An article on evaluation of dosage forms

1. EVALUATION OF DOSAGE FORMS
1. Solid dosage forms
1.1. Tablets
1.1.1. General appearance
1.1.2. Weight variation
1.1.3. Content uniformity
1.1.4. Mechanical strength of tablets
1.1.5. Disintegration
1.1.6. dissolution
1.2. Effervescent tablets
1.2.1. Effervescent tablets
1.2.2. Water content and moisture uptake studies
1.3. Buccal tablets
1.3.1. Determination of residence time
1.3.2. Swelling studies
1.4. Orally disintegrating tablets
1.4.1. Wetting time
1.4.2. Disintegration time
1.5. Sustained controlled dosage forms
1.5.1. Swelling index study
1.6. Capsules
1.6.1. Stablility tests
1.6.1.1. Shell integrity test
1.6.1.2. Determination of shelf life
1.6.2. Invariability tests
1.6.2.1. Weight variation
1.6.2.2. Content uniformity
1.6.3. Disintegration test
1.6.4. Dissolution test
1.6.5. Moisture permeation test
1.7. Granules
1.7.1. Flow properties
1.8. Powders
1.8.1. Particle size analysis
1.8.2. Angle of repose
1.8.3. Bulk density
1.8.4. Tapped density
1.8.5. Hausner’s ratio
1.8.6. Flowability
2. Semi solid dosage forms

2. 2.1. Ointments
2.1.1. Test of rate of absorption
2.1.2. Test of non-irritancy
2.1.3. Test of rate of penetration
2.1.4. Test of rate of drug release
2.1.5. Test of rheological properties
2.1.6. Test of content uniformity
2.1.7. Test of preservative efficacy
2.2. Creams
2.2.1. Rheology
2.2.2. Sensitivity
2.3. Suppositories
2.3.1. Appearance
2.3.2. Physical strength
2.3.3. Melting range
2.3.4. Uniformity of drug content
2.3.5. Softening time
3. Liquid dosage forms
3.1. Non-sterile liquid dosage forms
3.1.1. Syrups
3.1.1.1. Transmittance of light
3.1.1.2. Visual inspection
3.1.1.3. pH measurement
3.1.1.4. sucrose concentration
3.1.1.5. physical stablility in syrups
3.1.2. Elixirs
3.1.2.1. Determination of alcohol content
3.1.2.2. Viscosity measurement
3.1.3. Suspensions
3.1.3.1. Sedimentation method
3.1.3.2. Rheological method
3.1.3.3. Electrokinetic method
3.1.3.4. Micromeritic method
3.1.3.5. Freeze-thaw test
3.1.3.6. pH measurement
3.1.3.7. visual inspection
3.1.4. emulsions
3.1.4.1. Determination of particle size and particle count
3.1.4.2. Determination of viscosity
3.1.4.3. Determination of phase separation
3.1.4.4. Determination of electrophoretic properties

3. 3.1.4.5. Electrical conductivity
3.2. Sterile liquid dosage forms
3.2.1. Parenterals
3.2.1.1. Leaker test
3.2.1.2. Pyrogen test
3.2.1.3. Sterility test
3.2.1.4. Particulate evaluation
3.2.1.5. Weight variation or uniformity of content
3.2.2. Eye drops
3.2.2.1. Test for sterility
3.2.2.2. Test for ocular toxicity and irritation
3.2.2.3. Test for preservative efficacy
3.2.2.4. Clarity
3.2.2.5. pH
3.2.2.6. In vitro diffusion studies
3.2.2.7. Determination of viscosity
4. Aerosols
4.1. Flammability and combustibility
4.1.1. Flash point
4.1.2. Flame projection
4.2. Physico chemical characteristics
4.3. Performance
4.3.1. Aerosol valve discharge rate
4.3.2. Spray patterns
4.3.3. Dosage with metered valves
4.3.4. Net contents
4.3.5. Foam stability
4.3.6. Particle size determination
4.4. Biological testing
5. Nasal spray
5.1. Appearance, color and clarity
5.2. Drug content
5.3. Impurities and degradation products
5.4. Preservative and stablilizing excipient assay
5.5. Pump delivery
5.6. Spray content uniformity
5.7. Spray content uniformity through container life
5.8. Droplet size distribution
5.9. Foreign particulates
5.10. Microbial limits
5.11. Preservative effectiveness

4. 5.12. Net content and weight loss (stability)
5.13. Leakage testing
5.14. pH
5.15. osmolality
6. Cosmetics
6.1. Lipsticks
6.1.1. Surface anomalies
6.1.2. Thixotropic characters
6.1.3. Breaking point
6.1.4. Melting point
7. Novel drug delivery systems
7.1. Transdermal patches
7.1.1. Thickness
7.1.2. Uniformity of weight
7.1.3. Drug content determination
7.1.4. Content uniformity test
7.1.5. Moisture content
7.1.6. Moisture uptake
7.1.7. Flatness
7.1.8. Tensile strength
7.1.9. Peel adhesion properties
7.1.10. Tack properties
7.1.11. Thumb tack test
7.1.12. Rolling ball test
7.1.13. Quick stick test
7.1.14. Probe tack test
7.1.15. Shear strength properties

5. Drug substance are seldom administer alone; rather they are given as part of formulation in
combination with one or more non-medicinal agents that serve varied and specialized
Pharmaceutical functions. Selective uses of non medicinal agent referred to as
pharmaceutical ingredients or excipients, produces dosage form of various types.
EVALUATION OF DOSAGEFORMS:
1.SOLID DOSAGE FORMS:
Solid dosage forms are substances having definite shape and volume manufactured for the
administration of active and /or inert ingredient. Solids include tablets, capsules, granules,
powders etc…
1.1. EVALUATION OF TABLETS
Definition: These are solid dosage forms of medicaments which are prepared by moulding
or by compression with or without excipients.
TABLET EVALUATION:
 Introduction
1.1.1. General appearance
i. Size and shape
ii. Organoleptic characters or properties
1.1.2. Weight variation
1.1.3. Content uniformity
1.1.4. Mechanical strength of tablet
i. Hardness
ii. Friability
iii. Tensile strength
1.1.5. Disintegration test
1.1.6. Dissolution test
Why to evaluate tablets?
 To monitor the product quality.
 For quantitative evaluation and assessment of tablet properties
 To check chemical breakdown.
 To check the interactions between physical components of tablets.
1.1.1. General appearance:
i. Size and shape:
Tablet thickness varies with changes in-
a) Die fill
b) Particle size distribution and

6. c) Packing of the powder mix being compressed and with tablet weight.
The thickness of tablet is measured with a micrometer tablet thickness should be controlled
within a +-5% variation of a standard value.
ii. Organoleptic properties:
 Color (no mottling)
 Odour (e.g. film coated tablets)
 Taste (e.g. chewable tablets)
1.1.2. Weight variation:
Twenty tablets were selected randomly from each batch and weighed individually to check
for weight variation.
The USP has provided limits for the average weight of uncoated compressed tablets.
I.P Average weight (mg) USP % difference
Less than 85 130 mg or less 10
85-324 >130 mg but <324 mg 7.5
324 or more 324 mg (or) more 5
1.1.3. Content uniformity:
Every tablet contains the amount of drug substances intended with little variation among
tablets within a batch.
For content uniformity test, representative samples of 30 tablets are selected and 10 are
assayed individually. Nine of the 10 tablets must contain NLT 85 % or more than 115% of the
labeled drug content.
The three factors that directly contribute to content uniformity problems:
i. Non-uniformity distribution of drug substance throughout the powder
mixture or granulation.
ii. Segregation of powder mixture or granulation during various manufacturing
processes.
iii. Tablet weight variation.
1.1.4. Mechanical strength of tablets:
It provides a measure of the bonding potential of the material concerned and this
information is useful in the selection of excipients.
The excessively strong bonds prevent rapid disintegration and subsequent dissolution.Can
be quantified by

7. i.friability
ii. Hardness
iii. Tensile strength
i. Friability:
The friability test is closely related to tablet hardness and is designed to evaluate the
ability of the tablet to withstand abrasion in packaging, handling and shipping. It is
measured by the use of Roche friabilator.
Method:
A number of tablets (say 20) are weighed and placed in the apparatus where they are
exposed to rolling and repeated shocks as they fall 6 inches in each turn within the
apparatus.
After four minutes of this treatment or 100 revolutions, the tablets are weighed and
the weight compared with the initial weight.
The loss due to abrasion is a measure of the tablet friability. The value is expressed as a
percentage.
A maximum weight loss of NMT 1% of the weight of the tablets being tested during the
friability test is considered generally acceptable and any broken or smashed tablets or
not picked up.
ii. Hardness:
Hardness or crushing strength determinations are made during tablet
production, are used to determine the need for pressure adjustment on tablet
machine. The force required to break the tablet is measured in kilograms and a
crushing strength if 4 kg is usually considered to be the minimum for satisfactory
tablets. Oral tablets have 4 to 10 kg hardness. Hypodermic and chewable tablets
are usually much softer (3kg) and some sustained release tablets are much

8. harder (10-20 kg). Tablet hardness had been associated with other tablet
properties such as density and porosity.
Hardness of the tablets can be determined by using following apparatus:
 Stokes hardness tester
 Strong-cobb apparatus
 Schleuniger apparatus

9. iii. Tensile strength:
This is the force required to break a tablet in a diametric compression test. The
radial tensile strength, T, of the tablets can be calculated from the equation:
T=2F/∏dH
Where F is the load needed to break the tablet, d and H are diameter and
thickness respectively. It is determined by static and dynamic methods.
1.1.5. Disintegration:
For a drug to be absorbed from a solid dosage form after oral administration, it must first be
in solution, and the first important step toward this condition is usually the break-up of the
tablet; a process known as disintegration.
The disintegration test is a measure of the time required under a set of conditions for a
group of tablets to disintegrate into particles which will pass through a 10 mesh screen.
The disintegration test is carried out using the disintegration tester which consists of a
basket rack holding 6 plastic tubes, open at the top and bottom, the bottom of the tube is
covered by a 10 mesh screen.

