Nicolás Peñ
[email protected]/ Valentina
Ramí
[email protected]
I. INTRODUCTION
Pharmacaps is a Colombian company dedicated to the pro- duction of
pills in the presentation of hard gelatin capsules filled with
powdered medicine prescriptions. These types of capsules are solid
pharmaceutical forms of two pieces: Cap and body; and some of its
advantages in the industry are the great stability, the exact
dosage, the low cost, the use of plant derivatives in ingredients
to be environmentally friendly and finally an easily controllable
release of the drug.
Fig. 1. Logo
The production of medicines in any presentation requires
sophisticated equipment and processes in order to ensure a
consistently high quality product. In the pharmaceutical industry,
the dosage required by the regulatory standards of the World Health
Organization and the Ministry of Health for each drug is of great
importance in order to avoid errors that could have serious
consequences for patients. Therefore, automating the capsule drug
production process allows to increase productivity and ensure
compliance with the demanding quality standards for this industry,
avoiding human errors. The filling of hard gelatin capsules is an
established technol- ogy, with equipment ranging from manual
filling on a very small scale (24-200 capsules/hour) through
semi-automatic filling on an intermediate scale (200-3000
capsules/hour) to fully automatic filling on a large scale (up to
150,000 capsules/hour). The difference between the many methods
available is the way in which the dosage of material in the capsule
body is measured. As the need for uniformity in content increases
and regulations become more stringent, manufacturers must ensure
that capsule weights are within a limited range throughout
production. Because of this, an automated process is necessary to
ensure high volume production of standardized capsules.
Capsules are the second most frequently used solid oral dosage form
after tablets. Demand for capsules is expected to increase
substantially in the coming years, due to population growth and the
expansion of the global pharmaceutical industry. Moreover,
increased demand for nutraceuticals will also provide the global
capsule market an opportunity to expand as various dietary
supplements and
functional foods are encapsulated to make them convenient for
on-the-go consumption (Capuge,2017). Additionally, the demand for
encapsulated ingredients is also booming in the cosmetic sector. As
mentioned above, the market segment is in the pharmaceutical and
cosmetic industry, where the target audience consists of those
patients or customers of all ages who require a prescription powder
encapsulated in hard gelatin. The daily production demand was set
at 42,000 capsules per hour packed in blister packs. On the
document below it will be explained all the process and
requirements that are needed in order to created a automated
production of hard gelatines capsules.This automation will be
carried out by logic control, using sensors in the machines of each
process to monitor the critical variables and PLC’s to control the
actuators. This document is separated in sections which
are:Introduction, which is explained the reasons of the project,
the target market and a general introduction to medicine
production.In the other hand, the process description has the
layout of the plant and the flow diagram for each process that is
involved. In addition to this, the instrumentation section contain
pie diagrams that compare the sensor,actuators, acquisition systems
and PLC used on this project and the SCADA which show the
connection between the machines and the control room. The next
section is the protocol for each process,on it is include the black
box diagram, tables that mention the variable names assignee to
make the FSM and a explanation of each step. Finally on the
implementation, it is explain the human machine interfaces and one
of the implementation made to represent one process on
SIMULINK.
II. OBJECTIVES
A. General objective
The general objective is to automate the manufacturing process of
hard gelatin capsules filled with powdered drug formulations,
ensuring high quality and an adequate produc- tion volume to meet
demand.
B. Specific objectives
• Ensure accurate dosing that meets international stan- dards by
using appropriate sensors for critical variables and effective
control of the actuators.
• Design optimal and detailed protocols in order for each
sub-process to be performed successfully.
• Develop functional FSM and implement them in MAT- LAB Simulink
for each sub-process.
• Propose suitable sensors to monitor the critical variables of
each sub-process and use logic control to guarantee the correct
functioning of the actuators.
