Manufacturing of Olmesartan Intermediate

PROJECT ID: - 197385 CHEMICAL ENGINEERING
MANUFACTURING OF OLMESARTAN INTERMEDIATE
AN INTERNSHIP REPORT
Submitted by
PATEL JAY MAHENDRA KUMAR
151260105030
In partial fulfillment for the award of the degree of
BACHELOR OF ENGINEERING
In
Chemical Engineering
Sal Engineering and Technical Institute, Ahmedabad
Gujarat Technological University, Ahmedabad
[May,2022]
GUJARAT TECHNOLOGICAL UNIVERSITY SAL ENGINEERING AND TECHNICAL INSTITUTE

SAL Engineering and Technical Institute

Opp. Science city, Sola Bhadaj Road, Ahmedabad, Gujrat-380060
CERTIFICATE
This is to certify that the project report submitted along with the project entitled
Manufacturing of Olmesartan Intermediate At Almon Industries has been carried
out by Patel Jay Mahendra Kumar under my guidancein partial fulfillment for the
degree of Bachelor of Engineering in Chemical Engineering, 8th Semester of Gujarat
Technological University, Ahmadabad during theacademic year 2021-22.
Prof. Parth Desai Dr. Bhavna Soni
Internal Guide Head of the Department



SAL Engineering and Technical Institute

Opp. Science city, Sola Bhadaj Road, Ahmedabad, Gujrat-380060
DECLARATION
We hereby declare that the Internship submitted along with the Internship entitled
Manufacturing of Olmesartan Intermediate submitted in partial fulfillment for the
degree of Bachelor oEngineering in Chemical Engineering to Gujarat Technological
University, Ahmedabad, is a bonafide record of original project work carried out by me
at ALMON INDUSTRIES under the supervision of Mr. Brijesh Patel and that no part
of this report has beendirectly copied from any students’ reports or taken from any other
source, without providing due reference.
Name of the Student Sign of Student
Patel Jay Mahendra Kumar

ACKNOWLEDGEMENT
I would like to be my acknowledgements by thanking Mr. Brijesh

Patel, Director in ALMON INDUSTRIES. For permitting me for
Industrial training and good support. Along with that I would like
to thank my internal guide MR. Parth Desai for helping me
during my internship by assisting with theNecessary suggestions
and guidance in completing this internship.
My special thanks to Mr. Sameer Patel (Production manager) for

the help during the plant visit and also thank to Mr. Kaushal Patel
(R&D In charge) for their help and Co- operation during the plant
training.
Lastly My Special thanks to all the people who encourage me and

give opportunityto get training in ALMON INDUSTRIES.
Name: -
Enrollment no: -
GUJARAT TECHNOLOGICAL UNIVERSITY i SAL ENGINEERING AND TECHNICAL INSTITUTE

ABSTRACT
The global pharmaceutical industry is huge and the value chain is divided into
two categories namely API and finished goods. API forms the basis of the
drug that enables it to produce the desired effect.
China is one of the largest suppliers of API and when the world was hit by the
coronavirus pandemic, the pharma industry suffered losses due to a shortage
of raw materials.
API or Active Pharmaceutical Ingredient is an active component that is

included in medicines to produce the intended outcome. It makes up for one
of the two main ingredients in medicine, the other one being excipients which
deliver the effect of API.
In this report various types of detailed design, flow diagrams and Piping and
instrument diagram is also included.
So, in this report toxic nature of various raw materials is known. Requirement
and use of R&D Department pharmaceutical industries is known. R&D
Department incudes QA/QC labs.
Key Words: - API, Pharmaceutical, Piping and Instrumentation.
GUJARAT TECHNOLOGICAL UNIVERSITY ii SAL ENGINEERING AND TECHNICAL INSTITUTE

List of Figures
Fig 1.4.1 Organization Chart ............................................................................................. 2

Fig 2.3.1 Schematic Layout of The Plant .......................................................................... 6
Fig 4.1.1 Block Diagram .................................................................................................. 11
Fig 4.2.1 Process Flow Diagram ..................................................................................... 11
Fig 4.3.1 P&ID ................................................................................................................. 12
GUJARAT TECHNOLOGICAL UNIVERSITY iii SAL ENGINEERING AND TECHNICAL INSTITUTE

List Of Tables
Table 4.4.1 Raw Material................................................................................................. 13
Table 5.1.1 Stage 1 – Material Balance ........................................................................... 15
GUJARAT TECHNOLOGICAL UNIVERSITY iv SAL ENGINEERING AND TECHNICAL INSTITUTE

ABBREVIATIONS
TMOB: - Trimethyl Ortho Butyrate
GLR: - Glass Lined Reactor
SSR: - Stainless Steel Reactor
API: - Active Pharmaceutical Ingredient
Conc.: - Concentrate
TMOB: - Trimethyl Ortho Butyrate
GHS: - Globally Harmonized System
THF: - Tetra Hydro Furan
GUJARAT TECHNOLOGICAL UNIVERSITY v SAL ENGINEERING AND TECHNICAL INSTITUTE

