Inplant Training Report

ACKNOWLEDGEMENT

Firstly, I would like to thank Mr. Subrahmanya. A (DGM) and Mr. Vivin J Fernandes (DGM)
for providing me with an opportunity to do my internship in this esteemed organization from
which we have gained an invaluable experience.

I would also like to thank Mr. Hari Prasath A.R. (DM) for his kind and patient guidance and
support without which this training would not have been completed or written.

I would also like to express my deep gratitude to Mr. Sridhar I (Group leader R&D), Mr.
Prashanth Kumar G (Research Scientist) and Mr. Shaik Allauddin (Asst Manager) for all
knowledge and information imparted to me.

Last, but not the least, I would also like to thank the entire staff in the Pilot plant for taking
the time to share their expertise and knowledge of the field.

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 Inplant Training Report

CONTENTS

1. Introduction
2. Role of pilot plant
3. Scale-up
4. Agitation and Flow patterns
5. Corrosion Testing
6. Analytical Development Laboratory
7. Synthesis of ‘X’
8. Activity
9. Conclusion
10. References

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INTRODUCTION

Overall, pharmaceutical industries are classified under three categories based on their
specialisations –

1. Active Pharmaceutical Ingredients (API)

2. Chemical formulation
3. Clinical research

Jubilant Generics is an integrated global pharmaceutical and life sciences company engaged
in manufacture and supply of APIs. The Company’s strength lies in its unique offerings of
Pharmaceutical and Life Sciences products and services across the value chain.

They are engaged in continuous improvement of products and processes to enhance the
quality of production and cost competitiveness in order to build value for our customers.
Jubilant Life Sciences serves its customers globally with sales in over 100 countries and
ground presence in India, North America, Europe and China. Over the years, Jubilant Life
Sciences has extended its footprint beyond India in the USA, Canada, Europe, and other
countries across the globe.

Carbamazepine, Oxcarbazepine, Lamotrigine, Citalopram, Risperidone, Valsartan, Lorsartan,

Irbesartan are some of the products manufactured here.

The industry practises the 5S principle.

1S. Seiri – Organisation – Used or unused things should be separated

2S. Seiton – Neatness – Each and everything should be in its proper place

3S. Seison – Cleaning – Workplace and machinery should be clean

4S. Seiketsu – Standardisation – To enable easy to use technology to keep environment clean
and healthy

5S. Shitsuke – Discipline – To ensure use of innovative technology to sustain environment

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ROLE OF A PILOT PLANT

This report focuses on the relatively small-scale development operations found in the
pharmaceutical and fine chemical industries. These usually entail manual batch operation of
processes that are often not fully established, in standard chemical reactors. Even with the
increasing role of automated bench-scale reactors in process development, most processes
will be tested in the pilot plant before reaching commercial scale.

Here are some important functions that a pilot plant can perform in process development:
1. Produce developmental quantities of new compounds for evaluation, toxicity
testing, safety and stability studies, clinical trials, and introduction into the market.
Often the first few kilograms of a new compound are the most difficult to make,
since an optimized but established route has not yet been developed.
2. Demonstrate that processes can be successfully scaled up and that there are no
unexpected ramifications of extended operating times, slower rates of addition or
mixing effects at larger scale.
3. Ensure that no important details which have been overlooked.
4. Test materials of construction.
5. Complete a more detailed mass balance, and obtain better estimates of yield and
effluent stream generation.
6. Help to better estimate process costs and increase management confidence in investing
for full-scale production.
7. Obtain design data and optimum operating parameters for specifying larger-scale
equipment.
8. Train members of the technology transfer team preparing for commercial production.
9. Help develop a comprehensive and detailed operating procedure for transfer to
manufacturing.

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SCALE-UP

Factors in scale-up

The biggest problems faced by scale-up team are listed below:

