Quality control of solid dosage forms

Question 1

describe what is meant by quality control of solid dosage forms

what is the aim of carrying out quality control

Answer 1

involves a series of tests, procedures and checks applied throughout the drug manufacturing process of a drug

they cover everything, from raw materials to the final product during drug design, to emsure that each batch of a drug meets the regulatory and industrial standards before reaching patients

Question 2

what should be expected for the quality of medicines/ products

Answer 2

the products should be safe and efficacious

should deliver the same performance as described in the label

products should perform consistently over their shelf-life

products should be made in a manner that ensures quality

products should be available when needed

Question 3

what are some aspects of pharamaceutical quality control

i.e the different aspects of the drug or in the drug development process that are tested for quality control

Answer 3

raw material testing : ensure that all materials used in drug production including active pharmaceutical ingredients (APIs) and excipients meet specified quality standards

in-process control : occurs during the various stages of manufacturing to ensure consistency and that each phase complies with the required specifications

finished product testing: this is when the final product is tested to ensure that it meets pre-defined requirements for identity, purity, potency and stability

stability testing: here the product is exposed to different environmental conditions, i.e temp, humidity etc, to see how it changes over time

packaging and labelling control

documentation and compliance

note that finished product testing may be in the form of physical testing, chemical testing, microbiological testing…etc

Question 4

what is the PQS and it’s functions

Answer 4

it is a key system evaluated during regulatory body inspection

it is critical to assuring drug products are manufactured to meet the desired quality and performance attributes

it is also key in providing the regulatory body confidence that appropriate support information is used to make decisions

Question 5

what is meant by compendial tests

Answer 5

tests that conform to the requirements of the British Pharamcopoeia and the Unites states Pharmacopoeia

we could say these tests are standardised

Question 6

name some compendial tests carried out for the quality control of tablets

Answer 6

Uniformity of content of active ingredient (uniformity of weight and content uniformity)-i.e the correct dose should be included in the tablet

Disintegration test

Dissolution test(in this test it is expected that the drug is released in a controlled and reproducible manner)

Friability test(here it is expected that the tablet shows sufficient mechanical strength to withstand fracture and erosion during the manufacturing and handling stages)

appearance tests

Question 7

define non-compendial tests, and give examples

Answer 7

they are analytical tests with non-pharmacopoeial requirements , but are rather specific to a product. These are generally manufacturer-specific requirements

tablet thickness
tablet hardness

Question 8

in how many ways can dose variation between tablets be tested, and name them, and describe them

Answer 8

2

weight uniformity: test ensures that the weight of individual tablets falls within a specified range of a target weight

content uniformity: confirms that the active pharmaceutical ingredient(s) [API] in a product are uniformly distributed and within acceptable limits

If the drug forms greater part of the tablet (more than ≥25 mg and ≥25%), any variation in the tablet weight may indicate a variation in the active ingredient

Question 9

the purpose of the content uniformity test as described by the USP

Answer 9

used to ensure consistent dosage of the active pharmaceutical ingredient (API) in individual tablets, especially in cases where the API is either less than 25 mg or less than 25% of the total tablet weight.

it ensure that drugs with a low API have consistent content across individual units

Question 10

the minimum number of tablets that can be used in the content uniformity test and for weight uniformity tests

Answer 10

10
18-20

Question 11

name some of the analytical methods used in determining the content of each API in a drug during the CUT

Answer 11

High-Performance Liquid Chromatography (HPLC)
UV-Visible Spectrophotometry
Other suitable quantitative methods validated for accuracy and precision.

Question 12

during content uniformity test, it is said that the individual content is calculated as a percentage of the label claim for each tablet. explain this in your own terms

Answer 12

For example, if the label states the tablet contains 10 mg of the drug, and the test shows 10.1 mg, the percentage is 101%.

note that where the content uniformity test is required, weight uniformity tests are not

Question 13

how many stages involved in content uniformity test and describe what happens in each stage

Answer 13

3

Stage 1 (S1)
Test the first 10 tablets
Pass Criteria: All tablets must fall within the range of 85% - 115% of the label claim

Stage 2 (S2):
If the batch fails S1, test an additional 20 dosage units (30 total)
Pass Criteria: All tablets must fall within the range of 75% - 125% and not more than 1 tablet can be outside 85% - 115%

Stage 3 (S3):
If the batch fails S2, the entire batch fails content uniformity testing and an investigation is required

note that to pass a stage the criteria stated should all be met

Question 14

what are some causes of weight variation during tablet production

Answer 14

The size & distribution of the granules being compressed (presence of too large or too fine granules)

Poor flow and high turret speed (incomplete filling of die)

Poor mixing (sometimes the lubricants & glidants have not been well distributed)

Demixing or segregation of powder constituents of different crystallinity, size and densities; in direct compression

metal components that form the cavities in which the powder or granules are compressed to create tablets

Question 15

describe disintegration tests and how they are carried out

all tablets must pass this test, but there are exceptions, what are these exceptions

Answer 15

tests are used to assess how quickly a tablet or capsule breaks down into smaller particles, allowing for the release of its active ingredients

The test is carried out by agitating a given number of tablets in an aqueous medium (e.g. water or simulated gastric/ intestinal fluid) at a defined temperature (~37°C) & the time to reach the end-point of the test is recorded

chewable tablets and some extended release tablets

test crucial becauses disintegration is the first step towards drug dissolution and absoprtion

Question 16

The specific pass criteria for disintegration tests can vary depending on the type of dosage form, true or false

