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MANUFACTURING OF PIRORAFF TABLETS AND CORANT SYRUPS
A mini project report submitted to
Jawaharlal Nehru technological university, Anantapurfor the partial fulfilment of the requirement for award of the degree of
BACHELOR OF TECHNOLOGY
IN
BIOTECHNOLOGY
Submitted by
G. KEERTHI 08121A2315
C. SAI SAGAR 08121A2306
P. MOHAN KUMAR 08121A2323
Under the guidance ofDr. T. HARI PRASAD
Professor & Head
DEPARTMENT OF BIOTECHNOLOGY
SREE VIDYANIKETHAN ENGINEERING COLLEGE
(Affiliated to J.N.T.U.,Anantapur)
Sree Sainath Nagar, A.Rangampet-517102
Chittor Dist., A.P.,INDIA
2008-2012
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CERTIFICATE
This is to certify that the Mini project report entitled Manufacturing of Piroraff
Tablets and Corant Syrups is a bonafide work done by G. Keerthi (08121A2315),
C. Sai Sagar (08121A2306), P. Mohan Kumar (08121a2323) of the Department of
Biotechnology, Sree Vidyanikethan Engineering College, Tirupathi and is submitted to
Jawaharlal Nehru Technological University, Anantapur in partial fulfilment for the
award of the degree of Bachelor of Technology in Biotechnology. This Mini project
work is carried out by him/her under my supervision during the year 2010-2011.
GUIDE:
Dr. T. HARI PRASAD,
Professor
Department of Biotechnology,
Sree Vidyanikethan Engineering College
HEAD:
Dr. T. HARI PRASAD,
Professor,
Department of Biotechnology,
Sree Vidyanikethan Engineering College
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DECLARATION
We hereby declare that the Mini project work entitled Manufacturing of
Piroraff Tablets and Corant Syrups being submitted by me in partial fulfilment for the
award of Degree of Bachelor of Technology in Biotechnology in Sree Vidyanikethan
Engineering College, Affiliated to JNT University, Anantapur is a bonafide record of
work done by us.
G. KEERTHI
(08121A2315)
C. SAI SAGAR
(08121A2306)
P.MOHANKUMAR(08121A2323)
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ACKNOWLEDGEMENT
We owe a deep sense of gratitude and wish to express our indebtedness to our project
supervisor, Deputy Chief Chemist of Raffels pharmaceuticals pvt. Ltd for his intellectual
guidance and extending all the supports as and most need in spite of his official
responsibilities without which our work of this kind have been unthinkable.
We are extremely thankful to our beloved chairman Padma Shri Dr. M. Mohan
Babu garu who took keen interest and encouraged us in every effort throughout this course.
We express our sincere heartfelt gratitude to Dr. P. C. KRISHNAMACHARY,
principal, Sree Vidyanikethan Engineering Collegefor his encouragement.
We would like to express our fervent thanks and gratitude to Dr.T. Hari Prasad,
Guide and Head of the Department of Biotechnology, Sree Vidyanikethan Engineering
College, Tirupathi for his valuable guidance and constant encouragement throughout the
course of our project.
We have no words to thank all the staff members and all our friends of
biotechnology, Sree Vidyanikethan Engineering College for their co-operation and
encouragement.
Finally, I wish to thank to all my friends who cooperated all throughout my work.
Project Associates:
G. KEERTHI
C. SAI SGAR
P. MOHAN KUMAR
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CONTENTS
1. Abbreviations
2. About the company
3. Scope of Study
4. Methodology
5. Abstract
6. Production process of Tablets
6.1Dispensing
6.2Granulation
6.3Drying
6.4Tablet Compression
6.5Quality Control
6.6Coating
6.7Packing
7. Production Process of Syrups
7.1Dispensing
7.2Deionization of Water
7.3Preparation of Syrup
7.4Filling line
8. Finished Goods Inspection
9. Conclusion
10.References
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About the Company
Raffles Pharmaceuticals was established in 2003, as a small beginning with large hope, with
a vision towards empowering life and well being. The business focuses on the manufactureand marketing of pharmaceutical products.
The company produce wide range of quality, affordable medicines, trusted by healthcare
professionals and patients across the country.