Table of Contents
Acknowledgement ...............................................................................................................i
Abstract ...............................................................................................................................ii
List of Figures.....................................................................................................................iii
List of Tables.......................................................................................................................iv
List of Abbreviations............................................................................................................v
Table of Contents................................................................................................................vi
Chapter 1 Overview of the Company...............................................................................1
1.1 History………...……………………………………………………………….1
1.2 Product Capacity………………………………………………………………1
1.3 Different Product...……………………………………………………………1
1.4 Organization Chart……….…………………………………………………...2
Chapter 2 Overview of Different Department…………………………………………3
2.1 Introduction to different Department……………………..…………………..3
2.2 Technical Specification of Equipment………………………………………..4
2.3 Schematic Layout of the Plant……….……………………………………….6
Chapter 3 Literature Survey……………………………………………………………7
Chapter 4 Process Description………………………………………………………...11
4.1 Process Block Diagram……………………… ………………………………11
4.2 Process Flow Diagram……………………………………………………….11
4.3 P&ID…………………………………………….…………………………...12
4.4 Manufacturing Process……………………..………………………………..13
Chapter 5 Material and Energy Balance……………………………………………...15
5.1 Material Balance……..……………………… ……………………………..15
5.2 Energy Balance……………………………………………………………...17
Chapter 6 Equipment Design………………………………………………………….19
6.1 Process Design of Reactor ………………………………………………….19
6.2 Mechanical Design …………………………………………………………21
Chapter 7 Quality Assurance and Quality Control………………………………….23
7.1 Introduction of QA/QC……………………… ……………………………..23
7.2 Roles and Responsibilities…………………………………………………..23
7.3 Skills Required for QA/QC Lab…………………………………………….23
GUJARAT TECHNOLOGICAL UNIVERSITY vi SAL ENGINEERING AND TECHNICAL INSTITUTE

7.4 Purpose of QA/QC …………………………………………………………24

7.5 Laboratory Testing………………………………………………………….24
Chapter 8 Safety Measurement………………………………………………………26
8.1 Material Safety Data Sheet…………………………………………………26
Chapter 9 Conclusion and Future Scope…………………………………………….31
9.1 Conclusion……… …………………………………………………………31
9.2 Future Scope…….………………………………………………………….32
References……………………………………………………………………………...33
Appendix 1……………………………………………………………………………..34
GUJARAT TECHNOLOGICAL UNIVERSITY vii SAL ENGINEERING AND TECHNICAL INSTITUTE

Chapter1. OVERVIEW OF THE COMPANY
1.1 History
ALMON INDUSTRIES have couple of plants in Gujarat producing different products At

Vatva, Ahmedabad.
It is Established in 2011. In Land Area of 2000 sq. m.
They Manufactures Ethyl 4-(1-hydroxy-1-methylethyl) 2 propyl-1H-imidazole-5-

carboxylate which is more popularly known as Olmesartan Intermediate.
Almon Industries is Certified with ISO 9000 – 2012 Certificate.
1.2 Production Capacity
ALMON INDUSTRIES Has a total production capacity of around 1200 MT per annum.
1.3 Different Product
1 Olmesartan
2 Other API & API Intermediate
GUJARAT TECHNOLOGICAL UNIVERSITY 1 SAL ENGINEERING AND TECHNICAL INSTITUTE

1.4 Organization Chart
Fig 1.4.1 Organization Chart

Chapter 2 OVERVIEW OF DIFFERENT DEPARTMENTS
AND LAYOUT OF THE COMPANY
2.1 Introduction to Different Department
There are several departments in the company in order to maintain the working flow and
for easiness However there are five major departments where most of the work is carried
out.
1 Plant production area
This is the main area of the industry facility which is responsible for manufacturing of the
product.
2 Clinical research and trials
In this area research studies performed by the experts to find out a new treatment, like new
drug or diet or any development of the current product.
3 Quality assurance and Quality control laboratory
Here, raw materials and finish good products are being tested and analysed by the experts.
For instance, measurement of PH, moisture, viscosity, thickness, quality of material and
other important parameters of the material.
4 Utility areas
In utility department different raw materials are imported and stored from the various
dealers which are mostly in the liquid or solid phase.

5 Finish good area and storage area
In this department after getting approval from the QA QC department the product are stored
in storage area or dispatch to the buyers and traders.
2.2 Specification of Equipment
Various major equipment is used during the production of Olmesartan
• Boilers
➢ Boilers are generally applied for the generating the steam for heating
purpose.
➢ This steam is generally applied for the heating the process
• Glass Lined Reactor

➢ The glass lined reactor which is used for the production of Olmesartan.
➢ The capacity of this Reactor is 2500 liters.
➢ The wall thickness of main shell is 25 mm & the thickness of glass coating
is 5 mm.
➢ Pressure range in this process is 5 kg/cm2.
➢ The material of construction in mild steel & glass coating to protect against
hazardous material.
➢ The diameter of this reactor is 2 m and the height is 3 m.
• Stainless steel reactor

➢ There are 2 no of stainless-steel reactor for the process.
➢ The capacity of the S. S. Reactor in 2000 liters.
➢ The Diameter of the S. S. Reactor is 2.8 mm. The height of the S. S. Reactor
is 4 m and the thickness of S.S. Reactor is 10 mm.
➢ The steam is entered into the reactor at the pressure of 2 kg/cm.

