Industrial trip to,

Medicamen Biotech Ltd.

(Bhiwadi plant)

-Submited by,
Arpita Verma
7th semester
05519601111
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Contents
About Medicamen Biotech ltd.
Non- Beta lactam block: Tablets, capsules,
liquid oral preprations, ORS.
Beta lactam block
Quality assurance & Quality control
Conclussion

Medicamen Biotech Limited

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Medicamen Biotech Limited is a widely held, Globaly Recognized public limited

company engaged in manufacturing and marketing of pharmaceutical formulations in
overseas and domestic markets. Medicamen Biotech Limited is committed to produce
and provide quality medicines at competitive price for domestic as well as international
markets thereby being socially responsible and rendering services services to the
medical Fraternity since 1993.

BHIWADI PLANT
Medicamen Biotech Limited , Bhiwadi is spread over an area of 2,10,000 sq. ft. having
ultra modern production facilities incorporating latest state of the art technology with a
combination of technically qualified personnel and hardworking workforce. It makes us
comparable to any Multinational Company and eligible for any international inspection .
PRODUCTION CAPACITY
NON BETA-LACTUM
1. Tablets ____________________ 8 Million Per Day.
2. Capsules ___________________1 Million Per Day.
3. Oral Liquid _________________4600 Litres Per Day.
4. Dry Syrup __________________6000 K.G. Per Day.
5. ORS ________________________1,80,000 Sachets Per Day.
BETA-LACTUM
1. Tablets ____________________1 Million Per Day.
2. Capsules ___________________1 Million Per Day.
3. Liquid _____________________1300 Litres Per Day.
4. Dry Syrup __________________50,000 Bottles Per Day.

Non-Beta Lactam
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Tablet
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.

Classification
The compressed tablet is the most popular dosage form in use today.

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.
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.
Some tablets are in the shape of capsules, and are called "caplets". Other
products are manufactured in the form of tablets which are designed to dissolve
or disintegrate; e.g. cleaning and deodorizing products.
Medicinal tablets and capsules are often called "pills", though originally, "pill"
referred specifically to a soft mass rolled into a ball shape, rather than a
compressed powde

Tableting Formulations
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 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 can 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.

Compounding
Diluents:
Diluents are substances to increase bulk and convert in the compressible form, when
drug material is potent or inadequate to provide a suitable shape and size to tablet.
A tablet diluent must be compatible, inert, economic, easily available and
organoleptically acceptable, should not affect the bioavailability of a drug adversely.
Examples of tablet diluents include dibasic calcium phosphate, calcium sulphate, lactose,
lactose anhydrous, lactose spray dried, mannitol, sorbitol, sucrose, dextrose etc.
Examples of directly compressible diluents include Sta-Rx-1500, Emdex (contains
dextrose 90 to 92% a maltose 3 to 5%), Celutab (dextrose & maltose), Avicel
(Microcrystalline cellulose), Di-C (Dicalcium phosphate dihydrate), Cab-O-Sil (Colloidal
silica).

Binders and Adhesive:

These materials are used in dry or liquid form to reduce the amorphous nature of
substance and convert into compressible form (wet granulation).
Example include acacia, tragacanth, gelatin, alginates, methylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, PVP, Starch, sorbiol, ethylcellulose,
pregelatinized starch, glucose, iris moss, ghatti gum, arabogalactan, waxes, etc.

Lubricants:
Lubricants reduce inter-particular friction. It improves the ejection of tablet from die
wall and reduces the sticking problems and smooth tablets are produced. Examples
include Talc, magnesium stearate, calcium stearate, stearic acid, polyethyleneglycols,
starch derivative
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 Glidants:
Glidants act as a flow promoter and reduce the friction between particles. It improves the
flow properties of granules or powder through hopper to die. It is not deformed
compression pressure of the tablet machine. Examples include talc, starch, magnesium
stearate, calcium stearate, boric acid, sugar, lycopodium and sodium chloride.

