INTRODUCTION

INDUSTRY PROFILE

This chapter introduces the pharmaceutical industry its overview, economic value,
classification, future scenario and SWOT analysis of pharma sector.

1.1.1 Overview of Pharmaceutical Sector

Accounting for two percent of the world’s pharmaceutical market, the Indian
pharmaceutical sector has an estimated market value of about US $8 billion. It’s at 4 th rank in
terms of total pharmaceutical production and 13th in terms of value. It is growing at an
average rate of 7.2% and is expected to grow to US $2 billion by 2010.

Over the last two years the pharmaceutical market value has increased to about US
$355 million because of the launch of new products. According to an estimate, 3900 new
generic products have been launched in the past two years. These have been by and large
launched by big brands in the pharma sector. And in the year 2005 Indian pharmaceutical
companies captured around 70% of the domestic market.
As in the present scenario, only a few people can afford costly drugs, which have
increased the price sensitivity in the pharmaceutical market. Now the companies are trying to
capture the market by introducing high quality and low price medicines and drugs.

With the Product Patent Act, which came into action in January 2005, this industry is
able to attract big MNCs to India. Earlier these big firms had apprehensions in launching new
drugs in the Indian market.

At present, a large number of Indian pharmaceuticals companies are looking for tie-
ups with foreign firms for in-license drugs. GlaxoSmithKline is among the top choices for the
firms that wish to launch their product in India, but do not have any branch over here.

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 Contract research and pharmaceutical outsourcing are the new avenues in the
pharmaceutical market. Contract manufacturing is growing at a very fast pace and is
estimated to grow to US $30billion, whereas contract research is estimated to reach US$6-10
billion.

Indian multinational companies like Dr.Reddy's Lab, Cipla, Ranbaxy, etc have
created awareness about the Indian market prospects in the international pharmaceutical
market. Approvals given by Foods and Drugs Administration (FDA) and ANDA
(Abbreviated New Drug Application)/DMF (Drug Master File) have played an important role
in making India a cost-effective and high quality product manufacturer. Furthermore, the
changes that took place in the patent law, change of process patent to product patent, have
helped in reducing the risk of loss for intellectual property.

1.1.2 Indian pharmaceutical industry -Economic value

The Indian pharmaceutical industry, which is now meeting over 95% of the country's
pharmaceutical needs, was almost non-existent before 1970. With the compound annual
growth of 19.8% the industry has grown from Rs.4 billion in 1970 to Rs.290 billion in 2003.
The pharma sector has shown tremendous growth over the years. About 250 Indian
pharmaceutical companies hold 70% of the market share with top players controlling about
7% of the market share.

On 1st January 2005, the Government of India issued patent ordinance according to
which the Indian pharma companies can no longer produce patented drugs.

1.1.3 Classification of Indian Pharmaceutical Industry

The Indian pharmaceutical industry can be classified into organized and unorganized
sectors. Accounting for over 70% of total sales, the organized sector has about 250
manufacturing and formulation units. On the basis of management control, the organized
sector can be further classified into MNCs and Indian companies.

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 On the basis of the product manufactured, the pharmaceutical industry can be
classified into: Bulk drugs: They are the key ingredients that form the basic raw material for
the manufacture of formulations.

Formulation: Particular mixture of a bulk drug or a combination of different bulk

drugs.
Formulations constitute nearly 81% and bulk drugs account for the remaining 19%.
Indian pharmaceutical industry has about 2400 licensed manufacturers and more than
100,000 drugs.

On the basis of formulations, the pharmaceutical industry can further be classified into:

• Prescription medicines: Also known as ethical formulations. They can be dispensed

only on the prescription from a qualified medical practitioner.

• Over-the-counter medicines: Also known as OTC formulations. They can be

dispensed even in the absence of prescription, e.g. analgesics, cough drug, etc.

On the basis of formulations patent, pharmaceutical industry can be classified as

• Branded formulations: They are ethical formulations prepared using a bulk drug under
product patent and are marketed by a single pharmaceutical company.

• Generics: They are formulations that do not contain any patented bulk drug and can
be manufactured by more than one company.

1.1.4 Indian Pharmaceutical Sector: Future Scenario

The dream of Indian pharmaceutical companies for marking their presence globally
and competing with the pharmaceutical companies from the developed countries like Europe,
Japan, and United States is now coming true.

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 The new patent regime has led many multinational pharmaceutical companies to look
at India as an attractive destination not only for R&D but also for contract manufacturing,
conduct of clinical trials and generic drug research. With market value of about US$
45billion in 2005, the generic sector is expected to grow to US$ 100billion in the next few
years.

The Indian companies are using the revenue generated from generic drug sales to
promote drug discovery projects and new delivery technologies. Contract research in India is
also growing at the rate of 20-25% per year and was valued at US$ 10-120million in 2005.
India is holding a major share in world's contract research business activity and it continues
to expand its presence.

Clinical Research Outsourcing (CRO), a budding industry valued over US$ 118
million per year in India, is estimated to grow to US$ 380 million by 2010, as MNCs are
entering the market with ambitious plans.

By revising its R&D policies the government is trying to boost R&D in domestic
pharma industry. It is giving tax exemption for a period of ten years and relieving customs
and excise duties of all the drugs and material imported or exported for clinical trials to
promote innovative R&D.

The future of Indian pharmaceutical sector is very bright because of the following factors:
• Clinical trials in India cost US$ 25 million each, whereas in US they cost between
US$ 300-350 million each.

• Indian pharmaceutical companies are spending 30-50% less on custom synthesis

services as compared to its global costs.

• In India investigational new drug stage costs around US$ 10-15 million, which is
almost 1/10th of its cost in US (US$ 100-150million).

