A

Project Report
On
Submitted to
KURUKSHETRA UNIVERSITY,
KURUKSHETRA
IN THE PARTIAL FULFILLMENT OF REQUIREMENT FOR THE DEGREE
OF
BACHELOR OF SCIENCE
Industrial Microbiology (Vocational)
(Session 2014-2015)

By :
GURPREET KAUR
B.Sc. II (Ind. Microbiology)
Roll No. : 2363913

DEPARTMENT OF INDUSTRIAL MICROBIOLOGY

GURU NANAK KHALSA COLLEGE
YAMUNA NAGAR
 ACKNOWLEDGEMENT

I express my sincere thanks and profound gratitude to my esteemed

guide Dr. Neena Puri, U.G. Department of Industrial Microbiology for her
guidance, regular counseling and constant encouragement.

I express my sincere thanks to Prof. Amarjit Singh (Officiating

Principal) for providing me the opportunity to go for this project work.

I express my sincere thanks to Ms. Teena Mittal for her valuable

suggestions, advice & encouragement from time to time.

I have done my training in M/s Pharma Force Lab. (Paonta Sahib,

(HP). I have done my project report on tablet. I am work in company under
the guidance of Mr. Sukhjinder Singh (Q.C. Manager) and all the
members of industry for helping me throughout my project.

Gurpreet Kaur
B.Sc.- II (IMB)
 PREFACE

The role of Industrial Microbiology in every branch of science is

expanding greatly. Man's interest in the Industrial Microbiology is essential
a practical one. He is interested in the way materials in the universe
behave and react under different types of conditions and the ways in which
he can use these materials for his own purpose.
Industrial Microbiology has proved to be of great help in many fields
including civil services, medical and veterinary science, engineering and
dried subject areas.
Guru Nanak Khalsa College, Yamuna Nagar is making bid to impart
profession oriented education in subject like Industrial Microbiology,
Electronic, computer science order to make powerful potential
employees.
It was with these important points in mind that I decided to join B.Sc.
in Industrial Microbiology.
This course is particularly designed to prepared graduate for careers
in the increasingly important high technology industries.
With Industrial Microbiology one can be self employed and generate
jobs for other people. It is by the spirit to achieve this goal in future
that I completed my industrial training and worked this project report.
Hope you will enjoy it.
 TABLET

Common disk-shaped tablets

A tablet is a pharmaceutical dosage form. It comprises a mixture of active

substances and excipients, usually in powder form, pressed or compacted from a

powder into a solid dose. The excipients can include diluents, binders or

granulating agents, glidants (flow aids) and lubricants to ensure efficient

tabletting; disintegrants to promote tablet break-up in the digestive tract;

sweeteners or flavours to enhance taste; and pigments to make the tablets

visually attractive. A polymer coating is often applied to make the tablet smoother

and easier to swallow, to control the release rate of the active ingredient, to make

it more resistant to the environment (extending its shelf life), or to enhance the

tablet's appearance.

The compressed tablet is the most popular dosage form in use today. About two-

thirds of all prescriptions are dispensed as solid dosage forms, and half of these

are compressed tablets. A tablet can be formulated to deliver an accurate

dosage to a specific site; it is usually taken orally, but can be

administered sublingually, buccally, rectally or intravaginally. The tablet is just

one of the many forms that an oral drug can take such

as syrups, elixirs, suspensions, and emulsions. Medicinal tablets were originally

made in the shape of a disk of whatever color their components determined, but

are now made in many shapes and colors to help distinguish different medicines.

Tablets are often stamped with symbols, letters, and numbers, which enable

them to be identified. Sizes of tablets to be swallowed range from a few

millimeters to about a centimeter.

 TYPES OF TABLETS

Pill

"The Pill", a general nickname for the combined oral contraceptive pill(COCP)

Today, pills include tablets, capsules, and variants thereof like caplets

essentially anything with medication that can be digested, minus the liquid forms,

colloquially falls into the pill category.

