QUALITY CONTROL 2Drug Testing and Assay

with Instrumentation

An enteric coated tablet that

disintegrates in the stomach

Hardness of tablets

Change in pH for eye solutions

Capsules without fill

- Totality of characteristics of a product that bears on its capacity to satisfy stated or implied needs

QA- sum total of the organized arrangement ensuring the quality required by its intended use.

QC- part of GMP concerned with sampling, specifications, testing, organization, documentation and release procedures .

QA/QC

QA-policies are followed inept to economic

issues on manufacturing/distribution of product.

- cooperate with regulatory agencies (acceptance/rejection)

- identify and prepare SOP’s - Audit and Quality monitoring- systems,

facilities, written procedures.

FUNCTIONS

QC- testing and acceptance ( raw material, representative

sample)- IP tests against criteria- monitors environmental conditions- control packaging components.

FUNCTIONS

Solubility

Uniformity in size and shape

Microbial growth

7.It motivates the pharmaceutical/ medical profession to sell or prescribe the product.

POTENTIAL BENEFITS OF QUALITY CONTROL SYSTEMS

Quality characteristics are interpreted by descriptive words and measurements.

Characteristics are subject to variation.Quality variation which is not confined within a specific

range, tolerance or limit, will grow to uncontrolled magnitude and will encourage ERRORS DEFECTIVE PRODUCT.

Errors may be due to chance or assignable causes such as:1. MATERIALS2. MACHINES3. METHODS4. MENSTANDARDS and SPECIFICAIONS are developed to serve as

basis for ACCEPTING or REJECTING a product.

STANDARDS AND SPECIFICATIONS

DEFINITION OF TERMS

RAW MATERIALS

DEFINITION OF TERMS

a. The units may have to run at a high speed run.

DEFINITION OF TERMS

DEFINITION OF TERMS

Is an undesirable characteristics of a product.Defined as a failure to conform to specifications.A unit of a product which contains one or more

defects is called DEFECTIVE.Defects can be classified as follows:

DEFECTS

2. According to seriousness or gravity:a. Critical defect- a defect may endanger life or

property and may render the product non-functional.Absence of WARNING in the label for a product or DISINTEGRATION TIME of one hour for some.

DEFECTS

CONTINUATION.

DEFECT

The manufacture of a cosmetic or drug product frequently involves a series of simple to complex steps.

The risk of errors increases as the No. of materials used in the formulation becomes larger, and the manufacturing processes become more complex.

APPROACHES to minimize and eliminate sources of variation:

1. MATERIAL CONTROL2. GMP3. PACKAGING CONTROL4. AUTOMATION and STATISTICAL SAMPLING PLANS

SOURCES AND CONTROL OF QUALITY VARIATION

GENERAL SOURCES CAUSING PRODUCT QUALITY VARIATION

DURING MANUFACTURING

Question of Quality

Difference of bioavailability, drugs with low solubility as ascertained by blood level attainment studies, caused by formulation variables.

MONOGRAPH-documents that specifies all the tests

to be conducted on a product - appropriate references- detailed procedures- expected result

CERTIFICATE OF ANALYSIS- document indicating the result of all

tests- show compliance/non-compliance - standard specs.

Evidence of Quality

MONOGRAPHS

USP NFBritish PharmacopeiaPh Eur

CERTIFCATE OF ANALYSIS

ORGANIZATION OF QUALITY CONTROL

MATERIALS INSPECTION CONTROL

ANALYTICAL LABORATORY

ANALYTICAL LABORATORY

1. To evaluate and perform microbiological and pharmacological assay, sterility, pyrogen and bacteriological tests, irritation, safety or acute toxicity tests.

BIOLOGICAL TESTING LABORATORY

BIOLOGICAL TESTING LABORATORY

SPECIFICATIONS AND ANALYTICAL DEVELOPMENT

SPECIFICATIONS AND ANALYTICAL DEVELOPMENT

2.To be able to furnish data that will aid in analyzing product performance.

QUALITY COORDINATION OFFICE

QUALITY COORDINATION OFFICE

MAY appear varied and never quite identical in any two companies.

These functions can be classified into four categories:1. Analysis2. Monitor3. Record Review and release4. Audit function

CONTROL FUNCTIONS

ANALYSIS FUNCTION

1. RMQC- ID test, purity, limit test, physical test

2. IPQC- volume fill, detection of particles3. FPQC- stability test, leaker test,

sterility test

3 MAIN AREAS OF QC (ANALYTICAL TESTS)

What constitutes a STABLE FINISHED PRODUCT?

P- Physical appearance, palatability, uniformity, dissolution, suspendability.

C- chemical integrity within specified limits

M- retain its sterility

T- No significant in toxicity occurs

T- therapeutic effects remains unchanged .

STABLE PRODUCT

EXPIRATION DATEtime which the preparation will remain

stable when stored under a recommended condition.HARMFUL EVENTS

-decrease the therapeutic activity of preparation below some arbitrary

content.- appearance of toxic substance formed

as degradation product.Errors in estimating ED

Type 1- ά error- too earlytype 2 β error- later

Aims of the stable product

EXPIRATION DATE- Extension?

MONITOR FUNCTION

It is the responsibility of QC to sample and examine materials while they are being processes.

Another, would be ENVIRONMENTAL MONITORING.This is to control microbial and particulate matter

content of environmental air in areas where pharmaceuticals such as parenterals are processes.

