SCHOOL OF PHARMACEUTICAL SCIENCES

DEPARTMENT OF PHARMACEUTICS

PRACTICE SCHOOL REPORT

NAME : Santhosh K

REGISTRATION NUMBER : 20150218

YEAR /SEC : IV YEAR / ‘B’ SEC

PROGRAMME : B. PHARMACY

SEMESTER : VII SEM

SUBJECT : PRACTICE SCHOOL

SUBJECT CODE : BP706P

BATCH : 2020 - 2024

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 INDEX

S.NO CONTENT PAGE.NO MARK

1 INTRODUCTION
4

TABLETS
2.1 : PREPARATION OF PARACETAMOL
GRANULES
2 2.2 : EVALUATION OF PARACETAMOL 6
GRANULES
2.3: ANGLE OF REPOSE

TABLET PUNCHING
3.1: EVALUATION OF PARACETAMOL
3 12
TABLETS

TABLET COATING 18
4
4.1: DEMONSTRATION OF TABLET COATING

SUSPENSION
5.1 DETERMINATION OF SEDIMENTATION
VOLUME WITH EFFECT OF DIFFERENT
SUSPENDING AGENTS 23
5
5.2 DETERMINATION OF SEDIMENTATION
VOLUME WITH EFFECT OF DIFFERENT
CONCENTRATION OF SINGLE SUSPENDING
AGENT

6 STERLIZATION 27

7 ISOTONIC SOLUTIONS
29

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 EVALUATION SHEET :-

CLARITY AND
OBJECTIVES CONTENT ORGANIZATION
COLLABORATION
DEVELOPMENT AND REPORT
OF TEAM WORK

STAFF SIGNATURE HEAD OF THE DEPARTMENT

SIGNATURE

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1. INTRODUCTION:
Pharmaceutics is the area of study concerned with the formulation, manufacturing, stability and
effectiveness of pharmaceutical dosage form. There are many chemicals with pharmacological
properties but needs special measures to help them achieve therapeutically relevant amount at
their sites of action pharmaceutics helps to relate the formulation of drugs to their delivery and
disposition in the body.
FORMULATION:
Active pharmaceutical ingredients + Excipients /Non drug components = Pharmaceutical
dosage form
Pharmaceutical industry layout
The pharmaceutical industry is an important component of health care systems throughout the
world; it is comprised of many public and private organizations that discover, develop,
manufacture and market medicines for human and animal health.
What is a pharmaceutical plant layout?
Pharmaceutical plant layout/ factory layout refers to the allocation of space and the
arrangement of machines, furniture and other important administration and necessary services
needed in a production process within a factory building in other to perform the various unit
operations involved in the manufacturing process of dosage forms in a cost effective manner
and with the least amount of handling in processing the product from receipt of raw material
through the distribution of the finished product.
Features of a good pharmaceutical plant layout
✓ There should be adequate floor space for machines installation and utilization.
✓ The machines should be properly arranged to facilitate minimum material handling is
necessary for low-cost processing.
✓ The layout should facilitate smooth and continuous flow of production process from
one point to another without any form of delay.
✓ It must incorporate adequate health, safety and security features such as first aid box,
fire extinguisher, emergency exit and access point.
✓ A good layout should allow effective supervision, coordination and control of the
production processes.
✓ There should be room for adjustment and modifications whenever the need arises.
➢ Pharmaceutical process flow charts, also called workflows, process maps, or value
stream maps, are defined as diagrams of pharmaceutical business processes, created
graphically in software, drawn by hand, or even laid out with a series of post-it notes,
that are used to document procedures and steps of a finite scope of work.
Pharmaceutical workflows visually depict granular activities involved in developing a
new product, from the initial R&D work to the final packaging and shipping process.

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REGULATORY REQUIREMENTS FOR DRUG APPROVAL PROCESS IN INDIA:
Each country has its own regulatory requirements which have to be satisfied to approve a
new drug in that particular country. It is difficult to go for a single regulatory approach for
approval of a new drug in different countries. A Marketing Authorization Application (MAA)
is then submitted, which is approved by the competent authority, if the drug satisfies the
requirements of safety and efficacy and proves that its benefits outweigh its risks . New Drug
Application (NDA) is an application submitted to the individual regulatory authority for
authorization to market a new drug i.e. innovative product. To gain this permission a sponsor
submits preclinical and clinical test data for analyzing the drug information, description of
manufacturing trials.
Drug Approval Process in India: The Drug and Cosmetic Act 1940 and Rules 1945 were
proclaimed by the India’s parliament to regulate the import, manufacture, distribution and sale
of drugs and cosmetics. The Central Drugs Standard Control Organization (CDSCO) and the
office of its leader, the Drugs Controller General (DCGI) was established. In 1988, the Indian
government added Schedule Y to the Drug and Cosmetics Rules 1945. Schedule Y provides
the guidelines and requirements for In order to prove its efficacy and safety in Indian
population it has to conduct clinical trials in accordance with the guidelines specified in
Schedule Y and submit the report of such clinical trials in specified format. Rule 122A of the
Drug and Cosmetics Act says that the clinical trials may be waived in the case of new drugs
which are approved and being used for several years in other countries.

Types of Regulatory Documents :

1. Protocols
2. Clinical Study Reports (CSRs)
3. Investigator Brochures (IBS)
4. Common Technical Documents (CTDs)
5. Informed Consent Form (CF)
6. Risk Management Plans (RMPS)

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2. TABLETS :
Tablets are solid dose pharmaceutical preparation containing drug substances usually prepared
with the aid of suitable pharmaceutical excipients. They may vary in size, shape, weight,
hardness, thickness, disintegration, and dissolution characteristics and in other aspects,
depending on their intended use and method of manufacture.
Granulation:
➢ Granulation, is the process in which primary powder particles are made to adhere to
form larger, multi particle entities called granules. Granules used in the
pharmaceutical industry have particle size in the range of 0.2 - 4.0 mm
Methods of Granulation:
1. Dry granulation
2. Wet granulation
Dry granulation

DRY GRANULATOR (KALWEKA)

The primary powder particles are aggregated under high pressure. Used for drugs that do not
compress well after wet granulation, or those which are sensitive to moisture. There are two
main processes.
1. Slugging: a large tablet (known as a 'slug') is produced in a heavy-duty tabletting press
2. Roller compaction: the powder is squeezed between two rollers to produce a sheet of
material.
In both cases these intermediates products are broken using a suitable milling technique to
produce granular material, which is usually sieved to separate the desired size fraction. The
unused fine material may be reworked to avoid waste.