III. PROCESS DESCRIPTION
The production process of hard gelatin capsules begins with the
reception and storage of the raw material. Then, there are two
production lines: one dedicated to the man- ufacture of the
capsules and one dedicated to the pro- cessing of the medicine with
which the capsule is to be filled. The first line starts with the
gelatin solution mixing process where several ingredients are
combined at certain temperature and viscosity conditions, then
metal pins are immersed in the solution, rotated and dried to form
the capsules; subsequently, the capsules are demoulded and go on to
the encapsulation process. The second line starts with the grinding
and sieving processes to achieve the required size of the drug
components, then all the components are mixed and the mixture is
dried; once the powdered drug is ready, it is taken to the
encapsulation process, in which the capsule is filled. Finally, the
capsules are blistered and the blister packs are packed in boxes
and palletised.
A. Layout
The plant layout was designed taking into account the existence of
two production lines with parallel processes: the gelatin capsule
manufacturing line (2.2) and the line for processing the drug into
powder (2.1-5); both lines start with the reception of the raw
material and its storage, and converge in the encapsulation process
(6), where the capsules are filled with the powdered drug.
Subsequently, the filled capsules move through the line for
blistering, packaging and palletization processes. In addition, the
plant has three rooms: One for raw material storage, one for
quality control testing and one for finished product storage as
shown in the figure. There is also a reception area for raw
material trucks and another for finished product dispatch.
Fig. 2. Layout
B. Storage
The storage room is where all raw materials are stored for future
use. In addition, is where the materials are tested for quality
control before they can be use. It is very important to control the
room temperature, humidity and light intensity to prevent any
undesirable chemical reaction. The figure 3 shows the flow chart of
the storage process.
Fig. 3. Storage flow diagram
C. Capsule manufacturing line
Along this line are the processes necessary for the manu- facture
of hard gelatin capsules, from the preparation of the gelatin
solution to obtaining the final capsule that is going to be filled
with the powdered drug in the encapsulation process. Each process
will be explained in more detail below.
1) Gelatin solution mixing: A concentrated solution of gelatin
(40-40 percentage by weight) and demineralized water that has been
heated to 60-70°C is prepared. Dyes and pigments are then added to
achieve the desired final appearance of the capsule. The viscosity
of the gelatin solution is a critical parameter as it affects the
subsequent manufacturing process and plays an important role in the
thickness of the capsule wall, so it must be measured and adjusted
as necessary with hot demineralized water to achieve the desired
specification. Once the specification is met, the gelatin solution
is transferred to temperature- controlled tanks. The figure 4 shows
the flow chart of the mixing process.
Fig. 4. Mixing flow diagram
2) Dip coating: The capsules are manufactured under strict climatic
conditions by immersing pairs (body and lid) of standardized steel
dowels arranged in rows on metal bars in an aqueous gelatin
solution (obtained in the previous sub- process) kept at about 50°C
in the storage tank. As the molds are below the gelling
temperature, the gelatin begins to form a thin layer or gelatin
film on the molds, which will then become the capsule. The figure 5
shows the flow chart of the dip coating process.
Fig. 5. Dip coating flow diagram
3) Dip coated pins rotation: After adsorption of the gelatin
solution on the surface of the pins, the bar containing the pins is
removed and rotated several times to evenly distribute the solution
around the pins, as proper distribution
of the gelatin is critical for uniform and accurate capsule wall
thickness and dome strength.
4) Dip coated pins drying: Once the gelatin is evenly distributed
in the mold, a conveyor belt is used to ensure the drying of the
capsules and take them to the next process. The figure 6 shows the
flow chart of the dip-coated pins drying process.
Fig. 6. Drying flow diagram
5) Demolding: The capsules are removed from the punches,leaving the
cap and body for the encapsulation process. The figure 7 shows the
flow chart of the demolding process.
Fig. 7. Demolding flow diagram
D. Drug processing line
1) Grinding: This process receives as input the pharma- ceutic to
be processed as raw material ready to be grinded, after passing
through all the quality verifications on the reception of the
general process. The grinding recipient which has a pneumatic
actuator inside is filled up with raw material, and once the
recipient reaches the required level for the process to function
properly, the recipient is closed and the temperature of it starts
to rise. The temperature plays a key aspect in the process, because
for the raw material to be processed more efficiently, and more
fluidly, it must reach a high temperature so the material can be
grinded without the machine truncating. After the set grinding time
passes, the pneumatic actuator shuts down and after the temperature
lowers to room temperature so the processed material can unload for
the next sub process. The figure 8 shows the flow chart of the
grinding process.
