REPORT ON INDUSTRIAL TRAINING AT GOLDFISH

PHARMA PVT.LTD (Kukatpally, Hyderabad).

From:22-05-2019 to 22-06-2019.

By

ARASAVELLI SUKANYA

16Z31R0092

BOJJAM NARASIMHULU PHARMACY COLLEGE FOR WOMEN

17-1-383, Vinaynagar, Saidabad, Hyderabad, 500059.

Approved by AICTE, PCI.

Affiliated to JNTUH, Accredited by NBA.

 BOJJAM NARASIMHULU PHARMACY COLLEGE FOR
WOMEN

17-1-383, Vinaynagar, Saidabad, Hyderabad, 500059.

CERTIFICATE

This is to certify that Ms.ARASAVELLI SUKANYA D/O: A.RAMA RAO

bearing the register number 16Z31R0092 student of Bojjam Narasimhulu
Pharmacy College For Women (Sponsored by Sangam Laxmibai Vidyapeet,
Approved by AICTE and PCI affiliated to JNTUH) has undergone one month
training in an industry “Goldfish Pharma Pvt.Ltd” from:22-05-2019 to 22-06-
2019 for the period fulfillment for the award of degree of Bachelor of Pharmacy
for the academic year 2016 to 2020.

PRINCIPAL CLASS INCHARGE,

G.SIRISHA MAM,

ASSISTANT PROFESSOR,

BNPCW,

Hyderabad-059.
 ACKNOWLEDGEMENT

I would like to explicit my sense of gratitude to everyone who has supported me

in my industrial training.

I would like to thank my college principal Dr.P Mani Chandrika madam and my
class in-charge who granted me with this opportunity and also for their constant
support and encouragement.

I would like to thank GOLDFISH PHARMA PVT LTD and staff members for
their constant support and their guidance during the industrial training without
which my training would not be possible.
 CONTENTS

SOLID DOSAGE FORMS

TABLETS
 INTRODUCTION
 MANUFACTURING METHODS
 PUNCHING MACHINES
 COATING
 EVALUATION
CAPSULES
 INTRODUCTION
 FILLING EQUIPMENTS
 STABILITY
 EVALUATION
PACKAGING OF SOLIDS
 TABLETS
 CAPSULES
PELLET TECHNOLOGY
 TABLETS

INTRODUCTION:

Tablets represent unit solid dosage forms in which one usual dose of the drug has been accurately
placed.

ADVANTAGES:

 The tablet is an essentially tamperproof dosage form.

 These have the greatest capabilities of all the dosage forms.
 Their cost is lowest of all the oral dosage forms.
 They are better suited to large-scale production than the other unit oral forms.
 They are in general the easiest and cheapest to package and ship of all oral dosage
forms.
 They have the best combined properties of chemical, mechanical and
microbiologic stability of all the oral forms.

DISADVANTAGES:

 Some drugs resist compression into dense compacts making them flocculent and low
density in character.
 Drugs with poor wetting, slow dissolution, optimum absorption are difficult ot
formulate.
 Bitter tasting drugs, drugs with an objectionable odor or drugs that are sensitive ot
oxygen or entrapment prior to compression are prone to contamination.

PROPERTIES:

1. Tablets should be elegant product having its own identity.

2. They should be fee from chips, cracks, discoloration and contamination.
3. They should have strength to withstand the rigors of mechanical shocks.
4. They should have the physical and chemical stability to maintain its physical
attributes over time.
5. The tablet must be able to release the medicinal agent in the body in a predictable
and reproducible manner.
6. They should not allow any alteration of the medicinal agents.
 MANUFACTURING METHODS

A. Dry granulation.
B. Wet granulation.
C. Direct compression.

DRY GRANULATION:

It involves the compaction of the components of a tablet formulation by means of machinery

followed by milling and screening, prior to final compression into a tablet. When the initial
blend of powders is forced into dies of a large capacity tablet press and is compacted by
means of flat-faced punches, the compacted masses are called slugs, and the process is
referred to as slugging.

Slugging is an elaborate method of subjecting a material to increased compression time. The

act of slugging followed by screening and subsequent compression of the particles is roughly
equivalent to an extended dwell time during compression in a tablet machine. The material is
subjected to compaction pressures causes a strengthening of the bonds that hold the tablet
together. The resultant granules also increase the fluidity of these powder mixtures, which by
themselves do not flow well enough to fill the dies satisfactorily.

The compaction force of the roller compactor is controlled by:

a. The hydraulic pressure exerted on the compaction rolls.

b. The rotational speed of the compaction rolls.
c. The rotational speed of the feed screws.

Roller compactor are capable of producing as much as 500 kg per hour or more of compacted
ribbon-like material, which can then be screened or milled into a granulation suitable for
compression into tablets.

