2.

TABLET FRIABILITY A maximum mean weight loss from the three

• Important indicator of cohesiveness samples of not more than 1.0% is considered acceptable for most
• Limited value in predicting failure in the field products.
• Roche friabilator
• instrument is designed to evaluate the ability of the tablet to
withstand abrasion
A tablet property related to hardness is friability, and the measurement
is made by use of the Roche friabilator. Rather than a measure of the
force required to crush a tablet, the instrument is designed to evaluate
the ability of the tablet to withstand abrasion in packaging, handling,
and shipping. A number of tablets are weighed and placed in the
tumbling.
Friability – the percentage weight loss after tumbling.
FRIABILATOR
- Apparatus where they are exposed to rolling and repeated
shocks resulting from freefalls within the apparatus.
- After a given number of rotations the tablets are weighed.
and the loss in weight indicates the ability of the tablets to
withstand this type of wear
- used for storage
Three measurable hardness parameters that can give a clue to the
compatibility and. intrinsic strength of powdered materials. These include:
 bonding strength,
 internal strain, and
 brittleness
If the results are difficult to interpret or if the weight loss is greater than
the targeted value, the test should be repeated twice and the mean of
the three tests determined. A maximum mean weight loss from the three
samples of not more than 1.0% is considered acceptable for most
products.
If tablet size or shape causes irregular tumbling, adjust the drum base so
that the base forms an angle of about 10 with the horizontal and the
tablets no longer bind together when lying next to each other, which
prevents them from falling freely.
In the case of hygroscopic tablets, an appropriate humidity-controlled
environment is required for testing.
Drums with dual scooping projections, or an apparatus with more than
one drum, for the running of multiple samples at one time, are also
permitted.
SHIPPING TEST
– methods of transportation
- The condition of the product on its return indicates its ability to
withstand transportation handling.
• The measure of abrasion/ friability loss is usually expressed as
percentage loss in weight. It is calculated from the equation:

High percentage of weight loss – low quality tablet

The test is rejected if any tablet caps, laminates or breaks up in course of the test.
higher the bonding index- stronger a tablet As a rule of thumb, a maximum weight loss of not more than 1% generally is
higher is the strain index-weaker the tablet. considered acceptable for most pharmaceutical products. 

Friability drum 3. TABLET DIAMETER (USP 32)

Abrasion drum – with lamellas - value must not exceed 5% for tablets with diameter less than 12.5 and
-Modified version of friability drum 3% for diameter of 12.5mm or more.
- test done by using Tablet Testing Instrument (PHARMATEST PTB 311)
USP 32 ROCHE FRIABILATOR - thickness and hardness are non-compendial standards
– drum is attached to horizontal axis of a device that rotates at 25 ±1
rpm. Thus, at each turn the tablets roll or slide and fall onto the drum Deviation=[ |Initial diameter-Average diameter | ] / average diameter x
wall or onto each other. 100%
- 25 rpm • Average diameter =[ |12.82-12.82| ] / 12.82 x 100% =0%
- Most popular and reliable
What then is the acceptable range?
How to do (For compressed tablets) The deviation of diameter of the single tablet cannot exceed +/- 3%
• For tablets with a unit weight equal to or less for diameter of 12.5 mm or more.
than 650 mg, take a sample of whole tablets corresponding as near 12.82 mm X 3% = 0.3846 mm + 3% from the average value
as possible to 6.5 g. 12.82 mm + 0.3846 mm =13.2046 mm -3% from the average value
• For tablets with a unit weight of more than 650 12.82 mm - 0.3846 mm = 12.4354 mm 
mg, take a sample of 10 whole tablets. ** HENCE, the diameter of tablet should be in the range of between
• Accurately weigh the tablet sample, and place or equal 12.4354 mm to 13.2046 mm.
the tablets in the drum. Rotate the drum 100 times, and remove the
tablets ACCEPTANCE CRITERIA
• Remove any loose dust from the tablets as The deviation of individual unit from the mean diameter
before, and accurately weigh should not exceed +/- 5% for tablets with diameter of less
1st run – 10 tabs, if 3rd run, 30 tabs than 12.5 and +/- 3% for diameter of 12.5 mm or more.

Run the test once When to do uniformity of diameter testing?