Fig. 8. Grinding flow diagram
2) Sifting: Sifting is a simple process, which is in charge of
filtering by means of a kind of strainer, solids containing
impurities, dirt, or even lumps from the same mixture. This process
is carried out in order to have a homogeneous mixture and to
guarantee always the same structure in the
mixture. In the following flow chart 8 shows the sifting process.
The figure 9 shows the flow chart of the sifting process.
Fig. 9. Sifting flow diagram
3) Mixing: The mixing process comes right after the raw materials
were sifted and previous selected. It is where all materials are
mix with the reagents, water and heat to form the desired mix for
the capsules that are being manufactured at the moment. Its running
time, temperature and mix ingredients depend of the content
specifications. The figure 10 shows the flow chart of the mixing
process.
Fig. 10. Mixing flow diagram
4) Drying: Drying is a fundamental process in this pro- cess,
because it guarantees a dry, hygienic, and rested final product.
This is done by means of ventilation, sometimes natural and in
other situations artificial, being in this case an artificial
ventilation by means of extractors or blades. The figure 11 shows
the flow chart of the drying process.
Fig. 11. Drying flow diagram
5) Encapsulation: The encapsulation process is the point which join
the capsule manufacture and its content, the capsules came
separated and get filled with the content which cames from drying
process.Then,both ends of the capsule are united by using pressure
and heat. In conclusion, it is where the capsule gets created.
Therefore, it is a critical point of the production process. The
figure 12 shows the flow chart of the encapsulation process.
Fig. 12. Encapsulation flow diagram
6) Blistering: The blistering machine is a capsule plastic
packaging processor.Before starting the process, we must be sure
that the capsules to package are finished (with the content
inside).The machine starts rolling out the paper film bobbin, then
the film heats up to a specific temperature creating the cavities
and filling them with the product. Once the capsules are inside the
cavities, the machine covers them with aluminium, that will be at
the end cut and finally packaged. The figure 13 shows the flow
chart of the blistering process.
Fig. 13. Blistering flow diagram
7) Packaging: In this process, the individual boxes and the already
blistered capsule packs are put together. The process consists of
inserting the blistered box into each in- dividual box through the
machine specified for this purpose; then the individual boxes are
transported to the next process. It must be ensured that the
packaging is done correctly since this will be the first impression
of the customer. This process is done using an automated machine
which must ensure that the individual box contains a valid bar code
in order to continue with the process flow.
8) Palletizing: This process starts with the boxes loaded with the
packaged pills coming through from the packaging subprocess. Once
every box reaches the end of the electric band the machine will
push 4 boxes to a final platform in which an operating worker will
place these 4 boxes on the pallet. While the worker does this, the
machine prevents more boxes from passing onto this platform for a
determined set of time. After the worker has placed all boxes on
the pallet, the machine resumes its functioning and repeats the
process. The figure 14 shows the flow chart of the packaging and
palletizing process.
Fig. 14. Palletizing and Packaging flow diagram
IV. INSTRUMENTATION
A. SCADA Diagram
The SCADA diagram allows a high level overview of the capsule’s
manufacturing process, including all the devices and actuators
associated to each of the sub processes. It performs a supervisory
operation using the diagram to show functional manufacturing levels
using computerised control. This SCADA diagram is showed below this
section, in the
figure 15. The symbols corresponding to the diagram are shown in
the 43 in the annexes.
Fig. 15. SCADA diagram
B. Sensors and actuators used in the general process
The total count of control elements used in the automation
classified by the sub-process they belong to, is as follows. The
figure 16 shows the types and the total count of sensors in all
processes described before.
Fig. 16. Sensors in the company
The figure 17 shows the types and the total count of actuators in
all processes described before.
Fig. 17. Actuators in the company
C. PLC’s
There are 9 large PLCs in total. Large PLCs refer to a large number
of supported input/output signals, and the main reason for using
this reference is that the company wants a control unit for each
thread so that they can operate autonomously. The following are the
graphs of the PLC references are shown below in table I.