10. The basket is immersed in a bath of suitable liquid held at 37°C, preferably in a 1L beaker.
For most uncoated tablets, the BP requires that the tablets disintegrate in 15 minutes
(although it varies for some uncoated tablets) while for coated tablets, up to 2 hrs may be
required. To test for disintegration time, one tablet is placed in each test tube and basket
rack is positioned in a 1L beaker of water, simulated gastric fluid at 37°c ±2°c, such that
tablets remain 2.5 cm below the surface of liquid on their upward movement. A standard
motor driven device is used to move the basket assembly, at a frequency of 28-32
cycles/min. To be in USP tablets=5 min (aspirin tablets). Majority of tablets have a
disintegration time of 30 minutes. Enteric coated tablets = 2hrs + time specified in
monograph (simulated intestinal fluid).
TYPE OF TABLETS DISINTEGRATION TIME DISINTEGRATION MEDIA
UNCOATED TABLETS 15 min Water
SOLUBLE TABLETS 3 min Water
DISPERSIBLE TABLETS 5 min Water
EFFERVESCENT TABLETS 5 min Water
SUGAR COATED TABLETS 60 min Water / 0.1 M Hcl
FILM COATED TABLETS 30 min Water
ENTERIC COATED
TABLETS
120 min Water / 0.1 M Hcl
1.1.6. DISSOLUTION:
Dissolution is the process by which a solid solute enters a solution. Pharmaceutically, it may
be defined as the amount of drug substance that goes into solution per unit time under
standardized conditions of liquid/solid interface, temperature and solvent composition.
Dissolution kinetics is important in determining the bioavailability of a drug. Two objectives
in the development of in-vitro dissolution tests are to show;

11. 1. That the release of the drug from the tablet is as close as possible to 100%
2. That the rate of drug release is uniform batch to batch
Thus we can say that,
Rate of dissolution is directly proportional to efficacy of product
Rate of dissolution is directly proportional to bioavailability
It is carried out in apparatus which are given below:
TYPE OF
APPARATUS
I.P B.P E.P USP
TYPE-1 Paddle
apparatus
Basket
apparatus
Paddle
apparatus
Basket
apparatus
TYPE-2 Basket
apparatus
Paddle
apparatus
Basket
apparatus
Paddle
apparatus
TYPE-3 Flow through
cell apparatus
Flow through
cell apparatus
Reciprocating
cylinder type
apparatus
TYPE-4 Flow through
cell apparatus
TYPE-5 Paddle over
disc
TYPE-6 Rotating
cylinder type
TYPE-7 Reciprocating
type of
apparatus

12. In general a simple tablet is placed in a small wire mesh basket fastened. To the bottom
of the shaft connected to a variable speed motor.
The basket is immersed in the dissolution medium (as specified in the monograph)
contained in a flask. The flask is maintained at constant temperature of 37°c +- 5°c by a
constant temperature bath.
The motor is adjusted to turn at the specified speed and samples of fluid are withdrawn
at intervals to determine the amount of drug in solution1.
SPECIFIC TESTS:
1.2. EFFERVESCENT TABLETS
Effervescent tablets are uncoated tablets that generally contain acid substances and
carbonates or bicarbonates and that react rapidly in the presence of water by releasing CO2
EVALUATION:
1.2.1. EFFERVESCENT TIME:
Place one tablet in a 250ml beaker containing water at 20°c to 30°c numerous gas bubbles
are evolved. When the evolution of gas around the tablet or its fragments has ceased the
tablet shall have disintegrated being either dissolved or dispersed in the water so that no
agglomerates of particles remain.
Repeat the operation on a further 5 tablets. The tablets comply with the test if each of the 6
tablets disintegrates in the manner prescribed within 5 minutes (I.P. 2007).

13. 1.2.2. WATER CONTENT AND MOISTURE UPTAKE STUDIES:
Three tablets were exposed to three different humidity conditions at 23°c. Controlled
humidity chambers (31%, 45% & 79.3% RH) were constructed using various saturated salt
solutions in desiccators.
The 31% RH desiccators contained a saturated solution of CC the 45% RH contained
ammonium chloride. Tablets were subjected to these humidities for approximately 60 days.
Moisture studies check by Karl fischer method2.
1.3. BUCCAL TABLETS
Buccal medications are administered by placing them in the mouth between the gum and
the cheek. These medications dissolve rapidly and are absorbed through the mucous
membranes of the mouth where they enter into the blood stream.
Parameters of evaluation:
1) Determination of residence time
2) Permeation studies
3) Swelling studies
4) Release rate studies
5) Toxicity and irritation study
6) Bioadhesion measurement
7) Content uniformity
1.3.1. DETERMINATION OF RESIDENCE TIME:
DETERMINATION
OF RESIDENCE
TIME
INVITRO
RESIDENCE TIME
INVIVO
RESIDENCE TIME

14. INVITRO RESIDENCE TIME:
For this test we use the USP dissolution test apparatus. Composition of dissolution
medium=800ml isotonic phosphate buffer solution.
A segment of rabbit buccal mucosa, 3cm long, is glued to the surface of a glass slab. Whichis
vertically attached to the apparatus.
The mucoadhesive tablet is hydrated from one surface using 15ml IPB and then the
hydrated surface is brought into contact with the mucosal membrane.
The glass slab is vertically fixed to the apparatus and allowed to move up and down so that
the tablet is completely immersed in the buffer solution at the lowest point and is out at the
highest point.
The time necessary for complete erosion or detachment of the tablet from the mucosal
surface is recorded.
IN VIVO RESIDENCE TIME:
Plain bioadhesive tablets with optimized properties are selected for the evaluation.
Procedure:
The bioadhesivetablets is placed on the buccal mucosa between the check and gingival in
the region of the upper canine and gently pressed onto the mucosa for about 30 seconds.
The tablet and the inner upper lip are carefully moistened with saliva to prevent the sticking
of the tablet to the lip. The time necessary for complete erosion of the tablet is
simultaneously monitored by carefully observing for residual polymer on the mucosa. In
addition, any complaints such as discomfort, bad taste, dry mouth, or increase of salivary
flux, difficulty in speaking, irritation or mucosal lesions are carefully recorded. Repeated
application of the bioadhesive tablets is allowed after a two days period for the same
volunteer.
1.3.2. SWELLING STUDIES:
Buccal tablets are weighed individually (W1) and placed separately in 2% agar gel plates with
the core facing the gel surface and incubated at 37± 0.1°c . The tablet was removed from
the petri dish and excess surface water is removed carefully using filter paper. The swollen
tablet is then reweighed (W2), and the swelling index (SI) or percent hydration is calculated
using the following formula3,
% of hydration = (W2-W1)×100/W2

15. W1 = initial weight of tablet
W2 = weight of disk at time t
1.4. ORALLY DISINTEGRATING TABLETS:
An orally disintegrating tablet or orodispersible tablet (ODT) is a drug dosage form available
for a limited range of over-the-counter (OTC) and prescription medications. ODTs differ
from traditional tablets in that they are designed to be dissolved on the tongue rather than
swallowed whole.
1.4.1. Wetting time :
Wetting time of dosage form is related to the contact angle. It needs to be assessed to give
an insight into the disintegration properties ofWetting time of dosage form is related to the
contact angle. It needs to be assessed to give an insight into the disintegration properties of
the tablets; a lower wetting time implies a quicker disintegration of the tablet. For this
purpose, a tablet is placed on a piece of tissue paper folded twice and kept in a small Petri
dish (ID = 6.5 cm) containing 6 ml of water,and the time for complete wetting is measured.

