INTERNSHIP FINAL REPORT

Submitted by

Sabavat Vivek Vardhan

21CHB0B47

+919000807096

[email protected]

Under the guidance of

Mr. J. Praveen Kumar,

Deputy General Manager, HR

Apitoria Pharma Limited.

 ACKNOWLEDGEMENTS

We would like to first express my gratitude to Mr.J.Praveen Kumar sir,Deputy

General Manager, for granting the permission to complete internship at Apitoria
pharma limited

I would also like to thank the instructors in the company who provided
support and encouragement throughout the process. Their contributions have
been instrumental in the successful completion of this report. I am truly
grateful for their assistance.

We are sure that the lessons we learned throughout this work and our commitment to
excellence will help us in the future.
 CERTIFICATE

This is to certify that Mr. SABAVAT VIVEKVARDHAN (21CHB0B47), S/o Mr. S

Bheemsingh. is a bonafide student of the Department of Chemical Engineering.
National Institute of Technology Warangal, Telangana, Pin:506004, has undergone
Industrial Training in our Organization from 04/06/2024 to 19/07/2024 as a part of
Partial fulfillment of his B.Tech Chemical Engineering course.

During the period, he had interacted with different departments like Production,
Solvent Recovery Plant, Effluent Treatment & Multiple Effective Evaporation System
and acquired relevant basic knowledge in these areas.

During aforesaid period, we found him hard working, sincere and learning attitude.

J.Praveen kumar,

Deputy General Manager– HR,

Apitoria Pharma Pvt Ltd.

 DECLARATION

I hereby declare that the work presented in the dissertation has been originally
carried out by me under the supervision and overall guidance of Mr. J.PRAVEEN
KUMAR, Deputy General Manager – HR, Apitoria Pharma Limited.

I Further assure that this work has not been submitted either in whole or
other part of degree at any University.

S.Vivek Vardhan (21CHB0B47)

Date:19-07-2024
 CONTENTS

1. Introduction

2. Warehouse

3. Quality Control

4. Solvent Recovery Plant

5. Effluent Treatment Plant

6. Production And Unit Operations

7. Product

8. Conclusion

9. References
 CHAPTER - 1

INTRODUCTION

Apitoria pharma is a 100% subsidiary of Aurobindo Pharma.The company was

founded on 19/12/2017.This branch of Aurobindo pharma focuses on Active
Pharmaceutical Ingredients, we are built on the promise of Agility, Reliability, and
Innovation.
Aurobindo Pharma Limited is an Indian multinational pharmaceutical company
headquartered in Hyderabad, Telangana, India. The company was founded in 1986
and has since become one of the largest generic pharmaceutical companies in the
world.
Aurobindo Pharma is primarily engaged in the development, manufacturing, and
marketing of generic pharmaceuticals and active pharmaceutical ingredients (APIs).
The company's product portfolio includes a wide range of therapeutic categories,
including antibiotics, antiretrovirals, cardiovascular, central nervous system,
gastroenterology, and more.
The company has a strong global presence and exports its products to over 150
countries worldwide. It has manufacturing facilities in multiple countries, including
India, the United States, and several European countries. Aurobindo Pharma has
received approvals from various regulatory authorities such as the US Food and
Drug Administration (FDA), the European Medicines Agency (EMA), and others.
In addition to generic pharmaceuticals, Aurobindo Pharma has been expanding its
presence in other segments such as biosimilars, over-the-counter (OTC) products,
and custom synthesis. The company has also been actively involved in research and
development activities to develop new drugs and enhance its product
pipeline.Aurobindo has close to 500 patents in place. "To make APL as a Learning
organization towards sustained business performance through progressive talent
management."
• To attract, build and retain the right talent at all levels.
•To create and nurture performance culture through continuous capability building,
performance measurement and leveraging IT.
1.1 Process flowsheet and operations in Aurobindo Unit-1

The raw materials or the chemicals are obtained from a supplier which are used to
prepare products. The raw materials are first kept in a warehouse and if qualified by
the Quality control it is sent for the Production Unit. A stream from the Production
plant goes to the Unit operations whereas the other to the Solvent recovery plant in
which useful materials are separated and effluent is sent to the Effluent treatment
plant. In ETP the water is recycled and the unwanted slide is Discharged as sludge.
At the end of Unit operations the product is packed and sent back to the supplier.
 CHAPTER-2

WAREHOUSE

Warehouses in the pharmaceutical industry play a crucial role in the storage and
distribution of medications, vaccines, and other health-related products. Here are
some key aspects of pharmaceutical warehouses:

1. Temperature Control: Many pharmaceutical products require strict

temperature control to maintain their efficacy and safety. Warehouses often
have multiple temperature zones, including refrigerated and frozen storage
areas

.
 2. Regulatory Compliance: Pharmaceutical warehouses must adhere to
stringent regulations set by agencies like the FDA (Food and Drug
Administration) and EMA (European Medicines Agency). These regulations
cover aspects like storage conditions, record-keeping, and inventory
management.
3. Inventory Management: Efficient inventory management systems are
essential to track the movement of goods, manage expiration dates, and ensure
a first-expiry-first-out (FEFO) system to reduce waste and ensure product
safety.
4. Quality Control: Quality control processes are crucial to ensure that all
products meet the required standards. This includes regular inspections,
sampling, and testing of products.
5. Packaging and Labeling: Proper packaging and labeling are vital to ensure
product integrity and compliance with regulatory requirements. This includes
tamper-evident packaging and clear labeling of expiration dates and storage
instructions.
6. Distribution: Warehouses serve as central hubs for the distribution of
pharmaceutical products to healthcare facilities, pharmacies, and other
end-users. Efficient logistics and transportation systems are essential to ensure
timely and safe delivery.