Disintegrants:
Most of the tablets contain disintegrating agent. Disintegrating agents facilitate the
disintegration of the tablet in small particles in the gastrointestinal tract. Breaking of
tablet' based on the swellability, adsorption of water or chemical reaction.
Examples include soluble starch, pre-gelatinized starch (PGS), veegum HV, bentonite,
microcrystalline cellulose, sodium carboxy methylcellulose, PVP, guar gum, Isapgul,
primogel, explotab, aerosil, natural spon citrus pulp, Alginic acid and alginates, Ion
exchange resin, magnesium aluminium silicat modified corn starch, sodium dodecyl
sulphate, sodium starch glycollate, etc.

Antiadhesives or Antisticking agents:

These materials are used to reduce the adhesion of the tablet surface to dies and punches
during the compression of tablets. The pressure of the machine deforms these materials.
It reduces sticking, picking and chipping problems. Examples include paraffin, stearic
acid, cocoa butter, soaps, starch derivatives.

Sweeteners:
Chewable tablets have sweetening agents because such tablets remain in the mouth and
are not swallowed. Examples include saccharin sodium, aspartame, sugar, etc.

Advantages
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.

Manufacturing

Dispensing (weighing and measuring)

Sizing
Powder blending
Granulation
Drying
Tablet compression
Auxillary equipments
Packaging

Manufacture of the tableting blend : Granulation

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 overwetting 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
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.
Screening the damp mass through a mesh to form pellets or granules.
Drying the granulation. A conventional tray-dryer or fluid-bed dryer are most
commonly used.
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.

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 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.

 Typical Unit Operation Involved In Wet Granulation, Dry

Granulation And Direct Compression
WET GRANULATION

DRY GRANULATION

DIRECT COMPRESSION

1.
Milling
and mixing of drugs and excipients

1.
Milling
and mixing of drugs and excipients

1. Milling and mixing of drugs and

excipients

2.
Preparation
of binder solution

2.
Compression
into slugs or roll compaction

2.
Compression of tablet

3.
Wet
massing by addition of binder solution
or granulating solvent

3.
Milling
and screening of slugs and compacted
powder

4.
Screening
of wet mass

4.
Mixing
with lubricant and disintegrant

5.
Drying
of the wet granules

5.
Compression
of tablet

6.
Screening
of dry granules
7.
Blending
with lubricant and disintegrant to
produce running powder
8.
Compression
of tablet

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 staerate or stearic acid.

Drying
It is important to keep the residual moisture low enough to prevent product
deterioration and ensure free flowing properties.

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 The commonly used dryer includes Fluidized bed dryer, tray dryer etc.

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Fluidised bed dryers are used

almost in all chemical,
pharmeceutical,food, duestuff and
other process industries to dry
materials by fluidisation with hot
and/ or dehumified air, which
creates a turbulence in the wet
product while flowing through it.

Tray Drier

In tray dryers, the food is spread out, generally quite thinly, on trays in which the drying takes
place. Heating may be by an air current sweeping across the trays,
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by conduction from heated trays or heated shelves on which the trays lie, or by radiation from
heated surfaces.

Tablet compression
After the preparation of granules (in case of wet granulation) or sized slugs (in case of dry
granulation) or mixing of ingredients (in case of direct compression), they are compressed to
get final product. The compression is done either by single punch machine (stamping press)
or by multi station machine /rotary press.
The tablet press is a high-speed mechanical device. It 'squeezes' the ingredients into the
required tablet shape with extreme precision.
Each tablet is made by pressing the granules inside a die, made up of hardened steel.
The powder is compressed in the centre of the die by two hardened steel punches that fit into
the top and bottom of the die.
The punches and dies are fixed to a turret that spins round.
As it spins, the punches are driven together by two fixed cams - an upper cam
and lower cam. The top of the upper punch (the punch head) sits on the upper
cam edge .The bottom of the lower punch sits on the lower cam edge.
The shapes of the two cams determine the sequence of movements of the two punches. This
sequence is repeated over and over because the turret is spinning round.

