in plant training at arrow pharmaceuticals pvt ltd, Chagunarayan #pharma #pharmaceutical https://www.slideshare.net/NeerajOjha17/in-plant-training-at-arrow-pharmaceuticals-pvt-ltd-chagunarayan via @SlideShare

1. INPLANT TRAINING AT ARROW PHARMACEUTICALS PVT. LTD.
Submitted by
Neeraj Ojha
CIST College, New Baneshwor
Affiliated to Pokhara University
To
Nishant Kumar Gupta
QA Manager
Arrow Pharmaceuticals Pvt. Ltd.
Chagunarayan Municipality-8, Sudal
Bhaktapur, Nepal

2. Acknowledgement
I am extremely thankful to Mahesh Bhatta who introduced and helped me get this opportunity.
This was particularly special as I had undertaken Bachelor in Pharmacy course under his
counseling. He guided me from time to time during my period of internship and helped me in
course correction. He warned me from time to time what not to do while at the industry.

3. Abbreviations
BMR: Batch manufacturing record
BP: British Pharmacopoeia
BPR: Batch packaging record
DMW: De-mineralized water
DT: Disintegration time
FBD: Fluidized Bed Dryer
FG/FP: Finished Goods/ Finished Products
GLP: Good laboratory practice
GMP: Good manufacturing practice
HDPE: High Density Polyethylene
HEPA: High efficiency particulate air
HPLC: High performance liquid chromatography
HVAC: Heating ventilation and air conditioning
IP: Indian Pharmacopoeia
IPQC: In process Quality control
QC: Quality Control
QA: Quality Assurance
R&D: Research and Development
IPQC: In Process Quality Control
DDA: Department of Drug Administration

4. I. Company Profile Information
Arrow Pharmaceuticals Pvt. Ltd was established over 7 years ago under the
leadership of now technical director Mahesh Bhatta, a veteran in the field of
pharmacy education at institutions like Kathmandu University, with a worldwide
level of experience in the field of pharmaceutics. Currently there are over 57
shareholders at Arrow Pharmaceuticals including a local Khadka family which owns
several businesses and land all over Kathmandu. Due to involvement of locals at
different levels of the company, the industry is well taken care of in terms of
emergency and security. Over 1 arab rupees has been spent on the facility.
Arrow is a new pharmaceutical company as compared to many old ones in the same
line but is picking up the market and good-will at a great pace. Partnership with other
pharmaceutical companies is also taking place at a high speed. Madan Thapa is the
chief executive at the marketing department in Basundhara, Kathmandu with national
and international connections. Current products by Arrow in the market are helping
build the industrial goodwill.
The factory location in the Chagunarayan Municipality is very appropriate in many
ways. Very close to the tourist hot spot Nagarkot, it might be a prospective spot of
student exchange program or foreign pharmaceutical visiting tourism area in many
ways. Nearby nurseries and rice paddies provide a very peaceful background for the
busy workers of this company and the visitors.

5. 1.1.Objective of internship
General Objective
To fulfill the requirement of Pokhara University internship requirement;
Specific Objective
1. To learn from experienced pharmacists and operators;
2. To build a better networking with pharmaceutical professionals;
3. To be able to compare between different pharmaceutical establishments in
different parts of Nepal;
4. To be able to identify which area of pharmacetics appeals to my future career
choice or I naturally fit in ;
1.2.Time Frame
2 weeks.