In a pharmaceutical warehouse, the use of red, green, and yellow zones (or areas) is
often part of a color-coded system to manage and control inventory, ensure
compliance, and streamline operations. Here’s what each color typically represents:

1. Green Zone:
○ Purpose: This area is for products that have passed all quality control
checks, regulatory approvals, and are ready for distribution.
○ Procedures: Products in the green zone are considered safe, compliant,
and fit for use. They are available for picking, packing, and shipping to
customers or end-users.
○ Outcome: These products are actively managed as part of the
warehouse’s inventory and are the first choice for fulfilling orders.
2. Yellow Zone/ Quarantine zone:

○ Purpose: The yellow zone is used for products that are under review,
awaiting further inspection, or pending additional information. This
could include items undergoing re-testing, products with incomplete
documentation, or items flagged for potential issues.
○ Procedures: Items in the yellow zone require further action before they
can be moved to the green zone. This might involve additional quality
checks, waiting for regulatory clearance, or resolving discrepancies.
○ Outcome: Once any issues are resolved, products can be moved to the
green zone. If issues persist, they may be moved to the red zone.
3. Red Zone:
○ Purpose: This area is designated for products that have failed quality
control checks, are expired, damaged, recalled, or otherwise deemed
unfit for use.
○ Procedures: Items in the red zone are segregated to prevent accidental
use or distribution. They are typically labeled with red tags to indicate
their status.
○ Outcome: Products in the red zone are usually destined for destruction,
return to the manufacturer, or other forms of disposal as per regulatory
requirements.
 CHAPTER-3

QUALITY CONTROL

Quality control (QC) in the pharmaceutical industry is a critical process that ensures
the products manufactured meet predefined quality criteria and comply with
regulatory standards. It involves systematic measurement, comparison with a
standard, and monitoring of processes to prevent errors and defects in the final
products. Here’s an overview of key components and practices in pharmaceutical
quality control:

Key Components of Quality Control:-

1. Raw Material Testing:
○ Identity Testing: Ensuring that the raw materials are exactly what they
are claimed to be.
○ Purity Testing: Checking for the presence of any contaminants or
impurities.
○ Potency Testing: Verifying the strength and concentration of active
ingredients.
2. In-Process Control:
○ Monitoring During Production: Continuous checks during the
manufacturing process to ensure that products meet quality standards at
every stage.
○ Process Validation: Ensuring that the production process consistently
produces products meeting quality specifications.
3. Finished Product Testing:
○ Physical Testing: Assessing characteristics like color, shape, size, and
consistency.
○ Chemical Testing: Measuring the active ingredient’s concentration and
checking for degradation products.
 ○ Microbiological Testing: Ensuring that the product is free from
harmful microorganisms.
4. Stability Testing:
○ Shelf Life Determination: Testing products over time to ensure they
maintain their quality, safety, and efficacy until the expiration date.
○ Storage Conditions: Studying the effects of environmental factors like
temperature and humidity on the product.

Karl Fischer Titrators :-

Karl Fischer (KF) titration is a widely used analytical method in the pharmaceutical
industry for determining the water content in raw materials, intermediates, and
finished products. Accurate moisture determination is crucial as it can significantly
affect the stability, efficacy, and shelf life of pharmaceutical products.

Principles of Karl Fischer Titration:-

KF titration is based on the quantitative reaction of water with iodine and sulfur
dioxide in the presence of a base, typically methanol, which forms a non-aqueous
solution. There are two main types of KF titration: volumetric and coulometric.
 1. Volumetric Karl Fischer Titration:
○ Involves the addition of a reagent containing iodine to the sample.
○ The amount of water is determined by measuring the volume of titrant
required to react completely with the water in the sample.
○ Suitable for samples with a water content ranging from 0.1% to 100%.
2. Coulometric Karl Fischer Titration:
○ Electrochemical generation of iodine directly in the titration cell.
○ The amount of water is determined by measuring the electric charge
needed to generate the iodine that reacts with the water.
○ Ideal for samples with low water content (from 1 ppm to about 5%).

Key Components and Reactions:-

● Iodine (I2): Reacts with water.
● Sulfur Dioxide (SO2): Participates in the reaction to form an intermediate.
● Base (usually imidazole): Facilitates the reaction by stabilizing the
intermediate products.
● Methanol (or another solvent): Dissolves the reagents and the sample.

The chemical reaction can be represented as:

H2​O+I2​+SO2​+3RN→2RN⋅HI+RN⋅SO3​

Where RN represents a base, typically methanol.

Applications in Pharmaceutical Quality Control:-

1. Raw Material Testing:

○ Ensuring raw materials meet moisture specifications, as excessive
moisture can lead to degradation or other quality issues.
2. Intermediate Product Testing:
○ Monitoring moisture content during various stages of production to
ensure process consistency and product quality.
3. Finished Product Testing:
 ○ Verifying that the final product's moisture content is within the
specified limits to ensure stability and efficacy.
4. Packaging Material Testing:
○ Assessing the moisture content in packaging materials to ensure they
provide adequate protection against moisture ingress.

