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PHAR459

3. IN PROCESS QUALITY CONTROL

and QUALITY CONTROL MEASURES

IN PHARMACEUTICAL INDUSTRY

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QUALITY CONTROL

Definition

Quality control refers to the sum of allprocedures undertaken to ensure the identityand purity of a particular pharmaceuticalproduct.

quality control

QUALITY CONTROL

Quality control is an essential operation ofthe pharmaceutical industry.

Drugs must be marketed as safe andtherapeutically active formulations

Quality is the result of intelligent effort.

The quality in the pharmaceutical industry hasbecome a very important and sensitive issue.

THE IMPortance of quality and control ofquality

QUALITY CONTROL

The goal of the pharmaceutical quality control testing process is to produce satisfactory results by investigating and monitoring the quality of manufacturing pharmaceutical in accordance with compendial standards and specifications.


QUALITY CONTROL

The quality of pharmaceutical products is essential toassure the maximum level of patient’s satisfaction.

The most important criteria for quality of any drug indosage form are its safety, potency, efficacy, stability,patient acceptability and regulatory compliance.


QUALITY CONTROL

Counterfeit medicines;

The WHO defines a counterfeit drug as a productthat is with intent and illegally mislabelled withrespect to its identity and/or source.Counterfeiting of medicinal products, activepharmaceutical ingredients or product labels arecriminal offences, which may endanger patienthealth.


QUALITY CONTROL Counterfeit medicines may:

► contain no active ingredient

► contain the wrong active ingredient

► contain an incorrect quantity of the active ingredient

► be in low–quality packaging

► be manufactured using low–quality active ingredientor excipient

► be manufactured under poor standards of goodmanufacturing practice compliance.















Quality control is an essential operation of the pharmaceutical industry.

New and better medicinal agents are being produced at an accelerated rate. At the same time more exacting and sophisticated analytical methods are being developed for their evaluation.

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Quality Control in the pharmaceutical industry is required for :

Raw Materials and API: Finished Products :

Packaging Components :

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When the quality of any drug is given by industry, then it is responsible for any variation from the standard.

Quality Variation may occur due to any mistake during the whole process i.e. from the reception of raw material up to the final product in the packaged form.

The risk of error increases as the material increases and the method become very complicated..

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Improvement of the quality of production and reduction in the production cost.

Uniformity in the production and supply of standard quality goods to consumers.

Offering full return of the price paid by the consumers and giving convenience and satisfaction to consumers .

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Reduction in spoiled production and rejection from consumers and dealers.

Promotion of exports due to superior and standard quality production.

Reduction in inspection cost.

Making products popular in market.

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Organoleptic tests

Physical tests

Physicochemical tests

Microbiological tests

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Organoleptic tests:

are conducted to determine if the pharmaceutical products can transfer tastes or odors to the materials and components they are packaged in

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Physical tests

Physicochemical tests

Microbiological tests

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QUALITY CONTROL To further enhance the effectiveness and safety of the drug product after approval, many regulatory agencies such as

the United States Food and Drug Administration (FDA) also require that the drug product be tested for its identity, strength, quality, purity and stability before it can be released for use.

IN PROCESS QUALITY CONTROL

IPQC (in processquality control)

These are checks that are carried out before the manufacturing process is completed.

Rejected in-processmaterials should be identified and controlled under a quarantine system

IN PROCESS QUALITY CONTROL IPQC (in process quality control)

In process Quality Control, IPQC tests are mostly performed within the production area.

The control of the environment or equipment may also be regarded as a part of in process control (IPC).

They should not carry any risk for the quality of product.

In process testing enables easier identification of problems.

Failure to meet In process control specification indicates either that procedure were not followed or some factor were out of control.

Standard operating procedures (SOPs) should be established in the pharmaceutical industry and followed that describe the IPQCs and tests

IPQC TESTS FOR VARIOUS DOSAGE FORMS:

I.P.Q.C TESTS FOR TABLETS

IPQC TESTS FOR COATED TABLET

IPQC TESTS FOR CAPSULES:

I.P.Q.C TESTS FOR SYRUPS AND SUSPENSION

I.P.Q.C TESTS FOR SEMI- SOLIDs

I.P.Q.C TESTS FOR INJECTABLES


IPQC TESTS OF TABLETS

• Weight variation of tablets.

