PHARM ANA LEC FINALS 1.2

regulated the development,

manufacture and marketing of medical products by a number of laws and

guidelines to assure the safety, protection and well being of the patient.

Government health authorities

based on a correctly implemented system of

Quality Assurance incorporating ___ and ___ which involves performing various tests and analysis to elucidate

conformance to set standards and specifications.

Authorized manufacture

Good Manufacturing Practice

Quality

Control

broad term which includes

suitability of drugs and products for their utilization which is decided by

their efficiency and safety, according to label claim, or as promoted or

publicized, their conformity to specifications about identity, purity and

other characteristics.

quality

The quality of any product must be built all throughout the product life

cycle, including the?

testing, inspection, labelling, storage and

distribution.

It is part of Good Manufacturing Practice

● Involves operational techniques and activities that are used to fulfill

requirements for quality

● Aims to eliminate errors and production of end product of given

specifications

● In-Process Quality Control (IPQC) & Finished Product Quality Control

(FPQC)

QUALITY CONTROL

Monitor and adaptation of manufacturing processes in order to comply

to the given specifications

● Should be carried out before the manufacturing process is complete

● Physical parameters and its quality attributes, and may involve control

of equipment and environment

IN PROCESS QUALITY CONTROL

Qualitative and Quantitative Analysis of Product

● Determines the test and procedures and acceptance criteria/limit

● The product must comply with the acceptance limit for the approval of

complete batch manufactured.

FINISHED PRODUCT QUALITY CONTROL

IDENTIFICATION TESTS?

Particle size

● Colour and odor

● Unique identification marking (e.g. emboss, engraving, printing)

measured using a vernier caliper

Thickness

measured using a specialized tool (monsanto type)

Hardness tester

affected by compression of tablet and compressive

force, and method of granulation.

Hardness

physical condition that describes the tendency of tablets to

break into smaller pieces or to detach a percentage of powder or

powder loss from the tablet’s outer surface under mechanical and

physical stress. Capsules do not undergo this test.

Friability

Friability equipment

Roche Friabilator

Vanderkaamp friabilator

Friability Standard setting

25 rpm for 4 minutes (100 revolutions)

Friability samples condition

650 mg or greater - 6.5g dedusted sample

< 650 mg - 20 tablets

Friability formula

% Friable = [(initial weight - final weight/initial weight) x 100

Friability acceptance criteria

Separation of the

crown of the tablet

Capping

Splitting of the tablet

into layers

Lamination

Breaking of edges

Chipping

mechanical break up of

compressed tablets into smaller particles

Disintegration

Disintegration equipment

Basket Rack Assembly

Disintegration requirements

Six (6) cylindrical tubes; 10 mesh wire cloth at bottom portion and

disks

Disintegration temp

37 ± 2 oC; 29-32 cycles/min

medium and acceptance criteria of Plain, uncoated tablet

Sugar coated

Capsules

Distilled Water30 minutes

medium and acceptance criteria ofEnteric coated tablet

Distilled water (5 mins) | (None)

● Simulated Gastric Juice TS

pH 2.5 (1 hour) | (None)

● Simulated Intestinal Juice

TS pH 6.8 (1 hour) | (1 hour)

medium and acceptance criteria of Buccal tablet

Distilled Water

4 hours

medium and acceptance criteria of Sublingual tablet

Distilled Water

3 minutes

medium and acceptance criteria ofChewable tablet

None

None

process in which a substance forms a solution, and

an important parameter to assess bioavailability and therapeutic

effectiveness. Measures the extent and rate of

solution formation from a dosage form.

Dissolution

Dissolution media temp

35 ± 0.5 oC

Dissolution Aliquot

Midway from surface of the medium; 1cm from vessel wall.