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Wet Granulation :
The most widely used process of agglomeration in pharmaceutical industry is wet granulation.
Wet granulation process simply involves wet massing of the powder blend with a
granulating liquid, wet sizing and drying.
It involves the massive of a mix of dry primary powder particles using a granulating fluid.
The fluid contains a solvent which must be volatile so that it can be removed by drying, and be
non-toxic.
The granulation liquid may be used alone or, more usually, as a solvent containing a dissolved
adhesive (also referred to as a binder or binding agent) which is used to ensure particle adhesion
once the granule is dry.

2.1 PREPARATION OF PARACETAMOL GRANULES:

Aim:
To prepare and submit paracetamol granules using wet granulation method.
Requirements:
Chemicals: Paracetamol, Micro Crystalline Cellulose, Magnesium Stearate, Talc, Starch,
Apparatus: Mortar and pestle, sieve no 10.
Procedure:
1. Take 25g of paracetamol in mortar, add Micro Crystalline Cellulose, Talc,
Magnesium Stearate to the paracetamol present in the mortar.
2. Prepare 10% of Starch paste in boiling water and stir until it becomes transulent and
Starch paste drop wise in mortar to get cohesive mass.
3. Screen prepared cohesive mass through number 10 granulating sieve and collect it on
granulating tray.
4. Dry the granules using the hot air oven with a temperature of 60 degree Celsius for 30
minutes.
5. After dried take out the granules and proceed for evaluation.

TABULATION:
SI no Ingredients Quantity taken Uses
1 Paracetamol 25 g Drug (Anti pyretic)
2 Micro Crystalline Cellulose 117.5 g Diluent
3 Magnesium Stearate 7.5 g Lubricant
4 Talc 37.5 g Glidant
5 Starch Q. S Binder

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2.2 EVALUATION OF PARACETAMOL GRANULES:
Aim: To determine bulk density, tap density, compressibility index and Hausner’s ratioof
prepared paracetamol granules.
True density (ρ):
It is the weight of the powder divided by its volume excluding the voids and
intra particle pores of smaller dimensions. It is determined from helium densitometer. Helium
penetrates the smallest pores and crevices but is not adsorbed by powder. Percent porosity is
determined from true density.
Bulk density (ρb):
It is the weight of powder or granules divided by its volume. Bulk density is used to check
the uniformity in bulk powdered materials, to decide the size of container, equipment for
production,

size of packing material and selecting size of empty gelatin capsules.

The reciprocal of bulk density is called as 'bulkiness' or 'bulk'. Based on bulk, powders are
classified as light powders (having high bulk volume) and heavy powders (having low bulk
volume).
Tapped density (ρt): It is the weight of granules divided by its tapped volume.
Compressibility Index (Carr’s Index):
The compressibility index (CI) is a measure of tendency of a powder to
consolidate (i.e., unite to form a solid form). As such it is a measure of inter-particulate
interactions.
Compressibility Index (%) = ρt - ρb / ρt x 100
Where, ρt is tapped density
ρb is bulk density
Hausner’s ratio:
Hausner’s ratio can be calculated by using following formula
Hausner’s ratio = ρt / ρb

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Scale of flowability for compressibility index and Hauser ratio:

Flow character Compressibility index (%) Hausners ratio

Excellent ≤ 10 1.00-1.11
Good 11-15 1.12-1.18
Fair 16-20 1.19-1.25
Passable 21-25 1.26-1.34
Poor 26-31 1.35-1.45
Very poor 32-37 1.46-1.59
Very, Very, Poor ≥38 >1.60

Requirements:
Chemicals and Apparatus Required: Granules of Paracetamol, Bulk density apparatus,
weighing balance and measuring cylinder (100 mlcapacity).
Procedure : 1. Weigh accurately 10 g of powder/granules (W1).
2. Place it in dried graduated measuring cylinder and note the volume as V1 ml.
3. Place the cylinder containing sample in bulk density apparatus. Adjust the apparatus for 100
tapping and operate it. Record the volume occupied by the powder as V2 ml. (Note:Place
the sample in both cylinders of apparatus to balance the arms).
Observations
1. Weight of powder = 20 g
2. Bulk volume of powder = 45 ml
3. Tapped volume of powder = 40 ml
Calculations:
1. Bulk density (ρb)
Bulk density (ρb) = weight / Bulk volume = W1 / V1 g/ml
=19.8/35 = 0.56 g/ml.
2. Tapped density (ρt)
Tapped density (ρt) = weight / tapped volume = W1 / V2 g/ml
= 19.8/30 = 0.66 g/ml.
3. Compressibility index (%)
Compressibility index (%) = ρt - ρb / ρt x 100
= 0.66-0.56/ 0.66 x 100 = 15.15% GOOD

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4. Hausner’s ratio
Hausner’s ratio = ρt / ρb
= 0.66/0.56 = 1.178 Good
Result:
Bulk density = 0.56 g/ml
Tapped density = 0.66 g/ml
Compressibility index=15.15%
Hausner’s ratio=1.178

Conclusion:
The compressibility index and Hausner’s ratio of prepared paracetamol granules
indicates that the granules have Good flow property.