1. Expanded time scale: Charging the raw materials and solvents, heating or cooling
steps, simple distillation, isolation of a product in a centrifuge can take hours. Such
extended processes can cause decomposition, polymorphic shifts or other problems.
Steam stability is an important aspect of scale-up. It should be borne in mind
throughout the development process.
2. Chemical hygiene: Handling chemicals can increase risk and chances for exposure of
toxic substances. At pilot scale, electrostatic hazards of handling dry powders,
flammable solvents and wet filter cakes are greatly increased. All of this means that
personal protective equipment must be used. Safety devices and interlock systems
must be installed.
3. Heat transfer: In large reactors, heat transfer surface area/volume is greatly
diminished where heating and cooling is accomplished by means of heat transfer
medium. Heat removal rates in pilot plants are 30 times slower than in commercial
plants. This approaches adiabatic operation. The heat generated per unit volume in an
exothermic reaction remains constant as scale increases. However, the amount of heat
increases as cube of the reactor size. Other factors can also affect heat transfer, like –
heat transfer fluid, thickness and thermal conductivity of reactor walls and mixing
effects.
4. Temperature control: Maintaining constant temperature is very difficult on a larger
scale. Heat generated in the reactor must be removed at a rate matching its production.
If the role of mixing is not well understood, blend-times may be longer, temperature
gradients may also exist from the centre to the edge of the reactor. This may increase
rate of side reaction and formation of by-products.
5. Reactor mixing: Due to the increased geometry at large scales, blend times can be
longer than at bench. Local areas of excess reagents can cause formation of by-
products which affects reaction selectivity or yield. If rate of the reaction drops too
far, dangerous accumulations of unreacted reagents can occur. In case of mixing, it
cannot be scaled up by using geometrically similar but larger mixers.

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 Inplant Training Report

6. Operating volume: Evaporating to dryness or very good volumes is a convenient

laboratory technique. This isn’t possible at scale-up because most reactors have
maximum mixing levels of about 10-20% of their capacity.
7. Reaction control: Often, because of heat removal limitations, processes are designed
so that reaction rate can be regulated by controlled addition of a limiting reagent. But,
a greatly expanded time scale must be expected at the pilot plant as compared to the
bench. For very low temperature reactions the sensible heat of the reagent solution
can alone approach the heat of reaction.
8. Drying: It is often accomplished through vacuum ovens in the laboratory. Similar
vacuum tray driers can be used in pilot and commercial plants, but, with longer drying
cycles. Rotary cone driers, tumble driers, paddle dries are also common, but, they
produce materials with different physical characteristics that those of tray driers.
9. Raw material chargers: Owing to handling difficulties, charging of raw materials may
not be as accurate at large scale as at bench. So, limits or ranges of these changes
must be determined and tested. Also, in a pilot plant water and solvents may be much
colder.
10. Visibility: Relying on vision indication of reaction milestones such as initiation of
crystallization, may lead to disappointment as the best way to do it at scale is to peep
into a reactor through a small window. Instead, batch progress needs to be marked by
quantifiable properties that can be measured using analytical methods.
11. Reactor access: At large scale, adding of seed crystals by opening a reactor can often
compromise batch integrity or operator safety. It is necessary to use closed sampling
systems, solid addition chambers or add seeds in slurry.
12. Work-up: Pilot extractions and phase separations leave a lot of water behind than on
bench scale due to larger surface area of the banks and longer settling times. Water
removal, azeotropic drying or addition of drying agents become necessary. Liquid
phase batch processes are easiest to scale up than continuous reactors. Disadvantages
of operating in a batch mode are the long downtimes between batches, high labour
requirements and possible batch-to-batch variation in product quality. To minimize
downtime and obtain consistent results, it is important to plan carefully and to
understand these parameters that affect the yield and quality.

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Do’s and Dont’s during process scale-up

Sl DO’S DONT’S
No.
1. Develop operating guidelines before Avoid reactions that need highly
running of new processes. specialized equipment or that are
hazardous.
2. Set up operating and maintenance log Avoid “all-in and heat” operations –
books for each equipment – document adding all reagents to the vessel and
batches, cleaning operations, tests with then heating up. It is better to design
results, maintenance. reactions that can be controlled by
slow addition of limiting reagent at a
rate that matches equipment cooling.
3. Set up sample log book – list every sample Never heat a reactor without agitation
collected for testing or retain. This is an and never stop the agitator until
invaluable archive and will ensure that the reaction mixture cools down to a safe
important data is not lost. temperature.
4. Retain samples of all products or Do not operate a reactor less than 50°C
intermediates produced in the pilot plant. from the known onset temperature of
Store them in a cool, dark, dry place. an exotherm that may run out of
control.
5. Early involvement of engineers in process Avoid adding solids to a reacting, hot
development and route selection. or refluxing mixture because it can be
extremely dangerous and screws and
conveyors for solid additions are
unreliable and expensive.
6. Fix the process well prior to the scale-up – Never develop a process that relies on
focus on ensuring safe scale-up of batch. evaporating to dryness or to very low
volumes because of the minimum
mixing level in reactors.
7. Perform hazard and operability review Avoid reactions that have to be isolated
each time a new process is brought into the immediately as it can take up to 24
plant. hours.
8. Calorimetric testing to determine stability Avoid using methylene chloride or