• If obviously cracked, cleaved, or broken tablets
are present in the tablet sample after tumbling, the sample fails the
test.
• In doubtà the test should be repeated twice and
the mean of the three tests determined.
• Uniformity of diameter tests involves all the
uncoated and coated tablets except for the enteric
tablets, film-coated tablets and sugar-coated tablets.
4. TABLET THICKNESS
• May vary from production run to production run
 • Thickness can vary without a change in weight because of: For solid dosage forms: assay 10 units
 Difference in density of the granulation individually using appropriate analytical method. Calculate the
 Pressure applied to tablets acceptance value.
 Speed of compression
For liquid dosage forms: assay 10 units as
Tablets may have diff thickness, but have the same weight.
Why should we care? above. Carry out the assay on a well-mixed material that is removed
o Reproducing tablets identical in appearance from an indiviual container in conditions of normal use and express
o To ensure each production lot is usable with selected packaging the results as delivered dose. Calculate the acceptance value.
o IF they are thicker than should be= number of tablets that can fit in
bottle might change
o Some filling equipment use uniform thickness of tablets as counting
mechanism *i.e. column of tablets will be dropped into bottles of the
same height
o Variation in thickness can lead to variation in count.
o Other pieces of filling equipment can malfunction= i.e. wedging of
tablets in the counting slots (for a specified thickness only)

1. Identity
2. Packaging purpose
3. Filling equipment
4. Counting tablets

How to measure tablet thickness

• Determined by caliper or thickness gauge that
measures thickness in millimeters
• Plus or minus 5% may be allowed, depending
on the size of the tablet
• Featured: digital thickness gauge, digital caliper
5.1. TABLET WEIGHT FOR UNCOATED TABLETS
• Determined by volumetric fill of the die cavity
• Fill is adjusted to give desired weight
• Weight represents amount of granulation containing labeled amount of
ingredient
• As tableting machine is in operation, weight testing is done routinely
• Common with electronically controlled tablet presses

• Exemption: coated tablet (still requires content uniformity)

• ACCEPTANCE CRITERIA: Twenty tablets are weighed
individually. Calculate average weight

Requirements
• Applicable USP standards for when tablet has 50 mg or more of
drug OR when drug substance comprises 50% or more BY
WEIGHT of the dosage form
• Variation from average weight of NOT MORE THAN 2 of the
tablets must not differ by more than the percentage listed:

The uniformity of dosage units can be demonstrated by unit-dose either

of two methods
5. UNIFORMITY OF DOSAGE FORMS
5.1. CONTENT UNIFORMITY
5.2. TABLET WEIGHT

5.1 CONTENT UNIFORMITY

• USP includes conformity test for certain tablets.
• It has been extended to monographs on all coated and uncoated tablets
and all capsules intended for oral adminisitration with range of size
including 50 mg or smaller size, in which case the test is applicable to ALL
SIZES (50mg, and larger and smaller) of that tablet or capsule.
• Tablet monographs with a content uniformity requirement DO NOT have
a weight variation requirement.

How to do:
✦Weight Variation
 Select not fewer than 30 units
 Weight Variation is allowed for hard capsules, uncoated
Complete
tablets,disintegration
and film– is defined as that state in which any residue of the unit, except
fragmentscomprising
coated tablets containing 25 mg or more of the drug substance of insoluble coating or capsule shell, remaining on the screen of the test
25% or more of the weight of the dosage unit.  apparatus or adhering to the lower surface of the disk, if used, is a soft mass having no
palpably firm core.
How to do (Usp 905)
• HARD CAPSULE=After capsule is weighed, contents have to be
removed, and the net weight of the contents have to be calculated.
USP offers both documentary and physical reference standards to support
• SOFT CAPSULE= After capsule is weight (gross weight is noted) cut the capsule with
dosage form performance testing. 
scissors, clean6. with solvent, dry for 30 mins (take care to avoid uptake or loss of
• Dissolution and drug release measure the amount of active
moisture), net weight of content is calculated. Calculate acceptance value.
ingredient(s) released from the dosage form over time under
standardized conditions.
• Accurately weigh the amount of liquid that is removed from each of 10 individual
• Depending on the physical-chemical characteristics of the active
containers in conditions of normal use. Calculate amount of drug substance in the
ingredient and on the release mechanism of the drug product,
product from the volume used in testing and result of assay
dissolution testing may be replaced with disintegration with
• Calculate acceptance value.
appropriate justification. 

6.Dissolution and disintegration(next mtg)

DISINTEGRATION
• Dissolution, disintegration and drug release tests, also called
performance tests, are important tools that can be used during the entire lifecycle of a
drug product, from early development throughout its shelf life.

• The apparatuses and general procedures to carry out these

performance tests are detailed in the following General Chapters: 
• <701> Disintegration,
• <711> Dissolution
USP: Basket-rack
• The basket-rack assembly consists of 6 open-ended transparent tubes
The apparatus consists • Attached to the under surface of the lower plate is a woven stainless
steel wire cloth, which has a plain square weave with 1.8–2.2-mm

of a basket-rack apertures and with a wire diameter of 0.57–0.66 mm.

