MANUFACTURING OF PIRORAFF TABLETS AND CORANT SYRUPS

A mini project report submitted to

Jawaharlal Nehru technological university, Anantapur

for the partial fulfilment of the requirement for award of the degree of BACHELOR OF TECHNOLOGY IN BIOTECHNOLOGY

Submitted by
G. KEERTHI C. SAI SAGAR P. MOHAN KUMAR 08121A2315 08121A2306 08121A2323

Under the guidance of

Dr. 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

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

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)

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 College for 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

CONTENTS

1. Abbreviations 2. About the company 3. Scope of Study 4. Methodology 5. Abstract 6. Production process of Tablets 6.1 Dispensing 6.2 Granulation 6.3 Drying 6.4 Tablet Compression 6.5 Quality Control 6.6 Coating 6.7 Packing 7. Production Process of Syrups 7.1 Dispensing 7.2 Deionization of Water 7.3 Preparation of Syrup 7.4 Filling line 8. Finished Goods Inspection 9. Conclusion 10. References

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 manufacture and 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

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 have gathered through secondary research.

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 of sugar 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.
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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 are used 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 the granules 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 and mixing 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 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 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 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. 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 top of 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
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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.

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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.

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