Raffles Pharmaceuticals was a lone licensee manufacturer with production at Rexer Pharma
Pvt Ltd. Cherlapally, and Hyderabad for the last 4 years. They have their own marketing
team, which successfully marketed over 40 products all over Andhra Pradesh, few places in
Kerala and Karnataka.
Raffles Pharmaceuticals has its own production unit built with GMP guidelines at
Gajulamandyam, near Tirupati, the sacred abode of Lord Sri Venkateswara. Built on 1.5
acres of Industrial estate land, the Production Unit supports its ORAL LIQUID SECTION,
TABLET AND CAPSULE SECTIONS in its three floors building.
Raffles Pharmaceuticals is located very near to Tirupati City, compared to all other industrial
areas it is well connected with transport and other infrastructure facilities.
Fig: Raffles Pharmaceuticals Production Plant
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Scope of Study
The in-depth study of process and minute examination of each of the production process was
not allowed to us as the organization had concern regarding the secrecy of the process in
respect to their competitors. However the authorities were kind enough to let us know the
names of various machines that were used in the process. We have tried to develop an overall
understanding of the process of the manufacturing unit. Along with this we tried to develop
the understanding of working of various medicines by surfing through various websites. The
images of the machine given here are the ones we got from the website. We have tried to link
the various information we collected through our primary investigation with those we havegathered through secondary research.
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Abstract
Medicines play a critical role in delivering effective and efficient health care for
patients. Pharmaceutical procurement is a key component of medicine managements, with the
supply chain providing the critical link between the manufacture and the patient. It is
integrated with medicine management and need to be designed to ensure the right medicine is
available for patient at right time. Typically other developments in the hospital pharmacy
have assumed higher priority than a supply chain.
The demand for medicines increased a lot in the recent past. However the production
and supply have not increased to that extent. So that the large chain of the required medicines
is manufactured by some pharmaceutical companies to fulfil the requirements.
We did a project on manufacturing of Piroraff Tablets and Corant syrups. The
major composition of Piroraff Tablets is Piroxicam.This Piroraff Tablet is a nonsteroidal
anti-inflammatory drug (NSAID)that is effective in treating fever, pain, and inflammation
in the body. As a group, NSAIDs are non-narcotic relievers of mild to moderate pain of many
causes, including injury, menstrual cramps, arthritis, and other musculoskeletal conditions.
NSAIDs, including piroxicam, block the enzyme in the body that makes prostaglandins
(cyclooxygenase), resulting in lower levels of prostaglandins. Prostaglandins are responsible
for causing many types of pain, fever and inflammation. As a consequence of taking
NSAIDs, inflammation, pain and fever are reduced. The FDA approved piroxicam in 1982.
Piroxicam generally is used with caution in patients taking blood thinning
medications to prevent the clotting of blood (anticoagulants), such as warfarin (Coumadin),
because of an increased risk of bleeding. It works by reducing hormones that cause
inflammation and pain in the body and used to treat pain or inflammation caused by arthritis.
Syrup is a thick, viscous liquid consisting primarily of a solution ofsugar in water,
containing a large amount of dissolved sugars but showing little tendency to deposit crystals.
The viscosity arises from the multiple hydrogen bonds between the dissolved sugar, which
has many hydroxyl (OH) groups, and the water.
The Corant syrup is cough syrups & anti-cold syrup and the composition of the
Corant syrup is Ambroxol-15mg, Salbutamol-1mg, Guaiphenesin-50 mg, Menthol-0.5 mg
for 100 ml of water.
http://en.wikipedia.org/wiki/Viscoushttp://en.wikipedia.org/wiki/Solutionhttp://en.wikipedia.org/wiki/Sugarhttp://en.wikipedia.org/wiki/Crystalhttp://en.wikipedia.org/wiki/Hydrogen_bondhttp://en.wikipedia.org/wiki/Hydroxylhttp://en.wikipedia.org/wiki/Waterhttp://en.wikipedia.org/wiki/Waterhttp://en.wikipedia.org/wiki/Hydroxylhttp://en.wikipedia.org/wiki/Hydrogen_bondhttp://en.wikipedia.org/wiki/Crystalhttp://en.wikipedia.org/wiki/Sugarhttp://en.wikipedia.org/wiki/Solutionhttp://en.wikipedia.org/wiki/Viscous8/4/2019 Final Sags
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Methodology
The source of data used are primarily through interview of general manager and
operations personal, Journal and magazine, existing research and various websites were used
for secondary research.