Advantages of Karl Fischer Titration:-

● High Accuracy and Precision: Capable of detecting very low levels of water,
making it suitable for both high and low moisture content analysis.
● Specificity: Highly specific to water, reducing interference from other
substances.
● Versatility: Applicable to a wide range of sample types, including liquids,
solids, and gases.
● Speed: Provides rapid results, which is essential for timely quality control
decisions.

Implementation in Quality Control:--

1. Sample Preparation:
○ Samples must be prepared appropriately to ensure accurate results,
which may involve dissolving, grinding, or other pretreatment steps.
2. Calibration:
○ Regular calibration of the KF titration equipment using standard
solutions to ensure accuracy.
3. Method Validation:
○ Validation of the KF titration method according to regulatory guidelines
(e.g., ICH Q2) to demonstrate its suitability for the intended purpose.
4. Routine Analysis:
○ Integrating KF titration into the routine quality control workflow to
monitor water content throughout the manufacturing process.
5. Documentation and Compliance:
○ Maintaining detailed records of all KF titration analyses to ensure
traceability and compliance with regulatory requirements.
CHROMATOGRAPHY :-

Chromatography is a powerful and versatile analytical technique widely used in the

pharmaceutical industry for quality control. It involves separating, identifying, and
quantifying components in a mixture, making it essential for ensuring the purity,
potency, and safety of pharmaceutical products.

Types of Chromatography Used in Pharmaceutical Quality Control:-

1. High-Performance Liquid Chromatography (HPLC):

○ Principle: Separates components based on their interactions with the
stationary and mobile phases.
○ Applications: Used for quantifying active pharmaceutical ingredients
(APIs), detecting impurities, and analyzing complex mixtures.
2. Gas Chromatography (GC):
○ Principle: Separates volatile compounds based on their boiling points
and interactions with the stationary phase.
○ Applications: Suitable for analyzing volatile and semi-volatile organic
compounds, residual solvents, and degradation products.
Applications of Chromatography in Pharmaceutical Quality Control:-

1. Purity Testing:
○ Ensuring that the APIs and excipients are free from impurities and
contaminants.
○ Detecting and quantifying trace levels of impurities and degradation
products.
2. Assay of Active Ingredients:
○ Accurate quantification of APIs in raw materials, intermediates, and
finished products to ensure proper dosage.
3. Impurity Profiling:
○ Identifying and quantifying impurities to ensure they are within
acceptable limits.
○ Supporting the development of impurity control strategies.
4. Stability Testing:
○ Monitoring the stability of pharmaceutical products by analyzing
degradation products formed over time.
○ Supporting shelf-life determination and storage condition optimization.

Advantages of Chromatography in Quality Control:-

● High Sensitivity and Specificity: Capable of detecting and quantifying low

levels of compounds with high precision.
● Versatility: Applicable to a wide range of substances, including small
molecules, peptides, proteins, and complex mixtures.
● Reproducibility: Provides consistent and reliable results, which is critical for
regulatory compliance.
● Automation: Many chromatographic techniques can be automated, increasing
throughput and efficiency in quality control laboratories.
FTIR (Fourier Transform Infrared Spectroscopy):-

Fourier Transform Infrared (FTIR) spectroscopy is a crucial analytical technique in

the pharmaceutical industry for quality control. It involves the measurement of the
absorption of infrared radiation by a sample to obtain its molecular fingerprint. This
technique is widely used for identifying and characterizing materials, monitoring
production processes, and ensuring the quality and consistency of pharmaceutical
products.

Principles of FTIR Spectroscopy:-

FTIR spectroscopy measures the absorption of infrared radiation by a sample as a

function of wavelength or frequency. The basic principles include:

● Infrared Absorption: Molecules absorb specific frequencies of infrared light

that cause their chemical bonds to vibrate. The absorption pattern provides a
unique molecular fingerprint.
● Fourier Transform: The raw data collected in the time domain is converted
into a spectrum in the frequency domain using a mathematical algorithm
called the Fourier Transform.
● Interferometer: An interferometer is used to generate an interference pattern
from which the infrared absorption spectrum is derived.
Applications of FTIR in Pharmaceutical Quality Control

1. Identification of Raw Materials:

○ Verifying the identity and purity of raw materials to ensure they meet
specifications before use in manufacturing.
○ Detecting counterfeit or substandard materials.
2. Characterization of APIs and Excipients:
○ Identifying and characterizing active pharmaceutical ingredients (APIs)
and excipients based on their unique infrared spectra.
○ Ensuring consistency and quality of ingredients.
3. Detection of Polymorphism:
○ Differentiating between different polymorphic forms of a compound,
which can affect the drug's bioavailability and stability.

Apart from the above equipment Quality Control department contains Electronic
Balance, Polarimeter, Liquid Particle Counter, KBr Press, Melting Point Apparatus,
pH Meter, Centrifuge, Conductivity meter, Bursting Strength tester, Friability Test
Apparatus, Disintegration Tester, Humidity Chamber, Muffle Furnace, Refrigerator,
Bolometer, Vernier Caliper, Heating Mantle Oven, Hot Plate Magnetic Stirrer,
Polarising Microscope, TOC Analyser, Hardness Tester, Vacuum Pump, Viscometer,
Standard Weight Box, Dissolution Tester, Vacuum Oven, UV Chamber, Sieve
Shaker, Vertex Mixer, Stop Watch, Tap Density Tester, UV Spectrophotometer and
Sonicator
 CHAPTER-4

SOLVENT RECOVERY PLANT

A solvent recovery plant in the pharmaceutical industry is designed to capture and
reuse solvents that are used in the production process. This helps reduce waste,
lower costs, and minimize environmental impact.The process typically involves:

1. Collection: During pharmaceutical manufacturing, solvents are used for

various purposes such as extraction, crystallization, and purification. These
solvents evaporate and mix with other process gases. The first step in solvent
recovery is to capture these vapors from the production area. Ductwork and
ventilation systems are used to channel solvent vapors from equipment and
workspaces to the recovery unit.
2. Condensation:The collected solvent vapors are cooled down to condense
them back into liquid form. This is typically done using condensers.
Condensers (air-cooled or water-cooled) lower the temperature of the vapor,
causing the solvent to change from a gas to a liquid.
3. Purification: The condensed solvent often contains impurities that need to be
removed to ensure the solvent is pure enough for reuse. This purification is
usually achieved through distillation, adsorption, or membrane separation.
○ Equipment:
■ Distillation Columns: These separate the solvent from impurities
based on differences in boiling points. Components such as trays
or packing materials within the columns enhance the separation
efficiency.
■ Adsorption Units: Utilize materials like activated carbon to
capture and remove impurities.
■ Membrane Separators: Use selective permeability to separate
solvents from contaminants.
 4. Storage:The purified solvent is then stored in tanks until it is needed for reuse
in the manufacturing process. Storage tanks are designed to safely store the
solvent, ensuring it remains pure and uncontaminated.

A solvent recovery plant typically includes the following key equipment:-

1. Condensers:
○ Role: Convert vaporized solvents back into liquid form.
○ Types:
■ Air-Cooled Condensers: Use ambient air to cool and condense
the solvent vapors.
■ Water-Cooled Condensers: Use water as a cooling medium,
often in a shell-and-tube configuration to maximize heat
exchange efficiency.
2. Distillation Columns:

○ Role: Separate components of a liquid mixture based on boiling points.

○ Components:
■ Trays: Provide multiple stages for vapor-liquid contact.
■ Packing: Increases surface area for improved separation.
○ Variants:
■ Batch Distillation: Processes a fixed amount of solvent in a
batch.
■ Continuous Distillation: Continuously feeds and separates
solvent mixtures, ideal for large-scale operations.
3. Adsorption Units:

○ Role: Remove specific impurities from solvent vapors.

○ Materials: Typically filled with activated carbon or similar
adsorbents.Example:- Zeolite, Silica gel
○ Regeneration: Adsorbents can be regenerated by heating or pressure
changes to desorb captured impurities.

4. Absorbers:
○ Role: Capture solvent vapors using a liquid absorbent.
○ Design: Often configured as packed or tray towers to enhance
gas-liquid contact.
5. Vacuum Systems:
○ Role: Lower the pressure to reduce boiling points, aiding in solvent
recovery at lower temperatures.
○ Types:
■ Vacuum Pumps: Mechanically create low-pressure
environments.
■ Steam Ejectors: Use steam to create vacuum conditions.
6. Storage Tanks:
○ Role: Store recovered solvents safely and securely.
○ Design: Constructed from materials resistant to the stored solvent,
equipped with safety features like venting systems and level indicators.
7. Pumps:
○ Role: Move solvents through the recovery process stages.
 ○ Types:
■ Centrifugal Pumps: Ideal for low-viscosity solvents.
■ Diaphragm Pumps: Suitable for handling corrosive or abrasive
solvents.
8. Heat Exchangers:
○ Role: Transfer heat between process streams to improve energy
efficiency.
○ Types:
■ Shell-and-Tube: Consist of a series of tubes within a shell, used
for high-pressure applications.

■ Plate Heat Exchangers: Compact and efficient, suitable for low

to medium pressure applications.

The plant may use technologies such as distillation, adsorption, or membrane

separation to recover and purify solvents. This not only improves sustainability but
also helps comply with environmental regulations.

Benefits of Solvent Recovery in the Pharmaceutical Industry

● Cost Reduction: Reusing solvents reduces the need to purchase fresh
solvents, lowering operational costs.
● Environmental Impact: Decreases the amount of waste solvent disposed of,
minimizing environmental pollution.
 ● Regulatory Compliance: Helps meet environmental regulations and
standards, avoiding potential fines and penalties.
● Resource Efficiency: Maximizes the use of raw materials, contributing to
sustainable manufacturing practices.

By implementing a solvent recovery plant, pharmaceutical companies can enhance

their sustainability efforts, improve process efficiency, and reduce costs associated
with solvent use and waste management.
 CHAPTER-5

EFFLUENT TREATMENT PLANT

An Effluent Treatment Plant (ETP) in the pharmaceutical industry is designed to
treat wastewater generated during the manufacturing of pharmaceutical products.
This wastewater can contain a variety of harmful substances, including active
pharmaceutical ingredients (APIs), solvents, and other chemical residues. The
purpose of the ETP is to remove these contaminants and produce water that is safe
for discharge into the environment or for reuse.

Key Components of an ETP:-

1. Preliminary Treatment:
○ Screening: Removal of large solids and debris.
○ Grit Removal: Elimination of sand, grit, and other heavy particles.
2. Primary Treatment:
○ Sedimentation: Settling of suspended solids by gravity in
sedimentation tanks.
3. Secondary Treatment:
○ Biological Treatment: Use of microorganisms to degrade organic
pollutants. Common methods include activated sludge processes,
trickling filters, and bio-towers.
○ Aeration: Providing oxygen to support the biological treatment
process.
4. Tertiary Treatment:
○ Advanced Filtration: Removal of fine particles through sand filters,
multimedia filters, or membrane filtration.
○ Disinfection: Elimination of pathogens using chlorine, UV radiation, or
ozonation.
 ○ Adsorption: Using activated carbon to remove residual organic
compounds and trace pollutants.
5. Sludge Treatment:
○ Thickening: Increasing the concentration of solids in the sludge.
○ Digestion: Biological decomposition of organic matter in the sludge.
○ Dewatering: Removal of water from the sludge to reduce its volume.