➢ The temperature maintains nearly 110℃. During the process S.S. vessel,
condenser, separator is required.
• Nutache filter dryer

➢ Filtering surface from 0.07 up to 15 m².
➢ Operation capacity from 19L to 15,000L.
➢ Batch-wise operation and design with absolute vacuum drying under
vacuum and ultra-vacuum.
➢ Operating pressure is 3 bar(g) and operating temperature is up to 200*c.
➢ Cake washing system.
➢ Uses filtration under pressure or vacuum to isolate solids from liquids..
• Cooling plant
➢ Cooling towers are generally used for the cooling purposed in condenser &
Vessel Jacket, is generally recirculated though a cooling towers to reduced,
the water consumption.
➢ In the cooling tower water passed down through an upward current of air,
which cools the water mainly by evaporation, the loss of latent heat being
the major contribution to the drop in temperature.
➢ The capacity is based on 11 ℃ emp. Of chilled water and temperature for
chiller shall be 4℃.
• Effluent treatment plant

➢ Water is coming from the all the unit containing unwanted impurities and
having pH is being treated to make a harmless water & to maintain the pH
➢ Capacity of ETP is 50-300 KLD and the feed flow rate is 2000 m²/day.

2.3 Schematic layout of the plant
Fig 2.3.1 Schematic Layout of the plant

Chapter 3. LITERATURE SURVEY
• SUMAN AVULA, K. NAVEEN BABU and M.V RAMANA (2011):

A simple, selective, linear, precise and accurate RP-HPLC method was developed and
validated for rapid assay of Olmesartan in tablet dosage form. Isocratic elution at a flow
rate of 1.0ml/min was employed on a symmetry C18 (250x4.6mm, 5µm in particle size) at
ambient temperature. The mobile phase consisted of water: methanol 20:80 (V/V/V). The
UV detection wavelength was 265nm and 20µl sample was injected. The retention time for
Olmesartan was 2.287 min. The percentage RSD for precision and accuracy of the method
was found to be less than 2%. The method was validated as per the ICH guidelines. The
method was successfully applied for routine analysis of Olmesartan in tablet dosage form.
• Ann W. Newman and Stephen R. Byrn (2003)

The solid form of a drug substance is important when developing a new chemical entity.
The crystalline form used in development is significant based on possible
manufacturability, solubility, bioavailability and stability differences between the solid
forms. Regulatory issues require that the form present in a solid dosage form or liquids
containing undissolved drug substance be identified. Drug product samples can be analysed
by a variety of techniques to determine the crystal form present or changes that occur during
the manufacture of a drug product. The form present will affect development, regulatory
and intellectual property issues.
• Joe M. Wilson Jr.1 and Enno ‘‘Ed’’ Koehn (2000)
The philosophy of safety management is a relatively new method of controlling safety

policies, procedures, and practices within a company. This philosophy is currently being
implemented by many construction companies to limit their liabilities and costs, thereby
making them more competitive in the construction marketplace. While the principles
behind safety management are fairly simple in concept, it is during the implementation of
such a program that construction companies may encounter their most difficult obstacles.

In fact, it is often the workers who present the greatest opposition—the same individuals
who benefit the most by improved safety conditions on the site. Safety management is a
dynamic process operating in a constant state of change. Therefore, the process must be
constantly monitored and adjusted to achieve the desired goals. This paper presents a
discussion of the methods of safety management employed on a small-to medium-sized
project in the north western United States. The discussion will highlight several of the
problems encountered and the solutions utilized to overcome these problems
• Ali N. Saleemi a, Gerry Steelea, Nicholas I. Pedge b, Anthony Freemana,

Zoltan K. Nagy (2012):
Pharmaceutical regulatory bodies require minimal presence of solvent in an active

pharmaceutical ingredient (API) after crystallization. From a processing point of view
bigger crystals with minimal agglomeration and uniform size distribution are preferred to
avoid solvent inclusion and for improved downstream processing. The current work
addresses these issues encountered during the production of the potential anti-arrhythmic
cardiovascular drug, AZD7009. This paper demonstrates that by applying the automated
direct nucleation control (ADNC) approach problems with agglomeration and solvent
inclusion were resolved. This model free approach automatically induces temperature
cycles in the system, with the number of cycles, temperature range and adaptive heating
and cooling rates determined to maintain the number of particles in the system, as measured
by a focused beam reflectance measurement (FBRM) probe, within a constant range during
the crystallization. The ADNC approach was able to produce larger and more uniform
crystals and also removed the residual solvent trapped between the crystals compared to
the typical crystallization operation using linear cooling profile. The results illustrate the
application of process analytical technologies, such as FBRM and ATR-UV–vis
spectroscopy, for the design of optimal crystallization operating conditions for the
production of pharmaceuticals, and demonstrate that the ADNC approach can be used for
rapid crystallization development for APIs exhibiting problems with agglomeration and
solvent inclusion.

• Renata Toplak Časar, and Zdenko Časar (2009)

We have elaborated a one-pot three-component assembly of trityl Olmesartan medoxomil
starting from commercially available ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1H-
imidazole-5- carboxylate, 5-(4'-(bromomethyl)-[1,1'-biphenyl]-2-yl)-1-trityl-1H-tetrazole
and 4- (chloromethyl)-5-methyl-1,3-dioxol-2-one intermediates. The developed and
optimized one-pot process provides 72-75% yield of trityl Olmesartan medoxomil over
three steps, which represents in average ca. 90% yield per synthetic step, on a 300 g scale.
The process is conducted in simple fashion and provides highly pure trityl olmesartan
medoxomil (up to 97.5% by HPLC), which can be easily converted to olmesartan
medoxomil that fully complies with all ICH requirements. Furthermore, the described
process significantly improves the primary process to trityl olmesartan medoxomil by
drastic reduction of required unit operations and application of single reaction solvent
through the reaction sequence. Moreover, the amount of used organic solvents was notably
reduced. The developed process has provided solid bases for industrial production of trityl
olmesartan medoxomil.
• Bomana HANUMANTHA RAO, Inti Venkata SUBRAMANYESWARA