Answer 16

true

the pass criteria for each dosage form is defined by pharmacopoeias

Question 17

the pass criteria for disintegration tests in the following solid dosage forms;
immediate release tabs (uncoated or film-coated)

caps

sublingual and buccal tabs

efferverscent tabs

orally disintegrating tabs

Answer 17

15mins in water at body temp

30mins in water or a suitable medium at body temp

within 3 mins at body temp

less than 5 mins at room temp(22-24 degress)

btn 30 secs to 3 mins in water at body temp(37 degrees)

Question 18

the minimum amount of tabs that can be used in disintegration tests

if 2 or more tabs fail the disintegration test, how do we proceed

Answer 18

6

repeat test with 12 additional tablets: at least 16 of the 18 (6 + 12) tested tablets should pass the test

Question 19

during the disintegration tests, no tablet residues should not remain on the screen.
in which cases may residues be accepted in the test

Answer 19

If a residue remains, it consists of fragments of shell or,

Is a soft mass with no palpable core

If the disc is used, any residue remaining on its lower surface should only consist of fragments of shell

Question 20

what is the dissolution test

Answer 20

a laboratory procedure that measures how quickly and to what extent a substance dissolves into a solution

Question 21

start some important points to know about the dissolution test

Answer 21

it is a routine QC procedure

helps to correlate bioequivalence

Gives an indication of the performance of the preparation under the in vivo conditions

It differentiates between formulations and evaluates the possible effect of the formulation and other processes variables on drug bioavailability

Question 22

the most common dissolution apparatus used by the USP and what dossage form it is used for

other common dissolution apparatus

Answer 22

apparatus 2(paddle)- immediate release tabs

apparatus 1(rotating basket )-capsules and floating tabs

apparatus 3,4,5, 6, 7.

Question 23

name some factors that affect the dissolution of a tab

Answer 23

how well they disintegrate

particle size of drug

drug solubility (note that this is affected by the solubility of excipients used in the manufacturing process as well as their sizes and other properties )

manufacturing method, i.e, compactness of the granulation and compression force used in tableting

Question 24

name some of the media used in dissolution tests

Answer 24

Purified water
Simulated gastric fluid
Simulated intestinal fluid
Solvents mixture may be used if the drug solubility is very low
Buffer solutions e.g. Acetate, phosphate, citrate, or borate buffers
Surfactant solutions e.g. odium lauryl sulfate (SLS), polysorbates (Tween 80) or bile salts
Biorelevant media e.g. FaSSIF (Fasted State Simulated Intestinal Fluid), FeSSIF (Fed State Simulated Intestinal Fluid)
Organic solvent media e.g. Ethanol, methanol or isopropanol mixed with water or buffers

Question 25

some key factors in media selection for dissolution tests

Answer 25

Drug solubility: Aqueous or non-aqueous media depending on the drug’s characteristics

Target release site: Stomach, intestine or elsewhere in the GI tract

Physiological relevance: Use of biorelevant media for accurate prediction of in-vivo behaviour

Regulatory guidelines: Media and conditions often need to adhere to standards set by pharmacopoeias (e.g. USP, EP, BP)

Question 26

state some important things to remember about friability tests

Answer 26

Procedure:

Tablets (usually 20) are rotated in a friabilator for 4 minutes (100 revolutions).
The weight loss is measured to assess friability.

Acceptance Criteria:

Weight loss must not exceed 1% for most tablets. Excessive loss indicates poor tablet strength.

Purpose:

Ensures tablets can endure manufacturing and handling without significant damage.

Exemptions:

Not applicable for some tablets, e.g., chewable or effervescent tablets, as they are designed to break or dissolve.

Critical Factors:

Tablet hardness, binder concentration, and manufacturing process directly affect friability results.

Question 27

main factors that affect tablet hardness

Answer 27

compression force applied during tablet formation

concentration and type of binder

Question 28

why can tablets not be too hard or too soft

Answer 28

cant be too hard as they must be soft enough to disintegrate properly in the GI after swallowing
also hard tablets might have complications when it comes to dissolving

they must be hard enough to resist breaking during handling, packaging and shipping

Question 29

describe compression loading

Answer 29

a type of load that is applied vertically or distributed horizontally to a structure, causing it to deform or deflect.

Question 30

the test used to determine tablet hardness

Answer 30

compression loading(test)

after the test, the crushing strength that causes the tablet to break is recorded in kg or N(newton)

note that this strength should be between 6-10kg

Question 31

name some main factors used to determine tablet thickness

Answer 31

diameter of the die, the amount of fill permitted to enter the die and the force or pressure applied during compression

Question 32

what are some challenges encountered during tab processsing

Answer 32

Capping and lamination
Picking and sticking
Tablet mottling

Capping occurs when the upper segment of the tablet separates from the main portion of the tablet & comes off as a cap. In lamination, the tablet splits at the sides into two or more distinct layers

Picking is the removal of the surface material of the tablet by the punch (a portion of the tablet surface is missed). Sticking is the adhesion of the tablet materials to the die wall (dull, scratched, or rough tablet faces)

Mottling- unequal colour distribution, with light or dark areas. Occurs when a drug has different colour than the tablet excipients or intragranular migration of the soluble dye

Question 33

name some quality control tests for capsules

Answer 33

Size
Moisture content
Single wall thickness
Colour
Visual inspection
Weight variation
Content uniformity
Dissolution test
Disintegration test

note that it is important to carry out QC tests for all the stages of capsule manufacturing

Question 34

name some in-process and finished product QC testing for soft gels (caps)

Answer 34

In-process testing;

Gel ribbon thickness
Soft gel seal thickness at the time of encapsulation
Fill matrix weight & capsule shell weight
Soft gel shell moisture level and soft gel hardness at the end of the drying stage

Finished product testing;

Capsule appearance
Active ingredient assay & related substances assay
Fill weight
Content uniformity
Microbiological testing