6. 2. Production
Production department in the industrial pharmacy refers to the manufacturing area where the
mass manufacturing of the product is done as per the method developed and tested by R&D in
association with the marketing department and QC. The marketing department which has a
separate establishment comes up with a product that the market is demanding and develops a
general outline of the product details. That is forwarded to the R&D department at industry.
R&D develops the product accordingly performed stability tests with the help of QC and after a
certain period of time registers for the manufacturing license at DDA. This is done online in the
present moments through http://dams.dda.gov.np/login website. The documents are submitted
by R&D online and also in paper print form in person. After approval by DDA, manufacturing
license is received by the company for the product after necessary document submission.
R&D orders necessary packaging materials and labeling from companies abroad in the case of
Nepal. After all these primary tasks are completed, the matter goes to production department for
the bulk production of the first few batches under the direction of R&D officer. This process is
repeated by production department under the direction of production officer with the same
method every time the product is needed again in bulk.
Production department ast Arrow was comparatively larger than the ones I had seen during
industrial tours and had larger number of employees. During the first three days, I had an
opportunity to watch the dispensing, cleaning and resetting of punches and dyes, the tray drying
of blood pressure drug granules, blister packaging of pantoprazole tablets at the Alu-Alu
packaging unit etc.
QC officer Sujan Koju and Production Officer Pashupati Suwal were very helpful during the day
to day activities at Production department.
During this period, the hardness test, friability test and dissolution tests were performed on the
sample tablets many times. The adjustments were also made on the tablet compression machine
settings. After the sample tablets met the necessary requirements like dissolution time (less than
15 minutes), friability (less than 1) etc., the tablet compression was performed in bulk. On the
first day over 80000 tablets were produced by the compression machine. On the next day, several
lakhs of tablets were produced. This is called IPQC, in process quality control.

7. Dispensing and sampling were also being done at production while I was there. This was done
under the presence of IPQC person, Sabina in this case. The sampling of products like
permethrin and dispensing of products like menthol were done in my presence. Sampling is the
process of taking out small portion of products that are necessary to be tested at that period in
time by QC. Storage department determines which products needs to be sampled at that period in
time depending upon the several factors. “Swab pass” is a term used in this case. This is done
very frequently. Dispensing is the process of releasing the products necessary for the bulk
production according to the orders received by other departments like marketing and R&D. For
the purpose of dispensing, the machines are first calibrated with the standards. After they are
found fit and OK, the necessary products are dispensed in appropriate containers. The containers
and the ladles are properly washed first with soap and then wiped with isopropyl alcohol (IPA).
The dispensed products are then kept in the quarantine section. Dispensing machine is used
which exchanging items between storage and the production. This machine operates with UV
radiation that kills the harmful bacteria in the containers and packaging if exposed for at least 30
secs under UV.
Room Pressure difference is maintained very well in the production department. Every person is
required to wear apron and cap before entering the production. Different slippers are assigned for
production area and mask is necessary.
Tablets are compressed solid substances either round or cylindrical in shape containing certain
active along with several excipients meant to cure certain disease or mitigate certain medical
condition.
Creams are semisolid dosage forms containing dispersible and dispersion systems. They contain
more than 20% water or volatile components and typically less than 50% hydrocarbon or
waxes.
Ointments are also semisolid dosage forms meant especially for application on the skin. They
contain an active substance meant to act on a skin for a special purpose. They have oily or greasy
consistency and appear stiff upon application.
Granulation is a process of converting raw material particle into more spherical and uniform
structure that can be easily compressed into tablets. Granulation is generally of two types. Wet
and Dry granulations. Wetting agent or liquid is used in wet granulation while dry granulation is
performed without any liquid.

8. Wet granulation involves the size reduction of the particles using different kinds of mills,
sieving, shifting, mixing etc.
1.1. Weighing and dispensing:
Excipients in different containers were weighed and dispensed in a dust extraction hood. Then
the materials are sent to a cubic feet blender.
1. Pre-mixing:
Blender is used for the pre-mixing purpose. Then, it is discharged into the bins for milling.
2. Milling:
Milling is meant for size reduction. There are several methods that can be applied for the size
reduction process. Material is transferred from PK Blender to a Quadro Comil for milling. It is
used to feed other excipients and Pre-Mix. Then, the product is discharged into the drums.
3. Blending:
Blending is done with the lubricant. This is the last step at the granulation room before the
beginning of tablet compression at the different chamber.
4. Tablet Compression:
Tablet compression takes place in a very contained environment. It is a separate chamber at
Aadee Production department away from the granulation room. The blended product is
dispensed using drums and is fed through the hoppers at the top every few minutes. Following
compression, tablets pass through the deduster and a metal detector. Rejected tablets are passed
into the reconcilator for the disposal. Acceptable tablets are collected using drums or huge plastic
bags.
Few tablets are tested in the testing room for friability, weight variation, hardness etc before the
bulk production is begun.
2.2 Process equipment include the following:
1. Quadro Comil:

9. It consists of mill body, infeed chute, rotor shaft assembly with impeller and screen. All the parts
are constructed of 316 stainless steel. This is a high quality rust resistant steel.
2. Blender:
All the product contact surfaces are constructed of 316L stainless steel. All other components are
constructed of 304L stainless steel. A timer can vary the blending sequence time from 0 to 20
mins.
3. Tablet Press:
The station has certain capacity. It can prove over 1 lakh tablets in no time. The press is fully
automated with PCIPLC control, recipe and data logging system. Powder is fed from the top.
The tablet press has upper and lower cam tracks, upper and lower punches, dyes, hydraulic press
force control system
etc.
Thorough mixing is done first so that active is uniformly distributed throughout the mixture. This
is then sieved through meshes of different sizes. Active is carefully handled during this process
that no loss occurs. It is then granulated in the planetary mixer. A tapping hammer is used to
prevent the granules from remaining attached to the mixer. A solution is prepared. Wetting is
done with this help of this solution. Granules are then dried in a dryer at over 40 degree Celsius
of temperature. Glidants and lubricants are then added to the mixer. Final mixing is done with

10. the help of turbular mixer. The sample is given to the QC for confirmation. If it is approved,
compression is done at a different section with the help of tablet compressor. Necessary tests are
performed at this section before bulk product is underway.
2.2. Tablet coating was performed at the Production department while I was there. QA officer
Aarati Karki was there at the Production Department on the 2nd day of my being there. This
session was very educative and informational in many ways. Some of the topics discussed with
three of us interns at that time are as follows:
1. Tablet Coating:
Tablet coating is a process of covering up or designing of the outer covering of the
compressed tablet so as to increase its appeal or make it feasible for the consumer. Most
of the time, tablet coating may be sugar coated, enteric coated, film coated depending
upon the need or as per the timing.
Sugar coating is done in order for the tablet to be appealing in terms of taste. Most of the
time, children do not want to consume tablets despite the necessity. However, when the
same tablet is designed with sugar coating, it appeals to them as does candy.
Enteric coating is done to make the drug habitable to the intestinal environment. The
stomach ph is acidic while the intestine ph is alkaline. Enteric coating is done so that
drug is soluble in the alkaline environment. Enteric coated tablets should remain intact
in the gastric environment at least for a couple of hours.
Film coating is done for the protection from external environment or the targeted drug
release process. Thus, tablet coating has various functions depending upon the need of
the moment. Film coating is done to hide bitterness, make it smooth so that it can be
easily swallowed eg. Paracetamol. Besides the one mentioned here, there are various
other types of tablet coating.
Various advanced equipments like coating pans and other machines are used for the
purpose of tablet coating.

11. 2. Types of tablet coating:
 Enteric coating
 Gastric coating( Enteric coating and Gastric coating are terms very interchangeable. Dt of
the enteric and gastric coating tablets should be as such that the tablet will remain in the
gastric environment at least for 2 hrs. as mentioned earlier.) This is assured in the lab by
preparing a buffer solution out of HCL and examined whether the tablets will disintegrate in
the period of time.
 Film coating
 Sugar coating
 Compression coating
 Electrostatic coating
 Dip coating
 Vacuum film coating
 MAIC, Magnetically assisted impaction coating
 Electrostatic dry coating
 Gelatin coating: Although gelatin coating is done mostly in the case of capsules, it is
sometimes also applied in the case of tablets.
3. Critical parameters of tablet coating:
Critical parameters refer to those parameters that are set by pharmacopoeia for the
standard production of the pharmaceutical products. In the case of coated tablets, the
critical parameters are as follows:
o Spray rate: Spray rate refers to the quantity spray of the coating material per unit time.
Depending upon the thickness of coating spray rate is adjusted.
o Inlet air temperature: Air temperature determines the quality of tablet coating. Inlet air
temperature is increased or decreased as per the necessity.
o Pan speed: Pans are used for the purpose of coating of the tablets. Pan speeds are altered
according to the necessity.
o Relation between coating pan and spray gun: Distance between the coating pan and
spray gun determines the quality of tablet coating. So, it must be properly adjusted.