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of components, ease of reaction, potential other halogenated solvents that are

for decomposition and magnitude of environmental hazards. Similarly, even
thermal runaways. use of phosphates should minimized.
9. Create a log sheet for each batch Avoid hot filtrations or polish filtration
conducted. Master records should be of highly saturated solutions because
reviewed and signed by representatives of the solids can crash out and cause
the departments involved. clogging.
10. Use technical grade raw materials or Avoid reverse phase-splits as they
materials obtained directly from proposed increase the cost of manufacturing and
large scale suppliers – they will be more add time to the process cycle.
representative of future manufacturing
sources.
11. Always perform a bench scale test using all Avoid using chromatography for
raw materials and in-house intermediates purification because it requires large
earmarked for the pilot batch. Ensure that amounts of solvents and support
the product meets specification. materials.
12. Make maximum use of each batch. Take as Don’t risk all of your raw materials or
many samples as possible and retain a good intermediates on one batch.
number for later troubleshooting. And this
includes key effluent streams. Collect mass
balance data to test energy balance
relationships and to verify analytical
methods.

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MIXING AND AGITATION

Mixing is a random distribution of materials in different phases into another forming a

homogenous phase.

Agitation is an induced circular motion of the material in a container in a desired way.

Purpose for agitation:

 Suspending solids in liquids

 Homogenisation (blending miscible liquids)
 Sparging (dispersing a gas through a liquid in the form of bubbles)
 Emulsifying (dispersing two immiscible liquids within each other)
 Promoting heat transfer

Flow patterns:

It is very important to understand the different types of flow patterns induced by various
agitators as this helps in the selection process of agitators for operations.

The three types of flow patterns are as below:-

1. Axial mixing: the fluid motion is parallel to an axis of rotation, moving media from
the top to the bottom. In pharmaceutical applications, it is generally used for reactions
where there is less flow, low viscosity and for high speed applications. Pitched blade
turbines give axial flow.

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 Inplant Training Report

2. Radial flow: Here, the fluid is discharged radially outward to the vessel wall, drawing
media from the top and bottom. It is used for high flow and high viscosity
applications and used for polymerisation reactions. As compared with axial flow,
radial flow impellers provide higher shear and higher turbulence with lower pumping.
Retreat blade turbines, flat blade turbines, marine blade turbines, all give radial flow.

3. Tangential flow: Here, swirling of the contents is seen, often with a surface vortex. It
is used when mixing high viscosity at lower speeds. In pharmaceutical applications, it
is used mostly for crystallisation. The most common impellers used for this pattern
are anchors. In GLRs, as we cannot use baffles, the thermowells serve as baffles.

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Thermowell

Classification of turbines depending upon type of flow

Axial flow Radial flow

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CORROSION TESTING

Pitched Corrosion
Marineis a naturalRetreat
process, which converts
Twina refined metal to aFlat/disc
more stable form, such as Anchor
blade blade
its oxide, hydroxide, or sulphide. It is the agitator
curve blade (usually metals) by (GL/SS)
gradual destruction of materials
turbine turbine turbine (SS) turbine
chemical and/or electrochemical reaction with their environment. It is very important to keep
(SS) (SS) (GL) (SS)
a check on corrosion action in industrial equipment and to pick suitable MOC accordingly.
Corrosion tests are conducted for a number of reasons, some of which are:
Applications: Applications: Applications: Applications: Applications:

 Homogenisation 1. To provide an insight into corrosion

 Homogenisation mechanisms.
 Homogenisation  Homogenisation  Homogenisation
 Solid suspension  Solid suspension  Liquid – liquid  Solid suspension  Heat transfer
 Liquid – liquid
2. To compare resistance
 Liquid – liquid
of one alloy to another
 Solid – liquid
understandard conditions
Liquid – liquid
(in alloy
 Solid – liquid  Solid
development – liquid
work for example). Heat transfer  Solid – liquid
 Gas – liquid  Heat transfer  Heat transfer
 Heat transfer 3. As a quality control test for a given heat of alloy.
4. To provide a basis for estimating service life of process equipment.

The simplest, and longest-established, method of estimating corrosion losses in plant and
equipment is weight loss analysis. This can be done by coupon testing method.

General Requirements for Coupon Tests:

There are a number of "good practice" requirements which apply to all coupon testing.

1. The chemistry and processing history of the material in the coupon must be known.
2. The coupon must be positively identified, usually by code numbers stencilled into the
specimen.
3. Data about the specific coupon test should be recorded in a permanent log book. Items
which must be recorded are detailed information on the coupon (chemistry,
mechanical properties, and processing history), dimensions of the coupon, initial
weight of the coupon, and initial surface condition. Location, condition of exposure,
and time of exposure must also be recorded.