Caplet

Variations on a common tablet design, which can be distinguished by both color

and shape

A smooth, coated, oval-shaped medicinal tablet in the shape of a capsules, and

are called "caplets".

 Orally disintegrating tablet (ODT)

Olanzapine ODT blister pack with "wafer" tablets that which rapidly dissolves in

saliva.

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.

 TABLETTING FORMULATIONS

In the tablet-pressing process, it is important that all ingredients be fairly dry,

powdered or granular, somewhat uniform in particle size, and freely flowing.

Mixed particle sized powders segregate during manufacturing operations due to

different densities, which can result in tablets with poor drug or active

pharmaceutical ingredient (API) content uniformity but granulation should prevent

this. Content uniformity ensures that the same API dose is delivered with each

tablet.

Some APIs may be tableted as pure substances, but this is rarely the case; most

formulations include excipients. Normally, a pharmacologically inactive ingredient

(excipient) termed a binder is added to help hold the tablet together and give it

strength. A wide variety of binders may be used, some common ones

including lactose, dibasic calcium phosphate, sucrose, corn (maize) starch,

microcrystalline cellulose, povidone polyvinylpyrrolidone and modified

cellulose (for example hydroxypropyl methylcellulose and

hydroxyethylcellulose).

Often, an ingredient is also needed to act as a disintegrant to aid tablet

dispersion once swallowed, releasing the API for absorption. Some binders, such

as starch and cellulose, are also excellent disintegrants.

 ADVANTAGES AND DISADVANTAGES

Tablets are simple and convenient to use. They provide an accurately measured

dosage of the active ingredient in a convenient portable package, and can be

designed to protect unstable medications or disguise unpalatable ingredients.

Colored coatings, embossed markings and printing can be used to aid tablet

recognition. Manufacturing processes and techniques can provide tablets special

properties, for example, sustained release or fast dissolving formulations.

Some drugs may be unsuitable for administration by the oral route. For example,

protein drugs such as insulin may be denatured by stomach acids. Such drugs

cannot be made into tablets. Some drugs may be deactivated by the liver when

they are carried there from the gastrointestinal tract by the hepatic portal

vein (the "first pass effect"), making them unsuitable for oral use. Drugs which

can be taken sublingually are absorbed through the oral mucosae, so that they

bypass the liver and are less susceptible to the first pass effect. The oral

bioavailability of some drugs may be low due to poor absorption from the

gastrointestinal tract. Such drugs may need to be given in very high doses or by

injection. For drugs that need to have rapid onset, or that have severe side

effects, the oral route may not be suitable. For example salbutamol, used to treat

problems in the pulmonary system, can have effects on the heart and circulation

if taken orally; these effects are greatly reduced by inhaling smaller doses direct

to the required site of action. A proportion of the population have difficulties

swallowing tablets either because they just don't like taking them or because their

medical condition makes it difficult for them (dysphagia, vomiting). In such

instances it may be better to consider alternative dosage form or administration

route.[1]

Tablet properties

Tablets can be made in virtually any shape, although requirements of patients

and tableting machines mean that most are round, oval or capsule shaped. More

unusual shapes have been manufactured but patients find these harder to

swallow, and they are more vulnerable to chipping or manufacturing problems.

Tablet diameter and shape are determined by the machine tooling used to

produce them - a die plus an upper and a lower punch are required. This is called

a station of tooling. The thickness is determined by the amount of tablet material

and the position of the punches in relation to each other during compression.

Once this is done, we can measure the corresponding pressure applied during

compression. The shorter the distance between the punches, thickness, the

greater the pressure applied during compression, and sometimes the harder the

tablet. Tablets need to be hard enough that they don't break up in the bottle, yet

friable enough that they disintegrate in the gastric tract.