2.3 ANGLE OF REPOSE

Aim:
To determine angle of repose of paracetamol granules.
Principle:
Angle of repose is defined as the maximum angle possible between the surface of the pile of
powder and the horizontal plane. The angle of repose is designated by ‘θ’ and given by equation
(1)
tan θ = h / r or 2h / d
θ = tan-1)
where, h = height of the pile
r = radius of the base of the pile
d = diameter of the base of the pile

Angle of repose Flow ability

25-30 Excellent
31-35 Good
36-40 Fair – aid not needed
41-45 Passable – may hang up
46-55 Poor – must agitate, vibrate
56-65 Very poor
>66 Very, very poor

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 Chemicals and apparatus Required: Paracetamol granules,Glass funnel, an iron stand with
a clamp and weighing balance.
Procedure:
1. Take a clean and dry funnel with a round stem of 20-30 mm diameter and attach it to the
burette stand.
2. Place a graph paper sheet below the funnel, on a clean dry platform.
3. Adjust the distance between lower tip of the funnel and sheet to some specified height (1-2
cm).
4. Gently pour the sample in the funnel from top, till a heap of powder forms and touches the
lower tip of the funnel.
5. Using a pencil draw a circle around the heap covering approximately 90% of total powder.
6. Repeat the procedure three times to obtain average reading.
7. Find out average diameter and radius of each drawn circle.
Observations:
1. Height of the pile = 2.2 cm & 1.9cm & 2.1cm
Calculations:
1)tan θ = h\r 2) tan θ = h\r 3) tan θ = h\r

tan θ = 2.2 tan θ = 1.9/4.2 tan θ = 2.1/4

4.1

θ= tan−1(2.2) =tan-10.475 = tan-10.569

4.1

θ = tan−1 0.536 =25°40′ =27°69′

= 28°19′ Average== 27°093′
Excellent
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Result:
The average angle of repose (θ) of given sample of powder = 27°093′
Conclusion:
The angle of repose of prepared paracetamol granule is Excellent.

3. TABLET PUNCHING:
Tablet press also referred to as tableting machine, pharmaceutical tablet press, tablet
compressing machine, or tablet punching machine is a mechanical device that compresses
powders into tablets of uniform size, shape, and weight containing approximately the same
quantity of Active Pharmaceutical Ingredient (API) and excipients. All tablet press employs
the same basic principle of compression.
Types/Classification of Tablet Press:
➢ Single punch/single station/eccentric presses.
➢ Multi-station/rotary presses.

Single Punch
Single punch tablet press also known as eccentric press or single station press is the simplest
machine for tablet manufacturing. This machine uses a single set of station tooling (a die and
a pair of upper and lower punches).
The compaction force on the fill material is exerted by only the upper punch while the lower
punch is static; such action equivalent to hammering motion and as a result, the single punch
press is referred to as stamping process. The single punch tablet press produces about 60-85
tablets/min
Components/ functional parts of a single punch tablet press
➢ Hopper, Die cavity, Punches ,Cam truck, Tablet adjuster, Ejection adjuster

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The sequence of events involved in the formation of tablets.
1. Filing
2. Compression
3. Ejection

Advantages of Single Punch Tablet Press

1. The single punch structure is rational and small.
2. Easy to operate and it operates at a high utilization ratio.
3. It can manufacture odd-shaped products with a diameter of up to 20 mm.
4. It is ideal for the development of tablets and small batch production.
Multi-Station Press
Multi- Station press is a mechanical device that unlike the single punch tablet press has several
tooling stations which rotates to compress granules/powder mixture into tablets of uniform
size, shape, and uniform weight.

Pharmaceutical Excipients: Excipient is a pharmacologically inactive subs. formulated

Fillers:
Typically fill out the size of a tablet or capsule, making it practical to produce & convenient
for the consumer to use.Example: Plant cellulose & Dibasic calcium phosphate.Vegetable fats
& oils are used in soft gelatin capsules.
Binders:
Binders hold the ingredients in a tablet together. Binders ensure that tablets & granules formed
with required mechanical strength, & give volume to low active dose tablets . Eg: DryBinders
added to powder e.g.; Cellulose, methyl cellulose, Polyvinyl pyrrolidone, and Polyethylene
glycol.
Disintegrants:
Disintegrants are substance or mixture of substances added to the drug formulations, which
facilitate dispersion or breakup of tablets & contents of capsules into smaller particles for quick
dissolution when it comes in contact with water in the GIT.Examples: Polyvinylpyrrolidone ,
carboxymethyl cellulose.
Lubricants:
Lubricants prevent ingredients from clumping together and from sticking to the tablet punches
or capsule filling machine. Lubricants also ensure that tablet formation & ejection occur with
low friction between the solid and die wall.Example : Polyethylene glycol,Magnesium
Stearate, Stearic acid and its derivatives.

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Glidants:
A substance as colloidal silica that enhance the flow of a granular mixture by reducing inter-
particle friction & used in the pharmaceutical production of tablets & capsule.Example: Fumed
silica, talc, & magnesium carbonate.
Sweetening agents:
Sweetening agents employed in liquid formulations designed for oral administration
specifically to increase the palatability of the therapeutic agent.
Example: Sucrouse, Saccarine, Aspertame, Sorbitol.
Flavoring agents:
Flavoring agents are added to increase patient acceptance. The four basic taste sensations are
salty, sweet, bitter, sour. Certain flavors used to mask these specific taste sensations.
Eg: Clove oil, citric and syrup, glycerin, rose oil, orange oil, menthol.

3.1 EVALUATION OF PARACETAMOL TABLETS :

Tablet Evaluation:Before a tablet is released out into the market it has to pass a few quality
checks, which is mandatory. Evaluation of tablet includes the assessment of tablets physical,
chemical and biological properties. To studies them the following test are formulated,
• Weight Variation Test,
• Hardness,
• Friability,
• In vitro Disintegration Test,

WEIGHT VARIATION TEST

According to the USP, Weight variation test is run by weighing 20 tablets individually
calculating the average weights and comparing the individual tablet weights to the average.
The value of weight variation test is expressed in percentage. The following formula is used
to determine:
Weight Variation = (IW - AW)/AW X 100% Where,
IW: Individual weight AW: Average weight

Average Weight Percentage Difference

130 mg or less 10
More than 130 mg through
7.5
324 mg
More than 324 mg 5

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Calculations :
TABLET TABLET WEIGHT
(g)
1 0.593
2 0.599
3 0.603
4 0.600 →MAXIMUM DEVIATION
5 0.624 →MINIMUM DEVIATION
6 0.615
7 0.619
8 0.618
Average weight of tablets = 0.593 g
Maximum % deviation = Maximum deviation - Avg.wt x 100
Avg.wt
= 0.624-0.593x 100 = 5.2%
0.593
Minimum % deviation = Avg.wt - Minimum deviation x 100
Avg.wt
= 0.593-0.573 x 100 = 3.37 %
0.593
FRIABILITY TEST:
➢ "FRIABILITY is the phenomenon where the surface of the tablet is damage or shown
a site of damage due to mechanical shock."