12. 4. Problems in tablet coating:
 Blistering: Blistering is a process in which the coated tablet shows a particular nature of
sweating. Or, the tablets burst out of the blister. This can be overcome by proper care during
the coating process. Mild drying is recommended in this situation.
 Mottling: This is a process of the loss of color of the tablet. This may be due to
interaction with the air particles or due to reactive oxygen species, ROS. To overcome this,
proper packaging might be done. This is a problem due to the lack of proper color mixing.
To overcome this problem, coloring agent should be made into colloid.
 Chipping: This is a process of slight breakage of the tablet due to friction during the
packaging process. This can be overcome by properly testing for the hardness, friability,
dissolution, disintegration rate etc. and adjusting the tablet coating machine accordingly. Pan
should be filled with sufficient amount of core tablets. Appropriate baffle designs should be
used. High film strength coating formula should be used. Correct pan speed should be
recommended. Tablet tooling should be replaced. Proper tablet shape should be used.
Optimum spray rate should be used. Suspension solid level should be increased. Hardness of
the film should be increased by increasing the molecular weight of the coating polymer.
 Cratering: This is a process of formation of little crater like structures on the surface of
the tablets. Cratering can be overcome by proper mixing of the raw materials during the
granulation process. Spray rate should be decreased. Optimum drying condition should be
used. Viscosity of the coating solution should be increased.
 Picking:
 Pitting:
 Blooming: Low concentration or high molecular weight plasticizer is recommended in
this situation.

13.  Blusing:Drying air temperature should be decreased in this circumstance. The use of
HPMC, Cellulose etc with the sorbital should be avoided in this situation.
 Bridging:
 Capping:
 Erosion:
 Twinning: Tablet shape should be changed. Less tacky coating formulas should be used.
Appropriate tablet shape should be used. Pan speed should be increased. Atomizing speed
should be increased. Spray rate should be reduced. Optimum drying conditions should be
used.
 Peeling and frosting:
 Orange peel: Mild drying condition should be used. Viscosity suspension coating should
be used. Atomizing air pressure should be increased. The spray rate should be decreased.
Better spray guns should be used. Viscosity of the coating suspension should be decreased.
Gun should be adjusted to the bed distance.
 Color variation: Color variation can also happen in the tablet coating process. Variation
in the color can be overcome by proper temperature, proper color ratio etc.
At a time, only couple of problems listed above appears at the production house and they are
tackled by one or more methods as explained above. Experienced production managers come up
with extraordinary solutions whereas novice personnel cannot do so most of the time.
Clean Room Garments
Each and every department including the production had different aprons for the working staff,
visitors etc. These clothes were regularly washed. There were also disposable caps and gloves at
the production. Footwear is also classified to be used outside and inside. Wearing the same
slippers inside and outside was not allowed. This was fully enforced by QA personnel visiting
the production.
On the other hand, QC had separate thick gloves for use at the section containing muffle furnace
and different aprons for microbiology section.
Airlocks and Change-rooms in cGMP facility
I was questioned about the difference between the tray dryer and fluidized bed dryer by both
Pashupati Suwal and Sujan Koju at different times. Tray dryer was used for the drying of small
amount of powder or granules for example blood pressure drugs while fluidized bed dryer was