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1.1.5 SWOT Analysis of Pharma Sector

Strengths

• Cost effective technology

• Strong and well-developed manufacturing base

• Clinical research and trials

• Knowledge based, low- cost manpower in science & technology

• Proficiency in path-breaking research

• High-quality formulations and drugs

• High standards of purity

• Non-infringing processes of Active Pharmaceutical Ingredients (APIs)

• Future growth driver

• World-class process development labs

• Excellent clinical trial centers

• Chemical and process development competencies

Weaknesses

• Low Indian share in world pharmaceutical market (about 2%)

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 • Lack of strategic planning

• Fragmented capacities

• Low R&D investments

• Absence of association between institutes and industry

• Low healthcare expenditure

• Production of duplicate drugs

Opportunities

• Incredible export potential

• Increasing health consciousness

• New innovative therapeutic products

• Globalization

• Drug delivery system management

• Increased incomes

• Production of generic drugs

• Contract manufacturing

• Clinical trials & research

• Drug molecules

Threats

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• Small number of discoveries

• Competition from MNCs

• Transformation of process patent to product patent (TRIPS)

• Outdated Sales and marketing methods

• Non-tariff barriers imposed by developed countries

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 COMPANY PROFILE
Shasun Chemicals and Drugs Limited (SCDL) was incorporated in 1976 and is
headquartered in Chennai, India. Shasun has acquired a worldwide reputation for the
manufacture of Active Pharmaceutical Ingredients (APIs) and their intermediates. The
Company’s products are exported to customers in countries across Europe, North America,
Latin America & Asia.

It manufactures active pharmaceutical ingredients (APIs), their intermediates and

enteric coating excipients with a significant presence in some key generics. Shasun has
created a strong product portfolio, building on its R & D Expertise, regulatory capabilities
and multi scale production capacities. Shasun has also emerged as a key player in various
service segments in the pharmaceutical field besides APIs and intermediaries, and is
strengthening its offer of contract research, custom synthesis, contract manufacturing and
contract formulation services to clients.

SHASUN is derived from the name of the founder, Late Shri. Shankarlal Jain and his

wife Smt. Sundarbai.

2.1 Mile stones

1976-1990

• Incorporated as a private limited company, Shasun Chemicals in Chennai

• First production facility established at Velachery, Chennai, for manufacture of
Analgin (antipyretic).
• Second production facility was established at Puducherry for manufacture of
Ibuprofen (anti-inflammatory)
• +Ibuprofen
• The company signed a technology agreement with Chircotech, UK, for S+Naproxen.
• The company signed a joint venture agreement with Austin Chemical Company,
USA,

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1990-2000

• Third manufacturing unit set up at Cuddalore to manufacture the anti-ulcerative

Ranitidine HCI
• Shasun converted into a public limited company, incorporating its present name.
• US subsidiary, Shasun Inc., is established
• The company's shares were listed on Mumbai, Ahmedabad and Chennai stock
exchanges.
• Technology and joint marketing agreement signed with Nagase & Co., Japan.

2000-Present day

• The company's exports exceeded Rs.100 cr.

• Established a biotech laboratory in its R&D centre.
• Signed a letter of intent with Eli Lilly for supply and manufacture of an anti-TB drug.
• Multi Purpose Plant at Cuddalore was commissioned.
• Completed setting up its new Research Centre.
• Strategic partnership with Glenmark and Alpharma(now part of Actavis) for
Development & Supply of Formulation products.
• Completed its first ever acquisition of Rhodia Pharma Solutions business marking its
advent in the Global supply arena

2.2 Shasun infrastructure

Shasun Research Center

Shasun Research Center (SRC) is Shasun's state-of-the-art research & development

center established at Keelakottaiyur, around 35 km from Chennai. This facility is spread over
9.3 Acres of land approximately 377150 sq. ft. This project is executed in 3 Phases. The first
phase was completed in 2005 and has been fully functional. In the 2nd phase, SRC plans to
double the organic and analytical infrastructure by building another organic block and an
additional floor of the analytical department. The corporate office of Shasun is also planned
to shift to the center by the end of next financial year (2007-08).

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 • The overall objective of the center is to achieve excellence in chemistry for
manufacture of APIs and intermediates for the health care industry by complying with
full cGMPs standards and quality.
• It serves as a nerve center for research and development where activities includes
contract research and customs synthesis, in-house API research, technology
development etc. along with other innovative collaborative research with academics
as well as industries.
• Shasun Research Center creates an environment for innovation and learning that
fosters, in each one of us at Shasun, a desire to excel and willingness to experiment as
we believe – "For Life - Science works"

The R&D Centre has a total land area 9.36 Acres. The constructed total area is
1,38,748 sq.ft.

API Facility – Puducherry

Established in 1986, the Pondicherry facility is a dedicated plant for the manufacture
of Ibuprofen. Excellent product quality has helped Shasun grow over the years to become one
of the largest manufacturers of Ibuprofen in the world. Inspected multiple times by the FDA,
MCA and other regulatory bodies our product is sold in countries across Europe, North
America and others. Supply chain includes Boots Co, UK - the original innovator of
Ibuprofen. We pride ourselves with being the only company to offer the complete spectrum
of Ibuprofen derivatives such as S+ Ibuprofen, Ibuprofen Lysinate, and Ibuprofen Sodium.

Formulation-Puducherry

The newly commissioned Formulation facility will vouchsafe this statement.

Just enter into this techno-savvy facility and you will be spellbound to witness some of the
latest technologies that the Pharmaceutical world has moved towards.

Spread over an area of 100 000 sq.ft., the facility can handle Oral Solid Dosages
(OSDs), with an annual production capacity of over 3.0 billion tablets (including Film / Sugar
coated) and 120 million capsules (hard gelatin).

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Some of the key features of this facility are :

• Seamless, in situ cast terrazzo flooring for all manufacturing areas.