RAO (2015):
Drug product purity and potency are of most significance in the regulatory market as we
notice many recalled batches worldwide, particularly in the US and Japan. Olmesartan
Medoxomil is an anti-hypertensive drug. The present invention relates to a process for the
preparation of Olmesartan Medoxomil with 99.9% purity in an overall 62% yield. The
synthesis includes three isolations and one purification with easy plant operations. This
process describes the formation and control of each individual impurity in a stage. This
process for Olmesartan Medoxomil and its intermediates is competent for industrial
production in very short reaction time intervals with an appreciable yield and high purity

• Colin F. Poole (2003)

The purpose of this article is to identify core technologies with the potential to influence
the development of thin-layer chromatography over the next decade or so. Core
technologies are identified as: (i) methods to provide a constant and optimum mobile phase
velocity (forced flow and electro osmotically-driven flow), (ii) video densitometry for
recording multidimensional chromatograms, (iii) in situ scanning mass spectrometry, and
(iv) bioactivity monitoring for selective detection. In combination with two-dimensional,
multiple development and coupled column–layer separation techniques these core
technologies could dramatically increase the use of thin-layer chromatography for the
characterization of complex mixtures. It is also demonstrated that thin-layer
chromatography has strong potential as a surrogate chromatographic model for estimating
bio partitioning properties. To convert these opportunities into practice the current state-of-
the-art of the core technologies is described and the principal obstacles to progress
identified.

Chapter 4. PROCESS DESCRIPTION
4.1 Process Block Diagram
Fig 4.1.1 Block Diagram
4.2 Process Flow Diagram
Fig 4.2.1 Process Flow Diagram

4.3 P&ID
Fig 4.3.1 P&ID

4.4 Manufacturing Procedure
Table 4.4.1 Raw Material
Raw Material Use in Olmesartan Amount in kg
Diaminomalanonitrile 100
Trimethyl ortho butyrate 150
Methanol 200
Con. Hydrochloric acid 400
Thionyl chloride 200
Sodium hydroxide 50
Methyl magnesium chloride 900
Ethanol 300
Acetic acid 50
Toluene 300
Di isopropyl ether 150
Manufacturing process for the production of Olmesartan is generally Batchprocess.

It involves some stages for the process completion.
➢ Milling operation
➢ Dumping process
➢ Distillation
➢ Filtration
➢ Drying (Nutche filter dryer)
➢ Effluent treatment Plant

As per the block diagram material is dumped in GLR-1 (Glass Lined Reactor) along with
the solvent.
Raw material which are used in this stage are Diamino nitrile, Trimethyl Ortho butyrate
along with solvent Methanol and Reagent conc. HCL.
All these materials are added and mixed at the temperature between 100°C -110°C. This
whole process takes time about 6 hours and after that salt white coloured slurry is extracted
from the distillation column.
Filtration Centrifugation take place after distillation. After this wet cake is generated. Wet
cake is manually dumped for drying. After drying we get Diacid (Product from Stage-1).
After Stage-1 Stage-2 takes place. At Sstage-2 Diacid is being mix with another raw
material Thionyl Chloride and solvent Ethanol. This process takes place for 6 hours at 80-
90°C temperature. Once this prosses done distillation, filtration/centrifugation and drying
take place and after dying we get Diester along with recovered solvent.
After completion of Stage-2 Stage-3 takes place. In Stage-3 Diester reacts with 3M of
Mthylamagnasium Chloride in THF and solvent Toluene. This Process takes time nearly
5-6 hours at the temperature between 110-120°C.
After completion of this process slurry is generated which is ready for distillation. After
distillation solvent is recovered and bottom product of distillation column sent to the
filtration/centrifugation. After this process we get wet cake. Wet cake is sent for drying
where moisture will release from cake and final product is generated.
After getting final Product sample sent for Quality Assurance lab for quality analysis. Once
it done product is ready for packing and dispatch.

Chapter 5. MATERIAL AND ENERGY BALANCE
5.1 Material Balance
Stage 1: -
H
NC CN CH3 N
HOOC
H3CO 1) Methanol
+ H3CO N
H2N NH2
OCH3
2) Conc. HCl HOOC
Diaminomalenonitrile Trimethyl orthobutyrate 2-propyl-1H-imidazole-

Molecular Formula = C4H4N4 Molecular Formula = C7H16O3 4,5-dicarboxylic acid
Formula Weight = 148.20 Molecular Formula = C8H10N2O4
Formula Weight = 108.10
Formula Weight = 198.17
Diacid
Table 5.1.1 Stage1- Material Balance
Sr. Input Kg/ Remarks Output Kg/ Remarks

No. Batch Batch
1 Diaminomalanonitrile 100 Reactant Diacid 150 Product
2 Trimethyl ortho 150 Reactant Methanol 190 Reuse

Butyrate (Recovered)
3 Methanol 200 Solvent Effluent 480 To spray

dryer
4 Con. Hydrochloric acid 400 Reagent Drying loss 30
Total 850 Total 850
Stage 2: -
HOOC EtOOC
N Thionyl chloride N
CH3 CH3
HOOC Ethanol EtOOC
N N
H H
Diethyl 2-propyl-1H-imidazole-
2-propyl-1H-imidazole-4,5-
4,5-dicarboxylate
dicarboxylic acid
Molecular Formula. = C8H10N2O4 Molecular Formula= C12H18N2O4
Formula Weight= 198.17 Formula Wight= 254.28
Diacid Diester