• Hardness of tablets.

• Thickness.

• Friability.

• Uniformity of content.

• Disintegration time.

• Dissolution test.

• Content of active ingredients.


IPQC TESTS FOR COATED TABLET

• Moisture content of dried granulation

• Granulation particle size distribution

• Blend uniformity

• Individual tablet/capsule weight

• Hardness

• Thickness

• Disintegration

• Impurity profile


IPQC TESTS FOR CAPSULES:

• Assay.

• Weight variation test.

• Disintegration time.

• Dissolution time.

• Moisture test.

• Iron test.

• Hardness and flexibility of shell.

• Loss on drying.

• Stability test at different temperature.

QUALITY CONTROL EQUIPMENTS

Drug Content Determination

A physically sound tablet may not produce the desired effects. To evaluate a tablet potential for efficiacy, the amount of drug per tablet needs to be monitored from tablet to tablet and batch to batch, and a measure of the tablets ability to release the drug needs to be ascertained.



Moisture Content of granules

Granules should possess sufficient strength to withstand normal handling and mixing processeswithout breaking down and producing large amounts of fine powder.

On the other hand, some size reduction during compaction into tablets is desirable to expose the areas of clean surface necessary for optimum bonding to take place so moisture content is the very important factor for producing good pharmaceutical product.



Assay of active ingredient

In a tablet an active ingredient is present which is called active pharmaceutical ingredient(A.P.I).

So to prepare the tablet assay has to be done to produce good finished product.



Hardness testThe monitoring of tablet hardness is especially important for drug products that possess real or potential bioavailability problems that are sensitive to altered dissolution release profiles as a function of the compressive force employed .


QUALITY CONTROL EQUIPMENTSDisintegration test

A generally accepted maximum is that drug to be readily available to the body, it must be insolution.

For most tablets, the first important step towards solution is break down of the tabletinto smaller particles or granules, a process known as disintegration.



I.P.Q.C TEST FOR SYRUPS AND SUSPENSION

a) Drug contents determination.b) Assay of active ingredients.c) pH.d) Weight per ml.e) particle size



Drug content determination

Determination of drug content in suspension and syrups are important because theirconcentration has to be sufficient itself that it produce the pharmacological action.

A suspension is much prescribed to pediatrics so their concentration has to be sufficient not to less not to large.



Assay of active ingredient

Active ingredient means pure drug present in the product .An assay of active ingredient must be done because it is the only which is responsible for pharmacological action and in syrups and suspension a small and fine particles are included in syrups and suspension



pH of the product

pH affects the stability of the product so before filling and after filling of suspension and syrups pH has to be checked out for consistency of the product.



Particle size

In suspension and syrups a solute particles is dispersed in a suitable solvent so particle sizebecomes the important factor for the suitability of the product and all the particles has to be of same size and shape for proper dispersing in the solvent



I.P.Q.C TEST FOR SEMI- SOLIDs

a) Drug contents determination.b) Assay of active ingredients.c) Uniformity and homogeneity test.d) Viscosity and specific gravity test.e) Filling test.



Homogenecity test

The semi-solid preparations require further treatment are transferred or pumped to the proper homogenizer, the selection of which is governed by the degree and rate of shear stress required.



Viscosity and Specific gravity test

Once the desired semi-solid preparation have been chosen, a consistency that provides thedesired stability and has appropriate flow characterstics must be attained. For emulsion it is routinely observed that the building up of viscosity in a freshly prepared emulsion requires some time.



I.P.Q.C TEST FOR INJECTABLES

a) Drug contents determination.b) Clarity test.c) pH.d) Pyrogen test.e) Sterility test.f) Leakage test.g) Check up of particulate matters.



Pyrogen test

The presence of pyrogenic substance in parenterals is determined by a qualitative biologic test based on the fever response of the rabbits.