Treatment Processes

1. Physical Treatment:
○ Sedimentation, flotation, and filtration are used to remove suspended
solids and large particles.
2. Chemical Treatment:
○ Coagulation and flocculation to aggregate smaller particles into larger
ones for easier removal.
○ pH adjustment to neutralize acidic or alkaline waste streams.
○ Oxidation to break down harmful chemicals.
3. Biological Treatment:
○ Aerobic treatment where microorganisms use oxygen to break down
organic matter.
○ Anaerobic treatment where microorganisms degrade organic matter in
the absence of oxygen, producing biogas.
4. Advanced Treatment:
○ Membrane processes like reverse osmosis (RO) for removing dissolved
solids.
○ Advanced oxidation processes (AOPs) for the degradation of complex
organic molecules.

Effluent Treatment Plants (ETPs) use a variety of equipment to treat wastewater

effectively. The specific equipment used can vary based on the type of wastewater
and the desired level of treatment. Here are the common types of equipment used in
ETPs:
Preliminary Treatment Equipment
1. Screening Devices:
○ Bar Screens: Remove large solids and debris.
○ Fine Screens: Remove smaller particles and debris.
2. Grit Chambers:
○ Remove sand, gravel, and other heavy particles.

Primary Treatment Equipment

1. Sedimentation Tanks (Clarifiers):

○ Allow suspended solids to settle by gravity.
2. Oil and Grease Traps:
○ Separate oils, grease, and other floatable materials from the wastewater.

Secondary Treatment Equipment

1. Aeration Systems:
○ Diffused Aerators: Introduce fine bubbles of air into the wastewater.
○ Surface Aerators: Mix air into the water by agitating the surface.
2. Biological Treatment Units:
○ Activated Sludge Systems: Use aeration tanks and secondary
clarifiers.
○ Trickling Filters: Wastewater is sprayed over a bed of media where
biofilm grows and treats the wastewater.
○ Rotating Biological Contactors (RBCs): Rotating disks support
biofilm growth.
3. Membrane Bioreactors (MBRs):
○ Combine biological treatment with membrane filtration.

Tertiary Treatment Equipment

1. Filtration Systems:
○ Sand Filters: Remove fine particles.
○ Activated Carbon Filters: Remove organic compounds and odors.
○ Membrane Filters: Use ultrafiltration, nanofiltration, or reverse
osmosis.
 2. Disinfection Units:
○ Chlorination Systems: Use chlorine to disinfect treated water.
○ UV Disinfection Units: Use ultraviolet light to kill pathogens.
○ Ozonation Systems: Use ozone gas for disinfection.
3. Adsorption Systems:
○ Use activated carbon to remove trace organic contaminants.

Sludge Treatment Equipment

1. Thickeners:
○ Concentrate sludge by removing excess water.
2. Digesters:
○ Anaerobic or aerobic digestion to reduce the volume and stabilize
sludge.
3. Dewatering Equipment:
○ Centrifuges: Separate water from sludge using centrifugal force.
○ Belt Presses: Use pressure to squeeze water out of sludge.
○ Filter Presses: Use filtration and pressure to dewater sludge.

Chemical Treatment Equipment:-

1. Coagulation and Flocculation Units:

○ Mix chemicals with wastewater to aggregate fine particles into larger
flocs.
2. pH Adjustment Systems:
○ Acid and Alkali Dosing Systems: Adjust the pH of the wastewater.
3. Oxidation Units:
○ Chemical Oxidation Reactors: Use oxidizing agents like hydrogen
peroxide or ozone to break down contaminants.

Advantages:-

● Environmental Protection: Prevents the contamination of natural water

bodies, protecting aquatic life and human health.
● Regulatory Compliance: Ensures adherence to environmental regulations
and standards set by authorities.
 ● Resource Recovery: Enables the recovery of valuable materials and the reuse
of treated water, contributing to sustainability.

Disadvantages:-

● Complexity: Pharmaceutical effluents can be complex and variable, requiring

sophisticated and adaptive treatment processes.
● Cost: High operational and maintenance costs due to advanced treatment
technologies.
● Regulatory Pressure: Stringent regulations demand high levels of treatment
efficiency and monitoring.

Implementing an effective ETP in the pharmaceutical industry is crucial for

sustainable operations and environmental stewardship.