Equipment used in this test:

Roche friabilator tester is most commonly used for determining % friability of tablet.

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Procedure:
1. Take 20 tablets and take initial weight of it and put it into friabilator.
2. Now rotate the drum at 25 rpm per min or 100 rpm for 4 mins.
3. During this tablet gets dropped on plastic from 6 inches, it will pass through
mechanical shocks.
4. After 4 minutes.calculate final weightof tablets and that of % friability.
% Friability can be calculated by following formula
% Friability = W1- W2/W1 x 100
Where, WI = weight of tablets before testing
W2 = weight of tablets after testing

Standards for friability:

✓ % Friability should be upto 0.5 to 1% for all standard compressed tablets.
Calculations:
Friability = Initial weight - Final weight x 100
Initial weight
= 6.6519-6.6308 x 100 = 0.317 %
6.6519
HARDNESS TEST:
➢ This test is also known as "Crushing Strength Test".
➢ Tablets require a certain amount of strength, or hardness to withstand
mechanical shocks of handling in manufacture, packaging and shipping
Tablethardness has been defined as the force required to break a tablet in a
diametriccompression test.

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Equipments used in this test:
(a) Monsanto hardness tester
(b)Pfizer hardness tester
(a) Monsanto hardness tester:
Here,tablet is put between moving jaw and fixed jaw. Moving jaw is moved and pressure is
applied on tablet by means of screw knob.The point where tablet get break down.it is recorded
by means of scale. The hardness is measured in Kg/cm.
(b) Pfizer hardness tester:
The Pfizer tester compresses tablet between a holding anvil and a piston connected to a force-
reading gauge when its plier-like handles are gripped. The point where tablet gets break
down, it is noted by reading gauze.
Official standards for Hardness: 5-8 kg/cm² for standard compressed tablet except
Effervescent tablet, Dispersible tablet. Orodispersible tablet, Chewable tablet,etc.
Calculation:
Hardness of tablets was found to be
= 5.7 kg/cm−2

DISINTEGRATION TEST:
➢ Disintegration is a process in which tablets are break up into granules or smaller
particles.

Disintegration time:
Time required for breaking of tablet into small particles under influence of disintegrating
fluid.Disintegrating fluid may be either simulated gastric fluid or simulated intestinal fluid.

Equipment used in this test: Disintegration test apparatus is commonly used.

Apparatus construction:
➢ Two batches of six tablets can be simultaneously tested with this instrument.

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 ➢ The USP device to test disintegration uses 6 glass tubes that are 3 inches long,open at
the top and held against a 10-mesh screen at the bottom end of basket rack
assembly.Each glass tube has percolated sieve (no. 10) at the bottom.
Procedure:
➢ To test for disintegration time,one tablet is placed in each tube and the basket rack is
positioned in a 1-L beaker of water simulated gastric fluid or simulated intestinal
fluid.at 37°C+2°C.such that tablets remain 2.5 cm below the surface of liquid on their
upward movement and descend not closer than 2.5 cm from the bottom of beaker.A
standard motor-driven is used to move the basket assembly containing the tablets up
and down through a distance of 5-6 cm at frequency of 28-32 cycles per minute. Thus,
in this way.note the time required to complete disappearance of tablet from glass tube.
Official standards:
S.N TYPES I.P B.P U.S.P
O
1 Standard compressed tablet 15mins 15mins 5mins
(Uncoated)
2 Sugar coated tablet 60mins 30mins -
3 Film coated tablet 30mins 30mins -
4 Enteric control tablet 1hr 1-2 hrs 2 hrs
5 Effervescent tablet or <3mins <3mins <3mins
dispersible tablet
6 Orodispersible tablet <1mins <1mins <1mins

RESULT:
Weight variation test was found to be
Maximum% variation = 5.2%
1. Minimum % variation = 3.37%
2. Friability test value was found to be 0.317%
3. Hardness test was found to be 5.7kg/cm2
4. Disintegration time was found to be 2min 16sec.

4. TABLET COATING:
DEFINITION:
A tablet coating is a covering over a tablet, used to mask the taste, make it easier to
swallow, or protect the active medication inside.

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EQUIPMENTS:
The Equipments used for the tablet coating are
1. Standard coating pan
2. Perforated coating pan
3. Fluidized bed coater

Standard coating pan:

➢ It is also known as conventional pan system
➢ Consist of circular metal pan rotated on its horizontal axis by a motor
➢ Heated air is directed into the pan & on to the tablet bed surface and is exhausted by
means of ducts through the front of the pan
➢ Coating solution are applied to the tablets by spraying the material on to the rotating
tablet bed.
Use of spraying systems:
➢ Produces a faster, more even distribution of the solution or suspension.
➢ Reduces drying time between solution application in sugar coating.
➢ Allows continuous application of the solution in filating
In standard coating pan, the drying efficiency is improved by:
➢ Pellegrini pan
➢ The immersion sword
➢ Immersion tube systems
TABLET COATING PROCESS:
The coating of tablets classified into three types:
I Sugar coating
II. Film coating
III. Enteric coating