Tablets need to be strong enough to resist the stresses of packaging, shipping

and handling by the pharmacist and patient. The mechanical strength of tablets is

assessed using a combination of (i) simple failure and erosion tests, and (ii) more

sophisticated engineering tests. The simpler tests are often used for quality

control purposes, whereas the more complex tests are used during the design of

the formulation and manufacturing process in the research and development

phase. Standards for tablet properties are published in the various international

pharmacopeias (USP/NF, EP, JP, etc.). The hardness of tablets is the principle

measure of mechanical strength. Hardness is tested using a tablet hardness

tester. The units for hardness have evolved since the 1930s, but are commonly

measured in kilograms per square centimeter. Models of tester include the

Monsanto (or Stokes) Hardness Tester from 1930, the Pfizer Hardness Tester

from 1950, the Strong Cob Hardness Tester and the Heberlain (or Schleeniger)

Hardness Tester.

Lubricants prevent ingredients from clumping together and from sticking to the

tablet punches or capsule filling machine. Lubricants also ensure that tablet

formation and ejection can occur with low friction between the solid and die wall,

as well as between granules, which helps in uniform filling of the die.

Common minerals like talc or silica, and fats, e.g. vegetable stearin, magnesium

stearate or stearic acid are the most frequently used lubricants in tablets or hard

gelatin capsules.[citation needed]

 MANUFACTURING

Manufacture of the tableting blend

In the tablet pressing process, the main guideline is to ensure that the

appropriate amount of active ingredient is in each tablet. Hence, all the

ingredients should be well-mixed. If a sufficiently homogenous mix of the

components cannot be obtained with simple blending processes, the ingredients

must be granulated prior to compression to assure an even distribution of the

active compound in the final tablet. Two basic techniques are used to granulate

powders for compression into a tablet: wet granulation and dry granulation.

Powders that can be mixed well do not require granulation and can be

compressed into tablets through direct compression.

Wet granulation

Wet granulation is a process of using a liquid binder to lightly agglomerate the

powder mixture. The amount of liquid has to be properly controlled, as over-

wetting will cause the granules to be too hard and under-wetting will cause them

to be too soft and friable. Aqueous solutions have the advantage of being safer to

deal with than solvent-based systems but may not be suitable for drugs which

are degraded by hydrolysis.

Procedure

1. The active ingredient and excipients are weighed and mixed.

2. The wet granulate is prepared by adding the liquid binderadhesive to the

powder blend and mixing thoroughly. Examples of binders/adhesives

include aqueous preparations of cornstarch, natural gums such as acacia,

cellulose derivatives such as methyl cellulose, gelatin, and povidone.

3. Screening the damp mass through a mesh to form pellets or granules.

4. Drying the granulation. A conventional tray-dryer or fluid-bed dryer are

most commonly used.

5. After the granules are dried, they are passed through a screen of smaller

size than the one used for the wet mass to create granules of uniform size.

Low shear wet granulation processes use very simple mixing equipment, and can

take a considerable time to achieve a uniformly mixed state. High shear wet

granulation processes use equipment that mixes the powder and liquid at a very

fast rate, and thus speeds up the manufacturing process. Fluid bed granulation is

a multiple-step wet granulation process performed in the same vessel to pre-

heat, granulate, and dry the powders. It is used because it allows close control of

the granulation process.

Dry granulation

Dry granulation processes create granules by light compaction of the powder

blend under low pressures. The compacts so-formed are broken up gently to

produce granules (agglomerates). This process is often used when the product to

be granulated is sensitive to moisture and heat. Dry granulation can be

conducted on a tablet press using slugging tooling or on a roll press called a

roller compactor. Dry granulation equipment offers a wide range of pressures to

attain proper densification and granule formation. Dry granulation is simpler than

wet granulation, therefore the cost is reduced. However, dry granulation often

produces a higher percentage of fine granules, which can compromise the quality

or create yield problems for the tablet. Dry granulation requires drugs or

excipients with cohesive properties, and a 'dry binder' may need to be added to

the formulation to facilitate the formation of granules.

Granule lubrication

After granulation, a final lubrication step is used to ensure that the tableting blend

does not stick to the equipment during the tableting process. This usually

involves low shear blending of the granules with a powdered lubricant, such

as magnesium stearate or stearic acid.