14. used for the large amount. Fluidized bed dryer was called so because the particles took the form
of the fluid while drying which does not happen in the case of tray dryer. That means in the case
of FBD particles became suspended in the air stream. So, tray dryer is used in the cases which
need gentle streaming or for particles that can not be suspended in the air stream like it is done in
the FBD.
1st day (06/15/2022): Visited QA, QC, Production, Cepha-section, water treatment system,
Packaging – secondary packaging- Inspection of packaging;
I also visited Cepha section on the third day. The sieving was being done at no. 100. One had to
be very careful while working at this antibiotics section. If one was not properly covered and did
not have gloves on, it was very possible that one might end up having fever or other problems at
the end of the day. Companies usually arrange Jivan-jal (ORS solution) and other drugs for staffs
working at this department. However, the operators here complained that there was no such
arrangement at Arrow at that moment in time. Sieving #100 might take a day or two at Cepha
section.
2nd day( 06/16/2022): Visited Capsule filling room, Tablet compression, Friability, Weight
variation, Putting, taking down and cleaning of Dies and Punches, Dispensing of Gelatine etc at
the end of the day;
3rd day (06/17/2022): Sieving of Cefodel 200 (AF2206010), Blister packaging of Pantoprazole;
Cefodel is Cefodoxime proxetil, antibiotic of the group of Cephalosporins, used against the eyes,
ear and nose infections. It is also used for the treatment of gonorrhea, a venereal sexual disease.
Side effects of Cefodel include anxiety, back pain, abdominal pain, bloating, body aches etc.
Dose depends upon the body weight and is advised by the doctor. It is not recommended for the
kidney patients as the slow removal might lead to harmful consequences.
In the preference rating among children, azithromycin is rated higher than cefodoxime. It works
by killing bacteria or preventing their further growth. One should consult the physician strictly
before or while using this drug.
Antibiotics like Penicillin show significant hypersensitivity reactions. Thus they are processed in
separate block.
Alu-Alu packaging is done for most of the drugs processed at Arrow like Topcid (Pantoprazole) .
Strip packaging is prevented as plastics attract moisture and absorb it easily. However, strip

15. packaging is done for moisture-sensitive drugs like Cholecalciferol(AROVIT). Blister squeezes
air within.
In Alu-Alu, there are two types of foil. Printed and non-printed. There are two parts. Shiny and
non-shiny parts. PVDC coated site is shiny.
4th day (06/19/2022): Aromol (Paracetamol) Granulation was done on the 4th day. The material
was passed through sieve #60. After passing them through the quadro mill, to make particles of
uniform size, it was passed through another sieve of #7. Even if the particle size might be labeled
less than 0.3 microns, it must be passed through the sieving process to ensure that particles did
not clutter up during storage or packaging process.Sieve #100 means the presence of 100 pores
in an inch. This sort of process is called shifting.
RMG: Rapid mixer granulator was used for further processing. Impeller and chopper were the
most important part of this machine. Impeller and chopper rotation were constantly adjusted
throughout the granulation process by Jesus Shakya. Average speed was 135-140 RPM. Large
masses were disintegrated into smaller pieces manually.
In the RMG, granule formation occurs by the rising, whirling and tumbling motion of material.
The material was constantly monitored and water was added when necessary. During the
addition of binding solution, the speed of chopper and impeller was adjusted to low but after the
formation of the wet mass, the speed was gradually increased.
Binding solution was prepared by mixing gelatin with other combination and was stirred
constantly at a high temperature for a while. Then it was mixed with the shifted paracetamol
mass in the Quadro mill.
5th day (06/20/2022):
A detailed question answering with Pasupati Suwal was the key thing for this day. These were
the following topics discussed:
1. B-tooling and D-tooling:
Type of tooling Punch Dia. Mm Die Dia. mm Punch length mm Max size
Round/capsule

16. B tooling 19 30.16 133.60 16/19
D tooling 25.4 38.1 133.60 25/25
BB tooling 19 24 133.60 13/14
DB tooling 25.4 30.16 133.60 19/19
6th day (06/21/2022): Observation of RO system; Coating at R&D with Dipen (AMLOTUS-L);
Air Handing Unit AHU
It refers to the combination of different elements in box-shaped units called modules for the
purpose of purification of air or renewing the air in the building or premises. Other functions of
AHU unit include filtration and control of the quality of the air, control of the air temperature
and monitoring of the relative humidity.