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SUGAR COATING:
It involves the application of sugar solution with color for several times to give uniform and
elegant film.Sugar coating involves the following steps
➢ Sealing
➢ Sub-coating
➢ Syruping
➢ Finishing
➢ Polishing
SEALING:
It prevents moisture penetration in to the tablet core.Seal coating agents.Eg.shellac, Oleicacid,
PG, PEG4000,
SUB COATING:
Sub coating is applied: To form uniform edges, to build up the tablet size.Eg. Gelatin, Gum
acacia
SYRUPING:
It is done to cover the imperfections in the Tablet surface caused during sub coating step.Syrup
coating constituents- colorant, sub coating powder, calcium carbonate ,cane sugar powder, corn
starch, syrup, distilled water.
POLISHING:
The desired luster to the tablet is obtained by polishing.Tablets are polished in a Standard
coating pans by application of Bees wax(white), Paraffin wax
FILM COATING:
It is the process of polymeric solution to bring a uniform film.
FILM FORMING AGENTS:
The film forming agents tablet coating are classified into
1.Non - enteric film formers
2.Enteric film formers
NON-ENTERIC FILM FORMERS
They are incorporated to give uniform film with desired mechanical strength which are as
follows:HPMC (Hydroxy propyl methyl cellulose),MHEC (Methyl hydroxyl ethyl
cellulose),EC (Ethyl cellulose),HPC (Hydroxy
propylcellulose),POVIDONE,SCMC,PG,ACRYLATE POLYMERS

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ENTERIC FILM FORMERS : CAP (Cellulose acetate phthalate) and ACRYLATE
POLYMERS
1. Solvent
2.Plasticizers
3. Colorants
4. Opaquant extent
SOLVENT:.Eg. Ethanol, Methanol, Chloroform, Acetone.
PLASTICIZERS:It is used to modify the quality of the film. Plasticizing techniques involve
internal plasticizers and external plasticizers.Eg.Castor oil, Propylene glycol, Glycerin,
Surfactants - (tweens, spans)
COLORANTS:It is to provide the distinct color and Elegance to the dosage form.The
inorganic materials and the natural colorants are Iron oxides, Caramel, Carotenoid,
Chlorophyll, indigo, Flavones, turmeric and carminic acid.
OPAQUANT-EXTENDES:These are very fine inorganic powders used in the coating
solution formulation to provide more pastel colors and increase film coverage.Silicates like
(Talc, Aluminium silicate) Carbonates like-magnesium carbonate, Sulphates like calcium
sulphate
FILM DEFECTS:
STICKING AND PICKING - Attaching of tablet to another
➢ REASONS – Over wetting, Rapid drying tackiness of tablets.
➢ REMEDY – Reduce liquid application, control rate of drying, change formulations.
ROUGHNESS - Formation of rough or gritty surface.
➢ REASONS – Increase in path length of spray nozzle to tablet bed, Rapid drying.
➢ REMEDY – Decrease in path length, Control the drying rate.
ORANGE PEEL EFFECT- Inadequate of spreading coating solution
➢ REASONS – Rapid drying, High viscosity of coating solution.
➢ REMEDY – Decrease in drying rate, Decrease the viscosity by adding solvent.
BRIDGING - Shrinking or pulling away of film from corners.
➢ REASONS – Over wetting, less viscous liquids.
➢ REMEDY – Decrease the application rate, Increase viscosity.
BLISTERING- Removal of film due to rapid evaporation of solvent from tablet core.
➢ REASON – Rapid evaporation of solvent due to increase in temperature, High
viscosity of coating solution.
➢ REMEDY – Decrease the temperature of drying, Dilute the coating the solution.

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4.1 DEMONSTRATION OF TABLET COATING:
AIM: To perform film coating for the given tablets.
PRINCIPLE:
Tablet coating is required to mask the unpleasant taste, to improve elegance, to control
the distribution, to improve the stability of tablets by protection against oxidation, moisture,
light etc. In the preparation of coating solution, HPMC (Hydroxy Propyl Methyl Cellulose) is
commonly used as film coating agent. Propyleneglycol or Polyethyleneglycol are used asfilm
forming agents and castor oil is used as plasticizer. Acetone or ethyl alcohol is used as solvent.
A wide range of material incorporated in the coating material. They are film forming agent,
colouring agent, opacifying agent, plasticizer. Coating can be performed by dip coating, spray
coating process.
PROCEDURE:
Place the weighed amount of tablet on the coating pan. Spray the coating solution over the
tablet. Periodically tablets are taken and weighed. Percentage of weight gain to the tablet
indicates tablet coating has been completed.
TABULATION:
INGREDIENTS QUANTITY
HPMC 10 ml
Propylene glycol 1.2ml
Titanium di oxide 0.5%
Colorants q.s
Ethylene or acetone q.s

REPORT:
Film coating for the given tablet was prepared and submitted.

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5. SUSPENSION:
A pharmaceutical suspension is a biphasic coarse dispersion in which internal phase (
therapeutically active ingredient ) is dispersed uniformly throughout the external phase .
SUSPENDING AGENTS :
Suspending agents are substances that are used to keep finely divided insoluble materials
suspended in a liquid media by preventing there agglomeration (coming together ) and by
imparting viscosity to dispersion media so that particles settle more slowly . care must be taken
when selecting a suspending agent for oral preparations as the acidic environment of stomach
may alter the physical characteristics of the suspension and therefore the rate of release of the
drug from suspension.
CLASSIFICATION OF SUSPENDING AGENTS
1. NATURAL AGENTS: This class consists of those from.
a. Animal source Eg :Gelatin
b. Plant sourceEg. Acacia, Tragacanth, Starch, sea weed
c. mineral sources.Eg Bentonite, Kaoline
2. SEMI-SYNTHETIC AGENTS: These consist of substituted cellulose (minerals).Eg.
Hydroxyethylcellulose , Sodium Carboxymethyl cellulose , methyl cellulose, Microcrystalline
cellulose
3. SYNTHETIC AGENTS.
They are synthetic polymers Eg carboxypolymethylene, Polyvinyl Alcohol, Polyvinyl
Pyrolidone iodine complex (PVC).Most suspending agents perform two functions i.e. besides
acting as a suspending agent they also imparts viscosity to the solution. Suspending agents
form film around particle and decrease inter particle attraction.
Aqueous Suspending Agents
The most common suspending agents are aqueous biological polymers, including
methylcellulose (MC), sodiumcarboxymethylcellulose (CMC),and
Hydroxypropylmethylcellulose (HPMC). A range of viscosities of suspending agents is
available with different molecular weights. In particular, aqueous 1% w/v MC 400 cP has many
of the characteristics of an ideal vehicle:
1. Clear, colorless
2. Ideal viscosity; the most commonly used MC has a dynamic viscosity of 400 cP at 2% w/v
in water; in comparison, water has a viscosity of approximately 1 cP at room temperature
3. Biologically inert
4. Easily sterilized
5.Not ionic