The machine is capable of exerting known fixed pressures on any powdered material that
flows between the rollers.

Powdered material is fed between the rollers by a screw conveyor system.

The roller compactor offers the advantages over the slugging process of increased production
capacity, greater control of compaction pressure and dwell time.
 CHILSONATOR

WET GRANULATION:

This process forms the granules by binding the powders together with an adhesive, instead of
by compaction. This technique employs a solution, suspension or slurry containing a binder,
which is usually added to the powder mixture in dry form and the liquid may be added by
itself. The mass should be moist rather than wet or pasty and there is a limit to the amount of
solvent that may be employed.

The liquid plays a key role. Once the granulating fluid is added, mixing continues until a
uniform dispersion is attained and all the binder has been activated. During granulation,
particles and agglomerated are subjected to consolidating forces by action if machine parts
and of inter-particulate forces. Granulation in large blenders require 15 minutes to an hour.

The wet screening process involves converting the moist mass into coarse, granular
aggregates by passage through a hammer mill or oscillator granulator, equipped with screens
having large perforations. The purpose is to further consolidate granules, increase particle
contact points and increase surface area to facilitate drying.

A drying process is required in all wet granulation procedures to remove the solvent that was
used in forming the aggregates and to reduce moisture content to an optimum level of
concentration within the granules.
.

Automatic Wet Granulator, Capacity: 144 To 240 Kg, SIGMA GRAN 600

DIRECT COMPRESSION:

The processing of drug with excipients can be achieved without any need of granulation and
related unit operations. By simply mixing in a blender, formulation ingredients can be
processed and compressed into tablets without any of the ingredients having to be changed.
This procedure is called direct compression and it is used in the manufacture of tablets when
formulation ingredients can flow uniformly into a die cavity.

TECHNIQUES OF DIRECT COMPRESSION:

a) Direct compression technique using induced die feeders.

b) Direct compression technique using dry binders.
c) Direct compression technique using direct compression excipients.
 .ROTARY TABLET PRESS

The method of manufacturing tablets by direct compression method involves:

The required amount of drug or active pharmaceutical ingredient is added to

respective grinder which involves proper and uniform grinding of solids into granules.
The uniformly grinded particles are then transferred to a suitable mixer or blender for
mixing of drug and the excipients in a regular mode.
The remaining adjuvants like lubricants and glidants are added to the blender and set
to mix properly.
Now, the formed powder along with its adjuvants is set to compress for a required
period of time and after the stipulated time the tablets are ejected from the ejector.

LIMITATIONS OF DIRECT COMPRESSION:

1. High-dose drugs may present problems with direct compression if it is not easily
compressible by itself.
2. The choice of excipients used in the manufacture of tablets by direct compression technology
is highly restricted since most materials do not have inherent binding properties.
3. Low-dose drugs may not be uniformly blended.
4. Direct compression excipients are often more expensive than other tablet excipients used in
wet granulation or slugging.
 PUNCHING MACHINES

SINGLE PUNCH TABLET PRESS MULTI PUNCH TABLET PRESS

 COATING

The application of coating to tablets, which is an additional step in the manufacturing

process, increases the cost of the product; therefore, the decision to coat a tablet is usually
based on one or more of the following objectives:
To mask the taste, odour or colour of the drug.
To provide physical and chemical protection for the drug.
To control the release of the drug from the tablet.
To protect the drug from gastric environment.
To improve the pharmaceutical elegance.
The three primary components involved are:
A. Tablet properties
B. Coating process: Coating equipment
Parameters of the coating process.
Facility and ancillary equipment.
Automation in coating processes.
C. Coating compositions.

TYPES OF COATING:
1. Sugar coating: Sealing
Subcoating
Syruping
Finishing
Poloishing
2. Film coating: Panpour methods
Panspray methods

FLUIDIZED BED PROCESS:

This type of systems are successfully used for rapid coating of tablets, granules and capsules.
The coating solution formulations used with these processes are similar to those used for the
pan processes. Since air is used to move the tablets in the coating process, there are some
specific process controls unique to air suspension coaters.
The chamber design, together with the process air, controls the fluidization pattern. Tablet
shape, size, density and quantity of load affects the ability of the tablet mass to be fluidized.

PROCEDURE:

Load tablets into pan. Attach and adjust the spray nozzle to spray on upper half of
the tablet bed.
Turn on heat, drying air, exhaust and atomizing air.
Intermittently jog the pan while tablets are warming.
When exhaust temperature reaches 30 start spraying.
Apply 3 to 4 litres of colour solution at a rate of 70 to 100 ml/min.
Apply 1.5 to 2.5 litres of clear solution at this rate and adjust the rate downward fi
tablets become tacky. Allow tablets to dry in pan with air and heat on for 5 to 10
minutes.