Utilities & Effluent handling facilities

S.NO Utility Capacity

1 Coal/ Husk fired Boiler 39 TPH
2 Turbine & generator 3.95 MW
3 DG Sets 3 x 750; 4 x 1010 KVA
4 DM/ Softener 10 KL
5 Cooling Towers 2000 TR
4 Waste Water Treatment
plant 1. Stripper, Multiple Effect Evaporator
and ATFD System 1 x 500 KLD
2. RO System for Effluents –1x500 KLD
3. up-gradation of existing 200 KLD
Bio-ETP
Waste water generation and mode of treatment :-

S. No Stream Discharge in Mode of treatment proposed

KLD
1 Process 343.8 Stripper, MEE with ATFD - Condensates
to Bio ETP and RO
RO Rejects to MEE
(ZLD)
2 Reactor & Floor 20.0 Stripper, MEE with ATFD - Condensates
Washings to Bio ETP and RO
RO Rejects to MEE
(ZLD)

3 Scrubber 25.0 Stripper, MEE with

ATFD - Condensates
to Bio ETP and RO RO Rejects to MEE
(ZLD)

4 QC and R&D 15.0 Stripper, MEE with

ATFD - Condensates
to Bio ETP and RO RO Rejects to MEE
(ZLD)

5 DM/Softener 25.0 Stripper, MEE with ATFD - Condensates

(Regeneration) to Bio ETP and RO RO Rejects to MEE
(ZLD)
 6 Solvent 20.0 Stripper, MEE with ATFD - Condensates
Recovery plant to Bio ETP and RO RO Rejects to MEE
(ZLD)

7 Boiler 32.5 Stripper, MEE with

ATFD - Condensates to Bio ETP and
RO

8 Cooling Towers 25.0 RO Rejects to MEE (ZLD)

9 RO back wash 35.0 Stripper, MEE with ATFD -

Condensates to Bio ETP and RO RO
Rejects to MEE (ZLD)

10 Domestic 60.0 STP and used for gardening

11 Garment 10.0 STP and used for gardening

washings

12 Gardening Nil --

13 Ash handling Nil --

Total 611.3
 CHAPTER-6

PRODUCTION AND UNIT OPERATIONS

Reactors:-

A container where chemical feed streams are combined to create new compounds
through reaction. To ensure that the reaction occurs as intended, the reactor is
usually adjusted to the proper temperature, pressure, and/or fluid velocity.

An incorporated heating/cooling system and an agitator are features of a typical

batch reactor. The capacity of these containers ranges from less than one liter to over
fifteen thousand liters. Typically, steel, stainless steel, glass-lined steel, glass, or
exotic alloys are used in their fabrication.

The Production blocks consists of SS and glass lined reactors, storage tanks, shell &
tube heat exchangers, evaporators, vacuum pumps, packed columns, Agitated
Nutche Filter and Dryers, crystallizers, layer separators etc. The area shall be
provided with proper concealed drainage facility and all process facilities shall be
performed under protective environment.

Stainless steel reactor:-

Stainless steel reactors are crucial in the pharmaceutical industry for the production
of active pharmaceutical ingredients (APIs), intermediates, and other chemicals.
These reactors are preferred due to their excellent corrosion resistance, durability,
and ability to withstand high temperatures and pressures.They offer Reaction vessel
in designs such as double jacketed, Half Limpet coil, Full Limpet Coil, Welded
Types, Top open type etc.

Function:-
● Synthesis: Used for chemical reactions, including synthesis of APIs and
intermediates.
● Mixing: Homogenizing different reactants and solvents.
● Heating/Cooling: Regulating the temperature for optimal reaction conditions.
● Crystallization: Facilitating the formation of crystals from solutions.
● Fermentation: Used in bioprocessing for fermentation reactions.
● Storage: Holding chemical substances before further processing or packaging.

Capacity: 500-10000L

Steel Grade:-

● Common Grades:
○ 304: General-purpose grade, offers good corrosion resistance and is
widely used.
○ 316: Contains molybdenum, providing enhanced corrosion resistance,
especially against chlorides and other industrial solvents.
○ 316L: A low-carbon version of 316, used when welding is required, to
avoid carbide precipitation.
○ 904L: High-alloy austenitic stainless steel, providing excellent
corrosion resistance in highly acidic environments.
Advantages :-

● Corrosion Resistance: Excellent resistance to a wide range of chemicals and

solvents.
● Durability: Long lifespan, reducing the need for frequent replacements.
● Sanitary Design: Smooth surfaces and the ability to be easily cleaned, crucial
for maintaining product purity.
● Temperature and Pressure Resistance: Can handle high temperatures and
pressures, allowing for versatile use in various processes.
● Non-reactive Surface: Does not react with pharmaceuticals, ensuring the
integrity of the products.
● Compliance: Meets stringent regulatory standards (e.g., FDA, GMP) for
pharmaceutical manufacturing.

The stainless steel reactors are indispensable in the pharmaceutical industry due to
their robustness, versatility, and compliance with regulatory standards, ensuring
high-quality and safe production of pharmaceutical products.

Glass lined reactors:-

Glass-lined reactors are critical equipment in the pharmaceutical industry, designed

to handle highly corrosive chemicals while maintaining purity and integrity of the
products. These reactors consist of a steel shell lined with a layer of glass,
combining the strength of steel with the corrosion resistance of glass.
Function:-

● Reaction Vessel:For chemical reactions, especially those involving corrosive

substances.
● Mixing and Blending: Ensures homogeneity of reactants.
● Heating and Cooling: Integrated systems for temperature control.
● Capacity:- 50L to 50000L

Glass Type/Grade:-

● Borosilicate Glass (Type I): Commonly used due to its superior thermal and
chemical resistance.
● Enamel Coating: Fused onto the steel to create a smooth, non-porous surface
that resists corrosion and contamination.

Advantages:-
1. Corrosion Resistance: Ideal for handling highly corrosive chemicals without
degrading.
2. Purity: Non-reactive glass surface prevents contamination, crucial for
pharmaceutical products.
3. Durability: Combines the structural strength of steel with the protective
qualities of glass.
4. Easy Cleaning: Smooth, non-porous surface facilitates cleaning and
sterilization.
5. Heat Resistance: Borosilicate glass can withstand high temperatures and
thermal shock.
6. Pressure Resistance: Steel body provides excellent resistance to internal
pressures.
7. Versatility: Suitable for a wide range of reactions and processes in the
pharmaceutical industry.