• Air Handling Units with terminal mounted EU13 HEPA filters, to provide a class 100
000 environment in the manufacturing areas, continuously monitored and controlled
by Building Automation System.
• Vertical material flow in tablet compression areas, to avoid cross contamination.
• Bar-code readers for entire manufacturing activity starting from material dispensing
till equipment cleaning.
• Automatic container cleaning system, ensuring validation of cleaning procedures.
• 100% metal detection scanning of all the products.
• Access controls and CCTV monitoring of man movement to various areas inside the
facility, to avoid violation of GMP.
• Pharmacodes on all printed packaging materials.
• The facility is approved by US-FDA, MHRA and Schedule M of D&C Act of India

Cuddalore

• Spread over 64000 sq. meters, this facility manufactures anti-ulceratives Nizatidine
and Ranitidine as well as excipients.
• Possesses state-of-the-art packing and drying equipment, with multiple clean room
suites. Possesses a 95% efficiency solvent recovery system and a hydrogenation
facility. The site has a capacity of captive generation of 3000 KVA of power.
• Equipped with a vertically integrated effluent treatment plant approved by various
regulatory authorities in addition to being ISO 9001:2000-certified by BVQI.
• Sophisticated plant design - Designed with overhead addition tanks, mobile collection
tanks and streamlined pipe routing system.
• Equipped with reactor sizes to handle pilot to commercial volumes & Flexible
containment with LEV to avoid cross contamination
• Invested with high swing capacity to facilitate the manufacture of various products,
Provided with class 100,000 clean-room suites with crystallizers and dryers High
flexibility with respect to Material of constructions (MoCs) such as SS/Hastalloy
centrifuges) & RCVDs, SS-GLRs, PTFE lines

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 • Controlled area (designed for Class 10,000) clean-room suites w/ crystallizers ,
dryers, milling, sieving and packing installed
• Facilities include: addition control, Distillation (high vacuum with columns of
different sizes), Heating & Cooling control, Data logging, Clean room control with
Building Management System
• Created with a separate hydrogenation block and a utility support comprising of a
wide vacuum and temperature (–90° to +200°C) tolerance.

Biotech – Velacherry

Shasun recognizes the role of biotechnology as the future of the global pharmaceutical
industry in enhancing therapeutic effectiveness, improving lifestyle quality and strengthening
corporate profitability. In view of this, the company is involved in the creation of significant
biotechnology capabilities & capacities especially in the area of protein processing solutions
to provide services for the biotech & pharmaceutical companies.

Vizag

Shasun India has already purchased land in the special economic zone at the Pharma-
city, Vizag in Andhra Pradesh, India and is planning to build a multipurpose and multi-
product facility as its new manufacturing facility by the end of the year 2008.

UK

Shasun Pharma Solutions is the vertically integrated chemistry partner for the
pharmaceutical industry. Its services include innovative process research and development,
rapid response small scale manufacture for clinical trial supply and full scale commercial
manufacture of advanced intermediates and API’s, all with seamless technology transfer and
under cGMP.

Our capabilities are available as single or multisite offerings in order to create flexible
solutions that satisfy the development or commercial manufacturing challenges facing our
customers.

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Our chemistry and development expertise complements the manufacturing services, offering
customers a single source for the supply solution they now seek from multiple organisations.
Early stage development services provide seamless technology transfer to facilitate crucial
speed to market, and minimise potential risk in the transition to commercial scale
manufacture.

Shasun Pharma Solutions is accustomed to carrying out complex multistage organic

syntheses, including chemistry in liquid ammonia, organometallic chemistry, halogenations,
Friedel-Crafts reactions and reductions, as well as powerful chiral syntheses such as Jacobsen
chiral epoxidation and kinetic resolution.

Shasun Pharma Solutions, in touch with your every need from discovery to market.

Annan

• Development and launch pilot plant to 300-gallon scale

• Development and launch cGMP pilot plant (300 gallon with class 10,000 cleanroom)
• Full analytical/QA support
• Manufacturing facilities:
• Former Glaxo Wellcome facility on 154 acres
• Validated cGMP facility for pharmaceutical intermediate and API manufacture
• 3 high-quality production buildings with fully computerised sequence control
• 125m3 (30,000 gallon) reactor capacity, 31 reactor systems (GLS and Hastelloy) up to
9000L scale
• Purified water system
• FDA inspected most recently in September 2003
• Specialist reaction capabilities include: high volume distillation, organometallics,
hydrogenation
(up to 10 bar) and bromination
• Extensive bulk solvent supply and recovery system
• Modern scrubbed incineration facility (1250°C)

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Dudley

• 30 fume hoods
• Kilo lab facilities at 25L and 50L scale
• Pilot plant at 75 to 300 gallon scale
• Full analytical capability
• 40 Scientists focused on chemistry development and industrialisation
• Extensive Hazard Evaluation capability
• State-of-the-art cGMP pilot plant with full R&D support infrastructure
• Manufacturing facilities:
• Former Sterling Drug facility on 42 acres
• Large scale general purpose cGMP pharmaceutical intermediate and API manufacture
• 400m3 reactor capacity, 20 intermediate and 4 API reactor trains (GLS, SS and
Hastelloy) up to 13,000L scale
• Rapid entry for new product introduction to full cGMP
• 3 Production areas including special purpose area for aggressive products
• FDA inspected most recently in January 2002
• Purified water system capable of WFI grade
• Specialist reaction capability includes: liquid ammonia, organometallics,
carbonylation,
• hydrogenation, halogenations, Friedel-Crafts and cyanation
• Modern biological wastewater treatment facility

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PRODUCT PROFILE

Bulk API

Product Names Grades

Ibuprofen SN,S-250,S-380,S-500,SHD,
S+Ibuprofen,Iburofen Sodium,Ibuprofen
Ibuprofen Derivatives
Lysinate,DC Grades-DC-60,DC-90,DC-85
Ranitidine base
Ranitidine HCl Form I & Form II,- USP,BP/EP,IP, DC
Nizatidine
Methoxital
Isradipine
Gabapentine
Olanzapine
Quinapril HCl
Meprobamate