16. 1.4.2. Disintegration time:
The time for disintegration of ODTs is generally less than one minute and actual
disintegration time that patient can experience ranges from 5-30 seconds. The standard
procedure of performing disintegration test for these dosage forms has several limitations
and they are not suitable for the measurement of very short disintegration times. The
method needs to be modified for ODTs as disintegration is required without water; thus
the test should mimic disintegration in salivary contents. A modified dissolution apparatus is
applied to an ODT with a disintegration time that is too fast to distinguish differences
between tablets when the compendial method is used. A basket sinker containing the
tablets is placed just below the water surface in a container with 900 mL of water at 37 0C,
and a paddle rotating at 100 rpm is used. The disintegration time is determined when the
tablet has completely disintegrated and passed through the screen of the sinker404.
1.5. SUSTAINED CONTROLLED RELEASE DOSAGE FORMS
In sustained release concentration will be vary with time interval because in case of sustained
release initial release of drug sufficient to provide a therapeutic dose soon after
administration & then gradual release over an extent period. While in case of
controlled release dosage formrelease drug at a constant rate ...
1.5.1. Swelling index study:
The extent of swelling was measured in terms of percentage weight gain by the tablet. The
swelling behaviour of all formulation was studied. One tablet from each formulation was kept
in a petri dish containing pH 7.4 phosphate buffers. The tablet was removed every three hour
interval up to 12 hour and excess water blotted carefully using filter paper. The swollen

17. tablets were re-weighed (W2). The swelling index (SI) of each tablet was calculated
according to the following equation .S.I. = {(Wt-W0) / W0} ×100 Where- W0 = initial
weight, Wt = final weight5.
1.6. EVALUATION OF CAPSULES
Capsule is a solid dosage form in which the drug is enclosed in a hard or soft soluble
container, usually of a form of gelatin.
Following tests are carried out for the evaluation of capsules:
1.6.1. STABILITY TESTS
1.6.1.1. Shell integrity test
1.6.1.2. Determination of shelf life
1.6.2. INVARIABILITY TESTS
1.6.2.1. weight variation
1.6.2.2. Content uniformity
1.6.3. DISINTEGRATION TEST
1.6.4. DISSOLUTION TEST
1.6.5. MOISTURE PERMEATION TEST
1.6.1. STABILITY TESTS:
Stability tests for capsules are performed to know the integrity of gelatin capsule
shell (but not to known the stability of therapeutically active agent) and for
determining the shelf life of capsules. The test helps in improving the quality of
contents of capsule shell and for choosing the appropriate retail package.
Before actually performing the tests following fact:
The capsule shell are to be stabilized to know atmospheric condition with relative
humidity about 20-30% and temperature about 21-24⁰c.
a) Shell integrity test:
This test is performed to find out the integrity of capsule shell. The standard
capsule shells kept at the room temperature 40⁰c and 80% RH becomes more soft,
sticky and swollen.
b) Determination of shelf life:
Shelf life or the expiry date of packed capsules is determined under normal
storage conditions.
1.6.2. Invariability tests:

18. The invariability in the medicaments packed in the capsule shells can be
determined by performing the following tests:
a) Weight variation test
b) Content uniformity test
1.6.3. DISINTEGRATION TEST:
Disintegration test is a method to evaluate the rate of disintegration of solid dosage
forms. Disintegration is defined as the breakdown of solid dosage form into small
particles after it is ingested.
1.6.4. DISSOLUTION TEST:
Dissolution test is an official method to determine the dissolution rate of a solid
dosage form. Dissolution rate is defined as the rate at which the drug is released into
the systemic circulation from the dosage form.
Dissolution test apparatus:-
a) Apparatus-I (rotating basket dissolution apparatus):
Small wire mesh size basket – 22
Temperature - 37±5⁰c
Rotated speed – 25-150rpm
Dissolution medium height from the bottom of the vessel – 23-27mm.
b) Apparatus-2 (rotating paddle dissolution apparatus):
Small wire mesh size: 22
Dissolution medium height from the bottom of the vessel – 23-27mm
Temperature - 37±5⁰c
Rotated speed – 25-150rpm
1.6.5. Moisture permeation test:
This test is carried out to assure the suitability of containers for packaging of
capsules. The moisture permeating feature of capsules packaged in
 Single unit containers-blister pack or strip pack.
 Unit dose containers glass or plastic bottle is to be determined6.
1.7. EVALUATION OF GRANULES
Definition: Granules are multi particle entities in which primary powder particles are made
to adhere to form larger particle. Granules size range between 0.2 to 4 mm. In tablets and
capsules, granules are the intermediate product and having size of 0.2 to 0.5 mm.
1.7.1. Flow properties:
It is an ability of the granule to flow from hopper to die cavity for tablet uniformity. Flow
properties of granules are not uniform and then it leads to not getting tablet of uniform size.
Flow property of material results from many forces.
1. Frictional force

19. 2. Surface tension force
3. Mechanical force caused by interlocking of irregular shape particles.
4. Electrostatic forces
5. Cohesive/vanderwaals forces
Forces also affect granule property such as particle size, particle size distribution, particle
shape, surface texture, roughness and surface area. If particle size of powder is ≤ 150 µm
the magnitude of frictional and vanderwaals force predominate. When particle size
increases mechanical and physical properties become more important with packing
properties.
 In fig.(1) height is constant and powder is added through the hopper until
powder reaches tip of funnel.
 In fig.(2) height is varied and base cone is fixed, powder is added until height
reaches at max.
 In fig.(3) rectangle box is filled with powder and tipped until content begins
to slide.
 In fig.(4) revolving cylinder with transparent end is made to revolve
horizontally when half filled with powder.
 The maximum angle that the plane of powder makes with horizontal surface
on rotation is taken as the angle of repose.
 (1),(2) & (3) gives static angle of repose. While (4) gives kinetic or dynamic
angle of repose7.

20. 1.8. EVALUATION OF POWDERS
Powders are subdivided solids which are classified according to the size of their constituent
particles which range from <1.25 micrometer to 1.7mm
Classification of Powders:
1.Bulk powders
2.Divided powders
3.Dusting powders
4.Insufflations
Evaluation parameters to be performed are:
1.8.1. Particle size analysis
1.8.2. Angle of repose
1.8.3. Bulk density
1.8.4. Tapped density
1.8.5. Hausner’s ratio
1.8.6. Flowability
1. Particle Size Analysis:
The powders have been classified into:
As per vegetable & animal origin:
Very Coarse(#8): All particles pass through sieve no.8 and not more than 20% through sieve
no.20
Coarse (#20): all particles pass through sieve no.20 not more than 40% through sieve no.60
Moderate(#40): All particles pass through sieve no.40 and not more than 40% through sieve
no.60
Fine(#60): All particles pass sieve no.60 and not more than 40% through sieve no.80
Very Fine: All particles pass through this sieve. There is no limits as to greater fineness.
Powders of chemical drugs are classified as:
Coarse (#20): All particles pass through sieve no.20 not more than 40% through sieve no.60
Moderate(#40): All particles pass through sieve no.40 and not more than 40% through sieve
no.80
Fine(#60): All particles pass sieve no.60 and not more than 40% through sieve no.80
2.Powder Flowability:

21. Powder flowability is the ability of powder to flow in a desired manner in a specific piece of
equipment.
Flow of powders may be:
• Free flowing
• Non-flowing or cohesive.
Flow Patterns:
• Funnel Flow
• Mass Flow
Measurement of flow property:
 Powder Rheometer
 Cohesive index
 Flow through Orifice
 Carr’s Index &Hausner’s ratio
 Angle Of Repose
 penetrometry
Angle of Repose:
The internal angle between the surface of the pile and height of the pile.
Θ=Tan-1(h/r)
It depends upon:
• Density
• Surface area
• Shape of the particles
• The coefficient of friction of material
Flow property Angle of repose(degrees)
Excellent 25-30
Good 31-35
Fair-aid not needed 36-40
Passable-may hang up 41-45
Poor-must agitate, vibrate 46-55
Very poor 56-65
Very, very poor >66
Carr’s Index &Hausner’s Ratio:
Both are determined by measuring bulk volume and tapped volume of powder.
Compressibility index(%) Flow character Hausner ratio
10 Excellent 1.00-1.11
11-15 Good 1.12-1.18

22. 16-20 Fair 1.19-1.25
21-25 Passable 1.26-1.34
26-31 Poor 1.35-1.45
32-37 Very poor 1.46-1.59
>38 Very, very poor >1.60
Flow Through An Orifice:
• Useful only for free flowing powders.
Types Of flow Rate:
• Mass flow rate: Quantity of powder flow per minute.
• Volume flow rate: Time taken by the powder in a container to drain out.
COHESION INDEX:
• Determined by integrating the negative areas under force displacement curve.
Cohesion index (mm) = cohesion co-efficient (g,mm) / sample weight (g)
A low cohesion index is associated with non-cohesive free flowing powders
Cohesion index Flow behaviour
≥19 Hardened, extremely cohesive
16-19 Very cohesive
14-16 Cohesive
11-14 Easy flowing
≤11 Free flowing
POWDER RHEOMETER:
The forces causing deformation of powders is measured here.
This gives measurement of:
• Flow energy
• Shear properties
• Bulk properties
PENETROMETRY:
The pressure of penetration in pascal was used to estimate flow rate.
Particle size should be in the range of:
0.250-0.630 mm
Especially used for non-consolidated pharmaceutical powder excipients:
• Sodium chloride
• Sodium citrate
• Boric acid
• Sorbitol7

