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