17. Effluent Treatment Plant ETP
ETP is used for the removal of organic compounds, debris, dirt, grit, pollution and other toxic
material and polymers from the industrial waste.
The parameters examined at the ETP inlet are pH, TDS, Temperature, Dissolved oxygen,
Biological oxygen demand, Chemical oxygen demand, oil/grease etc.
Reverse Osmosis System (RO System)
 The boring water/tap water passes through a whole set water treatment system (sand
filter, carbon filter, softener, RO membrane, dosing system and CIP system);
 Effectively removes heavy metals and bacteria in water;
Overcoming coating problems
1. Blistering:

18. Blistering occurs when elasticity and adhesive properties are compromised. It is due to
high temperature during drying, spraying or at the end of coating. Overcoming this
problem requires moderation of temperature throughout the coating process
Overcoming tablet-compression problems
 Capping:
Capping problem arises frequently during compression. To overcome this
problem, hardness should be decreased. Machine’s hardness setting should be
decreased. 1%-2% moisture should be increased. After sieving through #40, the
granules should be worked up with additional water after removing talc etc. Water
should not be put without removing talc. Then, the binder should be added eg.
Starch, PPK-30, Ethyl cellulose etc;
7TH DAY (06/22/2022): Coating of AROVIA-M-50/850)-Packing Arovit(Duplex-Linagliptin)-
Granulation room-IPQC of Aromol
8th day (06/23/2022): Compress @Cepha section-Observation of Shrink machine at Packing
(AROLINA)-Packing of Empatus-25; Observation of Leak test with Sweta Jha-Dispensing of
AROFLAM;
9th day (06/24/2022): Packing of AROCAL; Internet study at office of Production Manager-
CEFODEL 200 Compression (AF2206010)-Disintegration tests at Cepha-Spoke to Parvati Dulal
at QC;
Suggestions:
Interrupted electricity is a very big problem at Arrow. From the very beginning day of my
being here, I have observed 2-3 hrs. of line outage at the industry almost on a daily basis.

19. This leads to common disarray among staffs in particular assignment and loss of raw
materials and various products.
This situation must be sorted out before the company can get into next level and attain a
competitive advantage. I am writing this at suggestion of production officer Pasupati
Suwal.
Following are my suggestions regarding management of electrical supply at Arrow.
1. Private Generator/Inverter: Inverters of large capacities are being used at places like
Dhangadhi to supply electricity in case of power outages. Currently, we have 15 kb
generator but it has not come into proper use up to this moment. This can be attributed to
nothing than the carelessness in the part of the management according to the general
staffs. An expense of extra 2 lakhs per month seems to be worth it considering the loss of
products and talent of already employed man-power at this facility;
AHU are installed separately here at the facility. But, the machines like FBD require
large amount of power. The camera system is supplied now by small generator when line
goes out.
Lights work by single line but the large machines operate by 3-line system at this facility.
2. Contract with local Nepal Electricity Authority: Arrow team can consider sitting down
with the local NEC body and discuss about the constant electricity supply to the industrial
supply through the establishment of separate transistor or some other way that might be
feasible. However, we do not seem to be at ease with the local NEC at this moment;
3. Sitting down with the officers of each department to discuss this situation and how it is
affecting their department on a daily basis can be considered. The staffs might come up
with some practical solution to this problem that might help industry save large sums of
expense in terms of materials or man-power at this moment;
4. Computer problems are appearing due to frequent line outages including hanging and
loss of work from time to time;
5. Dis-integration testing apparatus at Cepha-section and Production do not seem to be
well-conditioned. They were found to produce two different results for the same product.
In order to confirm, we had to go to the Quality Control department;