 MANUFACTURE OF THE TABLETS

Tablets that failed due to capping and lamination compared to a normal tablet

Whatever process is used to make the tableting blend, the process of making a

tablet by powder compaction is very similar. First, the powder is filled into the die

from above. The mass of powder is determined by the position of the lower

punch in the die, the cross-sectional area of the die, and the powder density. At

this stage, adjustments to the tablet weight are normally made by repositioning

the lower punch. After die filling, the upper punch is lowered into the die and the

powder is uniaxially compressed to a porosity of between 5 and 20%. The

compression can take place in one or two stages (main compression, and,

sometimes, pre-compression or tamping) and for commercial production occurs

very fast (50050 ms per tablet). Finally, the upper punch is pulled up and out of

the die (decompression), and the tablet is ejected from the die by lifting the lower

punch until its upper surface is flush with the top face of the die. This process is

repeated for each tablet.

Common problems encountered during tablet manufacturing operations include:

 Fluctuations in tablet weight, usually caused by uneven powder flow into the

die due to poor powder flow properties.

Fluctuations in dosage of the Active Pharmaceutical Ingredient, caused by

uneven distribution of the API in the tableting blend (either due to poor mixing

or separation in process.

Sticking of the powder blend to the tablet tooling, due to inadequate

lubrication, worn or dirty tooling, or a sticky powder formulation

Capping, lamination or chipping. This is caused by air being compressed with

the tablet formulation and then expanding when the punch is released: if this

breaks the tablet apart, it can be due to incorrect machine settings, or due to

incorrect formulation: either because the tablet formulation is too brittle or not

adhesive enough, or because the powder being fed to the tablet press

contains too much air (has too low bulk density).

Capping can also occur due to high moisture content.

Tablet compaction simulator

Tablet formulations are designed and tested using a laboratory machine called a

Tablet Compaction Simulator or Powder Compaction Simulator. This is a

computer controlled device that can measure the punch positions, punch

pressures, friction forces, die wall pressures, and sometimes the tablet internal

temperature during the compaction event. Numerous experiments with small

quantities of different mixtures can be performed to optimise a formulation.

Mathematically corrected punch motions can be programmed to simulate any

type and model of production tablet press. Initial quantities of active

pharmaceutical ingredients are very expensive to produce, and using a

Compaction Simulator reduces the amount of powder required for product

development.
 Tablet presses

The tablet pressing operation

An old Cadmach rotary tablet press

Tablet presses, also called tableting machines, range from small, inexpensive

bench-top models that make one tablet at a time (single-station presses), with
only around a half-ton pressure, to large, computerized, industrial models (multi-

station rotary presses) that can make hundreds of thousands to millions of tablets

an hour with much greater pressure. The tablet press is an essential piece of

machinery for any pharmaceutical and nutraceutical manufacturer. Common

manufacturers of tablet presses include Stokes, Fette Compacting, Korsch,

Kikusui, Manesty, B&D, PTK, IMA and Courtoy. Tablet presses must allow the

operator to adjust the position of the lower and upper punches accurately, so that

the tablet weight, thickness and density can each be controlled. This is achieved

using a series of cams, rollers, and/or tracks that act on the tablet tooling

(punches). Mechanical systems are also incorporated for die filling, and for

ejecting and removing the tablets from the press after compression.

Pharmaceutical tablet presses are required to be easy to clean and quick to

reconfigure with different tooling, because they are usually used to manufacture

many different products. There are 2 main standards of tablet tooling used in

pharmaceutical industry: American standard TSM and European standard EU.