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ROTARY TABLET PRESS

Common stages occurring during compression :

Stage 1: Top punch is withdrawn from the die by the upper cam.
Bottom punch is low in the die so powder falls in through the hole and fills the
die.
Stage 2: Bottom punch moves up to adjust the powder weight-it raises and expels
some powder.
Stage 3: Top punch is driven into the die by upper cam.
Bottom punch is raised by lower cam.
Both punch heads pass between heavy rollers to compress the powder.
Stage 4: Top punch is withdraw by the upper cam.
Lower punch is pushed up and expels the tablet.
Tablet is removed from the die surface by surface plate.
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 Stage 5: Return to stage 1.

Tablet coating
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.

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coating pan

There are two types of

coating machines used in
the pharmaceutical
industry: coating pans
and automatic
coaters. 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 explosionproof design is required
for alcohol containing
coatings.
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.
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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.

Packaging
The type of packaging will depend on the formulation of the medicine.
'Blister packs' are a common form of packaging used for a wide variety of products. They are
safe and easy to use and they allow the consumer to see the contents without opening the
pack. Many pharmaceutical companies use a standard size of blister pack.
Sometimes the pack may be perforated so that individual tablets
can be detached. This means that the expiry date and the name of the product have to be
printed on each part of the package.

Packing machine

CAPSULES
In the manufacture of pharmaceuticals, encapsulation refers to a range of dosage forms
techniques used to enclose medicinesin a relatively stable shell known as a capsule. The two
main types of capsules are:

Hard-shelled capsules, which are typically made using gelatin and contain dry, powdered
ingredients or miniature pellets made by e.g. processes of extrusion or spheronisation.
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These are made in two halves: a lower-diameter "body" that is filled and then sealed using a
higher-diameter "cape".

Soft-shelled capsules, primarily used for oils and for active ingredients that are dissolved
or suspended in oil.

Both of these classes of capsules are made from aqueous solutions of gelling agents like:

Animal protein, mainly gelatin;

Plant polysaccharides or their derivatives like carrageenans and modified forms
of starch and cellulose.

Soft gelatin capsules

Softgels can be an effective delivery system for oral drugs, especially poorly
soluble drugs. This is because the fill can contain liquid ingredients that help
increase solubility or permeability of the drug across the membranes in the body.
Liquid ingredients are difficult to include in any other solid dosage form such as a
tablet. Softgels are also highly suited to potent drugs (for example, where the dose is
<100 g), where the highly reproducible filling process helps ensure each softgel has
the same drug content, and because the operators are not exposed to any drug dust
during the manufacturing process.

Hard Gelatin Capsules

The hard gelatin capsule consists of a base or body and a

shorter cap, which fits firmly over the base of the capsule.
For human use, eight sizes of capsules are available. The capacity of each size
varies according to the combination of drugs and their apparent densities.
Capsules are available as clear gelatin capsules or in a variety of colors. The
pharmacist can use the different colored capsules to distinguish two capsule
formulations for the same patient, or to encapsulate unattractive ingredients. The
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pharmacist can add a dye to the powder before filling a clear capsule to impart a
color for identification or esthetics.
Some types of hard gelatin capsules have a locking cap, which makes it more
difficult to reopen the capsule.

Other ingredients can be added to the gelling agent solution like plasticizers such
as glycerin or sorbitol to decrease the capsule's hardness, coloring agents, preservatives,
disintegrants, lubricants and surface treatment.

Manufacturing process
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The process of encapsulation of hard gelatin capsules can be done on manual, semiautomatic and automatic machines. Softgels are filled at the same time as they are
produced and sealed on the rotary die of a fully automatic machine.

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Capsule Filling Machine

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Liquid Oral Dosage Form

Liquid preparations for oral use are usually solutions, emulsions or suspensions
containing one or more active ingredients in a suitable vehicle; they may in some cases
consist simply of a liquid active ingredient used as such. Liquid preparations for oral use
are either supplied in the finished form or, with the exception of Oral emulsions, may
also be prepared just before issue for use by dissolving or dispersing granules or powder
in the vehicle stated on the label.