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6. Can be used in combination with Surfactants such as Tween 80 to improve wetting and
enhance physical stability

5.1 DETERMINATION OF SEDIMENTATION VOLUME WITH

EFFECT OF DIFFERENT SUSPENDING AGENTS
Aim:
To find out the effect of different suspending agents on sedimentation volume of
suspension.

Requirements:
Zinc oxide/ calamine, 0.5% Acacia – 500mg, 0.5% Tragacanth- 500mg, 0.5% sodium
carboxyl methyl cellulose – 500mg and water.
Principle:
The effect of different suspending agents on sedimentation volume of suspension can
be determined by keeping a measuring volume of suspension in a graduated cylinder in an
undisturbed state for a certain period of time and noting the volume of suspension which is
expressed as sedimentation volume/ ratio [Hu/Ho]. Dependent on time, the sedimentation ratio
varies depending upon different suspending agents. The sedimentation ratios at different time
periods of time can be plotted against time abscissa to get a curve that indicates the
sedimentation pattern on storage. If the curve is horizontal to time axis it indicates a better
suspension, if it steeps down it indicates a poor formulation.
Procedure:
Different formulation were prepared by mixing Zinc oxide/ calamine (5g) with
suspending agents and made upto 100ml by adding distilled water. Each preparation is placed
in graduated cylinders the control is also taken in an graduated cylinders. All the cylinders are
shaken simultaneously and set aside. The height of sediments are noted after
5,10,20,30,40,5,60,75,90 minutes. The graph is plotted with time in minutes in X-axis and
sedimentation value in y-axis. There is no sedimentation in an ideal suspension. A stable
preparation sediment slowly and redistributes immediately after shaking
FORMULATION DRUG (ZINC SUSUPENDING AGENT WATER
OXIDE/
CALAMINE)
I 2.5g 0.25% acacia (250mg) 50ml
II 2.5g 0.25% tragacanth 50ml
(250mg)
III 2.5g 0.25% ( sodium 50ml
carboxymethyl
cellulose)
Control without 2.5g - 50ml
suspending agent

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OBSERVATION :
TIME CONTROL ACACIA TRAGACANTH SCMC
CALAMINE
SEDIMEN HU/HO SEDIMEN HU/HO SEDIMEN HU/HO SEDIMEN HU/H
TATION TATION TATION TATION O
VALUE VALUE VALUE VALUE
(HU) (HU) (HU) (HU)
5 36 0.72 48 0.96 49 0.98 50 1
10 23 0.46 48 0.96 46 0.92 50 1
20 18 0.36 47 0.94 45 0.90 50 1
30 15 0.30 47 0.94 45 0.90 50 1
40 14 0.28 47 0.94 44 0.88 50 1
50 11 0.22 46 0.92 43 0.86 50 1
GRAPH:

Report:
SCMC (sodium Carboxy methyl cellulose) was found to be the most stable suspending
agent which sediments the suspension slower that the control.

5.2 DETERMINATION OF SEDIMENTATION VOLUME WITH

EFFECT OF DIFFERENT CONCENTRATION OF SINGLE
SUSPENDING AGENT
Aim: To determine the sedimentation volume of calamine suspension containing different
concentration of single suspending agent.
Apparatus and chemicals required: Beaker – 250 ml, measuring cylinder- 50ml, mortar
and pestle, calamine- 2.5g, suspending agent- 0.5%, 1%, 1.5%, 2%.

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Principle:
Suspension or coarse dispersion in which insoluble solid particles of drugs are dispersed
in liquid medium. The condition in which the particles remain uniformly distributed
throughout the dispersion without aggregation is called physical stability of suspension. The
physical stability of suspension can be improved by using suspending agent, which usually
reduces the interfacial tension and contact angle and thereby promotes wetting and
deflocculation. Combination of suspending agent are sometimes preferred as they produce
excellent suspension. Sedimentation volume(f) is defined as the ratio of final or ultimate
volume of sediment to the original volume of suspension. It is a qualitative measure of
suspension stability. A suspension is said to be flocculated equilibrium when F=1 or nearby 1.
Such suspension are pharmaceutically stable and acceptable.
SEDIMENTATION VOLUME (f) = Ultimate volume of sediment (vu) / Original volume of
suspension (vo)
Procedure:
1. Triturate 2.5g of calamine with 0.25% of suspending agent in a mortar.
2. Make a smooth paste using small quantity of purified water and then add
approximately 20 ml of water and mix.
3. Transfer the slurry into 50ml graduated measuring cylinder.
4. Rinse the mortar with successive portions of water and transfer to the cylinder. Add
sufficient quantity of purified water to make 50 ml suspension and label.
5. Prepare calamine suspension using different concentration of suspending agent and
without suspending agent adapting the above steps.
6. Label the formulated suspension and place them on flat surface through shaking.
7. Note the volume of sediment at different time interval 0, 5, 10, 15, 30, 45, 60, and 90
mins and calculate the sedimentation volume using the formula.
8. Plot the graph between time Vs sedimentation volume and compare the physical
stability of formulation suspension.
TABULATION:
FORMULATION DRUG (CALAMINE) SUSPENDING AGENT WATER
1 2.5g 0 100ml
2 2.5g 0.5% 100ml
3 2.5g 1% 100ml
4 2.5g 1.5% 100ml
5 2.5g 2% 100ml

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OBSERVATION:

TIME VOLUME OF THE SUSPENSION CONTAINING VARYING PERCENTAGE

IN OF SUSPENDING AGENT
MINS 0 % Vu/Vo 0.5 % Vu/Vo 1% Vu/V 1.5% Vu/Vo 2% Vu/V
o o
0 100 1 100 1 100 1 100 1 100 1
10 95 0.95 97 0.97 94.5 0.945 97 0.97 95.5 0.955
20 95 0.95 97 0.97 95 0.95 97.5 0.975 96 0.96
30 93 0.93 98 0.98 96 0.96 97.5 0.975 97 0.97
40 90 0.90 98.5 0.985 96 0.96 98 0.98 97 0.97
50 85 0.85 99 0.99 96.5 0.965 98 0.98 97.5 0.975

GRAPH:

Report:
As the concentration of suspending agent increases, the sedimentation volume decrease.