TSM and EU configurations are similar to each other but cannot be

interchanged.[2]

Tablet coating

Many tablets today are coated after being pressed. Although sugar-coating was

popular in the past, the process has many drawbacks. Modern tablet

coatings[3] are polymer and polysaccharide based,

with plasticizers and pigments included. Tablet coatings must be stable and

strong enough to survive the handling of the tablet, must not make tablets stick

together during the coating process, and must follow the fine contours of

embossed characters or logos on tablets. Coatings are necessary for tablets that

have an unpleasant taste, and a smoother finish makes large tablets easier to

swallow. Tablet coatings are also useful to extend the shelf-life of components

that are sensitive to moisture or oxidation. Special coatings (for example with

pearlescent effects) can enhance brand recognition.

If the active ingredient of a tablet is sensitive to acid, or is irritant to the stomach

lining, an enteric coating can be used, which is resistant to stomach acid, and

dissolves in the less acidic area of the intestines. Enteric coatings are also used

for medicines that can be negatively affected by taking a long time to reach

the small intestine, where they are absorbed. Coatings are often chosen to

control the rate of dissolution of the drug in the gastrointestinal tract. Some drugs

will be absorbed better at different points in the digestive system. If the highest

percentage of absorption of a drug takes place in the stomach, a coating that

dissolves quickly and easily in acid will be selected. If the rate of absorption is

best in the large intestine or colon, then a coating that is acid resistant and

dissolves slowly would be used to ensure it reached that point before dispersing.

There are two types of coating machines used in the pharmaceutical industry:

coating pans and automatic coaters.[4] Coating pans are used mostly for sugar
coating of pellets. Automatic coaters are used for all kinds of coatings; they can

be equipped with remote control panel, dehumidifier, dust collectors. The

explosion-proof design is required for alcohol containing coatings.

Pill-splitters

It is sometimes necessary to split tablets into halves or quarters. Tablets are

easier to break accurately if scored, but there are devices called pill-

splitters which cut unscored and scored tablets. Tablets with special coatings (for

example enteric coatings or controlled-release coatings) should not be broken

before use, as this will expose the tablet core to the digestive juices,

circumventing the intended delayed-release effect.

Packaging
Tablets must be packaged before they can be sent out for distribution. The type

of packaging will depend on the formulation of the medicine.

Blister packs are a common form of packaging. They are safe and easy to use

and the user can see the contents without opening the pack. Many

pharmaceutical companies use a standard size of blister pack. This saves the

cost of different tools and changing the production machinery between products.

Sometimes the pack may be perforated so that individual tablets can be

detached. This means that the expiry date and the drug's name must be printed

on each part of the package.

 QUALITY CONTROL

Quality is important in every product or service but it is vital In

medicine as it involves life. Unlike ordinary consumer goods there can be

and there is no 'Second' quality in drugs.

Quality control is a concept, which strives to -produce a perfect

product by series of measures designed to prevent and estimate errors of

different stages of production. As a mater of fact it is built in from the time

of inception of the thought to make a product, to the time, it is finally made

and sent out with an ok quality report. In popular practices the quality of

medicines or pharmaceutical product is assured through quality control. It

is, therefore, essential that quality assurance department must adopt

"Good Laboratory Practice" to ensure reliability and accuracy of results

given out by them.

The assurance of the quality and the reliability of pharmaceuticals,

together with their careful control are out moral obligations arising from the

humanism towards the sick human beings. Consequently, the manufacture

and the control of the drugs are very responsible tasks and they need

substantial knowledge of the science.

 QUALITY CONTROL AND ITS RESPONSIBILITIES

Quality control is the part of good manufacturing practices concerned

with sampling specifications & testing & with the organization,

documentation and release procedures which ensure that the necessary

and relevant tests are actually carried out and that materials are not

released for user nor products for sale or supply until their quality has been

judged to be satisfactory. Quality control is not confined to laboratory

operations but must be involved to laboratory concerning the quality of the

product.

Each holder of the manufacturing authorization should have a quality

control department. The independence of quality control from production is

considered fundamental. The quality control department should be

independent than the other.

The basic requirements for quality control are as follows:

1. Adequate facilities, trained personnel and approved procedure must be

available for sampling inspecting and testing starting materials, packing

materials and intermediate, bulk and finished products and where

appropriate for monitoring environmental conditions for GMP purpose.