Apparatus I in dissolution

Basket

Apparatus II in dissolution

Paddle

Apparatus III in dissolution

Reciprocating cylinder

Apparatus IV in dissolution

Flow through cell

Apparatus V in dissolution

Paddle over disk

Apparatus VI in dissolution

Revolving cylinder

Apparatus VII in dissolution

Reciprocating holder

Height and inside diameter (mm) of dissolution test vessel 1 L

160 - 210

98 - 106 mm

Height and inside diameter (mm) of dissolution test vessel 2 L

280 - 300

98 - 106 mm

Height and inside diameter (mm) of dissolution test vessel 4 L

280 - 300

145 - 155 mm

Dissolution test formulas

Dissolution test acceptance criteria

degree of uniformity in the amount of drug

substance among dosage units ( dosage forms containing a single dose or

a part of a dose of drug substance in each unit)

Uniformity of dosage units

a method used to determine drug content

uniformity of drug distribution (based from USP XX).

Weight Variation Test

formula of Weight Variation Test

Ave. weight = Total wt. of 20 tablets/ 20

● Weight variation = [(individual weight - Average weight)/ average

weight] x 100

acceptance criteria of weight variation test

uniformity of dosage forms

content uniformity old acceptance criteria

10 dosage units are assayed individually

and requirements for content uniformity are met if amount of active

ingredient in each unit lies within the range of 85%-115% of Label

claim, with SD <6%

content uniformity new acceptance criteria

Acceptance Value (AV) calculated must

be less than or equal to L1 (maximum allowed AV; 15) for the first

10 units, if not met, retest.

content uniformity retest acceptance criteria

test 20 more units and the AV calculated must be equal to

L1 for 30 units

uniformity of dosage forms acceptance value formula

Variable letter symbols

Intermediate of both solid and liquid dosage forms which can be

used therapeutically and cosmetically.

SEMI-SOLIDS

SEMI-SOLIDS examples

Pastes

○ Jellies

○ Ointments

○ Creams

IDENTIFICATION TESTS of semi-solids

Physical appearance

● Texture

● Color – early signs of degradation

● Phase separation and homogeneity – instability

plays a necessary role in the administration of medicated

formulation in a standard dose into the skin

Spreadability

Spreadability is done by spreading ___ of sample between ___ (___times)

1gm

two horizontal glass plates

three

Spreadability types in adults

Face and neck: 2.5

○ Front of trunk: 6.8 (~7)

○ Back of trunk: 6.7 (~7)

○ Hand: 1.2 (~1-2)

○ Arm and forearm: 4

○ Leg and thigh: 5.8 (~6)

○ Foot: 1.8 (~2)

should be calibrated using prepared standard buffer solutions before each use.

pH meter

In pH, 1 gram of each formulation is dispersed in ___, and

the pH is determined with ___ measurements

25 mL deionized water

triplicated

Procedure for non-aerosols (melting range)

Remove any labeling, and clean and dry containers

● Weigh individually

● Remove contents from each container and dry

● Weigh each empty container

● Compute for the next content of each container

○ Net content = initial weight - final weigh

● Compute for the % labeled content

○ % labeled content = net content/ label content x 100

Acceptance criteria of non-aerosols

the % LC of any single container is NLT 90% where the

labeled amount is 60 g or 60mL or less; NLT 95% where the labeled amount is >60

g or 60mL but NMT 150g or 150 mL

Procedure for aerosols

Remove any labeling, and clean and dry containers

● Weigh individually

● Remove contents from each container by employing safe technique (e.g.,

chill to reduce internal pressure, remove the valve then pour)

● Remove any residual contents with suitable solvents, then add a few

portions of methanol

● Retain as a unit the container, the valve, and all associated parts, and heat

them at 100°C for 5 minutes, and then cool and weigh the empty container

● Compute for the net content and %LC

acceptance criteria for the Procedure for aerosols

Net content is NLT labeled amount

METAL PARTICLES IN OPTHALMIC OINTMENTS If for single use

must pass Sterility

METAL PARTICLES IN OPTHALMIC OINTMENTS for multiple use

must pass Antimicrobial effectiveness testing unless it is

bacteriostatic itself.

METAL PARTICLES IN OPTHALMIC OINTMENTS procedure

Extrude all the contents in a petri dish

2. Heat at 85°C for 2 hours and cool

3. Inert petri dish on the stage microscope

4. Examine the petri dish for metal particles

5. Count the number of of metal particles that are 50μm or larger in any

dimensions

6. Acceptance criteria: total number of particles in all 10 tubes does not exceed

50, and if not more than 1 tube is found to contain more than 9 such particles.

