further 6 tablets, replacing water with 0.1 M hydrochloric acid. If 1 or 2 tablets fail repeat the test on further 12 tablets.
Gastro-Resistant Tablets0.1 M Hydrochloric Acid37 ± 2°CAfter 2 h-3h no evidence of disintegrationLimit is typically 2 h to 3 h but even with authorized deviations is not less than 1 h.
pH 6.8 Phosphate Buffer37 ± 2°C60 MinutesIf fail to comply repeat the test on a further 6 tablets, omitting the discs.Place 1 tablet in a beaker. Repeat the operation on 5 other tablets.
Effervescent Tablets200 ml of Water15-25 °C5 mins or as specified in the individual product monograph.Place 1 tablet in a beaker. Repeat the operation on 5 other tablets.
Oral Lyophilisates200 ml of Water15-25 °CWithin 3 MinutesPlace 1 tablet in a beaker. Repeat the operation on 5 other tablets.
Soluble TabletsWater15-25 °CWithin 3 MinutesSoluble tablets are uncoated or film-coated tablets.
Dispersible TabletsWater15-25 °CWithin 3 MinutesFineness of dispersion: Place 2 tablets in 100 mL of water and stir until completely dispersed and passes through a sieve mesh 710 µm.
Orodispersible TabletsWater15-25 °CWithin 3 MinutesOrodispersible tablets are uncoated tablets intended to be placed in the mouth where they disperse rapidly before being swallowed.

Uniformity of Weight (Mass) of Tablet

Weight variation test is performed to determine that the consistency of formulated preparations. It is a pharmacopoeial test for the evaluation of tablets or quality control tests of tablets. According to USP, BP & IP the accepted limit of weight variation is given below:

IP/BP Average Mass LimitUSP
Tablet weight 80 mg or less± 10%Tablet weight 130 mg or less
More than 80 mg or Less than 250mg± 7.5%130 mg to 324 mg
250 mg or more± 5%More than 324 mg

Uniformity of Dosage Unit

The term “uniformity of dosage unit” is defined as the degree of uniformity in the amount of the drug substance among dosage units. To ensure the consistency of dosage units, each unit in a batch should have a drug content within a narrow range around the label claim. It is a pharmacopoeial test for the evaluation of tablets or quality control tests of tablets.

The uniformity of dosage units can be demonstrated by either of two methods, Content Uniformity or Weight Variation. The test for Content Uniformity of preparations presented in dosage units is based on the assay of the individual content of drug substance(s) in a number of dosage units to determine whether the individual content is within the limits set [2,3].

You may apply the content uniformity method in all cases. In addition, which method you select either Content Uniformity (CU) and Weight Variation (WV) to determine the uniformity of dosage unit depend on dose and ration of drug substance in a dosage form.

Uniformity of Dosage Unit

Dissolution test of Tablets

Dissolution is the process in which a substance forms a solution. In vitro dissolution testing measures the extent and rate of solution formation from a dosage form (the amount of percentage of the drug substance in a dosage form such as tablets, capsules to go into solution) within a specific time under a specified set of conditions. The terms dissolution and drug release are used interchangeably. The USP dissolution test in the monograph is related to Bioavailability and Bioequivalence study only when closely allied with a sound regulatory determination. Without this association, the dissolution test should be regarded solely as a quality control test for batch release [4]. It is a crucial pharmacopoeial test for the evaluation of tablets or quality control tests of tablets.

The volume of the dissolution medium is generally 500, 900, or 1000 ml. The use of a hydro-alcoholic medium is discouraged. Certainly conduct all dissolution tests for IR dosage forms at 37±0.5°C. You may find the dissolution data of drug products from: https://www.accessdata.fda.gov/scripts/cder/dissolution

Before the dissolution test you have to select the following information:

  • Apparatus
  • Speed (RPMs)
  • Medium Volume (mL)
  • Recommended Sampling Times (minutes)

Types of Dissolution Apparatus

The United States pharmacopeia and British pharmacopoeia recommend four types of dissolution apparatus for Test for Solid Dosage Forms:

General Name Types of Dissolution ApparatusCritical test parametersDosage form to be tested
Apparatus-1Basket Apparatus  Rotation SpeedConventional/Immediate-Release, Prolonged/Extended-Release, Delayed-Release Dosage Forms
Apparatus-2Paddle ApparatusRotation SpeedConventional/Immediate-Release, Prolonged/Extended-Release, Delayed-Release Dosage Forms
Apparatus-3Reciprocating CylinderDip RateConventional/Immediate-Release, Prolonged/Extended-Release,
Apparatus-4Flow-Through CellFlow Rate Of MediumConventional/Immediate-Release, Prolonged/Extended-Release,

Acceptable limit of Dissolution

Generally, Not less than 75% (Q) of the labeled amount of drug is dissolved in 45 minutes or specified in individual product monograph.