 QUALITY SYSTEM

The basic elements of quality and systemic action. The quality

system involves all phase from initial identification to final satisfaction of

requirements and customers expect action.

The first thing that a manufacturer will like to know is what product

should be manufactured survey. The next steps follow as under:

Procedurement of raw materials

Process planning

Production

Inspection & test

Packing

Storage

Sales & Distribution

 KARL FISCHER MOISTURE CONTENT DETECTOR

For the determination of small amounts of water, "Karl Fischer" in

(1935) proposed a reagent, is known of Karl Fischer reagent.

Principle

In this method, the action of sulphur dioxide upon a solution of Iodine

in a mixture of anhydrous pyridine and anhydrous methanol. Water reacts

with this reagent in a two stage process in which one molecule of iodine

disappears for each molecule of water.

The end point of the reaction is conveniently determined

electrometrically using the dead stop end point procedure.

 PREPARATION OF KARL FISCHER REAGENT

Mix in a 750ml combustion flask 400ml of dehydrated methanol & 80g

of dehydrated pyridine. Immerse the flask in ice and bubble dried sulphur

dioxide slowly through the mixture until its weight has increased by 20g.

Add 45g of iodine and shake until it dissolves. Allow the solution to stand

for 24hrs before use.

This solution deteriorates gradually, therefore standardize it within 1

hr before use.

Protect from light while in use. Shore any bulk stock of the reagent in

a suitably sealed, glass-stopped container, fully protected from light and

under refrigeration. A commercially available, stabilized solution of Karl

Fischer reagent may be used.

The reagent and the solution used in determination of water by the

Karl Fischer method must be kept anhydrous and precautions must be

taken throughout to prevent exposure to atmospheric moisture.

APPARATUS

A titration vessel of about 60ml capacity is fitted with two platinum

electrodes about 0.05 sq. cm in area and about 2.5cm apart, a nitrogen

inlet tube, a stopper which accommodates the burette tip and vent tube

protected by a suitable desiccant such as phosphorous pentoxide or silica

gel. The substance being examined is introduced through an intel which

can be closed by a ground stopper. Stripping is done by magnetically. The

air in the entire system should be kept dry during the titration.

The voltage across the electrodes may be obtained from a 1.5volt dry

cell and a variable resistance of about 2000hms. The resistance is adjusted

so that an initial current passes through the electrodes connected in series

to an ammeter. On adding the reagent the needle of the ammeter shows a

deflection but return immediately to its starting position. At the end point of

the titration a slight excess of the reagent produces a deflection which

persists for not less than half a minute.

PROCEDURE

Unless otherwise directed and about 20ml of dehydrated methanol to

the titration vessel and titrate to the electrometric end point with the Karl

Fischer reagent.
 Transfer quickly the prescribed amount of the substance being

examined, accurately weighted, to the titration vessel. Stir for 1 minute &

titrate again to the electrometric end point using Karl Fischer reagent.

CALCULATION

%age of moisture content = V x F x 100

W x 1000

V = Vol. of K.F.R. used with sample.

F = water equivalence factor

W = weight of sample.

PROCEDURE
Standardization of KF Reagent

1) Remove all the liquid from KF apparatus vessel, rinse it with methanol

twice and transfer about 30ml methanol into vessel.

2) Neutralization to end point with KF reagent.

3) Weight accurately about 0.2g of disodium tirtrate transfer it into KF

vessel, wait for about 10-15 seconds. Start addition of KF reagent record

the volume of KF reagent consumed.

Calculate the KF factor by the formula

F is mg/ml = F W x 1000 x 15.66

V x 100

W = weight of disodium tartrate in g

V= Volume of KF reagent consumed in ml.

Note:

Disodium tartrate can be replaced with water for standardization with

the change in step no. 3 ice weight accurately about 30-6 mg of water,

transfer it into KF vessel, start addition of KF reagent record the vol. of KF

reagent consumed and calculate the factor by formula.