IBU Profen

Ibuprofen is in a group of drugs called nonsteroidal anti-inflammatory drugs

(NSAIDs). It works by reducing hormones that cause inflammation and pain in the body.
Ibuprofen is used to reduce fever and treat pain or inflammation caused by many conditions
such as headache, toothache, back pain, arthritis, menstrual cramps, or minor injury.
Ibuprofen nomenclature iso-butyl-propanoic-phenolic acid) is a non-steroidal anti-
inflammatory drug (N-SAID) originally marketed as Brufen, and since then under various
other trademarks (see tradenames section), most notably Nurofen, Advil and Motrin. It is
used for relief of symptoms of arthritis, primary dysmenorrhea, fever, and as an analgesic,
especially where there is an inflammatory component. Ibuprofen is known to have an
antiplatelet effect, though it is relatively mild and short-lived when compared with that of
aspirin or other better-known antiplatelet drugs. Ibuprofen is a core medicine in the World
Health Organization's "Essential Drugs List", which is a list of minimum medical needs for a
basic health care system.

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Formulation – Introduction

Shasun Pharmaceutical Division develops and manufactures formulations for solid dosage
products. The Division is a vertically integrated formulations partner for the pharmaceutical
industry. Its services include formulation research and development activities, Analytical
method development and validation, scale-up and technology transfer, clinical supplies
manufacturing to full scale commercial manufacturing of oral solid dosage forms.

2.3.3 Contract Formulation

Shasun Pharmaceutical Division contract manufactures finished oral dosage forms for
a number of Pharmaceutical companies worldwide. These include film coated, sugar coated
and enteric coated tablets as well as hard gelatin capsules
Tablet compression machines are capable of manufacturing single as well as bi-layer tablets
and our coating technology includes film, sugar and enteric coated tablets as well as pellets
for encapsulation.

Our Packaging capabilities include bottle and blister packaging as well as bulk
granules. Blisters can be packaged cold and hot form materials. The final finished product
can be packaged and labeled as per regulatory requirements and ready for delivery to the
customer.

2.3.4 Formulation Development

Shasun Pharmaceutical Division offers formulation development services for

developing oral solid dosage forms to customers in the pharmaceutical industry. Our
technologies include both immediate release ,delayed release tablets and capsule products.
We also have state of the art coating equipment capable of manufacturing film, sugar or
enteric coated tablets as well as Wurster coating equipment for producing coated pellets for
encapsulation. All of these products can be developed for both pre-clinical activities as well
as for conducting clinical trials.

Our state of the art laboratories have all the required equipment to develop
formulations as well as analytical methods for drug products. Equipment train from
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development laboratories to pilot plant and commercial manufacturing areas is similar in
make and design to facilitate seamless technology transfer of our processes.

Clinical supplies are manufactured in cGMP space in our pilot plant or commercial
areas depending on the batch size requirements.Stability studies are conducted according to
both US FDA as well as ICH guidelines.Regulatory Documentation services for the
preparation and submission of dossiers are also available.

Shasun customer base includes several top pharmaceutical multi-national companies

as well as a large number of emerging pharmaceutical companies. Our development teams
are fully dedicated to their projects and follow strict project management schedules to deliver
products on time, and within budget.

2.4 REVIEW OF LITERATURE

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The aim of Pharmaceutical Product Development is to design a quality
product and the manufacturing process to deliver the product in a
reproducible manner

Development of formula and finalization of the formula is the main research function of
formulation development scientists. (e.g.: capsules / tablets, Oral solutions, suspensions, gels,
topical ointment, creams, lotions, sterile indictable, ophthalmic formulations, Sterile
lyophilized products and NDDS etc) and the process development includes Selection of
suitable process (e.g., Wet granulation /Direct granulation etc) selection of equipments (e.g.,
Twin shell blender/Fluid bed coater etc) and to study about process variable for process
optimization.

Evaluation suitable manufacturing processes: (For solid dosage

forms)

Granulation

Wet granulation (aqueous or non aqueous): high shear mixing / low shear mixing FBD spray
procedure, or Hot air oven, Determination of pre-mixing (in Granulator), Determination of
fluid addition (if relevant), Determination of LOD limits, Determination of testing
temperature for checking LOD limits, Determination of granulation time (chopper I & II),
Determination of torque end-point value, Determination of drying parameters, Dry
granulation and/'or slugging, Determination of order of mixing, Physical Properties of
Granulate.

• Flow properties, Density, Particle-size distribution and Compressibility

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Direct Compression

Pre-lubrication

Lubrication

Coating process parameters should include Inlet temperature, Bed temperature, Exhaust
Temperature, Spray rate, Pan RPM, Atomization pressure, Desired Weight gain, Coating
tablet parameters like weight, thickness, dimension, disintegration Compression physical
properties of compressed tablets :

Weight, • Hardness (justification of hardness range), • Thickness, • Friability• Disintegration

• Dissolution

Productivity measurement and Improvement

Globalisation is posing several challenges to the manufacturing sector. Design and operation
of manufacturing systems are of great economic importance. Factory performance remains
unpredictable, in spite of the considerable literature on manufacturing productivity
improvement and the long history of manufacturing, as there is no widespread agreement on
how it can best be performed (Gershwin, 2000). Productivity measurement and improvement
goes hand in hand, because one cannot improve what one cannot measure. The review of
literature on manufacturing systems productivity measurement and improvement has been
summarised under four categories; they are Operations Research- (OR-) based methods,
system analysis-based methods, continuous improvement methods and performance metrics-
based methods. A survey of commercial tools available to measure manufacturing system
performance is also performed. The review indicates that quantitative metrics for measuring
factory level productivity and for performing factory level diagnostics (bottleneck detection,
hidden capacity identification) are lacking. To address this gap, a factory level effectiveness
metrics-based productivity measurement and diagnostic methodology is proposed.

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Drug Product evaluation also includes the followings

Physical parameters:

1.Tablet / Capsule Shape.

2.Tablet / Capsule color.

3.Embosement / Printing.

4.PackSize.