Procedure of coupon test:

 Take a coupon of required material to be tested. Note down the initial weight, time,
area etc of the coupon.
 Immerse the coupon into the hazardous chemical and at regular intervals of time (24,
36, and 48 hrs ….), take out the coupon and weigh it again.

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Fig: Coupon

 Use these values in the formula below to calculate the corrosion in inch/year.

12×W
iPy =
ρ×A×T

inch
year
Where, iPy – corrosion loss in ,

W- Weight of coupon = initial – final,

ρ – Density,

A – Surface area of coupon,

T – Time of immersion

Recommendation inch
Corrosion Rate, year
Completely satisfactory < 0.01
Use with caution < 0.03
Use only for short exposures < 0.06
Completely unsatisfactory > 0.06

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ANALYTICAL DEVELOPMENT LAB

We had a brief visit to the analytical development lab where we learnt about two separation
techniques – High performance liquid chromatography and Gas chromatography.

High performance liquid chromatography (HPLC)

 Principle: High Performance Liquid Chromatography (HPLC) is a form of column

chromatography that pumps a sample mixture in a solvent (known as the mobile
phase) at high pressure through a column with chromatographic packing material
(stationary phase). It works on the principle of absorbance and dipole moment. The
sample is carried by a moving carrier gas stream of helium or nitrogen. HPLC has the
ability to separate based on polarities of the components, and identify compounds that
are present in any sample that can be dissolved in a liquid in trace concentrations as
low as parts per trillion. Because of this versatility, HPLC is used in a variety of
industrial and scientific applications, such as pharmaceutical, environmental,
forensics, and chemicals.
 Working: A reservoir holds the solvent [called the mobile phase, because it moves]. A
high-pressure pump (5000 psi) is used to generate and meter a specified flow rate of
mobile phase. An injector [sample manager or auto sampler] is able to introduce
[inject] the sample into the continuously flowing mobile phase stream that carries the
sample into the HPLC column. The column contains the chromatographic packing
material needed to effect the separation. The column is generally coated with silica or
silica coated with other chemicals depending on the requirements. This packing
material is called the stationary phase because it is held in place by the column
hardware. A detector is needed to see the separated compound bands as they elute
from the HPLC column [most compounds have no colour, so we cannot see them with
our eyes]. Here, a UV detector is used which is set to the desired wavelength range.
The mobile phase exits the detector and can be sent to waste, or collected, as desired.
This is the basic working technique of HPLC.
 HPLC is used for detection of solid materials which exhibit UV absorbance.
 A graph of absorbance versus retention time is plotted and the peaks determine the
impurities.
area under peak
Impurity content = ×100
 Percentage of impurities is determined as, total area

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 Ultra-High Performance Liquid Chromatography is a more developed technique

which works on the same principle with high pressures (15,000 psi) and reduced run
time.

Gas chromatography (GC)

 Principle: Gas chromatography involves a sample being vaporised and injected onto
the head of the chromatographic column. The sample solution injected into the
instrument enters a gas stream which transports the sample into a separation tube
known as the column. Helium or nitrogen can be used as the carrier gas. The various
components are separated inside the column. The detector measures the quantity of
the components that exit the column. To measure a sample with an unknown
concentration, a standard sample with known concentration is injected into the
instrument. The standard sample peak retention time (appearance time) and area are
compared to the test sample to calculate the concentration.
 Working: The sample is transported through the column by the flow of inert, gaseous
mobile phase. The capillary columns used are 30m in length with an internal diameter
of 0.53mm. They consist of three layers – polyamide, silica/glass and a binder which
is responsible for separation. The binder can be dimethylformamide. The column
itself contains a liquid stationary phase which is adsorbed onto the surface of an inert
solid. The carrier gas must be chemically inert. Commonly used gases include
nitrogen, helium, argon, and carbon dioxide. The choice of carrier gas is often
dependent upon the type of detector which is used. The carrier gas system also

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 Inplant Training Report

contains a molecular sieve to remove water and other impurities. The effluent from
the column is mixed with hydrogen and air, and ignited.
 Flame ionization detector (FID): Organic compounds burning in the flame produce
ions and electrons which can conduct electricity through the flame. A large electrical
potential is applied at the burner tip, and a collector electrode is located above the
flame. The current of any organic compounds is measured. FIDs are mass sensitive
rather than concentration sensitive; this gives the advantage that changes in mobile
phase flow rate do not affect the detector's response. The FID is a useful general
detector for the analysis of organic compounds; it has high sensitivity, a large linear
response range, and low noise. It is also robust and easy to use.
 A graph of concentration versus time is plotted and the peaks determine the
impurities.
area under peak
Impurity content = ×100
 Percentage of impurities is determined as, total area

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SYNTHESIS OF ‘X’

Process details:

The process takes place in 4 stages.