RECORD REVIEW AND RELEASE FUNCTION

AUDIT FUNCTION

1. PACKAGING- material type, special properties, integrity

2. IDENTITY TEST- physical, chemical: visible reactions

3. PHYSICAL PROPERTIES- gross, totality4. LIMIT TESTS- Biological, chemical,

gross5. POTENCY TEST- instrumental,

chemical, biological

QC TESTS OF PHARM. DOSAGE FORMS

PACKAGING1.material type2.special properties3. integrity

IDENTITY TEST1.Physical2.Chemical3.Visible reactions

PHYSICAL PROPERTIES1.Gross2.Totality

LIMIT TESTS1.Biological2.Chemical3.Gross

POTENCY TEST1. Instrumental2.Chemical3.Biological

-debasement of article.1.SOPHISTICATION -true adulteration

- addition of inferior material to any particleex. Teatree oil – olive oil Safflower – safron2. SUBSTITUTION - entirely different is used in place of the one requested.ex. Japanese anise- star anise3. ADMIXTURE- addition of an article to another through accident, ignorance, carelessness.

ADULTERATION

4. SPOILAGE- quality destroyed by action of microorganism

5. DETERIORATION- quality impaired by abstraction, destruction of valuable constituents due to environmental agents, insects etc..

ADULTERATION

ADULTERATION

1. HARDNESS- ‘ CRUSHING STRENGTH”- determine the resistance to

shipping, abrasion, or breakage under storage, transportation, handling before usage

Stokes hardness tester ( monsanto)- spring

Strong cobb - air pumpPfeizer hardness- hard pliersErweka tester -suspended weight, Schleuniger- horizontal position

x

QC PROCEDURES FOR: TABLET

2. FRIABILITY- ability to withstand abrasions in packaging, handling, shipping

- % loss of tab in packaging and transport

Thumbling apparatus-exposed to rolling and repeated shocks from free falls.

- RPM, min

3. THICKNESS- vernnier caliper, mm- < 5% of std thickness- requirement

4. DISINTEGRATION-- basket rack assembly- 6 cylindrical tubes- 10 mesh wire at the bottom, disks- TEMP.- 37± 2 ºc- media type- purified water

Plain CT & capsule - 30 minutesEnteric - 15 minutesBuccal - 4 hoursSL - 3 minutes5. DISSOLUTION-solid of fair solubility enters into solution

-evaluation of physiological availability of drug substance.

- basket and paddle typesample- finite no. are selected from the batch of the products.

Q- tolerance= % dissolved

7. UNIFORMITY OF DOSAGE UNITS- WEIGHT VARIATION- CONTENT UNIFORMITY

- Should settle- Pour readily- Particle remain fairly constant- Sedimentation volume1. SEDIMENTATION VOLUME

Vs= Vu/VoVu= settledVo= unsettled

2. REDISPERSABILITY- amount of force to redisperse particles.

- formation of hard cake .

SUSPENSIONS

3. PARTICLE SIZE MEASUREMENT- microscopy- coulter counter

4. RHEOLOGICAL PROPERTY- Viscosity5. TEMPERATURE AND GRAVITATIONAL STRESS

test for crystal growth usually at 40ºC6.ZETA POTENTIAL DETERMINATION

repulsive forces among particles.-desirable suspension .

1. TEST FOR PHASE INVERSION, CREAMING, CRACKING, PHASE SEPARATION

A. DYE SOLUBILITY TEST- amaranth green- O/W sudan red- W/O

B. UV FLOURESCENCE- C. CONDUCTIVITYD. COBALT CHLORIDE TEST- wet- pink; dry- blue

(o/w)E. DIRECTION OF CREAMING- O/W ( up-oil)

W/O ( down oil)2. ELECTROPHORETIC ANALYSIS3. PARTICLE SIZE4. GRAVITAIONAL AND TEMP STRESS TEST (50-70C)

EMULSIONS

PARTICLE SIZESIEVING- most rapidmesh #- # linear openings psi

ANGLE OF REPOSE1. STATIC ANGLE OF REPOSE

a. Fixed funnel methodb. Fixed bed conec. tilting box

2. KINETIC ANGLE OF REPOSEFLA; angle of repose= arc tan height

radius

GRANULES

BULK DENSITYBD= weight bulk volume

TAPPED DENSITYTD= weight tapped volume

CARR’S INDEX OF COMPRESSIBILITYCI= Bulk volume- tap volume x100

tap density

HAUSNER’S RATIOHR= tap density Good- < 1.25 Bulk density Poor. 1.25 Fair to pass- 1.25-1.5POROSITYP= voidx100Void= Bulk- True Volume x 100Bulk volume

MOISTURE CONTENTLack of moistureLimit 31-35%CONTENT UNIFORMITYSHAPE

spectrophotometry

HPLC GC FLUOROMETRY

MICROBIO LOGICAL

RABBIT Blood sugar

Vitamin A Vit.D Vit.E Vit.B1 Vit. B3 Insulinactivity

Vit. K (635 nm)

Vit. B6 Barbiturates

Vit. B2 Vit. B5

Vit. B12 (361 nm)

Vit. B9 Vit. B12

Vit. B3 (450 nm)

Steroids

Penicillinscephalosporins

ASSAY METHODS FOR SELECTED DRUGS

DRUG ANIMAL EMPLOYEDCorticotropin injection Rat (same but of either sex)

Cod liver oil Rachitic ratVasopressin injection Male ratChorionic gonadotropin FEMALE RAT (20-23 days old)DIgitalis PIGEONGlucagon injection CATOxytocin injection CHICKENParathyroid injection DOGHeparin and Protamine sulfate SHEEP BLOOD PLASMAINSULIN, METOCURINE, TUBOCURARINEINJECTIONS

RABBIT

ANIMALS USED IN TESTING DRUGS

Light Wavelength in nanometerUV 220-380 nmVisible 380-780 nmNear IR 780-3000 nmMedium IR 3.0 -15µmFar IR 15- 300µm

WAVELENGTHS