For rapidly dissolving products, generation of an adequate profile sampling at 5- or 10-minute intervals may be necessary. For highly soluble and rapidly dissolving drug products (BCS classes 1 and 3), a single-point dissolution test specification of NLT 85% (Q=80%) in 60 minutes or less is sufficient as a routine quality control test for batch-to-batch uniformity. On the other hand, for slowly dissolving or poorly water-soluble drugs (BCS class 2), a two-point dissolution specification, one at 15 minutes to include a dissolution range (a dissolution window) and the other at a later point (30, 45, or 60 minutes) to ensure 85% dissolution, is recommended to characterize the quality of the product [4].

Dissolution testing and interpretation can be continued through three stages if necessary. In stage 1(S1), six tablets are tested and are accept­able if all of the tablets are not less than the monograph tolerance limit (Q) plus 5%. If the tablets fail S1, an additional six tablets are tested (S2). The tablets are acceptable if the average of the twelve tablets is greater than or equal to Q and no unit is less than Q minus 15%. If the tablets still fail the test, an additional 12 tablets are tested. The tablets are acceptable if the aver­age of all 24 tablets is greater than or equal to Q and if not more than 2 tablets are less than Q minus 15% [2].

Assay test: crucial quality control tests of tablets

The assay is a specific and stability-indicating test to determine the potency (content) of the drug product. The assay of tablets expresses in the terms of grams, milligrams, or micrograms of drug per tablet. It is a crucial pharmacopoeial test for the evaluation of tablets or quality control tests of tablets.

Assay limit is mention in individual product monograph. Generally, according to BP, the Assay limit is between 95.0% and 105.0%. For example, Acetaminophen Tablets contain not less than 95.0% and not more than 105.0% of the labeled amount of paracetamol. According to USP, the Assay limit is between 90.0% and 110.0%. For example, Acetaminophen Tablets contain not less than 90.0 % and not more than 110.0 % of the labeled amount of acetaminophen.

Impurities determination

Impurities in tablets are specified in an individual product monograph or may calculate by ICH Q3B(R2) guideline. During product manufacture and over the shelf life of the product, impurities may come from the degradation of the drug substance or from interactions between the drug substance and excipient(s), among other factors. It is a crucial pharmacopoeial test for the evaluation of tablets or quality control tests of tablets. Besides process impurities, synthetic by-products, and other inorganic and organic impurities may be present in the drug substance and in the excipients used in the manufacture of the drug product.

Specific Pharmacopoeial Tests of Tablets

Microbiological Examination of tablets (Nonsterile Products)

This test is used to determine the absence or limited occurrence of specified micro-organisms that may be detected under the conditions described. Some liquid oral products can be subject to extreme microbiological control, and others require none. Generally, the microbial content test should not require for most of the tablets except vitamin tablets, sugar-containing tablets. It is a crucial pharmacopoeial test for the evaluation of tablets or quality control tests of tablets. Acceptance Criteria for Microbiological Quality of Nonsterile Dosage Forms [2]

Route of AdministrationTotal Aerobic Microbial Count (CFU/g or CFU/mL)Total Combined Yeasts/Molds Count (CFU/g or CFU/mLSpecified Microorganism(s)
Non-aqueous preparations
for oral use
103102Absence of Escherichia coli (1 g or 1 mL)

Acid-Neutralizing Capacity

Acid-Neutralizing Capacity is a pharmacopoeial test for the evaluation of tablets or quality control tests of tablets. Certainly, this test is applicable only to measure the acid-neutralizing capacity of an antacid tablet.

Limit: NLT 5 mEq of acid is consumed by the minimum single dose recommended in the labeling, and the number of mEq calculated by the formula [2]: Result = [0.8 × (FM × M)] + [0.9 × (FC × C)]

Quality test of Splitting Tablets with Functional Scoring

This test indicating that the label claim of the split portions should be a simple fractional part of the claim for the intact tablet based on the number of scores and the size of the split portion (for example, one-half, one-third, or one-quarter).

An acceptable tablet breaks into the designed number of segments, and each split portion has NLT 75% and NMT 125% of the expected weight of the split tablet portion. NLT 28 of the 30 tablets is acceptable [2]. It is a pharmacopoeial test for the evaluation of tablets or quality control tests of tablets only for scored tablets.

Water content determination

The water content of tablets before and after stability study at specified temperature and humidity for a fixed time may determine to find out moisture impact on tablets. Generally, water content calculated by using the method is Karl Fischer titration.

By using above all quality tests you may evaluate tablets and after a satisfactory results you may release manufacturing batch of tablets. If you have any question comments in the comments section and stay connected with pharmaeducation.net

References

1. Center for Drug Evaluation and Research (CDER) (2015). “Guidance for Industry: Size, Shape, and Other Physical Attributes of Generic Tablets and Capsules”. United States Food and Drug Administration.

2. United States Pharmacopeia and National Formulary (USP 43–NF 38). United States Pharmacopeial Convention; 2020.

3. British Pharmacopoeia Commission. British Pharmacopoeia 2021. London: TSO; 2021.

4. Center for Drug Evaluation and Research (CDER) (1997). Guidance document: Dissolution Testing of Immediate Release Solid Oral Dosage Forms”. United States Food and Drug Administration.