S1 S2
 Stage 1: R1 + R2 + A X1 1
X1
B

S1 was charged into the reactor along with R 1 and A. The temperature was raised to
appropriate conditions and R2 was charged. The temperature was raised again and S 2
was added. The temperature was raised and the reaction mixture was stirred. The
reaction mixture was then cooled to charge DM water. The reaction mixture was
stirred and allowed to settle and the layers were separated. The upper organic layer
was collected. This layer was charged into the reactor along with DM water and
stirred. The lower layer was discarded. This separation was repeated. The reaction
mixture was distilled out under vacuum and degassed. S 1 was charged and the
reaction mixture was stirred and cooled. Reagent B was added. The reaction mixture
is stirred and cooled followed by filtration. The filtrate obtained was washed with S 1.
The wet solid obtained was dried under vacuum. The product obtained was
hygroscopic in nature and was released using a gas.

S3 S3
 Stage 2: X1 X21 X2
C

S3 was charged into a reactor along with X1 at room temperature under a gas
atmosphere. Temperature was raised and purged gas D was sent into the reactor. The
reaction mixture was stirred and then distilled out under vacuum. The above process
was repeated but, this time, without purging and addition of X1. The reaction mixture
was degassed under vacuum. S3 was charged after which the reaction mixture was
stirred and cooled. C was added lot wise in order to prevent effervescence. The
reaction mixture was filtered out and washed with hot S 3. The filtrate obtained was
charged into the reactor and distilled under vacuum. The reaction mixture was cooled

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and then filtered out again. The wet solid obtained was washed with S 3 and then dried
under vacuum.

S4, S5, S1
 Stage 3: X2 + R3 X3
S5, X2 was charged into a reactor at room temperature. The reaction mixture obtained
was heterogeneous. DM water was added. S4, R3 was charged at room temperature.
The heterogeneous solution became very clear. The solution was stirred and allowed
to settle down and the layers were separated. The lower layer was collected and
charged into the reactor. The upper layer was discarded. The above procedure was
repeated three times and during the second time, the pH was adjusted using E if
required. During the third time, to the lower later, activated charcoal is added. The
final lower layer was filtered through hyflo beds. The filtrate obtained was distilled
out, then charged with S1 and then distilled again at raised temperature. S1 is charged
again and temperature was raised up to reflux temperature. The reaction mixture was
filtered out under vacuum. The wet solid obtained was washed with S1. This was
repeated. The final wet solid was dried under vacuum.

S1, S6
 Stage 4: X3 X
S1, X3 was charged into a reactor at room temperature. The temperature was raised to
appropriate conditions followed by stirring of the reaction mixture. S 6 was added. The
reaction mixture was stirred and cooled to obtain crystals. This is called cooling
crystallisation. The solids obtained were filtered under vacuum and the washed with
S1. The product obtained was dried under vacuum.

S1, S2, S3, S4, S5, S6 – Solvents

R1, R2, R3 – Raw materials
A, B, C, D, E – Reagents

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ACTIVITY

Determination of heat transfer coefficient (U) in R-6209

MOC: Hastelloy; Capacity: 100 lit; Agitator profile: Pitched blade turbine
1. Utility – steam heating

Reactor Jacket Jacket

Time Time temperature, T pressure temperature, Tj
(min) (hr) (°C) (kg/cm2) (°C) LMTD
0 0.00 25.3 1.8 100 0.0000
2 0.03 30.5 1.8 112 0.0619
4 0.07 45.6 1.8 112.1 0.2664
6 0.10 51.1 1.8 112.2 0.3522
8 0.13 57.5 1.8 112.3 0.4622
10 0.17 65.4 1.8 112.4 0.6169
12 0.20 71 1.8 112.5 0.7425
14 0.23 76.5 1.8 112.6 0.8831
16 0.27 81 1.8 112.7 1.0142
18 0.30 83.8 1.8 112.8 1.1043
20 0.33 85.7 1.8 112.9 1.1696
22 0.37 89 1.8 113 1.2959
24 0.40 92.9 1.8 113.1 1.4694
26 0.43 94.8 1.8 113.2 1.5638
28 0.47 98.2 1.8 113.3 1.7626
30 0.50 98.1 1.8 113.4 1.7506
32 0.53 99.2 1.8 113.5 1.8193
34 0.57 100.3 1.8 114 1.8679
36 0.60 101 1.8 114 1.9203
38 0.63 101.7 1.8 114 1.9757
40 0.67 102.4 1.8 114 2.0343
42 0.70 102.5 1.8 114 2.0429
44 0.73 102.7 1.8 114 2.0605