23. 2. SEMI SOLID DOSAGE FORMS
Semi solids are the topical dosage form used for the therapeutic, protective or cosmetic
function. They may be applied to the skin, or used nasally, vaginally, or rectally.
Semi solid dosage forms include ointments, creams, suppository, aerosols, transdermal drug
delivery systems, gels, paints, lotions, etc…..
2.1.EVALUATION OF OINTMENTS
Ointments are semisolid dosage forms in which are or more drug substances are
dissolved or dispersed or emulsified in a suitable ointment base and are meant for
application on skin or mucous membrane where it for application on skin or mucous
membrane where it exhibit local or systemic effects.
The different methods of evaluation of ointments are:
2.1.1. Test of rate of absorption
2.1.2. Test of non-irritancy
2.1.3. Test of rate of penetration
2.1.4. Test of rate of drug release
2.1.5. Test of rheological properties
2.1.6. Test of content uniformity
2.1.7. Test of preservative efficacy.
2.1.1. TEST OF RATE OF ABSORPTION:
The diadermatic ointment should be evaluated for the rate of absorption of drug
into the blood stream.
This test can be done in-vivo only. The ointment should be applied over a definite
area of the skin by rubbing.
At regular intervals of time, serum and urine samples should be analyzed for the
quantity of drug absorbed.
The rate of absorption i.e., the amount of drug absorbed per unit time should be
more.
2.1.2. TEST OF NON-IRRITANCY:

24. The bases used in the formulation of ointments may cause irritation or allergic
reactions. Non-irritancy of the preparation is evaluated by patch test.
In this test 24 human volunteers are selected. Definite quantity of ointment is applied
under occlusion daily on the back or volar fore arm for 21 days.
Daily the type of pharmacological action observed is noted.
No visible reaction or erythema or intense erythema with edema and vesicular
erosion should occur.
A good ointment base shows no visible reaction.
2.1.3. TEST OF RATE OF PENETRATION:
The rate of penetration of a semisolid dosage form is crucial in the onset and duration
of action of the drug. Weighed quantity of the preparation should be applied over
selected area of the skin for a definite period of time. Then the preparation left over
is collected and weighed. The difference between the initial and the final weights of
the preparation gives the amount of preparation penetrated through the skin and this
when divided by the area and tie period of application gives the rate of penetration of
the preparation. The test should be repeated twice or thrice.
2.1.4. TEST OF RATE OF DRUG RELEASE:
To assess the rate of release of medicament, small amount of the ointment can be
placed on the surface of nutrient agar contained in a petri dish or alternately in a
small cup cut in the agar surface. If the medicament is bactericidal the agar plate is
previously seeded with a suitable organism like S.aureus. After a suitable period of
incubation, the zone of inhibition is measured and correlated with the rate of release.
2.1.5. TEST OF RHEOLOGICAL PROPERTIES:
The viscosity of the preparation should be such that the product can be easily
removed from the container and easily applied to the skin. Using cone and plate
viscometer the viscosity of the preparation is determined.
2.1.6. TEST OF CONTENT UNIFORMITY:
The net weight of contents of ten filled ointment containers is determined. The
results should match each other and with the labeled quantity.
2.1.7. TEST OF PRESERVATIVE EFFICACY:
Using pour plate technique the number of micro-organisms initially present in the
preparation are determined. Solutions of different samples of the preparation are
made and mixed with TryptoneAzolectin (TAT) broth separately. All cultures of the
micro-organisms are added into each mixture, under aseptic conditions. All mixtures
are incubated. The number of micro-organisms in each sample will be counted on
7th,14th,21st,and 28th days of inoculation.
MICROBIAL LIMITS:-
On 14th day, the no. of vegetative cells should not be more than 0.1% of initial
concentration.
On 28th day, the number of organisms should be below or equal to initial
concentration8.

25. 2.2. EVALUATION OF CREAMS
As these products are used widely and for various parts of the body, stringent
evaluation and quality control is essential, appearance, spread ability, wash ability.
2.2.1. RHEOLOGY:
Rheology is very important as these creams are marketed in tubes (or) containers. The
rheology or viscosity should remain constant. As these products are normally non-
newtonian in nature, viscosity can be measured using viscometers used for such liquids.
Rheological measurements are utilized to characterize the ease of pouring from a
bottle, squeezing from a tube or other deformable container, maintaining product shape in
a jar or after extrusion, rubbing the product onto and into the skin and pumping the product
from mixing and storage to filling experiment.
2.2.2. SENSITIVITY:
As various types of ingredients are used with occasional use of antiseptics, hormones etc.,
there is a possibility of sensitization or photosensitization of the skin. This should be tested
before hand. This test is normally done by patch test on and can be either open or occlusive.
The test sample is applied along with a standard market product at different places and
effect is compared after a period of time9.
2.3. EVALUATION OF SUPPOSITORIES
A suppository is a drug delivery systemthat is inserted into the rectum (rectal suppository),
vagina (vaginal suppository) or urethra (urethralsuppository), where it dissolves or melts
and is absorbed into the blood stream.
Suppositories are evaluated for following parameters:
2.3.1. Appearance
2.3.2. Physical strength
2.3.3. Melting range
2.3.4. Uniformity of drug content
2.3.5. Softening time

26. 2.3.1. TEST FOR APPEARANCE:
All the suppositories should be uniform size and shape and should have elegant
appearance. Suppositories should be examined for cracks and pits on the surface of
suppositories.
2.3.2. TEST FOR PHYSICAL STRENGTH:
The strength of the suppositories should be considered to assess their ability during normal
handling. The apparatus used for this is called as breaking test apparatus, which contains a
double walled chamber in which water is pumped to maintain 37°C temperature in between
the two walls of the chamber. The inner chamber contains a disc for holding the
suppositories. To this disc a rod is attached. The other end of the rod contains a disc for
holding the weights. When the weights are added (upto 200gms) at one minute time
interval until the suppositories crumbles. All the weights used are added which gives the
tensile strength. Tensile strength is the maximum force which the suppository can withstand
during production packing and handling. Higher the tensile strength indicates less will be
tendency to fracture.
2.3.3. MELTING RANGE TEST:
Macro melting range – it gives the measure of thermal stability of the suppository. It is the
time taken by the entire suppository to melt in a constant temperature water bath. The test
is conducted using the tablet disintegration test apparatus. The suppository is immersed in a
constant water bath, finally the melting range is recorded.
Micromelting range – the melting range of fatty base is measured by using capillary tubes.
2.3.4. TEST FOR UNIFORMITY OF DRUG CONTENT:
This is carried out by performing assays for different suppositories. All the suppositories
should contain the same labelled quantity.
2.3.5. TEST FOR SOFTENING TIME:

27. This test measures the softening or liquefaction time of suppository which indicates the
hardness of the base.
Method:
The apparatus consists of cellophane tube tied at the two ends of condenser. The two ends
of the cellophane tube are opened. Water is circulated through the condenser at a definite
rate. As a result after sometime the upper half of the tube opens wide and lower half
collapses. The time period in which the suppository melts completely is considered as
softening time10.
3. LIQUID DOSAGE FORMS
A solution is a liquid preparation that contains one or more soluble chemical substances
dissolved in a specified solvent.
3.1. NON - STERILE LIQUID DOSAGE FORMS
3.1.1. EVALUATION TESTS FOR SYRUPS:
A concentrated solution of a sugar, such as sucrose, in water or other aqueous liquid, somet
imes with amedicinal agent added; usually used as a flavored vehicle for drugs. It is common
ly expanded to include any liquid dosage form (e.g., oralsuspension) in a sweet and viscid ve
hicle.
Following tests are carried out for the evaluation of syrups:
3.1.1.1. Transmittance of light :
A light transmittance meter is a newer tool that is used to check syrup color. In a
light transmittance meter, a syrup sample is checked for color by passing light
through the sample. The percent of light transmission is compared to light
transmission rates set for different grades. When using one, you need to be sure
there are no finger prints on the syrup test bottle, and that the syrup sample has no
bubbles or cloudiness. Any of these conditions may diminish the light that is
transmitted through the sample and therefore lowers the grade of the sample.

28. 3.1.1.2. Visual inspection:
With visual inspection, the ingredients and the final products are carefully examined
for purity and for appearance. Physical appearance of products for patient
adherence and compliance is critical so it should be
 Good looking
 Elegance in appearance
3.1.1.3. pH measurement:
The measurement and maintenance pH is also very important step in the quality
control testing. Generally there are two different types of methods used in the
measurement of pH.

29. Methods for pH measurement:
 The simplest and cheapest is to dip a piece of pH paper into the sample. The
paper is impregnated with chemicals that change color and the color may be
compared to a chart supplied with the paper to give pH of the sample.
 If greatest accuracy is required a pH meter should be used. A typical pH
meter consists of a special measuring glass electrode connected to and
electronic meter that measures and displays the pH reading.
3.1.1.4. Sucrose concentration:
The determination of sucrose concentrations is also very important in quality control
testing of syrups. It the concentration of sucrose in the syrup is very high it may
crystallize the syrup and less sucrose concentrations give favor for the microbial
growth.
There is no specific method for the determination of sucrose in syrup, we use HPLC
and UV- spectroscopy for this purpose.
3.1.1.5. Physical stability in syrups:
The syrups are must be stable physically.
Example:
 Its appearance (no crystallization and microbial growth)
 Color must be completely soluble with other ingredients
 Odour and taste(palatable)
 Solid material is completely miscible in liquid11.
3.1.2. EVALUATION OF ELIXIRS
Definition: Elixirs are clear, sweetened hydro alcoholic solutions intended for oral use and
are usually flavoured to enhance their palatability.
Evaluation parameters:
3.1.2.1. Determination of alcohol content:
Elixir usually contains 5 to 40% alcohol.The determination of alcohol unless otherwise
specified in the individual monograph. It is suitable for examining most fluidextracts and
tinctures and elixirs provided the capacity of the distilling flask is sufficient (commonly
two to four times the volume of the liquid to be heated) and the rate of distillation is
such that clear distillates are produced. Cloudy distillates may be clarified by agitation
with talc, or with calcium carbonate. And filtration is done. After which the temperature
of the filtrate is adjusted and the alcohol content determined from the specific gravity.
During all manipulations, take precautions to minimize the loss of alcohol by
evaporation.For Liquids it is presumed to Contain less than 30% of Alcohol.