6. STERILIZATION:
Sterilization is defined as the process where all the living microorganisms, including bacterial
spores are killed. Sterilization can be achieved by physical, chemical and physiochemical
means. Chemicals used as sterilizing agents are called chemisterilants.

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PHYSICAL METHODS OF STERILIZATION:
DRY HEAT:
Incineration: This is a method of destroying contaminated material by burning them in
incinerator. Articles such as solid dressings, animal carcasses, pathological material and
bedding etc,
Hot air oven: This method was introduced by Louis Pasteur. Articles to be sterilized are
exposed to high temperature (160o C) for duration of one hour in an electrically heated oven.
Since air is poor conductor of heat meshed shelves and must have adequate insulation.
Articles sterilized: Metallic instruments (like forceps, scalpels, scissors), glass wares (such
as petridishes, pipettes, flasks, all-glass syringes), swabs, oils, grease, petroleum jelly and
some pharmaceutical products.
Sterilization cycle: This takes into consideration the time taken for the articles to reach the
sterilizing temperature, maintenance of the sterilizing temperature for a defined period (holding
time) and the time taken for the articles to cool down. Different temperature-time relations for
holding time are 60 minutes at 160o C, 40 minutes at 170o C and 20 minutes at 180o C.
Increasing temperature by 10 degrees shortens the sterilizing time by 50 percent. The hot air
oven must not be opened until the temperature inside has fallen below 60o C to prevent
breakage of glasswares.
MOIST HEAT:
Moist heat acts by coagulation and denaturation of proteins.
At temperature above 100o C:
Autoclave: Sterilization can be effectively achieved at a temperature above 100o C using an
autoclave. Water boils at 100o C at atmospheric pressure, but if pressure is raised, the
temperature at which the water boils also increases. In an autoclave the water is boiled in a
closed chamber. As the pressure rises, the boiling point of water also raises. At a pressure of
15 lbs inside the autoclave, the temperature is said to be 121o C. Exposure of articles to this
temperature for 15 minutes sterilizes them. To destroy the infective agents associated with
spongiform encephalopathies (prions), higher temperatures or longer times are used; 135o C
or 121o C for at least one hour are recommended.
Different types of autoclave: Simple “pressure-cooker type” laboratory autoclave, Steam
jacketed downward displacement laboratory autoclave and high pressure prevacuum autoclave.
Construction And Operation Of Autoclave: A simple autoclave has vertical or horizontal
cylindrical body with a heating element, a perforated try to keep the articles, a lid that can be
fastened by screw clamps, a pressure gauge, a safety valve and a discharge tap. The articles to
be sterilized must not be tightly packed. The screw caps and cotton plugs must be loosely fitted.
The lid is closed but the discharge tap is kept open and the water is heated. As thewater
starts boiling, the steam drives air out of the discharge tap. When all the air is displaced and
steam start appearing through the discharge tap, the tap is closed. The pressure inside is allowed
to rise upto 15 lbs per square inch. At this pressure the articles are held for 15 minutes, after
which the heating is stopped and the autoclave is allowed to cool. Once the

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pressure gauge shows the pressure equal to atmospheric pressure, the discharge tap is opened
to let the air in. The lid is then opened and articles removed.

Articles sterilized:
Culture media, dressings, certain equipment, linen etc.
STERILITY TESTING:
• Are done to detect if viable forms of micro-organisms are present or not on or in the
pharmaceutical preparations.
TEST FOR STERILITY
• Membrane filtration
• Direct inoculation
Pyrogen: A fever producing substances that cause febrile reactions when sufficient amount
enter the circulatory.
Pyrogen test:
1. In Vitro Test / LAL Test.
2. In Vivo Test / Rabbit Test.

6. ISOTONIC SOLUTIONS
➢ "When two solutions have same osmotic pressure and salt concentration are said to be
isotonic solutions”. Iso (same) and tonic(concentration).
➢ Physiologically, isotonic solutions are solutions having the same osmotic pressure as
that of the body fluids when separated by a biological membrane. Biological fluids
including blood and lachrymal fluid normally have an osmotic pressure corresponding
to that of 0.9% w/v solution of sodium chloride. Thus 0.9% solution of sodium
chloride is said to be isotonic with the physiologicalfluids.
➢ In addition, to carrying out pH adjustments, pharmaceutical solutions that are meant
for application to delicate membranes of the body should also be adjusted to
approximately the same osmotic pressure as that of body fluidsHYPERTONIC
SOLUTION
➢ "A hyper-tonic solution is one that has greater concentration than reference solution
(i.e. RBCs Contents)."A hyper-tonic solution has greater osmotic pressure than that

29
 of reference solution.This exit of water from RBCs causes their shrinkage and RBCs
become wrinkled in shape. This shrinkage of RBCs is known as "Plasmolysis".
HYPOTONIC SOLUTION
➢ "Ahypotonicsolutionisonethathaslowerconcentrationthan reference solution (i.e.
RBCs contents).A hypo-tonic solution has lower osmotic pressure than that of
reference solution.
ISO-OSMOTIC OR ISOSMOTIC SOLUTIONS
➢ "Solutions having the same osmotic pressure but not necessarily the same
concentration are said to be iso-osmotic solutions."E.g. 2% w/v solution of boric acid
has the same osmotic pressure as 0.9% w/v solution of NaCI but not the same
concentration. So, both solutions are iso-osmotic but notisotonic.
Measurement Of Tonicity
• Haemolytic Method
• Colligative Method
➢ For making isotonic solutions, the quantities of substances to be added may be
calculated by following methods:
✓ Based on molecular concentration
✓ Based on freezing point data
✓ Based on sodium chloride equivalent (E)value
✓ White-Vincent method