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Observation:
Kg
3
Density of toluene, ρ = 867 m
Volume charged, V = 85 × 10-3 m3

Kcal
∘
Specific heat capacity of toluene, Cp = 0.41 Kg C
Surface area of reactor, A = 0.4 m2

Mass of solvent, M = density× volume = 867×( 85×10−3 ) = 73. 1 Kg

Calculations:


LMTD = ln
( )
T i −T 0
T j−T

=
ln (112−25
112−30 .5 ) = 0.0619
.3


m×C p ×M 3.006×0 . 41×73 . 7 Kcal
U= = = 225. 84
 A 0.4 hr m 2 ∘ C
W
2∘
U = 263.39 m C

Graph:

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Slope, m 3.006
mass, M (kg) 73.7
U (Kcal/hrm2°C) 225.84

U (W/m2°C) 263.39

W
2∘
Result: The overall heat transfer coefficient for R-6209 was found to be 263.39 m C

Utility – CT water cooling

2.

Reactor Jacket Jacket

Time Time temperature, T pressure temperature, Tj
(min) (hr) (°C) (kg/cm2) (°C) LMTD
0 0.00 100 1.8 25 0
2 0.03 89.6 1.8 25 0.1
4 0.07 71.1 1.8 25 0.5
6 0.10 58.1 1.8 26 0.8
8 0.13 49.3 1.8 26 1.2
10 0.17 43.2 1.8 26 1.5
12 0.20 39.1 1.8 26 1.7
14 0.23 36.2 1.8 26 2.0
16 0.27 34 1.8 27 2.3
18 0.30 32.6 1.8 27 2.6
20 0.33 31.5 1.8 27 2.8
22 0.37 30.7 1.8 27 3.0
24 0.40 30.2 1.8 28 3.5

Observation:
Kg
3
Density of toluene, ρ = 867 m
Volume charged, V = 85 × 10-3 m3

Kcal
∘
Specific heat capacity of toluene, Cp = 0.41 Kg C
Surface area of reactor, A = 0.4 m2

Mass of solvent, M = density× volume = 867×( 85×10−3 ) = 73. 7 Kg

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Calculation:


LMTD = ln
( )
T i −T 0
T j−T

=
ln ( 25−100
25−89 . 6 ) = 0.1492
m×C p ×M 2.9×0 . 41×73 .7 Kcal
U= = = 219 .07
 A 0.4 hr m2 ∘ C
W
2∘
U = 254.12 m C
Graph:

Slope, m (hr-1) 8.6357461

mass, M (kg) 34.68
U (Kcal/hrm2°C) 219.07
U (W/m2 °C) 254.12

Result: The overall heat transfer coefficient for R-6209 was found
W
2∘
to be 254.12 m C

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Determination of heat transfer coefficient (U) in R-6113

MOC: Glass lined reactor; Capacity: 100 lit; Agitator profile: Retreat curve blade
1. Utility – hot water heating

Reactor Jacket Jacket

Time Time temperature, T pressure temperature, Tj
(min) (hr) (°C) (kg/cm2) (°C) LMTD
0 0.00 25.10 0.3 55.00 0.000
2 0.03 25.50 0.3 60.00 0.012
4 0.07 26.00 0.3 60.00 0.026
6 0.10 27.20 0.3 60.00 0.062
8 0.13 28.90 0.3 60.00 0.115
10 0.17 30.80 0.3 60.00 0.178
12 0.20 33.20 0.3 60.00 0.264
14 0.23 36.00 0.3 60.00 0.374
16 0.27 38.60 0.3 60.00 0.489
18 0.30 41.30 0.3 60.00 0.624
20 0.33 44.40 0.3 65.00 0.661
22 0.37 47.00 0.3 65.00 0.796
24 0.40 49.00 0.3 68.00 0.814
26 0.43 51.10 0.3 68.00 0.932
28 0.47 53.20 0.3 69.00 1.022
30 0.50 54.90 0.3 69.00 1.136
32 0.53 56.40 0.3 70.00 1.194
34 0.57 57.70 0.3 72.00 1.188
36 0.60 58.70 0.3 74.00 1.162
38 0.63 59.60 0.3 76.00 1.133
40 0.67 60.40 0.3 78.00 1.101
0 0.00 25.10 0.3 55.00 0.000

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 Inplant Training Report

Observation:
Kg
3
Density of methanol, ρ = 792 m
Volume charged, V = 85 × 10-3 m3

Kcal
∘
Specific heat capacity of methanol, Cp = 0.605 Kg C
Surface area of reactor, A = 0.4 m2

Mass of solvent, M = density× volume = 792×( 85×10−3 ) = 67 . 32 Kg

Calculation:


LMTD = ln
( )
T i −T 0
T j−T

=
ln ( 60−25 . 1
)
60−25 . 5 = 0.012

m×C p ×M 67 . 32×0 . 605×2 . 14 Kcal

U= = = 217 . 59
 A 0. 4 hr m2 ∘ C
W
2∘
U = 252.40 m C

Graph:

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 Inplant Training Report

Slope (hr-1) 2.14

Mass (Kg) 67.32
U (Kcal/hr m2°C) 217.59
U (W/m2°C) 252.40
W
2∘
The overall heat transfer coefficient for R-6113 was found to be 252.40 m C
Result:

2. Utility – CT water cooling

Jacket
Time Time Reactor Average Jacket pressure
(min) (hrs) temperature (°C) temperature (°C) (Kg/cm2) LMTD
4 0.1 61.9 27.5 2.2 0.000
6 0.1 60.2 27.5 2.2 0.051
8 0.1 57.2 26.5 2.2 0.142
10 0.2 54 26.5 2.2 0.253
12 0.2 53.1 26.5 2.2 0.286
14 0.2 51.7 26.5 2.2 0.340
16 0.3 49.9 26.5 2.2 0.414
18 0.3 48.3 26.5 2.2 0.485
20 0.3 46.8 25.5 2.2 0.536
22 0.4 45.4 25.5 2.2 0.604
24 0.4 44.2 25.5 2.2 0.666
26 0.4 43.1 25.5 2.2 0.727
28 0.5 42.1 25.5 2.2 0.785
30 0.5 41.2 25.5 2.2 0.841
32 0.5 40.2 25.5 2.2 0.907
34 0.6 39.6 25.5 2.2 0.948
36 0.6 38.7 25.5 2.2 1.014
38 0.6 38.2 25.5 2.2 1.053

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 Inplant Training Report

40 0.7 37.6 24.5 2.2 1.049

42 0.7 37.1 24.5 2.2 1.088
44 0.7 36.6 24.5 2.2 1.128
46 0.8 36.1 24.5 2.2 1.171
48 0.8 35.6 24.5 2.2 1.215
50 0.8 35.3 24.5 2.2 1.242
52 0.9 34.9 24.5 2.2 1.280

Observation:
Kg
3
Density of methanol, ρ = 792 m
Volume charged, V = 85× 10-3 m3

Kcal
∘
Specific heat capacity of methanol, Cp = 0.605 Kg C
Surface area of reactor, A = 0.4 m2

Mass of solvent, M = density× volume = 792×( 85×10−3 ) = 67 . 32 Kg

Calculation:


LMTD = ln
( )
T i −T 0
T j−T

=
ln ( 27.27. 5−61.
5−60 .2 ) = 0.051
9

m×C p ×M 67 . 32×0 . 605×1 . 61 Kcal

U= = =163 . 59
 A 0.4 hr m2 ∘ C
W
2∘
U = 189.77 m C

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 Inplant Training Report

Graph:

Slope (hr-1) 1.61

Mass (Kg) 67.32
U (Kcal/hr m °C) 163.57
2

U (W/m2°C) 189.77

W
2∘
Result: The overall heat transfer coefficient for R-6113 was found to be 189.77 m C

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 Inplant Training Report

Determination of heat transfer coefficient (U) in R-6202

MOC: Stainless steel reactor; Capacity: 50 lit; Agitator profile: Anchor

1. Utility – hot water heating

Reactor Jacket Jacket

Time Time temperature, T pressure temperature, Tj
(min) (hr) (°C) (kg/cm2) (°C) LMTD
2 0.03 25.60 0.20 40.00 0.00
4 0.07 26.60 0.20 45.00 0.05
6 0.10 27.00 0.20 48.00 0.06
8 0.13 30.00 0.20 50.00 0.20
10 0.17 32.00 0.20 55.00 0.25
12 0.20 34.00 0.20 55.00 0.34
14 0.23 37.00 0.20 58.00 0.43
16 0.27 39.40 0.20 58.00 0.55
18 0.30 42.50 0.20 60.00 0.68
20 0.33 45.00 0.20 63.00 0.73
22 0.37 47.20 0.20 65.00 0.79
24 0.40 52.00 0.20 70.00 0.90
26 0.43 53.90 0.20 72.00 0.94
28 0.47 56.00 0.20 75.00 0.96
30 0.50 57.50 0.20 75.00 1.04
32 0.53 58.00 0.20 80.00 0.91
34 0.57 61.20 0.20 82.00 1.00

Observation:
Kg
3
Density of methanol, ρ = 792 m
Volume charged, V = 45 × 10-3 m3