30. 3.1.2.2. Viscosity measurement:
Viscosity is a property of liquids that is directly related to the resistance to flow.
Viscosity measurement is very important quality control test in case of syrups an elixirs.
Viscosity and consistency directly relates with stability of solutions. If viscosity increases,
then there is a chance of increase in stability11.
3.1.3. EVALUATION OF SUSPENSIONS
A pharmaceutical suspension is a coarse dispersion in which insoluble particles, generally
greater than 1 µm in diameter, are dispersed in a liquid medium, usually aqueous.
Following are the tests are carried out for the evaluation of suspensions:
3.1.3.1. Sedimentation method:
Two parameters are studied for determination of sedimentation. They are:
 Sedimentation volume:
The suspension formulation (50ml) was poured separately into 100ml measuring
cylinder and sedimentation volume was read after 1,2,3 and 7 days. And there after
at weekly intervals for 12 weeks. Triplicate results were obtained for each
formulation. Sedimentation volume was calculated according to equation:
F =Vu/Vo
Where, F = sedimentation volume
Vu=ultimate height of sediment
Vo= initial height of total suspension
 Degree of flocculation:
Degree of flocculation was calculated according to the equation
β=F/Fα
= flocculated sedimentation volume/deflocculated sedimentation volume
F has values ranging from less than one to greater than one.
Normally F < 1
When F < 1 ↔ Vu <Vo
When F = 1 ↔ Vu <Vo
The systemis in flocculated equilibrium and show no clear supernatant on standing.
When F > 1 ↔ Vu >Vo

31. Higher the value, higher will be the stability.
3.1.3.2. Rheological method:
Viscosity of suspensions is of great importance for stability and pourability of
suspensions. As we know suspensions have least physical stability amongst all
dosage forms due to sedimentation and cake formation.
So as the viscosity of the dispersion medium increases, the terminal settling velocity
decreases thus the dispersed phase settle at a slower rate and they remain dispersed
for longer time yielding higher stability to the suspension.
On the other hand as the viscosity of the suspension increases, it’s pourability
decreases and inconvenience to the patients for dosing increases. Thus, the viscosity
of suspension should be maintained within optimum range to yield stable and easily
pourable suspensions.
 A practical rheologic method involves the use of Brookfield viscometer mounted on
a helipath stand. The T-bar spindle is made to descend slowly into the suspension,
and the dial reading on the viscometer is then measure of the resistance the spindle
meets at various levels ina sediment.
 Data obtained on samples variously aged and stored indicate whether undesired
changes are taking place. This measurement is made on undisturbed samples of
different ages. The results indicate how the particles are settling with time.
 In screening study, the better suspensions show a lesser rate of dial reading with
spindle turns, i.e., the curve is horizontal for a longer period.

32. 3.1.3.3. Electrokinetic method:
In this zeta potential is measured by using micro electrophoresis apparatus and zeta
plus (Brookhaven instruments corporation, USA). It shows the stability of a disperse
system.
Eg: micro-electrophoresis apparatus MK 1
Zeta potential:
The zeta potential of the formulated suspensions was determined using a zetaplus
(Brookhaven instruments corporation, USA). Approximately 1ml of suspension was
transferred into a plastic cuvette using a pipette and diluted with distilled water. The
Brookhaven zeta potential software was used for the measurement. Parameters set
to a temperature of 25⁰c and refractive index (1.33). the zeta potential of the
formulations was determined on day 0,7,14,21 and day 28 post formulation.
3.1.3.4. Micromeritic method:
The stability of suspension depends on the particle size of the dispersed phase.
Change in the particle size with reference to time will provide useful information
regarding the stability of a suspension. A change in particle size distribution and
crystal habit can be studied by microscopy and coulter counter method.
Photo microscopy method:
The microscope can be used estimate and detect changes in particle size distribution
and crystal form. Rapid processing of photo micrographs in enhanced by attaching
polaroid camera to the piece of monomolecular microscope. By using this photo

33. micrographs we can determine the changes in physical properties and stability of
suspensions.
3.1.3.5. Freeze-thaw test:
Freeze-thaw test conducted by placing the sample in a freezer for 18 hours followed
by thawing at room temperature for 4 to 6 hours. Repeat the freeze-thaw cycle for
10 times. This test is conducted to determine the tendency to crystallize or color.
3.1.3.6. pH measurement:
The measurement and maintenance pH is also very important step in the quality
control testing. Generally there are two different types of methods used in the
measurement of pH.
Methods for pH measurement:
The simplest and cheapest is to dip a piece of pH paper into the sample.
3.1.3.7. Visual inspection:
With visual inspection, the ingredients and the final products are carefully examined
for purity and for appearance. Physical appearance of products for patient adherence and
compliance is critical so it should be:
 good looking
 Elegance in appearance12.
3.1.4. EVALUATION OF EMULSIONS
An emulsion is a systemconsisting of two immiscible liquid phases, one of which is
dispersed throughout the other in the form of fine droplets. A third component, the
emulsifying agent, is necessary to stabilize the emulsion.
Following are tests carried out for evaluation of emulsions:

34. 3.1.4.1. Determination of particle size and particle count:
Determination of changes in the average particle size or the size distribution of droplet
is an important parameter used for the evaluation of emulsions. It is performed by optical
microscopy, sedimentation by using Andreason apparatus and coulter apparatus.
3.1.4.2. Determination of viscosity:
Determination of viscosity is done to assess the changes that might take
place during aging. Emulsions exhibit non-newtonian type of flow characteristics.
The viscometer which should be used may be cone and plate viscometer.
3.1.4.3. Determination of phase separation:
This is another parameter used for assessing the stability of the formulation. Phase
Separation may be observed visually or by measuring the volume of the separated phases.
3.1.4.4. Determination of electrophoretic properties:
Determination of electrophoretic properties like zeta potential is useful for assessing
flocculation since electrical charges on particles influence the rate of flocculation.
o/w emulsion having a fine particle size will exhibit low resistance but if the particle
size increase, then it indicates a sign of oil droplet aggregation and instability.
3.1.4.5. Electrical conductivity:
It is determined by using platinum electrodes (diameter 0.4 mm, distance 4mm)
micro amperometrically to produce a current of 15 to 50mA. Measurements are
made on emulsions stored at room temperature or at 37⁰c for short time. Stable o/w
emulsion offer less resistance, but droplet aggregation increases resistance. A stable
w/o emulsion does not conduct electrodes, but with droplet coagulation
conductivity increases13.

35. 3.2. STERILE LIQUID DOSAGE FORMS
3.2.1. EVALUATION OF PARENTERALS
Following tests are carried out for the evaluation of parenterals:
3.2.1.1. Leaker test:
Leakage occur when a discontinuity exists in the wall of a package that can allow
the passage of gas under the action of a pressure or concentration differential
existing across the wall.
Presence of capillary pores or tiny cracks can cause microbes or other dangerous
contaminants to enter the ampoules or may lead to the leakage of contents to
outside. This may lead to contamination of the sterile contents and also spoilage
of appearance of the package.
Changes in temperature during storage can cause expansion and contraction of
the ampoule and its contents, there by accentuating interchange if an opening
exists.
Leaker test for ampoules is intended to detect incompletely sealed ampoules so
that they can e discarded in order to maintain the sterile conditions of the
medicines.
Tip seal are more likely to be incompletely closed than pull seals.
Open capillaries or cracks at the point of seal result in leakers.
Procedure:
Leakers are detected by this process in a visible manner. Ampoules are placed in
a vacuum chamber. Completely submerged in a deeply colored dye solution of
about 0.5-1% methylene blue.
A negative pressure is applied within the ampoule. Subsequent atmospheric
pressure causes the dye to penetrate on opening thus making it visible after the
ampoule has been washed. The vacuum, about 27 inches Hg, should be sharply
released after 30 minutes.
Detection of leakers is prominent when ampoules are immersed in a bath of dye
during autoclaving cycle as this has the advantage of accomplishing both leaker
detection and sterilization in one operation.
Result: the color from the dye will be visible within a leaker.
Disadvantages:
Capillaries of 15microns or smaller diameter cannot be detected by this test.
Vials and bottles are not subjected to such a leaker test as the rubber closer is
not rigid.