5.Packaging material (Containers and Closures).

7.Cotton.

8.Dessicant.

Physical Testing:

1.Weight

2.Thickness

3.Hardness

4.Dimensions

4.Disintegration Time

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 2.4 PROCESS DESCRIPTION

The production of IBUPROFEN takes place in four stages which is divided as six
different plants in the industry. They are as follows
1. IPCA plant

2. Aldehyde plant

3. IBU plant

4. Pharma plant

5. Purification

6. Packaging

In order to understand the purification process and the enhancement of the same it is
necessary that the general process that is carried out in each of the above mentioned plants
should be closely studied and analysed.

2.4.1 IPCA Plant

The term IPCA stands for iso proply chloro acetate. Here isopropyl chloro acetate and
mono chloro acetic acid is mixed and stirred for 30 minutes. Concentrated H2So4 is added and
the mixture is left for a period of 5 hours for reaction to take place. Further a settling time of
3 hours is given. The mixture is separated in a settling tank to two distinct top and bottom
layers. Out of which the bottom layer is removed for further reaction. NaHCO3 is added to
the top later which is the crude IPCA and it is stirred to neutralize. The bottom later of this
neutralized mixture is neutralized IPCA also called polypropylene reactor acid medium.
This mixture is transferred to a stainless steel reactor where a moisture level of 0.15 (standard
quantity) and a temperature of 105-110o C, vacuum pressure of 500 mmHg is maintained.

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The moisture content is checked regularly. The mixture is cooled to 40 o C after the reaction
time. It is then filtered using the leaf filter and the sample is checked for the end
requirements.

2.4.2 Aldehyde plant

1. Sodium section

Dissolved sodium is the basis for aldehyde production. Sodium metal and isopropyl
alcohol are charged into the reactor with FeCl3 as the catalyst. The moisture content of
isopropyl alcohol should be well within 0.2. the mixture is heated and when the temperature
reaches 60 oC it becomes an exothermic reaction at a temperature of 80o C the heavy reaction
begins. The total reaction time is about 7 hours

2. Esterification

The end product of IPCA plant and IBAP is charged to the reactor at 10 o C since ester
forms at this temp. And sodium propanoid is charged at 20 o C in order to reduce the cooling
time. The total reaction time is 2 hours.

3. Distillation

The reaction mixture is transferred to the distillation column at the temperature of 65oC
for 6 hours. The reaction mass is then cooled to 50 -60o C after which the ester is ready.

4. Hydrolysis

The process water and the caustic soda lye is charged to the reactor. The normality of
the mixture is checked to be within 1.9 to 2.0 N. The ester is now transferred to the reactor
and the temperature is raised to 65o C and the conditions are maintained by stirring it
constantly for 2 hours. Now HCL is charged at the same temperature and the sample is
checked for pH value, which should be around 3.80-4.20. the mixture is cooled to 40-50 oC
and is allowed to settle for 30 minutes. Drain the tower water from the jacket. The bottom aq.
Layer is transferred to storage tank and water is charged again. The mixture is stirred for 30
minutes and is allowed to settle for another 30 minutes. Now the bottom aq. Layer is
transferred to the storage tank for recovery. The top organic layer is the crude aldehyde.

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 The crude aldehyde is sent through the low and high vacuum distillation process for
the sake of improving its purity. The low vacuum distillation occurs at 400 mmHg and 120 C
and then later sent to the storage tank. From here it goes to the high vacuum distillation tower
which maintains a temperature of 175oC in the first fraction and 225o C in the second fraction
with a pressure of 730 mmHg.

2.4.3 Ibu plant

The jones reagent is added to the aldehyde (dilute h2so4 and sodium dichromate
forms chromic acid which is called the jones reagent). The acetone in the storage tanks are
mixed to the aldehyde and the mixture is cooled to 10 o C since the reaction occurring is
exothermic. The mixing has to take place before 25-29 o C after which the mixing wont be
complete and the end product wont t be obtained. After which the brine is sent for circulation.
The mixture is maintained for a period of 1 hour. The mixture separates into top and bottom
layer where the bottom layer possesses a specific gravity value of 1.2. then the mixture
surpasses simple distillation and then its crystallised. The mixture is washed using hexane to
minimize the losses involved. The waste dichromate is the by product obtained.

2.4.4 Pharma plant

The process is a batch process. Water is used for washing purpose and its purified 3
times. Along with the organic layer activated carbon is added. The mixture is filtered through
leaf filter first and then followed by catridge filter. The filtration is carried out at a
temperature of 40-50o C, The temperature is maintained at this value because the formation of
IBU takes place at 38o C and the total time is 7 hours. Then its sent to the crystallizer where
the required size of 50 – 90 is achieved. From here it is sent to the centrifuge for hexane
washing and separation. The final product is obtained by cone scrapping and later sent to the
packaging section.

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 2.4.5 Purification Process

Equipments Used For Purification

condenser

Leaf
filter

Distillation Catridge crystallizer centrifuge

column filter

product

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Distillation column
Distillation is a process in which a liquid or vapour mixture of two or more
substances is separated into its component fractions of desired purity, by the application and
removal of heat.

Distillation is based on the fact that the vapour of a boiling mixture will be richer in the
components that have lower boiling points.

Therefore, when this vapour is cooled and condensed, the condensate will contain more
volatile components. At the same time, the original mixture will contain more of the less
volatile material.

Distillation columns are designed to achieve this separation efficiently.

•
distillation is the most common separation technique

• it consumes enormous amounts of energy, both in terms of cooling and heating

requirements
•
it can contribute to more than 50% of plant operating costs

The best way to reduce operating costs of existing units, is to improve their efficiency and
operation via process optimisation and control. To achieve this improvement, a thorough
understanding of distillation principles and how distillation systems are designed is essential.