Liquid preparations for oral use may be supplied as multidose or as single-dose

preparations. Each dose from a multidose container is administered by means of a device
suitable for measuring the prescribed volume. The device is usually a spoon or a cup for
volumes of 5 mL or multiples thereof, or an oral syringe for other volumes or, for Oral
drops, a suitable dropper

The vehicle for any liquid preparation for oral use is chosen having regard to the nature
of the active ingredient(s) and to provide organoleptic characteristics appropriate to the
intended use of the preparation. Liquid preparations for oral use may contain suitable
antimicrobial preservatives, antioxidants and other excipients such as dispersing,
suspending, thickening, emulsifying, buffering, wetting, solubilizing, stabilizing,
flavouring and sweetening agents and authorized colouring matter. Liquid preparations
for oral use may be supplied as multidose or as single-dose preparations.

Oral solutions containing one or more active ingredients dissolved in a vehicle

containing a high proportion of sucrose or a suitable polyhydric alcohol or alcohols and
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which may contain ethanol have traditionally been called elixirs. Viscous oral solutions
containing one or more active ingredients dissolved in a vehicle containing a high
proportion of sucrose, other sugars or a suitable polyhydric alcohol or alcohols and
which are intended for use in the treatment or relief of cough have traditionally been
called linctuses. They are intended to be sipped and swallowed slowly without the
addition of water.

The industry provides regulatory, analytical and supply chain services to

support all projects . The industry has clear technical transfer procedures. The
company supplies product to over 30 countries worldwide.

Manufacture

The manufacturing process for liquid preparations for oral use should meet the
requirements of Good Manufacturing Practice (GMP).

The following information is intended to provide broad guidelines concerning the critical
steps to be followed during production of liquid preparations for oral use.

In the manufacture of liquid preparations for oral use, measures are taken to:

ensure that all ingredients are of appropriate quality

minimize the risk of microbial contamination (see recommendations in
chapter MICROBIOLOGICAL QUALITY OF NON-STERILE PRODUCTS: RECOMMENDED
ACCEPTANCE CRITERIA FOR PHARMACEUTICAL PREPARATIONS of the supplementary
information section.);
minimize the risk of cross-contamination
During the development of a preparation, the formulation for which contains one or more
antimicrobial preservatives, the effectiveness of the chosen preservative system shall be
demonstrated to the satisfaction of the relevant regulatory authority.

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Appropriate measures should also be taken to optimize the stability of the active ingredient(s) in
liquid formulations including those prepared from powder or granules. Additional measures
should be taken so that, when stored under the conditions stated on the label, oral solutions are
not subject to precipitation and oral suspensions are not subject to fast sedimentation, lump
formation or caking.
During development of a single-dose liquid preparation for oral use it shall be demonstrated
that the nominal content can be withdrawn from the container.
In the production of liquid preparations for oral use containing dispersed particles, measures
are taken to ensure a suitable and controlled particle size and, where appropriate, crystal
structure (polymorphic and/or solvated forms) with regard to the intended use.
Throughout manufacturing, certain procedures should be validated and monitored by carrying
out appropriate in-process controls. These should be designed to guarantee the effectiveness of
each stage of production. In-process controls during the manufacture of oral liquids should
include pH and fill volume. The validation of the manufacturing process and the in-process
controls are documented.

Uniformity of mass
Liquid preparations for oral use that are presented as single-dose preparations comply
with the following test. Weigh individually the contents of 20 containers, emptied as
completely as possible, and determine the average mass. Not more than 2 of the
individual masses deviate by more than 10% from the average mass and none deviates by
more than 20%.

Uniformity of mass of doses delivered by the measuring device

The measuring device provided with a multidose liquid preparation for oral use complies
with the following test. Weigh individually 20 doses taken at random from one or more
multidose containers with the measuring device provided and determine the individual
and average masses. Not more than two of the individual masses deviate by more than
10% from the average mass and none deviates by more than 20%.

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Containers
The containers should be made of material that will not adversely affect the quality of the
preparation by, for example, leaching or sorption. Liquid preparations for oral use that
contain light-sensitive active ingredients are supplied in containers that are lightresistant.

Except where indicated in the individual monograph, containers should be made from material
that is sufficiently transparent to permit the visual inspection of the contents.
If the preparation contains volatile ingredients, the liquid preparation for oral use should be
kept in a tightly closed container.