The steps involved in completion of our project can be depicted as under
Objective Formulation
Company Visit
Process Study
Process Analysis
Recommendations
Conclusion
Production process of Tablets
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Dispensing
Dispensing is the first step in any pharmaceutical manufacturing process. It means weighing
and measuring of the ingredients taken from raw material. Dispensing may be done manually
by hand scooping from primary containers and weighing each ingredient by hand on a weigh
scale, manual weighing with material lifting assistance.
Issue like weighing accuracy, dust control during manual handling is
considered during dispensing.
Granulation
When raw material characteristics make tableting difficult, wet granulation procedures areused which involves blending the raw materials with purified water, air drying the mixture,mill sizing the particles and then blending the resulting granules for tableting. 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 thegranules to be too hard and under-wetting will cause them to be too soft and friable.
Procedure:
Step 1: The active ingredient and excipients are weighed and mixed.
Step 2: The wet granulate is prepared by adding the liquid binderadhesive to the powder
blend andmixing thoroughly. Examples of binders/adhesives include aqueous preparations of
cornstarch, natural gums such as acacia, cellulose derivatives such as methylcellulose,gelatin, and povidone.
Step 3: Screening the damp mass through a mesh to form pellets or granules.
Step 4: Drying the granulation. A conventional tray-dryer or fluid-bed dryer are most
commonly used.
Step 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.
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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 itallows 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 is 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 attainproper 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 blendingof the granules with a powdered lubricant, such as magnesium stearate or stearic acid.
Power Blender:
The successful mixing of power is acknowledged to be more difficult operation because,
unlike the situation with liquids, perfect homogeneity is practically unattained. Here it is done
through machine called Mixer Granulator.
Fig: Octagonal Blender
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Drying:
Fig: Dryer
Drying is the most important step in the formulation and development of pharmaceutical product. It is
important to keep the residual moisture low enough to prevent product deterioration and ensure free
flowing properties.
Tablet Compression:
After 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) , these are compressed
to get final product. The compression is done either by single punch machine or by multi
station machine (Rotary Press).
Fig: Compressor
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The press is a high speed mechanical device. It squeezes the ingredients in to the required
tablets shape with extreme precision. It can make the tablet in many shapes, although they are
usually round or oval. Also it can press the name of the manufacture or the product in to topof the tablet.
Quality control:
Tablets are tested at the beginning of each batch and the beginning of each shift to ensure that
they meet requirements for weight conformity, requirements for disintegration and
requirements for friability, hardness and thickness. Every 15 minutes during operation, a
random sample of ten tablets is weighed, compared to specification, and the average weight is
recorded.
Each tablet machine operator is responsible for assuring that the tablets they manufacture
meet the exact specifications in the Manufacturing Batch Records (MBR). Each step of the
manufacturing process is monitored by supervisory personnel and verified by quality control.
Fig: Wet lab
Coating:
A coating machine is used for the following purposes. Modern tablet coatings are
polymer and polysaccharide based, with plasticizers and pigments included.
Enteric Coating: One protection layer is coated on the tablet to protect against stomach acid.
Sugar Coating: Many layers of sugar are coated on the surface to protect the tablet.
Film Coating: One thin film protection layer which is coated on the surface of tablet. The
process is as follows
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Procedure:
Preheating
Film Coating
Drying
Cooling
Finishing
Fig: Tablet Coating Machine
Packing:
Pharmaceutical manufacturers have to pack their medicine before they
can be sent out for distribution. The type of packing will depends on
formulation of medicine. Blister packs are common form of packing used for
wide varieties of products.
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Fig:Blistering machine
11.Production Process of Syrups
Dispensing
Dispensing is the first step in any pharmaceutical manufacturing process. It means weighing
and measuring of the ingredients taken from raw material. Dispensing may be done manually
by hand scooping from primary containers and weighing each ingredient by hand on a weigh
scale, manual weighing with material lifting assistance.Issue like weighing accuracy, dust
control during manual handling is considered during dispensing.