The presence of certain microorganisms in nonsterile preparations may

have the potential to reduce or even inactivate the therapeutic activity of

the product and has a potential to adversely affect the health of the

patient

● For non-sterile oral/ topical products

MICROBIAL CONTENT

used to measure Total Aerobic Microbial

Count (TAMC), what is the incubation?

Tryptone Soy Agar

30 - 35°C for 2 -3 days

measure Total Yeasts and Molds

Count (TYMC) what is the incubation?

Potato Dextrose Agar

20 - 25°C for 5 - 7 days

microbial content list with specified organisms

microbial content list with specified organisms p2

Significance of other microorganisms recovered should be evaluated in

terms of the following:

The use of the product; hazard varies according to ROA

● The nature of the product

● The method of application

● The intended recipient

● Use of immunosuppressive agents, corticosteroids

● The presence of disease, wounds, organ damage

pourable pharmaceutical formulations which

contain a mixture of active drug components and nondrug components

(excipients) dissolved or suspended in a suitable solvent or mixtures of

solvents.

● These preparations designed to give the max. therapeutic response

and produce rapid therapeutic effects.

Liquid dosage forms

visualization or using a homogenizer in liquids

Homogeneity Test

tests in liquid

Homogeneity Test

Viscosity and Specific Gravity Test

Leaker test

pH considerations in liquids

The effect on the body when the solution is administered

○ The effect on stability of the product

○ The effect on container-closure system pH measurement

(often used for ampoules and vials)

○ Test container is immersed in a dye bath. Pressure and vacuum is

applied for some time. From the dye bath the container is removed

and washed. The container is then analyzed for the presence of

dye either by means of UV-Spectroscopy or visually.

Leaker test or Dye bath test

provide assurance that oral liquids will, when

transferred from the original container, deliver the volume of dosage

form that is declared on the label of the article

Delivered Volume

Delivered Volume tests are applicable to products labeled to contain NMT

___, whether supplied as liquid preparations, or liquid

preparations that are constituted from solids upon the addition of a

designated volume of a specific diluent

250mL

Sample size in liquids

10 containers initially; 20 containers on retest

Delivered Volume

Procedure:

Gently pour the contents of each container into separate dry

graduated cylinders of a rated capacity not exceeding two 1/2 times

the volume to be measured, and calibrated to contain. Avoid the

formation of bubbles in doing this.

● Allow each container to drain for a period not to exceed 30 minutes

for Multiple-unit containers, and 5 seconds for Single-unit

containers

Sedimentation volume in suspension

settled volume / total or initial volume of suspension

Ideal SV

1

measurement of repulsion between particles

Zeta Potential Determination

Zeta Potential Determination is Related to the electrostatic forces which could affect the attraction

(aggregation) and/or repulsion of

colloids

Zeta Potential Determination is Determined by

microscopic electrophoresis

lead to the

attractive forces exceeding the repulsive forces, creating flocs (loose

agglomerates of particles)

Low zeta potential (or reduced to a certain value)

Degree of Flocculation

β = Ultimate sedimentation volume of flocculated suspension (Vu) /

Ultimate sedimentation volume of DEflocculated suspension

Ease of Redispersibility in suspension

Solute should be 100% redispersible with minimum agitation

Particle Size Determination in suspension

Optical Microscopy

○ Sedimentation Rate - based on Stoke’s Law

should pour readily and evenly from its container

Viscosity

A liquid disperse system that uses small globules of a liquid (dispersed

phase) distributed through another liquid in which it is immiscible

forming spherical bodies called ___.

micelles

EMULSIONS

Emulsifying agents

(gum arabic, lecithin, carrageenan, CMC,

polysorbate)

Based on nature of dispersed phase:

Oil in water (O/W)

○ Water in oil (W/O)

Based on globule size of emulsions

Microemulsons (0.01 um)

○ Fine emulsions (0.25 to 25um)

Tests for types of emulsions

Test for creaming

Upward creaming (O/W); Downward creaming (W/O)