Rabbits are used as test animal because they show a physiologic response to pyrogens similar to that of human beings. If a pyrogenic substance is injected into the vein of a rabbit, an elevation of temperature occurs in a period of three hours.



Sterility testAll products labeled “sterile” must pass through sterility test, having been subjected to aneffective process of sterilization

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With a terminal methods of sterilization of aparenteral product, particularly steam under pressure, a probability of no more than one sterile unit in a million is readily achievable.


QUALITY CONTROL EQUIPMENTSLeaking test

Ampules are intended to provide sealed container for a single dose of a product,thereby completely barring any interchange between the contents of the sealed ampule and its environment.

Should capillary pores or tiny cracks be present, microorganisms or other dangerous contaminants may enter the ampule or the contents may leak to the outside and spoil the appearance of the package.



Clarity test

Clarity is the relative term, the meaning of which is markedly affected by the subjective evaluation of the observer. Unquestionly a clean solution having a high polish conveys to the observer that the product is of exceptional quality and purity.

This clarity test is performed in industry by visual inspection machine by the light baffles againstreflection into the eyes, and views against a black and white background, with the contents set in motion with a swirling action


PHARMACOPOEIAL QUALITY CONTROL TESTS

According to BRITISH PHARMACOPOEIA QUALITYCONTROL TEST

FOR ALL TABLETS:

• Content of active ingredients

• General Appearance

• Disintegration (coated, uncoated & effervescent

tablet)

• Uniformity of weight

• Uniformity of content

• Dissolution test

• Uniformity of dispersion (for dispersible tablet)

• Tablet diameter

PHARMACOPOEIAL QUALITY CONTROL TESTS:


General Appearance:

Size, shape, and thickness:

This is important to facilitate packaging and to decide which tablet compressing machine to use.

Organoleptic properties:

include color and odor of the tablets.

Weight uniformity and content uniformity:

This test is to ensure that every dosage form contains equal amount of drug substance i.e. active pharmaceutical ingredient within a batch.

QUALITY CONTROL TESTS FOR TABLETS:



Dissolution test:

Drug should be released from tablet in a controlled and reproducible way.

Weight variation, thickness & diameter:

The appearance of tablet should be elegant & its weight, size & appearance should be consistent.

Hardness & friability: The tablet should show sufficient mechanical strength to withstand fracture & erosion during manufacture & handling.

PHARMACOPOEIAL QUALITY CONTROL TESTS:



comparison of different pharmacopoeial quality control tests :

BRITISH PHARMACOPOEIA:

FOR ALL TABLETS:

Content of active ingredients

Disintegration

Uniformity of content

Labeling

OFFICIAL STANDARDS AS PER B.P. /I.P./ U.S.P.:


Uncoated tablet:

- Disintegration test

- Uniformity of weight

Effervescent tablet:



Coated tablet:





Gastro resistant tablet:


Modified release tablet:

- Uniformity of weight.

Dispersible tablet:

- -Disintegration test

- - Uniformity of dispersion

- - Uniformity of weight



INDIAN PHARMACOPOEIA :

Uncoated tablet:

-Uniformity of container content

-Content of active ingredient

-Uniformity of weight

-Uniformity of content

-Disintegration test

Enteric coated tablet:




Dispersible tablet:

-Uniformity of dispersion

-Disintegration

Soluble tablet:


Effervescent tablet:

-Disintegration/ Dissolution / Dispersion test


QUALITY CONTROL EQUIPMENTSUNITED STATES PHARMACOPOEIA:

Physical tests applicable to tablet formulation:

-Bulk density /Tapped density of powder

-Powder fineness

-Loss on drying


-Tablet friability

-Dissolution test

-Drug release testing

-Uniformity of dosage form

-Container permeation test

-Labeling of inactive ingredients



OFFICIAL AND UNOFFICIAL TESTS:

Official Tests:

uniformity of active ingredient,

disintegration,

dissolution.

Non-Official Tests:

Hardness,

friability.



1-NON OFFICIAL TESTS:

HARDNESS (CRUSHING STRENGTH):

It measures crushing strength property defined as compressional force applied diametrically to a tablet which just fracture it.