Labelling
Every pharmaceutical preparation must comply with the labelling requirements
established under Good Manufacturing Practice.

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The label should include:

(1) the name of the pharmaceutical product;
(2) the name(s) of the active ingredients; INNs should be used wherever possible;
(3) the amount of active ingredient in a suitable dose-volume;
(4) the name and concentration of any antimicrobial preservative and the name of any other
excipient;
(5) the batch (lot) number assigned by the manufacturer;
(6) the expiry date and, when required, the date of manufacture;
(7) any special storage conditions or handling precautions that may be necessary;
(8) directions for use, warnings, and precautions that may be necessary;
(9) the name and address of the manufacturer or the person responsible for placing the product
on the market.
If the Liquid preparation for oral use is supplied as granules or powder to be constituted just
before issue for use, the label should include:
(1) that the contents of the container are granules or powder for the preparation of an oral
liquid;
(2) the strength as the amount of the active ingredient in a suitable dose-volume of the
constituted preparation;
(3) the directions for preparing the oral liquid including the nature and quantity of liquid to be
used;
(4) the storage conditions and shelf-life of the constituted preparation.

Requirements for specific types of liquid

preparations for oral use
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 Oral solutions
Definition
Oral solutions are clear Liquid preparations for oral use containing one or more active
ingredients dissolved in a suitable vehicle.
Visual inspection
Inspect the solution. It should be clear and free from any precipitate. A change in colour
or cloudiness of solutions may indicate chemical degradation or microbial
contamination.

Oral suspensions
Oral suspensions are Liquid preparations for oral use containing one or more active
ingredients suspended in a suitable vehicle. For oral suspensions containing more than
one active ingredient, some of the active ingredients may be in solution.
Oral suspensions may show a sediment which is readily dispersed on shaking to give a uniform
suspension which remains sufficiently stable to enable the correct dose to be delivered.
Visual inspection
Inspect the suspension. Evidence of physical instability is demonstrated by the formation
of flocculants or sediments that do not readily disperse on gentle shaking. A change in
colour may indicate chemical degradation or microbial contamination.

Uniformity of content. For oral suspensions that are presented as single-dose

preparations and that contain less than 5 mg of active ingredient per dose or in which the
active ingredient is less than 5% of the total weight per dose, carry out the following test.
Shake and empty each container as completely as possible and carry out the test as
described under 5.1 Uniformity of content for single-dose preparations. In such cases,
the test for Uniformity of mass prescribed above is not required.

Labelling
The label on the container should include a direction that the bottle should be shaken
before use.

Oral emulsions
Definition
Oral emulsions are Liquid preparations for oral use containing one or more active ingredients.
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They are stabilized oil-in-water dispersions, either or both phases of which may contain
dissolved solids. Solids may also be suspended in Oral emulsions.
Oral emulsions may show evidence of phase separation but are readily redispersed on shaking.
Visual inspection
Inspect the emulsion. Evidence of physical instability is demonstrated by phase separation that
is not readily reversed on gentle shaking. A change in colour of emulsions may indicate chemical
degradation or microbial contamination.
Containers
When issued for use, Oral emulsions should be supplied in wide-mouthed bottles.

Oral drops

Definition
Oral drops are Liquid preparations for oral use that are intended to be administered in small
volumes with the aid of a suitable measuring device. They may be solutions, suspensions or
emulsions.
Visual inspection
Inspect the drops. Drops that are solutions should be clear and free from any precipitate.
Evidence of physical instability of drops that are suspensions is demonstrated by the formation
of flocculants or sediments that do not readily disperse on gentle shaking. Evidence of physical
instability of drops that are emulsions is demonstrated by phase separation that is not readily
reversed on gentle shaking. A change in colour (or cloudiness of solutions) may indicate
chemical degradation or microbial contamination of the drops.
Dose and uniformity of dose of oral drops
Into a suitable, graduated cylinder, introduce by means of the dropping device the number of
drops usually prescribed for one dose or introduce by means of the measuring device the usually
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prescribed quantity. The dropping speed does not exceed 2 drops per second. Weigh the liquid,
repeat the addition, weigh again and carry on repeating the addition and weighing until a total
of 10 masses are obtained. No single mass deviates by more than 10% from the average mass.
The total of 10 masses does not differ by more than 15% from the nominal mass of 10 doses. If
appropriate, measure the total volume of 10 doses. The volume does not differ by more than 15%
from the nominal volume of 10 doses.
Containers
Oral drops are normally supplied in suitable multidose containers that allow successive drops of
the preparation to be administered.