F mg/ml = W x 1000

W = weight of water in g

V= vol. of KF reagent in ml.

Experiment

Weigh accurately about 1-2g. Sample an transfer it into KF vessel,

wait for about 10 second and start addition of KF reagent with continuous

starting, record the vol. of KF reagent.

Method

Add about 20m I of a dehydrated MeOH to the titration vessel and

titrate to the electrometric end point and the Karl Fischer reagent. Transfer

quickly the prescribed amount of the substance being examined accurately

weighted, to the titration vessel. Stir for min and titrate again to the

electrometric end point using Karl Fischer reagent.

The water content of the sample, in mg, is given by the expression S

X F, in which S is the volume in mi, of the Karl Fischer reagent and to titrate

the sample. F is the water equivalent factor.

 BULK DENSITY TEST APPARATUS

The bulk density of a solid is often very difficult to measure since the

slightest disturbance of the bed may result in a new bulk density. Moreover,

it is clear that the bulking properties of a powder are dependent on the

"history" of the powder (e.g. how it was handled), and that it can be packed

to have a range of bulk densities.

Because the inter particulate interactions that influence the bulking

properties of a powder are also the interactions that interfere with Powder

flow, a comparison of the bulk and tapped densities can give a measure of

the relative importance of these interactions in a given powder. Such a

comparison is often used as an index of the ability of the powder to flow.

The bulk density often is the bulk density of the powder "as poured"

or as passively filled into a measuring vessel. The 'tapped density is a

limiting density attained after tapping down usually in a device that lifts an

drops a volumetric measuring cylinder containing the powder a fixed

distance.
 BULK DENSITY

Bulk density is determined by measuring the volume of a known

mass of powder sample that has been passed through a screen into a

graduated cylinder.

A sufficient quantity of the test material is passed through a 1.0 mm

screen to break the agglomerates that may have been formed during

storage into a dry graduated cylinder. Say, M, g of sample is added in the

cylinder. The powder is carefully leveled without compacting. The unsettled

apparent volume is read, say, it is V0.

The bulk density is determined as

(M)/ V0

TAPPED DENSITY

Tapped density is achieved by mechanically tapping a measuring

cylinder containing a Powder sample. After observing the initial volume, the

cylinder is mechanically tapped, and volume readings are taken until little

further volume change is observed. The mechanical tapping is achieved

by raising the cylinder and allowing it to drop under its own weight a

specified distance. Device being used her rotate the cylinder during tapping
and hence minimizes any possible separation of the mass during tapping

down.

A sufficient known amount say, 'M' g of sample is passed to a dry

graduated cylinder. The cylinder is mechanically tapped by raising the

raising the cylinder and allowing it to drop under its own weight using a

suitable mechanical tapped density tester that provides a fixed drop at a

nominal rate. The tapped volume is measured, say , VA

The tapped density is calculated as

M/VA

The compressibility Index and Hausner Ratio are measures of the

property of a powder to be compressed. As such , they are measures of the

relative importance of inter particulate interactions. Ina free flowing powder,

such interactions, and a greater difference between the bulk and tapped

densities is observed. These differences are reflected in the

Compressibility Index and Hausner Ratio.

Compressibility Index = 100 (V0 - VA)

V0

Hausner Ratio = (V0 / VA)

 Determination of the particle size is another important test used for

the quality assessment of the powders specially, the finished products. For

measuring the PSD, Hosokawa Alpine Aktiengellschaft instrument of 200

LS-N series, attached with a NILFISK vaccum pump is being used here.

PSD of the compact as well as the powder material is checked through this

instrument. PSD of a material as per the customer specific order is also

determined using this.

PARTICLE SIZE DISTRIBUTION ESTIMATION BY ANALYTICAL

SIEVING

Sieving is one of the oldest methods of classifying powders by

particles size distribution. Sieving is most suitable where the majority of the

particles are larger than about 75 m , although it can be used for some

powders having smaller particle sizes where the method can be validated.

