NTA Level 6 • Semester 1 • PST06103

In-process Quality Control (IPQC)

Pharmaceutical Production • Source Session/Topic 22

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Session 22: In-process Quality Control (IPQC)

Total Session Time: 120 minutes

Pre-requisites

• None

Learning Tasks

By the end of this session students are expected to be able to:

• Explain the concept of in-process quality control

• List tests and equipment/apparatus used for in-process quality control of

tablets and capsules

• Explain the consequences of in-process quality control of tablets and

capsules

• List the objectives of in-process quality control

Resources Needed:

• Flip charts, marker pens, and masking tape

• Black/white board and chalk/whiteboard markers

• LCD projector and computer

SESSION OVERVIEW

SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning tasks and clarify

ASK students if they have any questions before continuing

STEP 2: The Concept of In-process Quality Control (25 minutes)

|Activity: Buzzing (5 minutes) |

| |

|ASK students to pair up and buzz on the following question for 2 |

|minutes |

| |

|What is in-process quality control? |

| |

|ALLOW few pairs to respond and let other pairs to add on points not |

|mentioned |

| |

|WRITE their response on the flip chart/board |

| |

|CLARIFY and SUMMARIZE by using the content below |

• In-process quality control is a type of quality control that provides

accurate specific and definite description of procedure to be employed

from the receipt of raw material to the release of the finished product

• In-process quality control performs checks during production in order to

monitor and, if necessary, to adjust the process to ensure that the

product conforms to its specifications

• In-process quality controls are usually performed within the production

area. The performance of such in-process controls should not have any

negative effect on the quality of the product or another product

• Generally, the in-process control procedures are usually rapid and simple

tests or inspections that are performed when the manufacturing of a

product batch is in progress

STEP 3: Objectives of In-process Quality Control (20 minutes)

• Some of the objectives of in-process quality control are;

o To minimize human errors

o To provide accurate, specific and definite description of the

procedure to be employed in manufacturing of a product

o To detect errors if and when they occur

o To pin point responsibility to the personnel involved in the operation

of the entire process

o To ensure that the flow of manufacturing and packing operations

according to established routes and practice is rigidly followed

o To detect abnormality immediately and at the same time indicate action

needed to correct the problem

STEP 4: In-process Quality Control Tests in the Manufacture of Tablets and

Capsules (55 minutes)

• Evaluation of dosage forms (tablets);

o General appearance

▪ Size, shape and texture

▪ Unique identification markings (embossing, engraving or printing)

▪ Organoleptic properties (e.g. colour distribution, taste, odour)

o Content uniformity test

▪ 30 tablets are kept aside (sampled), 10 tablets are assayed, 9

tablets should have percentage limit of 85-115%

▪ If more than 1 tablet has 85-115%, then, 20 tablets are assayed

and not more than 1 tablet should have 75-125%

o Tablet hardness test or tablet crushing strength

▪ Hardness of a tablet is the force required to break a tablet in a

diametric compression test

▪ Hardness testing is a laboratory technique used to test the

breaking point and structural integrity of tablet under conditions

of storage, transportation, and handling before usage (breaking

point of a tablet is based on its shape)

▪ Tablet hardness is tested by using Tablet Hardness Tester e.g.

Monstanto hardness tester, Stokes harness tester, Erweka tester,

Schleuniger or heberlein tester, Strong Cobb tester and Pfizer

hardness tester

▪ Conventional tablet hardness: 2.5 – 5 kg/cm2

▪ Dispersible/chewable tablet hardness: 2.25 -2.5 kg/cm2

▪ Extended release tablets hardness: 5-7.5 kg/cm2

o Friability

▪ Friability is the tendency of tablets to powder chip or fragment.

This affects the elegant appearance of tablets and consumer

acceptance of the tablets

▪ Friability leads to variation in the weight and content of

tablets

▪ Friability is related to hardness of a tablet

▪ Instrument used for friability testing is known as Friabilator

(e.g. Roche friabilator)