Powders for oral solutions, oral suspensions or oral drops

Presentations of powder (usually single-dose presentations, for example, a small sachet) that
are intended to be issued to the patient as a powder, to be taken in or with water or another
suitable liquid, are outside the scope of this general monograph. Such preparations are
controlled by the monograph for Oral powders.
Definition
Powders for oral solutions, suspensions or drops are multidose preparations consisting of solid,
loose, dry particles of varying degrees of fineness. They contain one or more active ingredients,
with or without excipients and, if necessary, authorized colouring matter and flavouring
substances. They may contain antimicrobial preservatives and other excipients in particular to
facilitate dispersion or dissolution and to prevent caking.
After dissolution or suspension in the prescribed liquid, they comply with the requirements for
Oral solutions, Oral suspensions or Oral drops, as appropriate.
Manufacture
In the manufacture of powders for oral solutions, suspensions or drops, the components of the
powder mixture are passed through a sieve to remove lumps and particle aggregates. The
weighed masses of the sieved components, preferably of a narrow particle size distribution, are
then transferred to a suitable mixer. The greatest risk of segregation of the powder mixture
usually occurs when emptying the mixer container and when the powder mixture is dosed into
the containers. Ensuring the suitability of the mixing equipment and the dosing devices is,
therefore, critical.
Visual inspection
Inspect the powder. Evidence of physical instability is demonstrated by noticeable changes in
physical appearance, including texture (for example, clumping). A change in colour may indicate
chemical degradation or microbial contamination.

Granules for oral solutions or suspensions

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Presentations of granules that are intended to be issued to the patient as granules to be

swallowed as such, to be chewed, or to be taken in or with water or another suitable
liquid, are outside the scope of this general monograph.
Definition
Granules for oral solutions or suspensions are multidose preparations consisting of
solid, dry aggregates of powder particles sufficiently resistant to withstand handling.
They contain one or more active ingredients with or without excipients and, if necessary,
authorized colouring matter and flavouring substances. They may contain antimicrobial
preservatives and other excipients in particular to facilitate dispersion or dissolution
and to prevent caking.
After dissolution or suspension in the prescribed liquid, they comply with the
requirements for Oral solutions or Oral suspensions, as appropriate.

Oral rehydration solutions(ORS)

Oral rehydration solutions (ORS) are used to treat dehydration caused by

diarrhea, a common illness in travellers. Unlike other fluids, the ratio of the ingredients
in an ORS matches what the body needs to recover from a diarrheal illness.
An ORS contains three ingredients:
1. Clean water that has been boiled or disinfected or from a commercially sealed
bottle.
2. Electrolytes (also called salts), which are chemicals that your body needs to
function properly.
3. Carbohydrates, usually in the form of sugar.

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Oral rehydration therapy (ORT) is a type of fluid replacement used as a treatment

for dehydration. It involves drinking water mixed with sugar and salt, while continuing
to eat. When dehydration is severe, the therapy also includes supplemental zinc.

Medical uses
Oral rehydration therapy is a treatment for the symptoms of dehydration. ORT is less
invasive than the other strategies for fluid replacement, specifically intravenous (IV)
fluid replacement. Mild to moderate dehydration in children seen in an emergency
department is best treated with ORT.
ORT in combination with anti-nausea drugs is indicated for vomiting patients as a
strategy to be able to take fluid orally. In an emergency department setting, vomiting,
dehydrated patients take these drugs as soon as possible to enable taking fluid by mouth
sooner.
Persons taking ORT should eat within 6 hours and return to their full diet within 2448
hours.