Table 5.1.2 Stage 2- Material Balance
Sr. Input Kg/ Batch Remarks Output Kg/ Remarks

No. Batch
1 Diacid 150 Reactant Diester 150 Product
2 Thionyl chloride 200 Reactant Ethanol 290 Reuse

(Recovered)
3 Sodium 50 Reagent Effluent 510 To spray
hydroxide dryer
4 DM water 300 Neutraliza Drying loss 50
tion
5 Ethanol 300 Solvent
Total 1000 Total 1000
Stage 3
H3C CH3
EtOOC
3M Methyl magnasium HO N
N
chloride in THF
CH3 CH3
EtOOC EtOOC
N Toluene N
H H
Diethyl 2-propyl-1H-imidazole- Ethyl 4-(1-hydroxy-1-methylethyl)-
4,5-dicarboxylate 2-propyl-1H-imidazole-5-carboxylate
Molecular Formula= C12H18N2O4 Molecular Formula= C12H20N2O3
Formula Wight= 254.28 Formula Wight= 240.29
Diester Olmesartan Intermediate

Table 5.1.3 Stage3- Material Balance
Sr. Input Kg/ Remarks Output Kg/ Remarks

No. Batc Batch
h
1 Diester 150 Reactant Olmesartan 110 Product
Intermediate
2 3 M Methyl 900 Reactant Toluene 290 Reuse

magnesium chloride (Recovered)
in THF
3 Acetic acid 50 Reagent Di isopropyl 145 Reuse
ether
(Recovered)
4 DM water 300 Neutralizati Effluent 1250 To spray
on dryer
5 Toluene 300 Drying loss 55
6 Di isopropyl ether 150 Solvent
Total 1850 Total 1850
5.2 Energy Balance
Heat added by utility = m Cp ΔT

= 100 x 1.996 (116-110)
= 9980 KJ/hr
Heat added by Methyl Magnesium Chloride = m Cp ΔT (Cp value of MMC = 1.10

KJ)
= 900 x 1.10 x (110-28)
= 81180 KJ/hr
Heat added by Toluene = m Cp ΔT (Cp value of Toluene 110 KJ)

= 300 x 110 x (110-28)
= 2706000 KJ/hr

Heat added by Diester = m Cp ΔT (Cp value of Diester = 1.84 KJ)

= 150 x 1.84 x (110-28)
= 22632 KJ/hr
Total heat added by feed = Heat added by utility+ Heat added by Diester+ Heat added
by Methyl Magnesium Chloride + Heat added by Toluene
= 9980 KJ/hr + 22632 KJ/hr + 81180 KJ/hr + 2706000 KJ/hr
= 2819792 KJ/hr
Total heat out by Olmesartan Intermediate: - (Cp value of Olmesartan Intermediate =

124 KJ)
= m Cp ΔT
=110 x 124 x 80
=1091200 KJ/hr
Heat Loss = Total heat added by feed - Total heat out

= 2819792 KJ/hr-1091200 KJ/hr)
=1728592 KJ/hr

Chapter 6. EQUIPMENT DESIGN
6.2 Process Design of Reactor
Performance equation of ideal mixed flow reactor is

Diester + Methylmangnasium Chloride = Olmesartan Intermediate
𝐕 𝐗𝐀
=
𝐅𝐀𝐎 −𝐫𝐀
V = volume of reactor
FAO = initial flowrate of limiting reactant
rA = rate of reaction
XA = conversion
V = V1 + V2
V1 for volume of Diester
M1 (mass of Diester) = 150 kg
ρ1 (density of Diester) = 873.9 kg/m3
𝑚1 150 𝑘𝑔
V1 = = 𝑘𝑔 = 0.17 m3
𝜌1 873.9 3
𝑚
V1= 0.17 m3
V2 for volume of MMC

M2 (mass of MMC) = 900 kg
ρ2 (density of MMC) = 1010.00 kg/m3
𝑚2 900 𝑘𝑔
V2= = 𝑘𝑔
𝜌2 1010
𝑚3
V2 = 0.9 m3
Total volume = V1 + V2 = 0.17 + 0.9 = 1.07 m3

In the reaction Methylmangnasium Chloride is limiting reactant so,

FAO in Kmol/s
Methylmangnasium Chloride mass = 900 kg

Molecular weight = 74.79 g/mol
Moles of MMC = 12.03 Kmol/h
FAO = 0.001 Kmol/s
Assume that reaction is 1st order reaction
𝑑𝑐𝐴
−𝑟𝐴 = = 𝑘. 𝐶𝐴 = 𝑘. . 𝐶𝐴𝑜 (1 − 𝑋𝐴)
𝑑𝑄
CAo = initial concentration of limiting reactant

= Initial flowrate / volume of limiting reactant
= 4 × 3600 × 0.0010 / 0.9
= 16.0 Kmol/m3
For the first order reaction K = 0.00976 s-1

All the value put in performance equation: -
𝐕 𝐗𝐀
=
𝐅𝐀𝐎 −𝐫𝐀
1.07 𝑋𝐴
=
0.001 0.00976 × 16 (1 − 𝑋𝐴 )
𝑋𝐴
1070 =
0.15616 (1 − 𝑋𝐴 )
𝑋𝐴
167.0912 =
1 − 𝑋𝐴