Based on molecular concentration

1% molecular concentration:
➢ If one gram molecule (i.e. one gram molecular weight) of a substance is dissolved in
100 ml of water, the resulting solution will be of 1% molecular concentration. A
depression of - 18.6 C° in freezing point of solution is due to = 1% Molecular
concentration
➢ A depression of 1 C° in freezing point of solution is due to = 1 / - 18.6 % Molecular
concentration
➢ A depression of - 0.52C° in freezing point of plasma is due to = 1 /- 18.6 x -0.52=
0.03% Molecular concentration
➢ So, molecular concentration of plasma is 0.03%. Therefore, any solution having the
molecular concentration of 0.03% will be isotonic with blood (having the same
concentration - which means isotonic).

The formula for calculating the w/v percent of ionizing and non-ionizing substances required
to make isotonic solutions with blood plasma is as follows;
• For non-ionizing substances
W / V % of substance required = 0.03% x Gram molecular weight

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 • For ionizing substances
W/V % of substance required=0.03%xGrammolecularweight / no. of ions yielded by the
molecule
1. Find the proportion of Boric Acid required to make a solution isotonic. The
molecular weight of boric acid is 62, and it is a non-ionizing substance
Solution: W/V % of boric acid required to make isotonic solution = 0.03% x gram molecular
weight
= 0.03 x 62 =1.86
So, 1.86 gms of boric acid is required to make 100ml isotonic solution.
2. Find the proportion of Sodium sulphate required to make a solution isotonic. The
molecular weight boric of sodium sulphate is 148, and it is an ionizing substance.
W/V % of ionizing substance required to make isotonic solution = 0.03%x gram molecular
weight / no. Of ions
Na2SO4 —> 2Na +SO4 [So, total no. of ions produced by sodium sulphate =3]
W/V % of Na2SO4 required to make isotonic solution = 0.03% x gram molecular weight / no.
Of ions
= 0.03 % x 148 / 3 =1.48
S0, 1.48 gm of sodium sulphate is required to make 100mlisotonic solution.
FREEZING POINT DEPRESSION METHOD
The plasma and blood freezing point temperature = -0.52°C .The dissolved substances in
plasma or tear depress the solution freezing point below 0.52°.Any solution that freeze at T=-
0.52°C is isotonic with blood and tear weight of substance that need to be adjusted to make it
hypotonic given by the following formula;

Where,
W=the weight, in g, of the added substance in 100ml of the final solution
a =the depression of the freezing point of water produced by the medicament already in the
solution
b=the depression of freezing of water produced by 1 per cent w/v of the added substance
1. Prepare and submit 500ml NaHCO3 (ΔT.f 1%=0.38) so that when it is dilute with the
same amount of water, it would be isotonic.
Solution;
Rx ΔT.f 1%
NaHCO3 Xg(13.7) 0.38
Water qs ad 500ml

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The solution is hypertonic When diluted
NaHCO3- Xg
Water qs ad 1000ml
This solution is isotonic = = 1.37g
NaHCO3 required to make the solution isotonic upon dilution is;
=[1.37 X 10 = 13.7g (to be dissolved to 500ml solution)]
2. NaCl EQUIVALENT METHOD (E)
➢ Based on the factor called the sodium chloride equivalent which can be used to
convert a specified concentration of medicament to the concentration of medicament
to the concentration of sodium chloride that will produce the same osmotic effect.
➢
➢ Method to calculate % at isotonic, ΔTf 1% =0.576 ~ NaCl

FORMULA: Amount of NaCl required = 0.9% - (E1% × w/v)

Example 2.1 ΔTf 1% ascorbic acid =0.105°C
ΔTf 1% NaCl = 0.576°C
What is the E for 1% ascorbic acid?
Solution - E 1% ascorbic acid=

3. WHITE VINCENT METHOD

Principle:

A Isotonic solution + B isotonic solution = C isotonic solution

This method involves the addition of water to medicament to obtain an isotonic solution.
Thisfollowed by the addition of isotonic buffer solution or preservatives isotonic solution to
the requiredvolume.
V = W X E1% X 111.1 Where; V= V (ml) of isotonic solution that
could be obtain in wg of drug in water (the amount of water to added to form isotonic solution)
W= amount of drug in the formula
E1%=NaCl equivalent of the drug

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Example 3.1
Rx E 1%
Ephedrine HCl 1g 0.3
Chlorobutol 0.5g 0.24
NaCl q.s
Distilled water 200ml isotonic
Solution;
For ephedrine HCl, V=1 X 0.3 X 111.1 = 33.33ml → This solution is isotonic (A)
For chlorobutol, V=0.5 X 0.24 X 111.1 = 13.33ml → This solution is isotonic (B)
200ml – (33.33 + 13.33) ml = 153.34ml
Amount of NaCl required to adjust 153.34ml to isotonic;
= ×153.34 ml solution = 1.38 g NaCl This solution is isotonic
➢ So the overall solution is isotonic
Saline Solution, 0.9% Sodium Chloride (NaCl)
➢ Makes 1000 ml. Store at room temperature (indefinitely).
➢ Note: This solution will be used for a mouthwash, so ensure that all
glassware/plasticware is clean and free of chemical residue.
➢ Dissolve 9 g NaCl (mw 58.44) in 700 ml deionized or distilled water in clean
container.
➢ Add water to bring total solution volume to 1000 ml.
➢ Make 10 ml aliquots in sterile 15 ml culture tubes.
➢ Note: If solution is to be used immediately, it need not be sterile. However, for long-
term storage, we recommend sterilizing by autoclaving for 15 minutes at 121°C or
passage through a .45- or .22-micron sterile filter.

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