There are many types of distillation columns, each designed to perform specific types of
separations, and each design differs in terms of complexity. The main types are batch and
continuous columns. Here batch type column is used. In batch operation, the feed to the
column is introduced batch-wise. That is, the column is charged with a 'batch' and then the
distillation process is carried out. When the desired task is achieved, a next batch of feed is
introduced.

~ 25 ~
Condenser

Condensation is the change in the phase of matter from the gaseous phase (of an element/
chemical species) into liquid droplets or solid grains of the same element/ chemical species.
Upon the slowing-down of the atoms/ molecules of the species, the overall attraction forces
between these prevail and bring them together at distances comparable to their sizes.

Since the condensing atoms/ molecules suffer from reduced degrees of freedom and ranges of
motion, their prior kinetic energy must be lost/ transferred to an adsorbing colder entity —
either a center of condensation within the gas volume (colder molecules of the species, cold
grains of dust etc.) or some contact surface. Condensation is initiated by the formation of
atomic/ molecular clusters of that species within its gaseous volume — like rain drop or
snow-flake formation within clouds — or at the contact between such gaseous phase and a
(solvent) liquid or soCondensation is a crucial component of distillation, an important
laboratory and industrial chemistry applicationlid surface.

Leaf filter

The Pressure Leaf Filter is a MS/SS Vertical Vessel with Filter Leaves inside. The leaves are
mounted vertically on a common manifold pipe, through which the filtered liquid flows out.
On the top, the leaves are held by a vibrating shaft . A mechanical vibrator driven by electric
motor/pneumatic vibrator is provided for vibrating the leaf shaft for cake discharge. Jacket
for hot filtration can be offered if desired Over flow, vent/steam/air charging, pressure gauge
& safety valve are provided on the top. The top cover is provided with devit arm mechanism
for raising the lid for cleaning/ removing the leaves. “I” bolts are provided for quick opening
and closing of top lid. A mechanical jack is provided to lift the top for cleaning/removing the
leaves. Lugs are provided for mounting the PLF.

~ 26 ~
The Filter leaves filter on both sides and hence a large filtration area is obtained in a
relatively small vessel.

Leaf Filters are ideal for Solid-Liquid Separation & work on principle of Precoating &
pressure. The Pump is stopped & steam /air pressure is applied from the top ( without
dropping the filter pressure) to filter the material around the leaves held up in the tank & to
squeeze the cake further & reduce the liquid retention in it . The hold up unfiltered liquid in
the conical portion is taken back.

Catridge filter
A filter for the clarification of process liquids containing small amounts of solids; turgid
liquid flows between thin metal disks, assembled in a vertical stack, to openings in a central
shaft supporting the disks, and solids are trapped between the disks. Early engine oil filters
were of cartridge (or replaceable element) construction, in which a permanent housing
contains a replaceable filter element or cartridge. The housing is mounted either directly on
the engine or remotely with supply and return pipes connecting it to the engine. In the mid-
1950s, the spin-on oil filter design was introduced: a self-contained housing and element
assembly which was to be unscrewed from its mount, discarded, and replaced with a new
one. This made filter changes more convenient and potentially less messy, and quickly came
to be the dominant type of oil filter installed by the world's automakers. Conversion kits were
offered for vehicles originally equipped with cartridge-type filters. In the 1990s, European
and Asian automakers in particular began to shift back in favor of replaceable-element filter
construction, because it generates less waste with each filter change. American automakers
have likewise begun to shift to replaceable-cartridge filters, and retrofit kits to convert from
spin-on to cartridge-type filters are offered for popular applications. Commercially available
automotive oil filters vary in their design, materials, and construction details. These variables
affect the efficacy, durability, and cost of the filter.

~ 27 ~
Crystallizer

In chemical engineering crystallization occurs in a crystallizer. Crystallization is a unit

operation through which a chemical compound, dissolved in a given solvent, precipitates
under certain conditions to allow successive separation between the phases.

Crystallization is therefore an aspect of precipitation, obtained through a variation of the

solubility conditions of the solute in the solvent, as compared to precipitation due to chemical
reaction.

Crystallization is one of the pristine unit processes. It may be assumed that our ancestors used
sodium chloride found in crevices of the surface rocks after drying caused by the sun: this
process is still in use in modern solar ponds.

Other crystallization processes, for example sucrose production (this is the crystalline product
with the largest world production, followed by sodium chloride), or in pigment
manufacturing, were used in ancient times. These substances were sometimes produced by
crystallizing the solutes of some more or less natural brine.

In more recent times, the fast expansion of the chemical industry has required a thorough
study of the dynamics of crystallization, and this unit operation is now used in many
industrial manufacturing areas: table salt, sugar, sodium sulfate, urea, just to name a few, are
produced by crystallization from solutions.

Crystallizer technology has progressed alongside with the new processes. Once simple tanks
in which, through cooling, evaporation or maybe through pH variation a crystal was obtained,
nowadays continuous machines ensure a remarkable consistency in the product
characteristics. Among the first models of modern crystallizers were probably the calandria
type, being today the standard crystallizer for sucrose, and the Oslo, named after the
Norwegian capital, since it was developed to produce salt in a climate not particularly fit for
solar ponds, salt being widely used in Norway in stockfish production. The Oslo type was
probably the first crystallizer designed specifically for the control of crystal growth.

~ 28 ~
Centrifuge

A centrifuge is a piece of equipment, generally driven by an electric motor (some older

models were spun by hand), that puts an object in rotation around a fixed axis, applying a
force perpendicular to the axis. The centrifuge works using the sedimentation principle,
where the centripetal acceleration causes more dense substances to separate out along the
radial direction (the bottom of the tube). By the same token, lighter objects will tend to move
to the top (of the tube; in the rotating picture, move to the centre).

In the picture shown, the rotating unit, called the rotor, has fixed holes drilled at an angle (to
the vertical). Test tubes are placed in these slots and the rotor is spun. As the centrifugal force
is in the horizontal plane and the tubes are fixed at an angle, the particles have to travel only a
little distance before they hit the wall and drop down to the bottom. These angle rotors are
very popular in the lab for routine use.