167.0912 − 167.0912 𝑋𝐴 = 𝑋𝐴
167.0912 = 168.0912 𝑋𝐴
𝑋𝐴 = 0.9940
𝑿𝑨 = 𝟗𝟗. 𝟒𝟎%
6.1 MECHANICAL DESIGN OF REACTOR
Reactor with Plain Jacket
GIVEN DATA:
• Pressure (P) = 1atm = 1.0322 kg f/cm2

• Material of shell = SS 316
• Di (inside diameter of shell) = 1600 mm
• F (maximum allowable stress at design temperature) = 1416.139 kg f/cm2
• J (Joint efficiency) = 0.90
• CA (corrosion allowance) = 6 mm
• Inside diameter of jacket = 1700 mm
REACTOR WITH PLAIN JACKET:
𝑝𝑑𝑖
Shell thickness t = 2𝑓𝐽−𝑃 + 𝐶𝐴
1.0322(1600)
t= +6
2 × 1416.139 × 0.90 − 1.0322
1651.52
t = 2548.018 + 6
Shell thickness t = 6.65 mm
Use t = 8 mm, Thickness of shell should be checked also for external pressure.
So, use 8 mm thickness of shell with plain jacket

THICKNESS OF PLAIN JACKET
𝑷𝒓 𝒊
t = 𝒇𝑱−𝟎.𝟔𝑷 + 𝑪𝑨
GIVEN DATA: -
• ri = 1700/2 = 850 mm
• P = 1atm = 1.0332 kg f/cm2
• J = 0.90
• f = 2598.332
• CA = 1.75 mm
𝑖 𝑃𝑟
Thickness of plain jacket: t = 𝑓𝐽−0.6𝑃 + 𝐶𝐴
1.0332 (850)
t = 2598.32 × 0.90 − 0.6 × 1.0332 + 1.75
877.37
t = 2338.488 − 0.61932 + 1.75
877.37
t = 2337.87 + 1.75
t = 2.125 mm
Thickness of plain jacket t = 2.125 mm
Use 2.5mm thick plate for plain Jacket.

Chapter 7. QUALITY ASSURANCE AND QUALITY
CONTROL
7.1 Introduction of QA/QC
Quality control is concerned with the control of quality of the product during the process
of production. It aims at achieving the predetermined level of quality in a product. In
other wood quality control is concerned with controlling those negative variances which
ultimately affect the excellence of a manufacturer in producing the products.
The goal of quality assurance and quality control (QA/QC) is to identify and implement
sampling and analytical methodologies which limit the introduction of error into analytical
data.
7.2 ROLES AND RESPONSIBILITIES
• To analysed the stability and hold time study samples

• To check the purity and quality of the raw materials
• Maintaining the Lab equipment
• To record raw data and analytical results
7.3 SKILLS REQUIED FOR QA/QC LAB
• Analytical and research skills

• Problem solving
• Team work and communication skills
• Ability to manage multiple priorities

7.4 PURPOSE OF QA/QC
To evaluate the methods and processes of production and suggest further improvements in
their functioning.
To steady and determine the extent of quality deviation in a product during the
manufacturing process.
To establish the desired quality standards which are acceptable to the customers.
To analysed in detail the causes responsible for such deviation.
To minimize the production and waste.
7.5 LABORATORY TESTING
The lab contains several equipment such as, pH meter, UV calibration, sterilizer, oven, etc.
For one month I worked in QA/QC lab, where I learn about the various methods of testing
and sampling along with the importance of conducting the lab tests.
pH Meter
pH meter, electric device used to measure hydrogen-ion activity (acidity or alkalinity) in

solution
The degree of hydrogen ion activity is ultimately expressed as pH level, which generally
ranges from 1 to 14.
The most useful way to categorise pH meters is into three main group or types. These
are pen testers, handheld/portable meters and benchtop meters.

UV calibration test
It is basically use to carried-out the TLC check. In this the UV lights are used to perform a
test this is because it is non-destructive and simple to carried-out the test. Here, the sample
is placed inside the equipment and then the UV rays are passed through the sample.
During the calibration process we get the data of the material on the bottom screen where
it shows the quality, purity of the product.
However, because of the UV lights it becomes necessary to perform this test under
supervision with protective equipment for the safety.
I also learn about the safety parameters and methods in lab.

Chapter 8. SAFETY MEASUREMENT
8.1 Material Safety Data Sheet
• Physical-chemical Properties: -
➢ Molecular Formula: -C12H20N2O3

➢ Molar Mass: - 240.29
➢ Melting point: - 400.886 °C
➢ Particle shape: - White Powder
➢ Density: - 1.161g/cm3
➢ Flash Point: - 196.248 °C
• Most Wide Application of Olmesartan Intermediate:
➢ Olmesartan is an effective medication treatment used for a Hypertension.

Olmesartan is used to treat High Blood Pressure (Hypertension).
➢ It works by relaxing blood vessels so that blood can flow more easily.
➢ Olmesartan belongs to a class of drugs called angiotensin receptor
blockers (ARBS).
• Side Effect
➢ cough or cough producing mucus

➢ difficulty with breathing
➢ ear congestion
➢ fever
➢ headache
➢ loss of voice
➢ sneezing
➢ tightness in the chest
➢ unusual weakness

• Health data sheet
Identification of product Ethyl 4-(1-hydroxy-1-methylethyl) 2-propyl 1H-

Generic name imidazole-5-carboxylate more popularly Known as
Olmesartan
Colour index No. 74260
CAS number 144689-93-0
• Warning
➢ May cause skin and eye irritation.