36. 3.2.1.2. Pyrogen test:
i) LAL bacterial endotoxin test:
The LAL (limulus amebocyte lysate) assay is an in vitro assay used to detect the
presence and concentration of bacterial endotoxins in drugs and biological
products.
Endotoxins, which are a type of pyrogen, are lipopolysaccharides present in the
cell walls of gram-negative bacteria.
Pyrogens as a class are fever inducing substances that can be harmfull or even
fatal if administered to humans above certain concentrations. Water can be a
source of pyrogens, so it may be important to routinely monitor water systems
using the bacterial endotoxins test.
Procedure:
The solution of endotoxins containing preparation is added to the lysate derive
from haemolymph cells of horse shoe crab (limulus polyhemus).
The result of the reactions is turbidity or precipitation or gelation of the mixture.
This is used as a quantitative measure to estimate the endotoxin content. The
rate of reaction depends upon concentration of endotoxins, pH, temperature
and presence of clotting enzyme and clottable proteins from lysate.
The quantities of endotoxins are expressed in defined endotoxin units (EU)
The endotoxin limit for a given test preparation is calculated from the expression
k/M; where M is maximum dose administered to adult per kg/hr. The value for K
is 5.0 EU/kg for parenteral preparations and it is 0.2EU/kg for intrathecal
preparations.

37. Criteria for limulus test result:
LAL TUBE TEST
SAMPLE/CONTROL
RESULT
1. Negative control (pyrogen
free saline)
Should be -ve
2. Positive control(pyrogen) Should be +ve
3. Positive internal control
(test sample containing
exotoxins)
Should be +ve
4. Test sample May be +ve or -ve
Pyrogen test ‘fever response of rabbit’:
SHAM TEST: it is performed to select the proper animals for the main tests.
Rabbit test: qualitative fever response test
The rabbit pyrogen test in an in vivo test to detect pyrogens qualitatively.
Rabbits have a similar pyrogen tolerance to humans, so by observing a change in body
temperature in rabbits it is possible to make a determination of the presence of pyrogens.
This method can detect non-bacterial endotoxin .
Procedure:
Withheld food in the day of experiment.
Record the initial temperature of the rabbits, any rabbit show temperature more than 39⁰c,
should be excluded.
Inject the sample into the ear vein of each rabbit.
Check the temperature after 30 minutes, 1, 2 and 3hrs.
Disadvantages:
 Biological variation
 Expensive
 Laborious
 Dose dependent
 Not for antipyretic drug
Result:
 The test is positive when each rabbit show increase in temperature.
 If only two of the three rabbits show increase in temperature, repeat the test using
group of five, and test will be positive if the four of the five rabbits show increase in
temperature.
3.2.1.3. Sterility test:
Sterility testing attempts to reveal the presence or absence of viable micro
organisms in a sample number of containers taken from batch of product.
Based on results obtained from testing the sample a decision is made as to the
sterility of the batch.
The primary official test is performed by means of filtration but direct transfer is
used if membrane filtration is unsuitable.
Membrane filtration method:

38. Media suitable for sterility tests are:
- Fluid thioglycolate medium
- Soya bean casein digest medium
Wash the filters with fluids to remove inhibitory properties, cutting the
membranes aseptically into equal parts and transferring one of the parts to each
type of culture medium used.
The media are then incubated under prescribed conditions.
Direct inoculation method:
This method is only used when membrane filtration is not possible the sample is
inoculated directly into the media or the device is placed directly into the media.
Result: If no growth in the media then test is positive.
3.2.1.4. Particulate evaluation:
- It has been shown that particles of lint, rubber, insoluble chemicals and other
foreign matter can produce emboli in the vital organs of animals and human
beings.
- The USP specifies that good manufacturing practice(GMP) requires that each
final container of an injection be subjected individually to a visual inspection and
that containers in which visible particles can be seen should be discarded.
- Therefore, all of the product units from a production line currently are being
inspected individually by human inspectors under a good light, baffled against
reflection into the eye and against a black-and-white back ground.
- The USP has identified two test methods.
- The first test to be used is the light obscuration test, which uses and electronic
instrument designed to count and measure the size of the particles by means of a
shadow cast by the particle as it passes through a high-intensity light beam.
- If the injection formulation is not a clear, colorless solution, it exceeds the limits
specified for the light obscuration test, it is to be subjected to the microscopic
count test.
3.2.1.5. Weight variation oruniformity of content:
- This test is intended for sterile solids used for parenteral preparations.
- The weight of 10 individual sterile units is notes and the content is removed
from them and empty individual sterile unit is weighed inturn.
- Then content of active ingredient in each sterile unit is calculated by
subtracting empty sterile unit is calculated by performing the assay according
to the individual monographs.
- Then net weight is calculated by subtracting empty sterile unit weight form
gross weight.
- The content in 10 sterile units is calculated by performing the assay.
- The dose uniformity is met if the amount of active ingredient is within the
range of 35-115% of label claimas determine by the content uniformity
method or weight variation method.

39. - The dose uniformity is also met if the potency value is 100% in the individual
monograph or less of label claimmultiplied by average of limits specified for
potency in individual monograph divided by 100 provided that the relative
standard deviation in both the cases is equal to or less than 60%. The fore
mentioned test is carried for 20 more sterile units14.
- The sterile units meet the requirements if not more than one unit is outside
the range of 85-115%, no unit is outside the range of 75-125% and the
calculated
Relative standard is NMT 7.8%.
3.2.2. EVALUATION OF EYE DROPS
Following tests are carried out for the evaluation of eye drops:
3.2.2.1. Test for sterility
All the ophthalmic preparations should be sterile i.e., free from any viable organism
and its spores. Ophthalmic preparations are tested for their sterility.
The following criteria should be followed while carrying out sterility testing. Two
sterile culture media are prepared for the detection of aerobic and anaerobic bacteria and
fungi.
Table: culture media in test for sterility
Medium Micro organism
1. Fluid thioglycollate medium Detects the presence of aerobic and
anaerobic bacteria.
2. Soybean casein digest medium. Detects the presence of fungi and aerobic
bacteria.
Test samples are transferred into test tubes containing clear medium. If the sample contains
microorganisms, then the medium becomes turbid. If the sample is free from
microorganisms, then the medium remains clear. The tests should be carried out in aseptic
conditions.
Procedure:
a. Membrane filtration method/method A
This method is generally followed for the products which can be easily filtered and is carried
out in aseptic conditions.

40. The apparatus consists of a sterilized filter unit with sterile membrane filter of 0.45 µ pore
size. A single membrane filter is divided into two equal halves. The test solution is filtered
through the membrane filer. One half of the membrane is placed in fluid thioglycollate
medium at 30-35°C and other half is placed in soybean casein digest medium at 20-25°c for
7 days.
Result: If the medium shows no growth, then the sample solution passes the test. If the
medium shows growth, then the test is repeated. If the growth is observed again, then the
sample solution fails the test.
b. Direct inoculation method/method B
Specified quantity of the solution to be tested is drawn through a sterile syringe or pipette.
It is mixed with the medium and incubated for 14 days at a specific temperature. Between
3rd and 7th day of incubation, a portion of medium is transferred to a fresh medium, if it
shows turbidity, then both the old and fresh media are incubated for 14 days.
Result: If the medium shows no growth, then the sample solution passes the test. If the
medium shows growth, then the test is repeated. If growth is observed again, then the
sample fails the test.
3.2.2.2. Test for ocular toxicity and irritation
This test assesses the isotonicity of the preparation.
Procedure:
Five albino rabbits are selected, the iridal vessels of whom can be easily observed for
toxicity and irritation. Based on the type of dosage form, the medicament is extracted using
cotton seed oil or saline. Small quantities of the extract are instilled into one eye of all the
rabbits, while sterile saline solution is instilled into the other eye. After one hour all the
rabbits are observed for irritation, swelling or shrinkage of the eye.
Result: No change in the eye into which the preparation is instilled indicates that the
preparation under test is safe for use.
3.2.2.3. Test for preservative efficacy
a. Cultures of microorganisms like Aspergillusniger, Candida albicans, Escherchia coli and
Pseudomonas aeruginosa, each containing about 10,000 – 10,00,000 organisms per ml are
selected.
b. Three to four samples of each preparation are taken in sterile test tubes and inoculated
with few ml of each culture separately.
c. They are incubated at 20 - 25°C for a period of 28 days and are observed weekly for the
appearance of turbidity.
d. No growth of microorganisms indicates that the preservative is totally effective.
3.2.2.4. Clarity
The clarity of the formulations before and after gelling was determined by visual
examination of the formulations under light alternatively against white and black
backgrounds.

41. 3.2.2.5. pH
The pH of each of prepared ophthalmic formulations was determined by using pH meter
(equip-tronics). The pH meter was calibrated before each use with standard pH 4, 7 and 9.2
buffer solutions.
3.2.2.6. In vitro diffusion studies
In vitro release studies were carried out using bi chambered donor receiver compartment
mode (Franz diffusion cell). In vitro release was carried out in formulations with different
concentrations of gelrite using dialysis membrane. The diffusion medium 26ml of simulated
tear fluid stirred at 50 rpm at 370 C ±0.50 C. One end of the diffusion tube was covered by a
dialysis membrane. The1 ml formulation were spread on the dialysis membrane and
membrane was placed such that it just touches the diffusion medium (STF) present in
receptor compartment. The drug samples were withdrawn at the interval of one hour for
the period of 8 hrs from diffusion medium and analyzed by a UV spectrophotometer at 261
nm using simulated tear fluid as blank.
3.2.2.7. Determination of viscosity
The specified volume of prepared ophthalmic solution was transferred in sample cell which
was placed carefully within the adaptor (Brookfield DV-II + PRO viscometer, Adapter spindle
No-18).The water of 25°C was circulated through jacket of the adaptor. The viscosity values
were recorded.
4. EVALUATION TESTS FOR AEROSOLS
Following tests are carried out for the evaluation of aerosols:
4.1. Flammability and combustibility:
4.1.1. Flash point:
Apparatus : open cup tag apparatus.
Test liquids temperature is allowed to increase slowly and temperature of which vapors
ignite is called is called as flash point.