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Beta lactam Antibiotics

The industrial application of beta lactam antibiotics by fermentation is one of the
outstanding eg of biotechnology.
-Lactam antibiotics (beta-lactam antibiotics) are a broad class of antibiotics,
consisting of all antibiotic agents that contains a -lactam ring in their molecular
structures. This includes penicillin derivatives
(penams), cephalosporins (cephems), monobactams, and carbapenems.

Most -lactam antibiotics work by inhibiting cell wall biosynthesis in the bacterial
organism and are the most widely used group of antibiotics. Up until 2003, when
measured by sales, more than half of all commercially available antibiotics in use were
-lactam compounds.

Bacteria often develop resistance to -lactam antibiotics by synthesizing a -lactamase,

an enzyme that attacks the -lactam ring. To overcome this resistance, -lactam
antibiotics are often given with -lactamase inhibitors such as clavulanic acid.

Liophilisation & Vial solutions : The industry develop, manufacture and pack
injectable cytotoxics vials( lyophilized or solutions) at sit, which has gained FDA-pre
approval recently. It performs formulations and manufacturind of clinical batches in its
beta lactam antibiotics manufacturing services. It manufactures cephalosphorins and
penicillins in solid or liquid forms

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Quality

Quality Assurance: Products are designed and developed in a way that takes account
of the requirements & implementation of current Good Manufacturing Practices (cGMP) and
current Good Laboratory Practices (cGLP). Our Production and all other operations are clearly
specified in a written form and Standard Operating Procedures (SOPs) are adopted. All
necessary controls on starting materials including vendor audit, intermediate products, and bulk
products and other in-process controls, calibrations, and validations are carried out regularly.

Quality Control: We ensure the quality of starting and packaging materials by following
Specifications & Standard Test Procedures. Our Quality control deptt. is responsible for all
sampling & analysis work related to raw material, in -process and finished goods validation
samples & stability samples and aim at carrying out all requirements of current Good
Laboratory Practices (cGLPs). We ensure that the incoming, in-process and final inspection is
done as per documented procedures.

Quality control test of Tablets:

Disintegration:
An orally administered drug must disintegrate to attain good absorption of its active
substance. The first step toward dissolution is usually the break-up of the tablet; a
process described as disintegration. The disintegration test results in a time necessary to
disintegrate a group of tablets into small particles under standard conditions.

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The disintegration test is a valuable tool in quality control environments. The test is
used for batch release and trending of lot-to-lot variations during manufacturing of
tablets. However, it is not a bioavailability indicator.

Friabililty Hardness:
Tablets must be able to withstand mechanical stresses during their
manufacturing, distribution and handling by the end-user. Does your tablet
remain intact during coating, packaging and printing processes? Is your
tablet broken when the patient accidently drops it onto the floor? Both
friability and hardness measure the mechanical integrity of tablets.
Friability is a measure of the resistance of the tablets to shipping and
abrasion by tumbling them in a rotating drum. After tumbling, the integrity
of the tablets and the weight loss are evaluated. Anabiotec has a Sotax F1
friability tester. With this equipment it is possible to measure in two
modes: a specific time interval or a specified number of rotations.
Tablet hardness testing is also called tablet breaking force testing. For
this test the tablets are placed between two plates. One of the plates moves
in order to damage the tablet.
The breaking force is the force required to break or damage the tablets in a
specific plane. Tablet breaking force measurement is frequently used as an
alternative to compression force measurement. Models of tester include the
Monsanto (or Stokes) Hardness Tester from 1930, the Pfizer Hardness
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Tester from 1950, the Strong Cob Hardness Tester and the Heberlain (or
Schleeniger) Hardness Tester .

This is an essential quality control parameter since compression influences

many tablet properties including disintegration, dissolution and friability.
We have a Sotax HT1 hardness tester that can perform your hardness
measurements in two modes: constant plate movement or constant loading
rate. This equipment is also capable of measuring tablet weight, thickness,
width and diameter.

Tablet Friability Test Apparatus

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Pfizer hardness tester

All equipments for disintegration, friability and hardness testing
are validated according GMP requirements.