➢ May cause respiratory irritation.
• HAZARDS IDENTIFICATION
➢ Olmesartan is not a hazardous substance according to GHS

(Globally Harmonized System)
• Physical data sheet:
Appearance White Powder

Odour None
Solubility in Water Soluble
Ph 4.5 to 6

• Reactivity data
Stability Stable under recommended storage

conditions.
Hazards Will not occur
Incompatible materials Strong oxidizing agents
Hazardous decomposition Carbon dioxide, Nitrogen oxides
• Fire & Explosion Hazard Information
Flash point Not applicable

Extinguishing media Use firefighting measures that suit the
environment and a solid water stream may
be inefficient
Special firefighting procedure Not known
Unusual hazards Handle carefully to avoid dusting
conditions. Like most organic products,
dust of this products if Mixed in critical
proportions and in Presence of a source of
ignition.)
• Health Hazardous Information
Inhalation Irritating
Skin Irritating
Eyes Irritating
Ingestion Harmful if swallowed.

• Special protection information
Respiratory Wear a noise approved dust respirator or a dust mask if

dusty conditions are present.
Ventilation Use local exhaust to minimize exposure
Eye protection Wear safety glasses or chemical splash goggles.
Protective gloves Impervious rubber or plastic gloves.
Other protective measures Wear an apron, normal work close; others with long
sleeved shirt to avoid skin contact.
Note Eye wash stations should be easily. Accessible. Shower
after handling this product. Work Cl2 others should be
washed before reuse. Wash well before eating
• Special precaution
➢ Keep container closed, when not in use. Store in dry and dark place away from
excessive heat or open flames. Maintain good housekeeping avoiding dust build up.
According to good industrial practice, handle with due care and avoid unnecessary
exposure.
• Emergency first aid procedure
Inhalation Remove to fresh air, if difficulty in Breathing, administer oxygen

and get Immediate medical attention.
Ingestion skin Get immediate medical attention, wash, thoroughly with soap and
water for 15 Minutes. If skin irritation develops, seek immediate
medical attention.
Eyes Flush immediately under running Water for 15 minutes checks the
eyes by medical examiner

Chapter 9. CONCLUSION AND FUTURE SCOPE
9.1 Conclusion
To recapitulate, this internship has been an excellent and rewarding experience. I can
conclude that there have been a lot I have learnt from my work ALMON Industries. After
complete my industrial training. I had been exposed to a process engineer and laboratory
working life.
Throughout my internship, I could understand more about the definition of a process

engineer and lab and prepare myself to become a responsible and innovative technician and
programmer in future. Along my training period, I realize that observation is a main
element to find out the root cause of a problem. Not only for my project but daily activities
too.
During my project, I cooperate with my colleagues and operators to determine the

problems. Moreover, the project indirectly helps me to learn independently, discipline
myself, be considerate patient, self-trust, take initiative and the ability to solve problems.
Besides, my communication skills y strengthens as well when communicating with others.
In the course of my training period, I have received criticism and advice from engineers
and technician when mistakes were made. However, those advices are useful guidance for
me to change myself and avoid myself making the same mistakes again.
Apart from that, I had also developed my technical skills through various activities that I
had done. This also helps sharpen my abilities. In sum, the activities that I had learned
during industrial training really are useful for me in future to face challenges in a working
environment. Throughout the industrial training, I found that several things are important:
• Time Management
• Critical and Analytical Thinking
• Colleague Interactions
• Goal Management

9.2 Future Scope
• Company is planning to install more new plants for Olmesartan Intermediate and
improve Quality and Quantity of Product.
• They have planning of automated plant in future.

REFERENCES
Bibliography
1. Stoichiometry by B I Bhatt, S M Vora, Tata McGraw-Hill, 2nd edition
2. Mass Transfer Operations 3rd Edition by Robert Tribal, Tata McGraw-Hill
3. Introduction to Process Engineering and Design, 2nd Edition by Shuchen B.

Thakore, Bharat I. Bhatt, Tata McGraw-Hill
4. Heat Transfer Principle and Applications by Binay K Dutta, Prentice Hall of India.
5. Illustrated Process Equipment Design,4th Edition by S B Thakore and D A Shah,

Atul Prakashans.
6. A study on HPLC METHOD FOR THE ESTIMATION OF OLMESARTAN IN
FORMULATION from SUMAN AVULA, K. NAVEEN BABU and M.V
RAMANA, International Journal of Advances in Pharmaceutical Sciences, volume
2 issue 2-3, June 2011, ISSN 2231-0541.
7. A study on Solid-state analysis of the active pharmaceutical ingredient in drug
products from Ann W. Newman and Stephen R. Byrn, research focus, volume 8,
issues 19, 19 October 2003, ISSN 1359-6446.
8. A Study on SAFETY MANAGEMENT: PROBLEMS ENCOUNTERED AND
RECOMMENDED SOLUTIONS By Joe M. Wilson Jr. and Enno ‘‘Ed’’ Koehn,
JOURNAL OF CONSTRUCTION ENGINEERING AND MANAGEMENT, Vol.
126, No. 1, FEBRUARY 2000, ISSN 0733-9634.
9. A study on Enhancing crystalline properties of a cardiovascular active
pharmaceutical ingredient from Ali N. Saleemi, Gerry Steelea, Nicholas I. Pedge,
Anthony Freemana, Zoltan K. Nagy, International Journal of Pharmaceutics, march
2012, ISSN 0378-5173.
10. A study on A Competent and Commercially Viable Process for the Synthesis of the
Anti-Hypertensive Drug Olmesartan from Bomana HANUMANTHA RAO, Inti
Venkata SUBRAMANYESWARA RAO, Scientia Pharmaceutica, Volume 83,
Issue 3, march 2015, ISSN 1502-04.
11. A study on Thin-layer chromatography: challenges and opportunities from Colin F.
Poole, Journal of Chromatography, volume 3, issue 1, 2003, ISSN 0021-9673.