Process PLC I/O ADC DAC Storage FX3G-14MR/DS 14 - FX2N-2DA Grinding
FX3G-14MR/DS 14 FX2N-2AD - Sifting and drying FX3G-14MR/DS 14
FX2N-8AD - Mixing FX3G-14MR/DS 14 FX2N-2AD - capsule manufacturing
FX3G-60MR/DS 60 FX2N-8AD FX3U-4DA Encapsulation FX3G-60MR/DS 60
FX2N-8AD FX3U-4DA Blistering FX3G-24MR/DS 24 FX2N-2AD FX3U-4DA
Packaging FX3G-14MR/DS 14 - - Palletizing FX3G-14MR/DS 14 FX2N-2AD
-
TABLE I PLC’S IN THE COMPANY
Fig. 18. PLCs in the company
Fig. 19. Analogue to Digital conversors in the company
Fig. 20. Digital to Analogue conversors in the company
V. PROTOCOL
A. General
The processes to be automated are raw material storage, milling,
sieving, mixing, drying, manufacture of hard gelatin capsules,
encapsulation, blistering, packaging and palletiz- ing. This
automation will be carried out by means of logic control with the
use of finite state machines and using sensors in the machines of
each process to monitor the critical variables. In addition,
acquisition systems will be used where necessary to convert analog
signals to digital before entering the PLC where the algorithm of
the desired activities that will control the actuators will be
stored. In order to automated all the process several FSM were
design as part of the protocols.Each FSM used different symbols and
timers, each symbol has a meaning, it can be observe on the annexes
of this work on tables XXVIII and XXIX . In additions, all sensors
and actuator represented on the SCADA diagram has a meaning that
can be found on figure in the annexes of this document.
B. Storage protocol
1) The goal of the process is to control the environmental
conditions of the raw material to produce hard gelatin capsule and
its content
2) This process can be divided in two different sub process:
• Chiller’s storage: This part of the process is about taking care
of the temperature and illumination conditions of the raw material
before it can be used.
• Transport: This is the process which the raw mate- rial is
selected to be transport to the first transforma- tion process. It
is important to ensure the humidity, temperature and illumination
conditions during this process.
3) The interaction between the operator and the machine is by a
start/stop button located in two places. The first one is on the
machine interface screen and the second one is on the main computer
controller.
4) In order to carry on this process it is important to ensure
constant flow of raw material trough the chillers. In the other
hand, it is required to ensure enough room space for the equipment
placement.
5) The tables II and III below shows the sensors and actuators with
their FSM variable name, sensor signal type,acquisition system and
its corresponding PLC.
Sensors Variable name Signal type Adquisiton system Presence p1
Digital - Presence p2 Digital - Humidity h1 Digital -
TABLE II SENSOR TABLE FOR STORAGE PROCESS
Actuator Variable name adquisition system Conveyor Belt M
Digital
Fan ve Analogic TABLE III
ACTUATOR TABLE FOR STORAGE PROCESS
6) The storage process requires three different sensors to control
itself, on the black box diagram 21 below it shows the inputs and
desire outputs.
Fig. 21. Storage black box diagram
7) The FSM in fig 44 that will control this process has 4 states
which are: Resting, moisture controlg , waiting and transport. It
also has a counter that will activate the conveyor belt. It also
has timers to control the switching on and off of the conveyor belt
to control the speed.
C. Capsule manufacturing line
1) Gelatin solution mixing protocol:
1) During the gelatin preparation process, it is necessary to
efficiently control critical variables to ensure the quality of the
solution.
2) The preparation of the gelatine solution is carried out by
mixing the required amounts of water, gelatine, colorants and
preservatives. During the sub-process, the temperature and
viscosity of the solution, the level in the mixing tanks and the
weights of the ingredients in the mixture are controlled.
3) The interaction between the operator and the machine is via a
start/stop button located in two places: on the machine interface
screen and on the host computer controller.
4) For proper operation there must be a supply of gelatine, water,
colouring agents and preservatives. To control the critical
variables, level, weight, temperature and viscosity sensors are
required.
5) The tables IV and V below shows the sensors and actuators with
their FSM variable name, sensor signal type and the acquisition
system.