Deionization of Water
Deionized water, also known as dematerialized water is water that has had its mineral ions
removed, such as cations from sodium, calcium, iron, copper and anions such as chloride and
bromide. Deionization is a physical process which uses specially-manufactured ion exchange
resins which bind to and filter out the mineral salts from water. Because the majority of water
impurities are dissolved salts, deionization produces a high purity water that is generally
similar to distilled water, and this process is quick and without scale buildup. However,
deionization does not significantly remove uncharged organic molecules, viruses or bacteria,
except by incidental trapping in the resin. Specially made strong base anion resins can
remove Gram-negative bacteria. Deionization can be done continuously and inexpensively
http://en.wikipedia.org/wiki/Waterhttp://en.wikipedia.org/wiki/Cationhttp://en.wikipedia.org/wiki/Sodiumhttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Ironhttp://en.wikipedia.org/wiki/Copperhttp://en.wikipedia.org/wiki/Anionhttp://en.wikipedia.org/wiki/Chloridehttp://en.wikipedia.org/wiki/Bromidehttp://en.wikipedia.org/wiki/Gram-negativehttp://en.wikipedia.org/wiki/Gram-negativehttp://en.wikipedia.org/wiki/Bromidehttp://en.wikipedia.org/wiki/Chloridehttp://en.wikipedia.org/wiki/Anionhttp://en.wikipedia.org/wiki/Copperhttp://en.wikipedia.org/wiki/Ironhttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Sodiumhttp://en.wikipedia.org/wiki/Cationhttp://en.wikipedia.org/wiki/Water8/4/2019 Final Sags
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using electrodeionization. Deionization does not remove the hydroxide or hydronium ions
from water. These are the products of the self-ionization of water to equilibrium and therefore
are impossible to remove.
Preparation of the Syrup
Tanks used in preparation of syrup have the capacity of 5000 to 20,000 lit. The tank is
double jacketed. The deionized water is transferred through pumps in to the tank and boiled.
Inside the tank there are paddles where this paddles rotate at variable speed. This paddles is
used for thorough mixing. The ingredients are added in to the tank after dispensing. Heat
and/or agitate actively until the dissolution of all ingredients. If at least one of the ingredients
is sensitive to temperature, mixing should take place without heating. Finally add sufficient
purified water to make the right weight or volume.
Fig: Tanks
Filling line
Tank is attached to the filling line for transferring syrup to filling machine. This filling
machine is used to fill the syrup in to the bottles. This filling machine is automatic after
filling the bottles these bottles is caped and sealed by sealing machine.
http://en.wikipedia.org/wiki/Electrodeionizationhttp://en.wikipedia.org/wiki/Hydroxidehttp://en.wikipedia.org/wiki/Hydroniumhttp://en.wikipedia.org/wiki/Self-ionization_of_waterhttp://en.wikipedia.org/wiki/Chemical_equilibriumhttp://en.wikipedia.org/wiki/Chemical_equilibriumhttp://en.wikipedia.org/wiki/Self-ionization_of_waterhttp://en.wikipedia.org/wiki/Hydroniumhttp://en.wikipedia.org/wiki/Hydroxidehttp://en.wikipedia.org/wiki/Electrodeionization8/4/2019 Final Sags
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Fig: Filling machine
Finished Goods Inspection
As each batch is completed, a representative sample is tested in the laboratory.
Manufacturing Batch Record (MBR) and finished goods records are thoroughly reviewed and
verified for accuracy before the product is given a final stamp of approval and released for
packaging and shipment.
Conclusion:
As we students, we need to have theoretical as well as practical and industrial knowledge. In
plant training helped us to acquire knowledge on drug manufacturing and manufacture
management and it will be very much useful in our professional life. The two weeks of
industrial visit proved to be a golden opportunity for us in letting to understand various
operations involved in pharmaceutical industry. During our training period we came very
close to all aspects and analysis which were carried out in the industry, at the same time we
learned how to follow the rules and regulations as per CGMP and GLP and according to
WHO and ISO 9001.