Quality control II lecture 1
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Transcript of Quality control II lecture 1
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
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
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?
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
PACKAGING
1.material type2.special properties3. integrity
IDENTITY TEST
1.Physical2.Chemical3.Visible reactions
PHYSICAL PROPERTIES
1.Gross2.Totality
LIMIT TESTS
1.Biological2.Chemical3.Gross
POTENCY TEST
1. Instrumental2.Chemical3.Biological
-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
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 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
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