Quality control test of Capsules:

Quality control should be carried out during all stages of manufacturing
operation which is the primary requirement of good manufacturing
practices.
Weight variation
For hard capsules: Accurately weigh 10 capsules. By suitable
means the contents of each capsule should be removed. The weights
of emptied shells should be recorded individually. The difference of
both the weights will yield the net weight of the contents. Then
calculate acceptance value.
For soft capsules: pre weigh 10 capsules. Cut the capsules by suitable
means (either scissors or any open blade) remove the contents by washing
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with a suitable solvent and let the solvent evaporate by placing them at
room temperature for about 30 mins. Weigh the individual shells. Calculate
the acceptance value.
Content uniformity:
Hard capsules containing 25 mg or more of the drug contents should
meet content uniformity requirements.
Assay 10 capsules individually and calculate the acceptance value.
The requirement is met if the acceptance value of 10 capsules is less than or
equal to 15%. If acceptance value is greater than 15% or is about 25 % then,
test the next 20 units and calculate the acceptance value. The 30 capsules if
less than or equal to 15% and no individual unit is 1-25*0.01 nor more than
1+25*0.01.
Calculation of acceptance value:
(Reference value-mean of individual contents ) + acceptability constant *
sample standard deviation
Disintegration:
The disintegration of capsules is different from those of tablets
because the determination of end point is difficult owing to the
adhesive nature of shell. The shell pieces after disintegration may
agglomerate forming large mass of gelatin taking more time to
dissolve and may adhere to the mesh thus, blocking the holes.
According to USP, place one dosage unit in each of the tubes of the
basket with water or any other specified medium (depends on
individual monograph) maintained at 37 + 20C. Attach a removable
wire cloth with a plain square weave of 1.8-2.2 mm of mesh aperture
and a wire diameter of 0.60-0.655 mm to the surface of upper rack of
the basket assembly. Observe the capsules for a time limit (specified
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in individual monograph), at the end of prescribed time, all of the

capsules must have been disintegrated excluding the fragments from
the capsule shell. If 1 or 2 capsules fail, the test should be repeated on
additional of 12 capsules. Then, not fewer than 16 of the total 18
capsules tested should disintegrate completely.
Dissolution:
Place each of the capsules in the apparatus 1, excluding air bubbles
from the surface of the capsule. Operate immediately at specified rate
within specified dissolution medium at 37 + 0.50C. Aliquots should be
withdrawn at specified time points mentioned in individual
monograph.

Dissolution Apparatus

The requirements are met if the quantity of active ingredients

dissolved conforms the following:
1) At stage 1 (S1): When 6 capsules are tested, amount of each of the

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dissolved content should not be less than +/- 5% of the mentioned in

monograph.

2) At stage 2 (S2): when 6 capsules are tested, the average of 12 (both

from step 1and 2) should be equal to or greater than 15% and no
capsule should be than 15%.

3) At stage 3 (S3): when 12 capsules are tested, the average of 24

capsules (all 1,2 and 3 steps) should be equal to or greater than the
amount mentioned in the monograph, not more than two units are
less than 15% and no unit s less than 25%.
NOTE: 15%, 25% represent Q1 and Q2 unless and otherwise
mentioned in the monograph.

"Quality is not the step that can be incorporated at last, it is

mandatory and should be inbuilt into the products" to, make this
happen, apart from all these mandatory tests certain other tests can
be performed like

Moisture content:
Moisture content can be monitored with the aid of data the drying
kilns can be adjusted.

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 Loss on drying :
Determination of loss on drying via the oven method consumes more
time. To prevent this advanced methods like infrared balances etc.

Printing inspection:
Quality inspectors sample the lot and are inspected for quality of
print. The results will again be compared with the inspection plan and
in case if it does not match then, either capsules should be resorted or
rejected depending upon number of faults present.

Automatic Inspection Machines

Conclussion

40

Industrial trip to Medicamen Biotech td. Proved to be a very fruitful

experience for us. It was quite a knowledgeable experience, we got to learn
about various unit operations involved in manufacturing of various dosage
forms. Different manufacturing, packaging, Annalytical equipments were
shown and very well described to us. There was great cooperation of entire
staff of Medicamen biotech ltd., who very enthusiastically accompanied us
to all the blocks of the industry.

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