~ 29 ~
2.4.6 Packaging Process :

Drying process:

The wet IBU Profen materials sent to the wet material storage room by the conveyer.
250 kg of wet materials are filled in the 4 bowl respectively. Then Bowl fixed on the 4 dryer
for drying process at 40-50o C after 70 minutes it sent to the milling process then it packed by
35 kg and keep it in the dry material storage room.

Blending process:

Dry materials are charge to the blender for blending process. Then it is packed in the
50 kg drums and it stored in the packed drum storage room. The packaging process layout is
show in the below fig.

~ 30 ~
 CONVEYOR

DRYER 1

WET MATERIAL
STORAGE ROOM

DRYER 2

DRYER 3

DRYER 4
MILLER COLLECTION

MILLER 1

DRY MATERIAL STORAGE ROOM

ROOM

MILLER 2

BLENDERS

Packing Process

~ 31 ~
NEED FOR THE STUDY

• This study is mainly to improve the On Time delivery process of the products in
Shasun Chemicals And Drugs Ltd, Puducherry

• This study is also used to suggest about the reduction of unwanted employees in the
packing section of the company.

• This study is also used to improve the production rate of the products in Shasun
Chemicals And Drugs Ltd, Puducherry.

~ 32 ~
 3. OBJECTIVE OF THE STUDY

3.1 MAIN OBJECTIVE

• To measure productivity in packing section to meet the customer demand.

• To identify the On Time delivery process of the product.

• To reduce the Packing time of the product.

• To increase the Production rate of the company

~ 33 ~
3.1.1 WORK STUDY

Work study deals with the techniques of method study and work measurement, which
are employed to ensure the best possible use of human, machine and material resources in
carrying out a specified activity.

3.1.2 PROCESS LAYOUT

A process layout, similar machines and services are located together. Process layout is
normally used when the production volume is not sufficient to justify a product layout.
Typically, job shops employ process layouts due to the variety of products manufactured and
their low production volumes.

3.2 LIMITATIONS OF THE STUDY

• The research is confined to Puducherry branch only.

• This study is limited to Two month only.

• The Result of the study stands upon the information provided by the company

employees only.

~ 34 ~
 4.WORK STUDY

4.1 Description

Work study deals with the techniques of method study and work measurement, which
are employed to ensure the best possible use of human, machine and material resources in
carrying out a specified activity.

Work study is concerned with finding better ways of doing work and avoiding waste
in all its forms. As such the objective of work study is to assist management to obtain the
optimum use of the human, machine and material resources available to the organization for
the accomplishment of the work upon which it is engaged.

The description has three aspects:

• The most effective use of plant and equipment

• The most effective use of human effort

• The evaluation of human work

Work study has two broad areas viz., method study and time study.

Method study is concerned with finding the facts about a situation and after a critical
examination of these facts, developing a new and better method of doing that work. It is
defined as the existing and proposed ways of doing work and the development and
application of easier and more productive methods.

Time study is concerned with the establishment of time standards for a qualified
worker to perform a specified job at a defined level of performance.
Method study must precede time study before any attempt is made to measure and set
standards for the various jobs concerned.

~ 35 ~
4.2 METHOD STUDY

It is the systematic recording, analysis and critical examination of existing and

proposed ways of doing work and the development and application of easier and new
production methods.

Areas and application of method study

It can be applied to any field of work, but the most important areas where it plays a
major role in improving productivity are as follows:

• Improved layout of office, working areas of factories

• Improved design of plant and equipment

• Improved use of materials, plant, equipment and manpower

• Most effective handling of materials

• Improved flow of work

• Standardization of methods and procedures

• Improved safety standards

• Better working conditions

Multiple Activity Chart

In this project, Multiple Activity chart is used. In many situations, certain

facilities/machines/equipments will be managed by a single individual or by a group of

~ 36 ~
individuals. A multiple activity chart is a pictorial representation of activities of individuals
and associated facilities/machines/equipments simultaneously on a common time scale.

4.3 PROCESS FLOW:

The process flow of the production has been identified with the drying operation and
Blending operation.

By shifting the weighing machine would minimize the weighing time. So it minimizes
the overall production time of 1 minute/ Drum which is shown in the below fig.

The multiple activity chart is applied to API Packaging process which is shown in the Fig.
Man 1  Empty drum weighing worker
Man 2  Keep and open Safety cover worker
Man 3  Fill and weighing worker
Man 4  Worker putting tag on the cover
Man 5  Note and push drum to the store room

Process Time Table

Figures in Secs.
Drum No. 1 5 10 15 20 Avg. time

Man 1 17 15 16 13 15 15

Man 2 35 29 30 28 30 30

Man 3 155 147 148 152 148 150

Man 4 16 15 15 14 15 15

Man 5 30 31 31 30 28 30

BEFORE PROCESS IMPROVEMENT ACTIVITY CHART

Man 1 = 15 sec.

~ 37 ~
Man 2 = 30 sec.
Man 3 = 150 sec.
Man 4 = 15 sec.
Man 5 = 30 sec.

The Chart is shown in the next page.

~ 38 ~
 M1 M2 M3 M4 M5
0
Working Idle Idle Idle Idle
20 Working
Working
Idle
40
Working
60 Working
Idle
80 Working
10 Idle
Idle
0
12 Working
0 Idle
14
0 Idle
16
0
18
0
20 Working
0 Working
22
Working
0 Working
24
0
26
Working
0
Idle
28
0 Idle
30 Idle
Idle
0
32
0
34
0 Working
36 Working
0
Working
38 Working
0
40
0 Working
42
0
44
0
46
0
48
0
50
0
Before Process Improvement Chart

~ 39 ~
 Seconds Man 1 Man 2 Man3

Man 1= 45 Sec. 20 Working Idle Idle

Man 2= 150 Sec. 40

Man 3= 45 Sec. 60 Working

80
10
0
12 Working Idle
0
14 Idle
0
16
0
18
0
20
0 Working Working
22
0
24
0
26
0
Working
28
0 Idle Idle
30
0
32
0
34
0
36
0
38
0
40
0
42
0
44
0
46
0
48
0
50
0

After Process Improvement Chart

~ 40 ~
4.4 MAN POWER REDUCTION PROCESS :

The workers will be idle for certain portion of the above work cycle that is during

M1- Empty Drum weighing and

M4- put tag on the cover.