42. Standard tag open cap
apparatus
4.1.2. Flame projection:
Product is sprayed for 4 seconds onto flame and exact length is measured with ruler.
4.2. Physicochemical characteristics:
Property Method
Vapor pressure Can puncturing device
Density Hydrometer
pycnometer
Moisture Karl fischer method
Gas chromatography
Identification Gas chromatography
IR spectroscopy
4.3. Performance:

43. 4.3.1. Aerosol valve discharge rate:
Aerosol product of known weight is discharged for specific time. By reweighing the
container, the change in the weight per time dispensed is the discharge rate in gm/sec.
4.3.2. Spray pattern:
This method is based on the impingement of spray on piece of paper that has treated with
Dye-Talc mixture.
4.3.3. Dosage with metered valves:
Reproducibility of dosage determined by:
Assay :
Accurate weighing of filled containers followed by dispensing several dosages. Containers
again reweighed and differ in weight divided by number of dosage dispensed gives average
dose.
4.3.4. Net contents:
Tared cans placed on filling lines are reweighed and then difference in weight is equal to net
content.
In destructive method: Opening the container and removing as much of product possible.
4.3.5. Foam stability:
Various methods are there namely,
Visual evaluation
Time for given mass to penetrate the foam
Time for given rod to fall which is inserted into the foam
Rotational viscometer.
4.3.6. Particle size determination:
Methods :cascade impactor, light scattering decay.
Cascade impactor:
Principle: Stream of particle projected through a series of nozzle and glass slide and at high
velocity. Larger particles are impacted on low velocity stage and smaller on higher velocity
stage.

44. Light scattering decay:
Principle: As aerosol settles under turbulent condition, the changes in the light of a tyndall
beam is measured.
4.4. Biological testing:
Therapeutic activity:
For inhalation aerosols – is depends on the particle size.

45. For topical aerosols - is applied to test areas and adsorption of therapeutic ingredient is
determined.
Toxicity:
For inhalation aerosols: Exposing test animals to vapor sprayed from aerosol container.
For topical aerosols: Irritation and chilling effects are determined15.
5. EVALUATION OF NASAL SPRAY
Following are tests carried out for the evaluation of nasal spray:
5.1. Appearance, Colour, and Clarity:
The appearance of the content of the container (i.e., formulation) and the container closure
system (e.g., pump components, inside of the container) should confirm totheir respective
descriptions as an indication of the drug product integrity. If any colour is associated with
the formulation (either present initially or from degradative processes occurring during shelf
life) then a quantitative test with appropriate acceptance criteria should be established for
the drug product by the manufacturer.
5.2. Drug Content (Assay):
The assay of drug substance in the entire container should be determined analytically with a
stability indicating procedure. This test provides assurance of consistent manufacturing
(e.g., formulation, filling, sealing). The acceptance criteria (assay limits as specified in official
books) should be tight enough to ensure conformance in other related attributes (e.g., spray
content uniformity). A suitable assay procedure should be designed to address any
degradation of the drug substance, adherence of the drug substance to the container and
closure components, and the potential effect of formulation evaporation and/or leakage.
5.3. Impurities and Degradation Products:
The levels of degradation products and impurities should be determined by means of
stability indicating procedure(s). Acceptance criteria should be set for individual and total
degradation products and impurities. For identification and qualification thresholds, refer to
the appropriate guidance. All related impurities appearing at levels of 0.1 percent or greater
should be specified. Specified impurities and degradation products are those, either
identified or unidentified, that are individually listed and limited in the drug product
specification.
5.4. Preservative(s) and Stabilizing Excipient(s) Assay:
If preservatives, antioxidants, chelating agents, or other stabilizing excipients (e.g.,
benzalkonium chloride, phenylethyl alcohol, edetate) are used in the formulation, there
should be a specific assay for these components with associated acceptance criteria (At a
concentration of 0.10 percent or 1.0 milligram per day).

46. 5.5. Pump Delivery:
A test to assess pump-to-pump reproducibility in terms of drug product performance and to
evaluate the metering ability of the pump should be performed. The proper performance of
the pump should be ensured primarily by the pump manufacturer, who should assemble the
pump with parts of precise dimensions. Pump spray weight delivery should be verified by
the applicant for the drug product. In general, pump spray weight delivery acceptance
criteria should control the weight of the individual sprays to within ±15 percent of the target
weight and their mean weight to within ±10 percent of the target weight.
5.6. Spray Content Uniformity (SCU):
The spray discharged from the nosepiece should be thoroughly analyzed for the drug
substance content of multiple sprays from an individual container, among containers, and
among batches of drug product. This test should provide an overall performance evaluation
of a batch, assessing the formulation, the manufacturing process, and the pump. The
number of sprays per determination should not exceed the number of sprays per single
dose. A single dose represents the minimum number of sprays per nostril specified in the
product labelling. To ensure reproducible in vitro dose collection, the procedure should
have controls for actuation parameters (e.g., stroke length, depression force). The test may
be performed with units primed following the instructions in the labelling. The amount of
drug substance delivered from the nosepiece should be expressed both as the actual
amount and as a percent of label claim. This test is designed to demonstrate the uniformity
of medication per spray (or minimum dose), consistent with the label claim, discharged from
the nosepiece, of an appropriate number (n = 10 is recommended) of containers from a
batch. The primary purpose is to ensure SCU within the same container and among multiple
containers of a batch. The following acceptance criteria are recommended:
The amount of active ingredient per determination is not outside of 80–120 percent of label
claim for more than 1 of 10 containers, none of the determinations is outside of 75–125
percent of the label claim, and the mean is not outside of 85–115 percent of label claim.
If 2 or 3 of the 10 determinations are outside of 80–120 percent of the label claim, none is
outside of 75–125 percent of label claim, and the mean is not outside of 85–115 percent of
label claim, an additional 20 container should be sampled (second tier). For the second tier
of testing of a batch, the amount of active ingredient per determination is not outside of
80–120 percent of the label claim for more than 3 of all 30 determinations, none of the 30
determinations is outside of 75–125 percent of label claim, and the mean is within 85–115
percent of label claim.
5.7. Spray Content Uniformity (SCU) through container life:
The purpose of this test is to assess whether the product delivers the labelled number of full
medication sprays meeting SCU acceptance criteria throughout the life of the nasal spray

47. unit. The test involves determining the SCU from the beginning of unit life and at the label
claim number of sprays per container for an appropriate number of containers (n = 5 is
recommended). The following acceptance criteria are recommended.
The amount of active ingredient per determination is not outside of 80–120 percent of label
claim for more than 1 of 10 determinations from five containers, none of the
determinations is outside of 75–125 percent of the label claim, and the means for each of
the beginning and end determinations are not outside of 85–115 percent of label claim.
If 2 or 3 of the 10 determinations are outside of 80–120 percent of the label claim, none is
outside of 75–125 percent of label claim, and the means for each of the beginning and end
determinations are not outside of 85–115 percent of label claim, an additional 10 containers
are sampled at the beginning of unit life and at the label claim number of sprays (second
tier). For the second tier of testing of a batch, the amount of active ingredient per
determination is not outside of 80–120 percent of the label claim for more than 3 of all 30
determinations, none of the 30 determinations is outside of 75–125 percent of label claim,
and the means for each of the beginning and end determinations are not outside of 85–115
percent of label claim.
5.8. Droplet Size Distribution:
For both suspension and solution nasal sprays, the specifications should include an
appropriate control for the droplet size distribution (e.g., 3 to 4 cut-off values) of the
delivered plume subsequent to spraying under specified experimental and instrumental
conditions. Appropriate and validated dynamic plume droplet size analytical procedures
should be described in sufficient detail to allow accurate assessment by Agency laboratories
(e.g., apparatus and accessories, software version and calculation algorithms, sample
placement, laser trigger condition, measurement range, beam width).
5.9. Foreign Particulates:
For both solution and suspension nasal sprays, there should be validated tests and
associated acceptance criteria for foreign particulates. Foreign particulates may originate
during manufacturing, from formulation components, and, in particular, from the container
and closure components. Levels of foreign particulates in the drug product may increase
with time, temperature, and stress.
5.10. Microbial Limits:
The microbial quality should be controlled by appropriate tests and acceptance criteria for
total aerobic count, total yeast and mold count, and freedom from designated indicator
pathogens. Acceptance criteria should be reflective of the data for the submitted batches
(e.g., clinical, preclinical, biobatch, primary stability, production), but at a minimum should
meet the recommended microbial limits acceptance criteria in USP <1111>, Microbiological