Why do we measure hardness?

To determine the need for pressure adjustments on the tableting machine.

Hardness can affect the disintegration.



Results:

In general, if the tablet hardness is too high, we first check its disintegration before rejecting the patch. And if the disintegration is within limit, we accept the patch.

If hardness is high + disintegration is within time we accept the batch .



FRIABILITY:

The tablet may well be subjected to a tumbling motion.

For e.g: Coating, packaging, transport, which are not severe enough to break the tablet, but may abrade the small particle from tablet surface.

To examine this, tablets are subjected to a uniform tumbling motion for specified time and weight loss is measured.



OFFICIAL TESTS:

DISINTEGRATION:

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



Uniformity of Active Ingredients:

It is measured to ensure a constant dose of drug between individual drugs

Traditionally, dose variation between tablet is tested in two separate tests namely

A) Weight variation

B) Content uniformity



DISSOLUTION TEST:

The release of drug from the tablet into solution per unit time under standardize condition is called dissolution test.

Media used in dissolution testing may be purified water, simulated gastric fluid, simulated intestinal fluid or others. Organic solvents are not recommended.

The most commonly used are USP apparatus I (basket) and USP apparatus II (paddle).


Quality control of capsules

Whether capsules are produced on a small scale or large scale all of them are required to pass through certain tests i.e., quality control tests to test the quality of the finished product.


Quality control tests aredivided into

PHYSICAL TEST

• Disintegration test

• Weight variation

CHEMICAL TEST

• Dissolution test

• Assay

• Content uniformity

• Moisture permeation test


Quality control tests for parenterals



Test for volume of liquid

Test for pyrogen

Test for sterility

Clarity of solution

Uniformity of weight

Test for bacterial endotoxin

Leakage test


30 sterile units are selected from each batch.

• The weight of 10 individual sterile units is noted and the content is removed from them and empty individual sterile unit is weighed accurately again.

• Then net weight is calculated by subtracting empty sterile unit weight from gross weight.

• The dose uniformity is met if the amount of active ingredient is within the range of 85-115.0% of label claim. UNIFORMITY OF CONTENT


Relative standard deviation is equal to or less than 6.0%.

If one unit is outside the range of 85-115.0%, and none of the sterile unit is outside the range of 75-125.0% or if the relative standard deviation of the resultant is greater than 6.0% ,or if both condition prevail, an additional 20 sterile unit should be tested.

The sterile units meet the requirements if not more than one unit is out side the range of 85-115%, no unit is outside the range of 75-125.0% and the calculated relative standard deviation is 7.8%.


TEST FOR VOLUME OF LIQUID

Test applies to liquid supplied in single dose , only part of the content is used

Empty the contents of one container& determine the volume of contents

Emulsions & suspensions shake the container before the determination

The volume is not less than the amount stated on the label.

Test for sterility

Sterility is defines as freedom from the presence of viable microorganism

Leakage test

Leakage test is employed to test the package integrity.

Package integrity reflects its ability to keep the product in and to keep potential contamination out.

Which is the flow of matter through the barrier itself.

1. using methylene blue solution

2. spark test

Leakage test

Leakage Test (with methylene blue solution):

The ampoules are immersed in vacuum chamber consisting of 1% methylene blue solution

A vacuum of about 27 inch Hg is created for about 15 to 30 min.

This causes the solution to enter the ampoules with defective sealing.

The vacuum is released and ampoules are observed.

If a leakage is present, the solution in the ampoules appear blue color.

Leakage test

Leakage Test machine:

Leakage test

Spark Test: The machine uses high precision electrodes to inspect

the full circumference of the containers, including the closure zone.

All containers are presented individually to the electrodes.

Any moisture that has penetrated through capillary forces in a crack, pinhole or just weak glass is registered as a change in resistance.

All products with a measured voltage higher than a defined maximum value are separated from the good products.

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ENTEROPATOJENLERİN SON YILLARDAKİ EFENDİSİ …opencourses.emu.edu.tr/pluginfile.php/52993/mod... · IPQC (in process quality control) In process Quality Control, IPQC tests are