Kcal
∘
Specific heat capacity of methanol, Cp = 0.605 Kg C

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 Inplant Training Report

Surface area of reactor, A = 0.2 m2

Mass of solvent, M = density× volume = 792×( 45×10−3 ) = 35 . 505 Kg

Calculation:


LMTD = ln
( )
T i −T 0
T j−T

=
ln ( 4545−26 .6 ) = 0.05
− 25 .6

m×C p ×M 2 .129 ×0. 605×35 .505 Kcal

U= = = 228 .629
 A 0 .2 hr m2 ∘ C
W
2∘
265.209 m C
U=

Graph:

Slope, hr-1 2.129

Mass, Kg 35.505
U, Kcal/hr m2 °C 228.629
U, W/ m2 °C 265.209

W
2∘
Result: The overall heat transfer coefficient for R-6202 was found to be 265.209 m C

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 Inplant Training Report

2. Utility – CT water cooling

Reactor Jacket Jacket

Time Time temperature, T pressure temperature, Tj
(min) (hr) (°C) (kg/cm2) (°C) LMTD
2 0.03 62.80 2.00 25.00 0.00
4 0.07 62.70 2.00 25.00 0.00
6 0.10 61.80 2.00 25.00 0.03
8 0.13 59.30 2.00 25.00 0.10
10 0.17 56.70 2.00 25.00 0.18
12 0.20 54.50 2.00 25.00 0.25
14 0.23 52.00 2.00 25.00 0.34
16 0.27 50.00 2.00 25.00 0.41
18 0.30 48.10 2.00 25.00 0.49
20 0.33 47.00 2.00 25.00 0.54
22 0.37 45.00 2.00 24.00 0.61
24 0.40 43.50 2.00 24.00 0.69
26 0.43 42.30 2.00 24.00 0.75
28 0.47 41.20 2.00 24.00 0.81
30 0.50 40.20 2.00 24.00 0.87
32 0.53 39.20 2.00 24.00 0.94
34 0.57 38.50 2.00 24.00 0.98
36 0.60 37.50 2.00 24.00 1.06
38 0.63 37.00 2.00 24.00 1.09
40 0.67 36.50 2.00 24.00 1.13
42 0.70 35.80 2.00 24.00 1.19
44 0.73 35.00 2.00 23.00 1.20
46 0.77 34.20 2.00 23.00 1.27
48 0.80 33.80 2.00 23.00 1.30
50 0.83 33.00 2.00 23.00 1.38
52 0.87 32.00 2.00 23.00 1.49

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 Inplant Training Report

54 0.90 31.00 2.00 22.00 1.51

56 0.93 30.50 2.00 22.00 1.57

Observation:
Kg
3
Density of methanol, ρ = 792 m
Volume charged, V = 45 × 10-3 m3

Kcal
∘
Specific heat capacity of methanol, Cp = 0.605 Kg C
Surface area of reactor, A = 0.2 m2

Mass of solvent, M = density× volume = 792×( 45×10−3 ) = 35 . 505 Kg

Calculation:


LMTD = ln
( )
T i −T 0
T j−T

=
ln ( 25−61
25−62 . 8 ) = 0.03
.8


m×C p ×M 1.803 ×0. 605×35 . 505 Kcal
U= = = 193 . 672
 A 0.2 hr m2 ∘ C
W
2∘
U = 224.660 m C

Graph:

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 Inplant Training Report

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 Inplant Training Report

Slope, hr-1 1.803

Mass, Kg 35.505
U, Kcal/hr m2 °C 193.672
U, W/ m2 °C 224.660

W
2∘
Result: The overall heat transfer coefficient for R-6202 was found to be 224.660 m C

CONCLUSION FROM EXPERIMENTS

W
Reactor MOC m2 ∘ C Theoretical U,
Experimental U, W
m2 ∘ C

Heating Cooling Heating Cooling

R6209 Hastelloy 263.39 254.12 350-400 300

R6113 Glass lined 252.4 189.77 200-250 193

R6202 Stainless Steel 265.209 224.660 250-300 250

From the above table, we can conclude that the overall heat transfer coefficient is more for
heating than for cooling.

We can also conclude that the overall heat transfer coefficient for SSR is more than GLR.

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 Inplant Training Report

CONCLUSION

10 days of in-plant training was completed and the studies of each reactor in the pilot plant
were done. We could conclude that a Pilot plant helps to make process corrections &
improvements.

REFERENCES

 Unit Operations of Chemical Engineering - McCabe Smith

 The Pilot Plant Real Book – A Unique Book for Chemical Processing Industry

 Jubilant Generics Web Page

 www.google.com

 www.wikipedia.org

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