Glass-lined reactors are indispensable in the pharmaceutical industry due to their

unique combination of chemical resistance, durability, and ability to maintain high
levels of purity. Their customizable capacities and dimensions make them adaptable
to various pharmaceutical processes, ensuring both efficiency and safety in
production.
Multiple Effect Evaporator:-

Multiple effect evaporators (MEEs) are widely used in the pharmaceutical industry
due to their efficiency in concentrating solutions, recovering solvents, and reducing
waste volumes. Their ability to operate under varying pressures and temperatures
makes them highly suitable for handling sensitive pharmaceutical products.

Working Principle:-

First Effect: The feed solution is heated using an external heat source (usually
steam). The vapor generated in this effect is used as the heating medium for the next
effect.
Second Effect and Subsequent Effects: The vapor from the first effect heats the
solution in the second effect. This process continues through multiple effects. Each
subsequent effect operates at a lower pressure and temperature than the previous
one, utilizing the energy from the vapor more efficiently.

Applications in the Pharmaceutical Industry:-

1. Concentration of Active Pharmaceutical Ingredients (APIs):
○ MEEs are used to concentrate APIs from dilute solutions. This step is
crucial for ensuring that the final product has the desired potency and
efficacy.
 2. Solvent Recovery:
○ During the manufacturing process, solvents are often used to dissolve
and purify pharmaceutical compounds. MEEs help in recovering these
solvents for reuse, which is both cost-effective and environmentally
friendly.
3. Wastewater Treatment:
○ Pharmaceutical production generates wastewater containing valuable
materials and solvents. MEEs concentrate these wastes, reducing the
volume and enabling the recovery of valuable substances.
4. Purification of Intermediates:
○ Intermediates in pharmaceutical synthesis often require concentration
and purification. MEEs provide an efficient means to achieve this,
maintaining the quality and purity of the product.

Types of Multiple Effect Evaporators

1. Forward Feed: The feed flows from the first effect to the last effect, and the
product is taken from the last effect.

2. Backward Feed: The feed flows from the last effect to the first effect, with
the product taken from the first effect.
3. Mixed Feed: A combination of forward and backward feed, optimized for
specific process requirements.
Advantages
● Energy Efficiency: By reusing the vapor generated in each effect, multiple
effect evaporators significantly reduce the amount of energy needed compared
to single-effect evaporators.
● Lower Operating Costs: Reduced energy consumption leads to lower
operational costs. Efficient recovery of solvents can lead to substantial cost
savings, especially in industries like pharmaceuticals.
● Improved Concentration: These systems can achieve higher concentrations
of the final product compared to single-effect systems.

Multiple effect evaporators are a vital component in the pharmaceutical industry,

providing efficient and cost-effective solutions for concentration, solvent recovery,
and waste reduction. Their ability to maintain product quality and comply with
regulatory standards makes them indispensable in modern pharmaceutical
manufacturing.

Vacuum Tray Dryer:-

A vacuum tray dryer (VTD) is a type of industrial drying equipment used for
removing moisture from various materials, such as pharmaceuticals, chemicals, food
products, and other substances that require gentle and uniform drying under
controlled conditions.It dries on the conduction principle. The vacuum tray dryer
operates under a vacuum, reducing the boiling point of the liquid to be evaporated
and allowing drying at lower temperatures, which is beneficial for heat-sensitive
materials.Valuable organic solvents can also be conveniently condensed and
recovered.
Spray Dryer:-

A spray dryer operates on the principle of transforming a liquid feed into a dry
powder through the rapid evaporation of moisture by introducing hot gas. The
process begins with the preparation of the liquid or slurry feed, which is often
homogenized to ensure uniformity. This feed is then pumped to an atomizer, which
breaks the liquid into fine droplets. The atomizer can be of different types, including
rotary disk, single-fluid nozzle, or two-fluid nozzle, each serving the purpose of
maximizing surface area for efficient drying.

Once the liquid is atomized, the fine droplets are introduced into a drying chamber.
In this chamber, the droplets come into contact with hot gas, usually air, which has
been heated to a high temperature using an air heater. The hot gas rapidly evaporates
the moisture from the droplets, turning them into dry particles. The design of the
drying chamber and the distribution of the hot gas are crucial to ensure uniform
drying and to prevent agglomeration or incomplete drying of the particles.

As the drying process completes, the dry particles are separated from the exhaust air.
This is typically achieved using cyclones, bag filters, or electrostatic precipitators,
which efficiently collect the dry powder while allowing the spent air to be exhausted.
The collected powder is then ready for further processing or packaging.
 CHAPTER-7