They can be assigned more than one work which is shown in the below Figure.

~ 41 ~
MATERIALS FLOW BEFORE AND AFTER MAN POWER REDUCTION
BEFORE MAN POWER REDUCTION PROCESS
PACKED DRUM
STORAGE ROOM

BLENDER
5 TONES

MAN 1 MAN 2 MAN 3 MAN4 MAN 5

AFTER MAN POWER REDUCTION PROCESS PACKED DRUM

STORAGE ROOM

BLENDER
5 TONES

MAN 1 MAN 2 MAN 3

~ 42 ~
BEFORE SHIFTING WEIGHING MACHINE

BLENDER 5 TONES

50 KG

WEIGHING MACHINE

AFTER SHIFTING WEIGHING MACHINE

BLENDER 5 TONES

50 KG

WEIGHING MACHINE

~ 43 ~
PROCESS TIME OF BEFORE SHIFTING WEIGING MACHINE :

Quantity of material Required to pack = 1 tone

Drum capacity = 50 kg
No.of. Drums Required = 20
From the Activity chart we, know that
Time taken to pack a drum = 4 mins
Total time taken to pack 20 Drum = 20*4 mins
= 1 Hour . 20 mins

Time taken to charge material in Blender = 20 mins

Time take for Blending process = 20 mins
So, Total time Required to pack 1 tone = 2 Hours

PROCESS TIME OF AFTER SHIFTING WEIGHING MACHINE :

Quantity of material Required to pack = 1 tonne

Drum capacity = 50 kg
No.of. Drums Required = 20

From the Activity chart we, know that

Time taken to pack a drum = 3 mins
Total time taken to pack 20 Drum = 20*3 mins
= 1 Hour

Time taken to charge material in Blender = 20 mins

Time take for Blending process = 20 mins
So, Total time Required to pack 1 tone = 1 Hours. 40 mins

~ 44 ~
PACKING IMPROVEMENT PER DAY :

Working hours per day = 20 Hours (Without break time )

BY BEFORE IMPROVEMENT PROCESS

Time takes to pack 1 tone = 2 Hours

We can pack only 10 tonnes / day

BY AFTER IMPROVEMENT PROCESS

Time takes to pack 1 tone = 1 Hour.40 mins

We can pack only 12 tonnes / day

Cost of 1 ton of IBUPROFEN= Rs 3 lakhs

So, Rs 6 lakhs Productivity could be increased per day

~ 45 ~
 5. PROCESS LAYOUT

5.1DESCRIPTION

Process layout is a floor plan of the physical facilities which are used in production.
Layout planning refers to the generation of several possible plans for the spatial arrangement
of physical facilities and select the one which minimizes the distance between the
departments.

The objectives of plant layout are:

• Minimize investment in equipment

• Minimize overall production time

• Utilize existing space most effectively

• Provide for employee convenience, safety and comfort

• Maintain flexibility of arrangement and operation

• Minimize materials-handling cost

• Facilitate the manufacturing process

• Facilitate the organizational structure

5.2 PROCESS LAYOUT DESIGN

A flow analysis can be combined with an activity analysis to develop the relationship
diagram. The space relationship diagram is constructed by combining space considerations
with the relationship diagram.
Based on the space relationship diagram, modifying consideration and practical
limitations, a number of alternative layouts are designed and evaluated which is shown in
below Figure.

~ 46 ~
 PACKED DRUM
STORAGE ROOM

BLENDER
5 TONES

MAN 1 MAN 2 MAN3

EMPTY DRUM STORAGE ROOM

BEFORE MODIFICATION OF PROCESS LAYOUT

~ 47 ~
 AFTER MODIFICATION OF PROCESS LAYOUT PACKEDDRUM
STORAGE ROOM

BLENDER
5 TONES

MAN 1 MAN 2 MAN 3

CONVEYOR

EMPTY
After DRUM STORAGE
modification ROOM
of Process layout

6. Findings
~ 48 ~
• A lot of time is wasted in weighing the drum and then in filling.

• The company uses 5 workers in the packing section. Among five employees few are
idle for most of time during packing process.

• Conveyor is not used in moving the empty drums.

• The drum is filled manually without any advanced technique.

~ 49 ~
 7. Suggestions
• By shifting the weighing machine would minimize the overall production time of 1
minute/drum and utilizing this time to increase 2 tonnes/day i.e. 6 lakhs/day

• Instead of 5 workers, only 3 workers could be deployed for packing process by

reduction of two employees.
• Installation of conveyor for empty box flow as mentioned in the figure for utilizing
existing space most effectively
• Automation of filling machine would be used to get planned productivity

15 tonnes/day

~ 50 ~
 8. Conclusion
This project was carried out in production & packing section in Shashun Chemicals
and Drugs Ltd. The main objective of the project was to analyze the existing production
pattern and to offer better design and suggestions to improve the productivity.

The study presumed that the company could not achieve 100% productivity per day.
This project reviewed the production plan of the company by using the method study and
process layout design. Method study is used in the project to find the facts about a situation
and to develop a new and better method of doing packing.

By implementing this study, the company can achieve planned productivity of

15 tonnes/day.

~ 51 ~
 9. BIBLIOGRAPHY

BOOKS

• Production and Operations Management / R. Panneerselvam – Second edition, Prentice-

Hall of India, 2006.
• Operations Management / Jay Heizer and Barry Render, Prentice Hall, 2006.

Web Sites

• www.shasun.com

• www.google.com

~ 52 ~