Sugar Coating Solutions:
TYPE OF COATING
MATERIALS
Seal coating solutions
Subcoating solutions
Subcoating powders
Syrup solutions
Polishing solutions
FLUIDIZED BED COATER
EXAMPLES
Cellulose acetate phthalate, zein, propylene glycol, oleic acid.
Gelatin, acacia, distilled water, sugarcane, syrupcorn.
Kaolin, dextrin, cocoa powder, talc, starch, calcium sulfate.
Colorant, calcium carbonate, distilled water.
Wax, carnauba, yellow beeswax, paraffin, white wax.

Film coating compositions:

NON ENTERIC POLYMERS ENTERIC POLYMERS
Hydroxypropyl methylcellulose, methyl Cellulose acetate phthalate, polyvinyl acetate
hydroxyl ethyl cellulose, ethyl cellulose, phthalate, poly methacrylic acid,
povidone, acrylate polymers. hydroxypropyl methylcellulose phthalate.
 EVALUATION
To design tablets and later monitor tablet production quality, quantitative evaluations and
assessments of a tablet’s physic-chemical properties along with its stability profile.
TESTS INCLUDED IN EVALUATION:
1) Organoleptic properties
2) Hardness
3) Friability
4) Drug content and release
5) Weight variation
6) Disintegration
7) Dissolution
Organoleptic properties:
Many pharmaceutical tablets use colour as a vital means of rapid identification and consumer
acceptance. Uniformity of the colour should be maintained to attain aesthetic appeal of the
tablet. The presence of an odour in a batch of tablets could indicate a stability problem, such
as characteristic odour of acetic acid in degrading aspirin tablets. Taste is important in
consumer acceptance of chewable tablets.
Hardness:
Tablets require a certain amount of strength or hardness to withstand mechanical shocks of
handling in manufacture, packaging and shipping. Hardness is sometimes termed as tablet
crushing strength.
DEVICES:
Monsanto hardness tester
Strong-Cobb tester
Pfizer tester
Erweka tester
Schleuniger tester
RANGE:4 TO 4.2 Kgs

MONSANTO HARDNESS TESTER

Friability:
Tablets require resistance to friability. The laboratory friabilator tester is known as Roche
friabilator. It subjects a number of tablets to the combined effects of abrasion and shock by
utilizing a plastic chamber that revolves at 25 rpm, dropping the tablets a distance of six
inches with each revolution.
LIMITS: 0.5 to 1 %

ROCHE FRIABILATOR
Drug content and release:
To evaluate a tablet’s potential for efficacy, the amount of drug per tablet needs to be
monitored from tablet to tablet and batch to batch, and a measure of the tablet’s ability to
release the drug needs to be ascertained.
Weight variation:
The weight of the tablet being made is routinely measured to help ensure that a tablet
contains the proper amount of drug.
LIMITS:
As per I.P
AVERAGE WEIGHT OF TABLETS (mg) MAXIMUM % DIFFERENCE ALLOWED
Less than or equal to 80 10
80 to 250 7.5
More than 250 5
As per USP:
AVERAGE WEIGHT OF TABLETS(mg) MAXIMUM % DIFFERENCE ALLOWED
Less than or equal to 130 10
130 to 324 7.5
More than 324 5
Disintegration:
The breakdown of the tablet into smaller particles or granules is known as disintegration. It is
used as a guide to the formulator in the preparation of an optimum tablet formula and as in-
process control test to ensure lot-to-lot uniformity.

TABLET DISINTEGRATION TESTER

LIMITS:
TYPE OF TABLET DISINTEGRATION TIME
Uncoated 15 minutes
Film coated 60 minutes
Sugar coated 30 minutes
Enteric coated 120 minutes

Dissolution:
The disintegration test offers no assurance that the resultant particles will release the drug in
solution at an appropriate rate. For this reason, dissolution tests and test specifications have
now been developed for nearly all the tablet products.
TYPE OF APPARATUS:
1) BASKET TYPE: A single tablet is placed in a mesh basket and connected to a speed
motor. Which is then immersed in the dissolution medium maintained at a body
temperature at a specific rate and withdrawn at regular intervals to determine the
amount of drug.
 2) PADDLE TYPE: This consists of a paddle in place of basket, formed from a blade
and a shaft as a stirrer. Dosage form is allowed to sink to the bottom which have a
few turns of wire helix attached to prevent floating.

DISSOLUTION TESTER

LIMITS:
STAGE NUMBER OF TABLETS ACCEPTANCE CRITERIA
I 6 Q+5
II 6 Avg of tablets Q+5
III 12 Avg of tablets Q+15

TABLETS
 CAPSULES

INTRODUCTION:

Capsule is a unit solid dosage form in which the drug is enclosed in a hard or soft soluble
container, usually made of gelatin.