▪ Consisting of a plastic chamber that revolves at 25 rpm dropping

the tablets through a distance of 6 inches in the friabilator,

which is then operated for 100 revolutions

▪ From the friabilator, the tablets are reweighed

▪ Loss in weight is determined

▪ Allowable range is 0.5 – 1.0%

o Weight variation

▪ 20 tablets are taken (sampled) and weighed individually

▪ Average weight of the 20 tablets is determined

▪ Weight of individual tablet is compared to the average weight

▪ Not more than 2 of the individual tablet weights deviate from the

average weight by more than the prescribed percentage deviation and

none deviates by more than twice that percentage (e.g. USP limits,

I. P limits)

o Disintegration test

▪ For most tablets, the first important step towards formation of

solution is break down of the tablet into smaller particles or

granules i.e. disintegration

▪ Disintegration test is performed by use of the disintegration

apparatus

▪ The disintegration apparatus is comprised of glasses and a mesh

screen at the bottom and operates at a temperature of 35℃ to 39℃

and speed of 28-32 rpm

▪ Tablets are sampled and placed in the glass and the apparatus is

run for specified period of time

▪ Tablets pass the test if they disintegrate and all particles

past through the screen in the time specified

▪ For uncoated tablets, disintegration time should be 15 minutes

▪ For coated tablets, disintegration time should be 30-60 minutes

▪ For enteric coated tablets, disintegration time should be 60

minutes

▪ Dispersible and soluble tablets should disintegrate in 3 minutes

▪ Effervescent tablets disintegrate in 5 minutes

o Dissolution test

▪ Dissolution is a process by which a solid solute enters into a

liquid and form solution

There are different types of dissolution apparatus

▪ Basket type, paddle type, reciprocating paddle, flow through

cell, paddle over disc, cylinder with membrane, reciprocating

cylinder

▪ Conditions maintained include temperature (36.5℃ to 37.5℃) and

speed (25-150 rpm)

▪ Test done according to compendial monographs or non compendial

o Tablet thickness

▪ May be measured by micrometer or by other device

▪ Tablet thickness should be controlled within a ± 5% variation of

standard value

o -Blister or strip sealing test

▪ To ensures that only intact blisters are realised

• Quality control tests during production of Capsules (Hard shell)

o Content uniformity

▪ 10 capsules are taken and subjected to assay

▪ 9 out of 10 capsules should be in the range of 85-115% and the

10th capsule in the range of 75-125%

▪ If 2 capsules are beyond the prescribed range, then 20 capsules

are assayed. All capsules should be in the range of 75-125%

o Bloom strength

▪ Gelatin is weighed into water to typically create a 6.67%

solution in standard Bloom bottles

▪ The mix is then stirred and kept for 3 hours at room temperature

▪ Bottles are placed in a 65℃ bath for 20 minutes

▪ The bloom jars are allowed to cool for 15 minutes at room

temperature

▪ The bloom jars are then conditioned for 16 hours in 10℃ water

bath

▪ When conducting a gelatin Bloom test, the Bloom jar is centred

with the probe just above the sample surface

▪ The probe penetrates the gelatin to a target depth of 4 mm at a

speed of 0.5 mm/s, and then retracts

▪ The peak force is the gel strength in Grams Bloom

o Weight variation

▪ A total of 20 capsules are individually weighed and standard

deviation from mean is measured

▪ It should not be less than 90% or greater than 110%

o Other tests include;

▪ Assays

▪ Dissolution test

▪ Disintegration time

▪ Moisture content

▪ Iron test

▪ Hardness and flexibility of shell

▪ Loss on drying

• In-process quality control tests during production of Capsules (Soft

shell)

o There are four important test during encapsulation process;

▪ Gel ribbon thickness

▪ Soft gel seal thickness at the time of encapsulation

▪ Fill matrix weight and capsule shell weight

▪ Softgel moisture level and hardness and the end of the drying

stage

STEP 5: Key Points (5 minutes)

• In-process quality control is a type of quality control that provides

accurate specific and definite description of procedure to be employed

from the receipt of raw material to the release of the finished product

• Generally, the in-process control procedures are usually rapid and simple

tests or inspections that are performed when the manufacturing of a

product batch is in progress

• In-process quality testing is achieved by conducting various tests on the

critical stages of the manufacturing process

STEP 6: Evaluation (5 minutes)

• What is in-process quality control?

• How does in-process quality control differ from quality control?

• Lit the in-process quality control test performed during production of

tablets and capsules

References

Aulton M.E & Kevin M.G., (Eds): (2013) Pharmaceutics: The design and

manufacture of medicines, (4th ed.)Churchill Livingstone

Hugo and Russell (2011), Pharmaceutical Microbiology (8th ed.), Willey-

Blackwel publications

Gennaro, R. A, et al. (Eds) (1995) Remington: The Science and Practice of

Pharmacy, Volume I & II, (19th ed.): Mack Publishing Company, Easton,

Pennsylvania 18042

Liebsch, B., et al (1988): Tanzania Pharmaceutical Handbook, Dar es Salaam

University Press.

Lund, W. Editor (1994). The Pharmaceutical Codex, Principles and Practice

of Pharmaceutics (12th ed.): The Pharmaceutical Press, London

Polderman, J., (1990) Introduction to Pharmaceutical Production: Novib, The

Hague

Rawlins E.A, Editor: (1977) Bentley’s Textbook of Pharmaceutics, (8th ed).

Baillie're Tindall. London Kamm, G. and Kohler, B. Editors: (1995)

Manual for Decentralized Infusion Production, Infusion Unit Project

Tanzania

Schmidt, O. (ed) (2000) Pharmaceutical Quality systems, Interpharm Press,

Colorado.

Shayne C et al. (2008), Pharmaceutical Manufacturing Handbook: Production

and processes, John Wiley & Sons

Watson, D. G., (1999) Pharmaceutical Analysis: A Textbook for Pharmacy

Students and Pharmaceutical Chemists: Churchill Livingstone, Edinburgh.

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