quality control ii lecture 1
TRANSCRIPT
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QUALITY CONTROL 2Drug Testing and Assay
with Instrumentation
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An enteric coated tablet that
disintegrates in the stomach
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Hardness of tablets
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Change in pH for eye solutions
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Capsules without fill
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- 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
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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
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QC- testing and acceptance ( raw material, representative
sample)- IP tests against criteria- monitors environmental conditions- control packaging components.
FUNCTIONS
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Solubility
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Uniformity in size and shape
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Microbial growth
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Question of Quality
Difference of bioavailability, drugs with low solubility as ascertained by blood level attainment studies, caused by formulation variables.
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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
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MONOGRAPHS
USP NFBritish PharmacopeiaPh Eur
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CERTIFCATE OF ANALYSIS
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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)
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What constitutes a STABLE FINISHED PRODUCT?
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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
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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
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EXPIRATION DATE- Extension?
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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
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PACKAGING
1.material type2.special properties3. integrity
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IDENTITY TEST
1.Physical2.Chemical3.Visible reactions
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PHYSICAL PROPERTIES
1.Gross2.Totality
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LIMIT TESTS
1.Biological2.Chemical3.Gross
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POTENCY TEST
1. Instrumental2.Chemical3.Biological
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-debasement of article.1.SOPHISTICATION -true adulteration
- addition of inferior material to any particleex. Teatree oil – olive oil Saffl ower – 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
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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
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ADULTERATION
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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
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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
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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
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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
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7. UNIFORMITY OF DOSAGE UNITS- WEIGHT VARIATION- CONTENT UNIFORMITY
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- 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
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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.
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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
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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
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BULK DENSITYBD= weight bulk volume
TAPPED DENSITYTD= weight tapped volume
CARR’S INDEX OF COMPRESSIBILITYCI= Bulk volume- tap volume x100
tap density
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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
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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
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DRUG ANIMAL EMPLOYED
Corticotropin injection Rat (same but of either sex)
Cod liver oil Rachitic rat
Vasopressin injection Male rat
Chorionic gonadotropin FEMALE RAT (20-23 days old)
DIgitalis PIGEON
Glucagon injection CAT
Oxytocin injection CHICKEN
Parathyroid injection DOG
Heparin and Protamine sulfate SHEEP BLOOD PLASMA
INSULIN, METOCURINE, TUBOCURARINEINJECTIONS
RABBIT
ANIMALS USED IN TESTING DRUGS
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Light Wavelenght in nanometer
UV 220-380 nm
Visible 380-780 nm
Near IR 780-3000 nm
Medium IR 3.0 -15µm
Far IR 15- 300µm
WAVELENGTHS