• A suitable means is provided to suspend the basket-rack assembly from
the raising and lowering device using a point on its axis.
assembly, a 1000-mL • If the use of disks is specified in the individual monograph, add a disk
to each tube, and operate the apparatus as directed under Procedure.
low-form beaker 138– The disks conform to dimensions found in Figure 1

160 mm in height and How to perform:

Place 1 dosage unit in each of the 6 tubes of the basket-rack.
having an inside Operate the apparatus, using water or the specified medium as the
immersion fluid, maintained at 37 ± 2°.
If 1 or 2 tablets fail to disintegrate completely, repeat the test on 12
diameter of 97–115 mm additional tablets.

for the immersion fluid, Criteria for uncoated

1.If 6 tablets are tested, all 6 of the tablets are disintegrated.
a thermostatic 2.If 18 tablets are tested, the requirement is met if not fewer than 16 of
the total of 18 tablets are disintegrated
arrangement for heating
the fluid 35°–39°, and a
device for raising and
lowering the basket in
the immersion fluid at a
constant frequency rate
29–32 cycles/min
through a distance of
NLT 53 mm and NMT 57
mm. The volume of the
fluid in the vessel is such
that at the highest point
of the upward stroke,
the wire mesh remains
DISSOLUTION TESTING
at least 15 mm below evaluates the rate and extent that a compound forms a
under carefully controlled conditions.
the surface of the fluid helps evaluate the performance of a drug
. Although passing the test does not definitively
and descends to NLT 25products, failure is a cause forofconcern.
demonstrate bioavailability the sample or bioequivalence to other

mm from the bottom ofrelease of product the USP dissolution test helps safeguard against the
that does not perform acceptably.

the vessel on the 1. basket apparatus

downward stroke. At nothe rotating basket method of dissolution testing was the first official method.
time should the top of
 the basket-rack
assembly become
-
submerged. The time
required for the upward
stroke is equal to the
time required for the
downward stroke, and
the change in stroke
direction is a smooth
transition, rather than
an abrupt reversal of
motion. The basket-rack
assembly moves
vertically along its axis. 4. FLOW-THROUGH CELL
- The cell is immersed in a water bath, and the temperature is maintained
There is no appreciable at 37±0.5°
- The pump forces the Dissolution Medium upwards through the flow-
horizontal motion or through cell
- Pump delivers constant flow with pulsation of 120±10 pulses per minute
(option: without pulsation)
movement of the axis - mounted vertically
2. PADDLE - It has a filtration system that prevents escape of undissolved particles
- from The the vertical.
paddle blade and shaft may be coated from the top of the cell
formed from a blade and a shaft is used as the stirring ele- with a suitable Apparatus consists of:  reservoir, pump, a flow through cell, water bath.
coating so as to make them inert.

Pump delivery—240 & 960ml/hr with standard flow rates of 4,8,16 ml per minute.

Flow must be volumetric and sinusoidal at a pulsation rate of 120 + 10

pulses per minute.

3. RECIPROCATING CYLINDER
- set of cylindrical, flat-bottomed glass vessels; a set of glass VERTICALLY
reciprocating cylinder
- Evaporating cap remains in place for the test
- 37±0.5 C during the test
 Extended-Release Dosage Forms
• requirements are met if the quantities of active ingredient dissolved from
the dosage units tested conform to Acceptance Table 2. Continue testing
through the three levels unless the results conform at either L1 or L2.
Limits on the amounts of active ingredient dissolved are expressed in
terms of the percentage of labeled content.
FOR STERILE PREPARATIONS (USP 797)
describe conditions and practices to prevent harm, including death, to
patients that could result from (1) microbial contamination (nonsterility)
(2) excessive bacterial endotoxins
(3) variability in the intended strength of correct ingredients that exceeds
either monograph limits for official articles or 10% for nonofficial articles
(4) unintended chemical and physical contaminants
(5) ingredients of inappropriate quality in compounded sterile preparations
(CSPs).

Four specific categories of CSPs are described in this chapter:

low-risk level, medium-risk level, and high-risk level, and immediate use.

DELAYED RELEASE STAGE

• Acid stage = requirements of this stage are met if the percentage
of labeled content, of active ingredient dissolved from the units
tested conform to Acceptance Table 3
• Continue testing through all levels unless the results of both acid
and buffer stages conform at an earlier level.
• defines delayed-release tablets as enteric-coated to delay release
of the medication until the tablet has passed through the stomach to
prevent the drug from being destroyed or inactivated by gastric juices
or where it may irritate the gastric mucosa.

extended-release tablets "formulated in such a manner to make the

contained medicament available over an extended period of time following
ingestion."

Buffer stage
• The value of Q in Acceptance Table 4 is 75% dissolved