48. Attributes for Non-sterile Pharmacopoeial Articles. Furthermore, appropriate testing should
show that the drug product does not support the growth of microorganisms and that
microbiological quality is maintained throughout the expiration dating period. For a
description of this test, refer to the procedure in USP <61>.
5.11. Preservative Effectiveness:
For nasal sprays that contain a preservative(s), stability testing should include microbial
challenge studies performed on the first three production batches of drug product.
5.12. Net Content and Weight Loss (Stability):
Nasal spray drug products should include acceptance criteria for net content and weight loss
on stability. Since storage orientation plays a key role in any weight loss, the drug product
should be stored in upright and inverted or upright and horizontal positions to assess this
characteristic.
The total net content of all formulation components in the entire container should be
determined. The net content ofeach of 10 test containers should be in accordance with the
release specification. For a description of this test, refer to the procedure in USP Chapter
<755> Minimum Fill.
5.13. Leakage testing:
The drug product should be evaluated for compounds that leach from elastomeric or plastic
components of the container closure system, such as nitrosamines, monomers, plasticizers,
accelerators, antioxidants, and vulcanizing agents. The development of appropriate
analytical procedures to identify, monitor, and quantify the leached components in the drug
product should be done during investigational studies. These validated procedures can, in
turn, be used for testing of the drug product throughout the expiration dating period.
Appropriate acceptance criteria for the levels of leached compounds in the formulation
should be established.
5.14. pH:
For both solution and suspension nasal sprays, the apparent pH of the formulation should
be tested and an appropriate acceptance criterion established. Lysozyme is found in nasal
secretions, which is responsible for destroying certain bacteria at acidic pH. Under alkaline
conditions, lysozyme is inactivated and the nasal tissue is susceptible to microbial infection.
It is therefore advisable to keep the formulation at a pH of 4.5 to 6.5 keeping in mind
thephysicochemical properties of the drug as drugs are absorbed in the un-ionized form.
5.15. Osmolality:
The osmolality of the formulation should be tested and controlled with an appropriate
procedure and acceptance developed by manufacturer16.

49. 6. COSMETICS:
6.1. EVALUATION OF LIPSTICKS:
Following are the tests carried out for the evaluation of lipsticks:
6.1.1. Surface anomalies:
This is studied by the surface defects such as formation of crystals on surface,
contamination by moulds and fungi etc.
6.1.2. Thixotropic characters:
This is an indication of thixotropic quality and is done by using penetrometer. A standard
needle of specific diameter is allowed to penetrate for 5 seconds under 50gms load at
room temperature. Penetration of the needle upto 9-10.5 mm is indicative of soft and
thixotropic structure.
6.1.3. Breaking point:
This test is done to determine the strength of lipsticks. The lipstick is held horizontally
and weights are applied on the lipstick and increase the weights at a specific time
interval of 30 seconds. The weight at which the lipstick breaks is considered as breaking
point.
6.1.4. Melting point:
This is carried out by using capillary tube method.
7. NOVEL DRUG DELIVERY SYSTEMS:
7.1. EVALUATION OF TRANSDERMAL PATCHES
Development of controlled release transdermal dosage form is a complex process involving
extensive research. Transdermal patches have been developed to improve clinical efficacy
of the drug and to enhance patient compliance by delivering smaller amount of drug at a
predetermined rate. This makes evaluation studies even more important in order to ensure
their desired performance and reproducibility under the specified environment conditions.
These studies are predictive of transdermal dosage forms and can be classified into
following types:
I. Physicochemical evaluation
II. In vitro evaluation
III. In vivo

50. Physicochemical evaluation:
7.1.1. Thickness:
The thickness of transdermal filmis determined by travelling microscope, dial gauge,
screw gauge or micrometer at different points of the film.
7.1.2. Uniformity of weight:
Weight variation is studied by individually weighing 10 randomly selected patches
and calculating the average weight. The individually weight should not deviate significantly
from the average weight.
7.1.3. Drug content determination:
An accurately weighed portion of film (about 100 mg) is dissolved in 100 ml of
suitable solvent in which drug is soluble and then the solution is shaken continuously for
24hrs in shaker incubator, then drug in solution is estimated spectrophotometrically by
appropriate dilutions.
7.1.4. Content uniformity test:
10 patches are selected and content is determined for individual patches. If ali
quotes of 10 patches have content between 85% to 115% of the specified value and one has
content NLT 75% to 125% of the specified value, then transdermal patches pass the test of
content uniformity. But if 3 patches have content in the range of 75% to 125%, then
additional 20 patches have range from 85% to 115% then the transdermal patches pass the
test.
7.1.5. Moisture content:
The prepared films are weighed individually and kept in a desiccators containing
calciumchloride of room temperature for 24 hrs. The films are weighed again after a
specified interval until they show a constant weight. The % moisture content is calculated
using following formula.
%moisture content = initial weight – final weight × 100/ final weight
7.1.6.Moisture uptake:
Weighed films are kept in desiccators at room temperature for 24hrs. These
are then taken out and exposed to 84% relative humidity using saturated solution of
potassium chloride in desiccators until a constant weight is achieved. % moisture uptake is
calculated as given below.
% moisture uptake = final weight – initial weight × 100/ final weight

51. 7.1.7.Flatness:
A transdermal patch should possess a smooth surface and should not
constrict with time. This can be demonstrated with flatness study. For flatness
determination, one strip is cut from the centre and two from each side of patches. The
length of each strip is measured and variation in length is measured by determining percent
constriction. Zero percent constriction is equivalent to 100% flatness.
% constriction = I1 – I1/ I1 × 100
I2 = final length of each strip
I1= initial length of each strip
Folding endurance:
Evaluation of folding endurance involves determining the folding capacity of
the films subjected to frequent extreme conditions of folding. Folding endurance is
determined by repeatedly folding the films at the sample place until it break. The number of
times the films could be folded at the same place without breaking is folding endurance
value.
7.1.8. Tensile strength:
To determine tensile strength, polymeric films are sandwiched separately by corked linear
iron plates. One end of the films is kept fixed with the help of an iron screen and other end
is connected to a freely movable thread over a pulley. The weights are added gradually to
the pan attached with the hanging end of the thread. A pointer on the thread is used to
measure the elongation of the film. The weight just sufficient to break the film is notes. The
tensile strength can be calculated using the following equation.
Tensile strength = F/a.b(l+L/l)
F is the forced required to break;
a is width of film
b is the thickness of film
L is length of film
l is elongation of film at break point.
7.1.9. Peel adhesion properties:
It is the force required to remove adhesive coating from test substrate. It is
tested by measuring the force required to pull a single coated tape, applied to substrate at
180⁰ angle. The test is passed of there is no residue on the substrate.
7.1.10.Tack properties:

52. It is the ability of the polymer to adhere to substrate with little contact
pressure. Tack is dependent on molecular weight and composition of polymer as well as on
the use of tackifying resins in polymer.
7.1.11. Thumb tack test:
The force required to remove thumb from adhesive is a measure of tack.
7.1.12. Rolling ball test:
This test involves measurement of the distance that stainless steel ball travels
along an upward facing adhesive. The less tacky the adhesive, the further the ball will travel.
7.1.13. Quick- stick (peel tack):
The peel force required breaking the bond between an adhesive and
substrate is measured by pulling the tape away from the substrate at 90⁰at the speed of
12inch/min.
7.1.14. Probe tack test:
Force required to pull a probe away from an adhesive at a fixed rate is
recorded as tack.

53. 7.1.15. Shear strength properties (or) creep resistance:
Shear strength is the measurement of the cohesive strength of an adhesive
polymer i.e., device should not slip on application determined by measuring the time it
takes to pull an adhesive coated tape off a stainless plate17.
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http://apps.who.int/phint/en/p/docf/
2. Abolfazl Aslani* "Formulation, Characterization and Physicochemical Evaluation of
Ranitidine Effervescent Tablets" Adv Pharm Bull. 2013 Dec; 3(2): 315–322.
3. P.Chinna Reddy* " A review on bioadhesive buccal drug delivery systems: current status of
formulation and evaluation methods" Daru. 2011; 19(6): 385–403.
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Pharmaceutical Research, April 2009; 8 (2): 161-172
5. SANTOSH GIRI,SELLAPPAN VELMURUGAN*"
FORMULATION AND EVALUATION OF GLIPIZIDE SUSTAIN RELEASE MATRIX TABLETS"
International Journal of Pharmacy and Pharmaceutical Sciences, Vol 5,Suppl 1, 2013.
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capsules?qid=50bcc48e-5203-48ab-a3f2-4f675ea6d407&v=default&b=&from_search=1
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b8fd-b4b8c3bc9ad2&v=default&b=&from_search=2
8. http://www.pharmainfo.net/evaluation-ointments
9. http://www.slideshare.net/VIJAYSINGH158/evaluation-ofsemisoliddosageforms?qid=02d672e8-
4d5e-48a7-b2bd-fb7a6a25677c&v=qf1&b=&from_search=3
10. M.A.Saleem* "Formulation and Evaluation of Tramadol hydrochloride Rectal
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54. 11. http://www.slideshare.net/bhatti106/quality-control-tests-for-syrups-and-elixirs
12. .Indian pharmacopoeia 2014, 7th edition
13.Indian pharmacopoeia 2014, 7th edition
14. http://www.slideshare.net/anniechocolateprincess/quality-control-of-parenteral-
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