Appendix 1
Weekly Reports: -

Manufacturing of Olmesartan Intermediate

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Manufacturing of Olmesartan Intermediate

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PROJECT ID: - 197385 CHEMICAL ENGINEERING

MANUFACTURING OF OLMESARTAN INTERMEDIATE

PATEL JAY MAHENDRA KUMAR

In partial fulfillment for the award of the degree of

Gujarat Technological University, Ahmedabad

GUJARAT TECHNOLOGICAL UNIVERSITY SAL ENGINEERING AND TECHNICAL INSTITUTE

SAL Engineering and Technical Institute

Manufacturing of Olmesartan Intermediate At Almon Industries has been carried

degree of Bachelor of Engineering in Chemical Engineering, 8th Semester of Gujarat

Technological University, Ahmadabad during theacademic year 2021-22.

Prof. Parth Desai Dr. Bhavna Soni

Internal Guide Head of the Department

GUJARAT TECHNOLOGICAL UNIVERSITY SAL ENGINEERING AND TECHNICAL INSTITUTE

GUJARAT TECHNOLOGICAL UNIVERSITY SAL ENGINEERING AND TECHNICAL INSTITUTE

GUJARAT TECHNOLOGICAL UNIVERSITY SAL ENGINEERING AND TECHNICAL INSTITUTE

SAL Engineering and Technical Institute

Manufacturing of Olmesartan Intermediate submitted in partial fulfillment for the

degree of Bachelor oEngineering in Chemical Engineering to Gujarat Technological

University, Ahmedabad, is a bonafide record of original project work carried out by me

source, without providing due reference.

Name of the Student Sign of Student

Patel Jay Mahendra Kumar

GUJARAT TECHNOLOGICAL UNIVERSITY SAL ENGINEERING AND TECHNICAL INSTITUTE

I would like to be my acknowledgements by thanking Mr. Brijesh

My special thanks to Mr. Sameer Patel (Production manager) for

Lastly My Special thanks to all the people who encourage me and

GUJARAT TECHNOLOGICAL UNIVERSITY i SAL ENGINEERING AND TECHNICAL INSTITUTE

API or Active Pharmaceutical Ingredient is an active component that is

Key Words: - API, Pharmaceutical, Piping and Instrumentation.

GUJARAT TECHNOLOGICAL UNIVERSITY ii SAL ENGINEERING AND TECHNICAL INSTITUTE

Fig 1.4.1 Organization Chart ............................................................................................. 2

GUJARAT TECHNOLOGICAL UNIVERSITY iii SAL ENGINEERING AND TECHNICAL INSTITUTE

Table 4.4.1 Raw Material................................................................................................. 13

Table 5.1.1 Stage 1 – Material Balance ........................................................................... 15

Table 5.1.2 Stage 2 – Material Balance ........................................................................... 16

Table 5.1.3 Stage 3 – Material Balance ........................................................................... 17

GUJARAT TECHNOLOGICAL UNIVERSITY iv SAL ENGINEERING AND TECHNICAL INSTITUTE

TMOB: - Trimethyl Ortho Butyrate

GLR: - Glass Lined Reactor

SSR: - Stainless Steel Reactor

API: - Active Pharmaceutical Ingredient

TMOB: - Trimethyl Ortho Butyrate

GHS: - Globally Harmonized System

THF: - Tetra Hydro Furan

GUJARAT TECHNOLOGICAL UNIVERSITY v SAL ENGINEERING AND TECHNICAL INSTITUTE

GUJARAT TECHNOLOGICAL UNIVERSITY vi SAL ENGINEERING AND TECHNICAL INSTITUTE

7.4 Purpose of QA/QC …………………………………………………………24

GUJARAT TECHNOLOGICAL UNIVERSITY vii SAL ENGINEERING AND TECHNICAL INSTITUTE

Chapter1. OVERVIEW OF THE COMPANY

ALMON INDUSTRIES have couple of plants in Gujarat producing different products At

It is Established in 2011. In Land Area of 2000 sq. m.

They Manufactures Ethyl 4-(1-hydroxy-1-methylethyl) 2 propyl-1H-imidazole-5-

Almon Industries is Certified with ISO 9000 – 2012 Certificate.

1.2 Production Capacity

1.3 Different Product

2 Other API & API Intermediate

GUJARAT TECHNOLOGICAL UNIVERSITY 1 SAL ENGINEERING AND TECHNICAL INSTITUTE

1.4 Organization Chart

Fig 1.4.1 Organization Chart

GUJARAT TECHNOLOGICAL UNIVERSITY 2 SAL ENGINEERING AND TECHNICAL INSTITUTE

Chapter 2 OVERVIEW OF DIFFERENT DEPARTMENTS

AND LAYOUT OF THE COMPANY

2.1 Introduction to Different Department