In pharmaceuticals terms, sieving is usually the method of choice for

classification of the coarser grades of single powders.

It is particularly attractive method in that powders are classified only

on the basis of particle size, and in most cases the analysis can be carried

out in the dry state. Among the limitations of the sieving method are the
need for an appreciable amount of sample (normally at least 25g) and

difficulty in sieving oily or other cohesive powders that tend to clog the

sieve openings.

The method is essentially a two-dimensional estimate of size

because passage through the sieve aperture is frequently more

dependent on maximum width and thickness than on the length. Test

sieves are made form stainless steel or, less preferably from brass or other

suitable non reactive wire.

This method is intended for estimation of the total particle size

distribution of a single material it is not intended for determination of

proportion of particle passing or retained on one or two sieves.

PRINCIPLES OF ANALYTICAL SIEVING

Analytical test sieves are constructed from a woven -wire mesh,

which is of simple weave that is assumed to give nearly square apertures,

and is sealed into the base of an open cylindrical container.

The basis analytical method involves stacking the sieves on top of

one another in ascending degrees of coarseness and then placing the test

powder on the top sieve. Sieves are selected to cover the entire range of
particle sizes present in the test specimen. The nest of sieves is completed

by a well-fitting collecting pan at its base and lid at its top.

The nest of sieve is subjected to a standardized period of agitation,

and then the weight of material retained on each sieve is accurately

determined. The test gives the weight percentage of powder in each sieve

size range.

The sieving process for estimating the particle size distribution of a

single pharmaceuticals powder is generally intended to use where at least

80% of the particles are larger than 75 m. The size parameter involved in

determining particle size distribution by analytical sieving is the length of

the side of minimum square aperture through which the particle will pass.
 SAMPLING OF RAW MATERIAL

Method of sampling: -

1) Took a clean dried bottle or a sampling bag for taking sample.

2) Took a sampling tool from sampling tool rack.

3) See the sampling plan for choosing the containers to be sampled on the

basic of total no. of containers per patch.

Acc. To the formula n+1

Where n= total no. of containers

4) Then go to the RM and PM ware house and check the following

condition.

A. SFG:-

1) Quantity.

2) No. Of Containers.

3) Pharmacopical status (IP/BP/USP/OTHERS/NONE)

4) Storage Temperature.

5) Humidity.
 6) Conditions of containers/ packs/ consignment.

B) Raw Material:

1) Ut labels affixed on containers.

2) Containers sealed.

3) Containers stored in appropriate area.

4) Tanker no.

5) No. of compartments.

6) Compartment sealed.

7) Compartment sealed after sampling.

8) Vendor name.

9) Vendor bath no.

10) Approved vendor.

11) Date of mfg.

12) Date of expiry.

13) Suppliers certificate available.

C) Physical inspection :

1) General Condition.

2) Lumps.

3) Abnormal odour.

4) Foreign matter. 5) Heterogeneity.

6) Others.

After sampling analysis of raw material can be done in the Q.C.

lab.
 REFERENCES

Books

1. Aneja K.R. A text book of basic and applied microbiology 2nd edition

(2009), New Age International Publisher.

2. Dubey R.C. and Maheshwari D.K. A text book of microbiology 2nd

edition (2009).

3. Singh B.D. (Biotechnology Expending Horizons), 3rd edition (2010).

Websites :

www.google.co.in
 CONTENTS

ACKNOWLEDGEMENT

PREFACE

TABLET

TYPES OF TABLETS

TABLET FORMULATION

ADVANTAGES AND DISADVANTAGES

TABLET PROPERTIES

MANUFACTURING

MANUFACTURING OF TABLET

TABLET PRESSES

QUALITY CONTROL

QUALITY CONTROL AND ITS RESPONSIBILITIES

QUALITY SYSTEM

K.F. MOISTURE CONTENT DETECTOR

BULK DENISTY TEST APPARATUS

SAMPLING OF RAW MATERIAL

REFERENCES