Transcript
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
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