PRODUCTS

List of Products With Quantity of Production per Month :-

S. No. Name of the Product Production Capacity

Kgs/Month Kgs/Day
1 Amisulpride 500.00 16.67
2 Aripiprazole 500.00 16.67
3 Atorvastatin 4000.00 133.33
4 Bisprolol Fumarate 500.00 16.67
5 Bupropion HCl 500.00 16.67
6 Candesartan Cilexetil 1000.00 33.33
7 Cefaclor Monohydrate 1000.00 33.33
8 Cefadroxil 3000.00 100.00
9 Cefalothin Acid 2000.00 66.67
10 Cefazolin Sodium 3000.00 100.00
11 Cefdinir 2500.00 83.33
12 Cefditoren Pivoxil 500.00 16.67
13 Cefepime HCl 2000.00 66.67
14 Cefixime Trihydrate 1500.00 50.00
15 Cefotaxime 3000.00 100.00
16 Cefoxitin Sodium 500.00 16.67
17 Cefpirome Dihydroiodide 200.00 6.67
18 Cefpodoxime Proxetil 3000.00 100.00
19 Cefprozil 3000.00 100.00
20 Cefradin 2000.00 66.67
21 Cefsulodin Sodium 500.00 16.67
22 Ceftazidime 2000.00 66.67
DiHydrochloride
23 Ceftibuten Dihydrate 2000.00 66.67
24 Ceftiofur HCl 3000.00 100.00
25 Ceftizoxime Acid 500.00 16.67
26 Ceftriaxone Disodium 3000.00 100.00
Hemiheptahydrate
27 Cefuroxime Axetil 23500.00 783.33
28 Cephalexin Monohydrate 15000.00 500.00
29 Cephapirin Benzathine 500.00 16.67
30 Ciprofloxacin HCl 7000.00 233.33
31 Citalopram Hydrobromide 2500.00 83.33
32 Donepezil Hydrochloride 500.00 16.67
33 Doxazosin Mesylate 500.00 16.67
34 Entacapone 3000.00 100.00
35 Escitalopram Oxalate 2000.00 66.67
36 Famciclovir 2000.00 66.67
37 Florfenicol 5000.00 166.67
38 Fluvastatin 500.00 16.67
39 Gabapentin 40000.00 1333.33
40 Gemfrozil 10000.00 333.33
41 Glyburide 2500.00 83.33
42 Irbesartan 5000.00 166.67
43 Lamivudine 1000.00 33.33
 44 Lisinopril 1000.00 33.33
45 Losartan Potassium 5000.00 166.67
46 Metformin HCl 200000.00 6666.67
47 Metoprolol Succinate 2000.00 66.67
48 Metoprolol Tartrate 10000.00 333.33
49 Mirtazapine 2000.00 66.67
50 Modafinil 1000.00 33.33
51 Nevirapine 5000.00 166.67
52 Ondansetron 200.00 6.67
53 Pantoprazole Sodium 3000.00 100.00
Sesquihydrate
54 Paroxetine HCl 3000.00 100.00
55 Perindopril tert-Butylamine 500.00 16.67
56 Rabeprazole Sodium 500.00 16.67
57 Ritonavir 2000.00 66.67
58 Ribavirin 500.00 16.67
59 Risperidone 500.00 16.67
60 Sevelamer HCl/Carbonate 1000.00 33.33
61 Simvastatin 7000.00 233.33
62 Stavudine 1000.00 33.33
63 Telmisartan 2000.00 66.67
64 Terazosin HCl Dihydrate 300.00 10.00
65 Terbinafine HCl 3000.00 100.00
66 Topiramate 5000.00 166.67
Total Monthly production (TPM) 412.2

Daily production Kgs 14040.00

Product Quality:-

Product quality in the pharmaceutical industry is critical as it directly impacts patient

safety, therapeutic efficacy, and compliance with regulatory standards. Ensuring high
product quality involves multiple facets, including stringent manufacturing
processes, rigorous testing, and continuous monitoring.

Quality Control (QC) and Quality Assurance (QA):

● QC: Involves the testing of raw materials, in-process materials, and finished
products to ensure they meet specified standards.
● QA: Focuses on the systematic monitoring and evaluation of various aspects
of production to ensure compliance with standards and regulations.

Adherence to GMP guidelines ensures that products are consistently produced and
controlled according to quality standards.Detailed SOPs are essential for maintaining
consistency in manufacturing processes.

Maintaining high product quality in the pharmaceutical industry requires a holistic

approach involving stringent adherence to regulatory standards, robust quality
control and assurance mechanisms, risk management, technological innovations, and
continuous improvement practices. This ensures that the products are safe, effective,
and reliable for patient use.
 CONCLUSION

In conclusion, my internship at Apitoria pharma has been an invaluable experience

that significantly contributed to my understanding of the pharmaceutical industry.
Throughout my tenure, I had the opportunity to work with professionals in the
pharmaceutical Industry, which allowed me to apply theoretical knowledge gained
from my academic studies to real-world scenarios.I have acquired knowledge about
Unit operations such as synthesis, purification, formulation, and packaging play
pivotal roles in ensuring the efficiency, safety, and quality of the final product.

To reduce impurities and byproducts, the right solvents, reaction conditions, and
separation methods must be used. Purification is a crucial unit activity that improves
the API's purity by removing contaminants. Filtration, centrifugation, and
chromatography are among the techniques used to separate products from unwanted
components in order to minimize health hazards and ensure regulatory compliance.
In the manufacturing process, optimizing unit operations improves consistency in
quality, lowers production costs, and increases process efficiency. Pharmaceutical
companies have the capacity to make products that meet safety criteria and have
high yield, purity, and batch-to-batch consistency by carefully controlling and
refining each process.

Overall, unit operations in the pharmaceutical sector are critical to the development
and manufacturing of high-quality pharmaceuticals. Continuous research and
innovation in optimizing these activities are crucial for developing pharmaceutical
production, improving patient outcomes, and effectively addressing healthcare
requirements.
 REFERENCES

1) Aurobindo Pharma Limited – Unit I Environmental Impact Assessment

Report
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