ADVANTAGES DISADVANTAGES
I. Capsules are tasteless, odorless and I. Hygroscopic drugs are not
are easily administered. suitable to be filled into capsules.
II. They can be filled quickly and II. The concentrated solutions which
conveniently. require previous dilution are
III. They are attractive in appearance. unsuitable for capsules because if
IV. They are economical and easy to administered as such it leads to
handle. irritation in the stomach.

TYPES OF CAPSULES:

SOFT GELATIN CAPSULES HARD GELATIN CAPSULES

It consists of one piece and It consists of large body and small
hermetically sealed. cap.
Round and oval in shape. Cylindrical in shape.
Molten gelatin is used. Gelatin in hard form is used.

STAGES OF CAPSULE PRODUCTION

HARD GELATIN CAPSULES SOFT GELATIN CAPSULES

Preparation of gelatin solution. Preparation of gelatin solution.

Preparation and filling of hard gelatin shells. Preparation and filling of soft gelatin shells.

Packing and labelling. Packing and labelling.

 FILLING EQUIPMENTS

Common working principle of all capsule filling machines:

Powder from the storage hopper

Separation of body and cap parts of the capsule.

Powder filled into the empty capsule body.

Close the body of capsule with the cap.

Eject the filled capsule.

EQUIPMENTS:

Eli lily
Farmatic
Hofliger and Karg
Macofar SAS
Osaka
Parke-Davis
Perry
Zanasi

ELI LILY FARMATIC

HOFLIGER and KARG MACOFAR

OSAKA PARKE-DAVIS

MANUAL FILLING MACHINE

 STABILITY
Physical stability means the formulation is totally unchanged out its shelf-life and has
not suffered any changes by way of appearance, organoleptic properties, hardness,
brittleness, particle size and shape.
Unprotected soft gelatin capsules rapidly reach equilibrium with the atmospheric
conditions under which they are stored.
The variety of materials are capsulated, which may have an effect on the gelatin shell,
together with the many gelatin formulations that can be use.
The inherent characteristics warrants a brief discussion of the effects of temperature
and humidity on the products.

EVALUATION

Content uniformity
Weight variation
Moisture permeation test
Disintegration test
Dissolution test

Content uniformity:

NUMBER OF CAPSULES RANGE

9-10 15%
10 +15%
30 +25

Weight variation:

AVERAGE NET WEIGHT PERCENTAGE NUMBER OF CAPSULES

OF CAPSULES DEVIATION
<300mg +10 Minimum 18
+20 Maximum 2
>300mg +7.5 Minimum 18
+15 Maximum 2
Moisture permeation test:

Expose the packed unit to known relative humidity over a specified time.
Observe the capsule for color change.
Any change in color indicates absorption of color, which indicates the presence of
moisture in the formulation.

Disintegration test:

TYPE OF CAPSULE LIMIT

Hard gelatin 30 minutes
Soft capsule 60 minutes

Dissolution test:

STAGE NUMBER OF CAPSULES ACCEPTANCE CRITERIA

I 6 Q+5
II 6 Avg of 12 capsules:Q+5
III 12 Avg of 24 capsules:Q+15

PACKAGING OF SOLIDS
TYPES:

Primary packaging: It is the material that envelops the product and holds it.
Secondary packaging: It is present outside the primary packaging and is used to
group primary packages together.
Tertiary packaging: It is used for bulk handling, warehouse storage and transport
shipping. The most common form is a palletized unit load that packs tightly into
containers.

TABLET PACKAGING:

Blister packs:

These are commonly used as unit dose packaging for tablets. These can
provide barrier protection for shelf life requirements and a degree of tamper resistance.

Strip packs:

It is an alternative form of packaging for unit dose forms like tablets.

CAPSULE PACKAGING:

Blister packs
Strip packs
Alu-alu packs
Bottle packs
 PELLET TECHNOLOGY
It involves the manufacture of agglomerates with a narrow size range, usually with a mean
size of 0.5 to 1.5mm called as pellets.

ADVANTAGES:

Uniformity of dose.
Excellent flow properties.
Prevention of dust formation.
Low surface area to volume ratio.
Disperse freely through GIT.

DISADVANTAGES:

Expensive process.
Complicated with too many variables as well as formulation variables.

TECHNIQUES;

Extrusion-Spheronization
Hot melt extrusion
Layering
Balling
Globalization
Cryo pellitization

EQUIPMENT USED IN PELLETS PRODUCTION

 CONCLUSION

Through my industrial training I was given the opportunity to get exposed about
the technicalities that goes into the manufacturing the tablets, capsules and
pellets which also includes its evaluation and packaging.