Sensors Variable name Signal type Acquisition system Level Nagua
Digital - Level Nmax Digital - Level Nmin Digital -
Weight SP1 Analogic ADC Weight SP2 Analogic ADC Weight SP3 Analogic
ADC
Viscosimeter viscosimetro Analogic ADC Temperature Tmin Analogic
ADC
TABLE IV SENSOR TABLE FOR GELATIN SOLUTION MIXING PROCESS
Actuator Variable name Signal type Acquisition system Valve V_gel
Digital - Valve V_agua Digital - Valve V_col Digital - Valve V_con
Digital - Valve V_tolva Analogic DCA Valve V_tanque Analogic
DCA
TABLE V ACTUATOR TABLE FOR GELATIN SOLUTION MIXING PROCESS
6) As can be seen in the black box diagram 22, 3 level sensors, 3
weight sensors, 1 thermometer, 1 viscometer and 2 push buttons are
required; in terms of actuators, 6 valves are required for the
inlet of the ingredients, a resistor and a motor for the
agitator.
Fig. 22. Gelatin solution mixing black box diagram
7) The FSM in figure 45 that will control the process has 9 states.
The process leaves the NOT_WORKING state when the Start button is
pressed, opening a valve to fill the tank with water until a level
sensor is turned on (FILL_WATER state). Then, sequentially, valves
are opened for gelatin (FILL_GELATIN state), colourants
(FILL_COLORANTS state) and preserva- tives (FILL_PRESERVATIVES
state) filling the hopper, using weight sensors to meet the
requirements. After- wards, the contents of the hopper are
transferred to the tank with water by means of a valve
(EMPTY_HOPPER state), where the temperature is measured with a
ther- mometer; if the temperature is suitable, mixing starts with
the help of a mechanical stirrer (MIXING state), otherwise the
heating element is activated (HEAT state). If, during the mixing
process, the temperature exceeds the minimum level, the heating
element is activated. Mixing is carried out until the viscometer
registers the correct viscosity, after which the solution is
transferred to the storage tank (EMPTY state).
2) Dip coating protocol: 1) During this sub-process it is necessary
to correctly
control the critical variables to guarantee the quality of the
capsule coating.
2) The sub-process consists of immersing metal pins (moulds) in the
tank containing the solution obtained in the previous sub-process,
in order to create the capsules by coating.
3) The interaction between the operator and the machine is via a
start/stop button located in two places: on the machine interface
screen and on the host computer controller.
4) For proper operation there must be a continuous supply of the
solution and metal pins. For control, level, temperature and
presence sensors are required, as well as a resistor and a
piston.
5) The tables VI and VI below shows the sensors and actuators with
their FSM variable name, sensor signal type,and the acquisition
system.
Sensors Variable name Signal type Acquisition system Level Nmin
Digital -
Temperature T Analogic - Presence Po Digital - Presence Pf Digital
-
TABLE VI SENSOR TABLE FOR DIP COATING PROCESS
Actuator Variable name Signal type Acquisition system Resistance R2
Analogic DCA
Piston P1 Digital - TABLE VII
ACTUATOR TABLE FOR DIP COATING PROCESS
6) As can be seen in the black box diagram 23, 2 presence sensors,
a level sensor, a thermometer, a piston, a resistor and 2 push
buttons are required.
Fig. 23. Gelatin solution mixing black box diagram
7) The FSM in figure 46 that will control the process has 4 states.
The sub-process leaves the REST state, once the storage tank
reaches the minimum level and the start button is pressed, as it is
connected by a valve with the gelatine mixing tank. Then, a
thermometer is used to determine whether it is necessary to
activate the HEAT state to heat up the mixture; otherwise, the pins
are lowered by means of a piston (DOWN state) until the piston
reaches its end position (presence sensor) and the
time set for a timer (coating time) has elapsed. Finally, the
piston returns to its initial position (UP state) and then to the
REST state.
3) Dip-coated pins rotation protocol: 1) During this sub-process it
is necessary to control the
rotation of the pins covered by the solution to ensure an even
distribution.
2) The interaction between the operator and the machine is via a
start/stop button located in two places: on the machine interface
screen and on the host computer controller.
3) For correct operation, a presence sensor and an optical sensor
are required, as well as a motor to rotate the moulds.
4) The tables VIII and IX below shows the sensors and actuators
with their FSM variable name, sensor signal type,and the
acquisition system.
Sensors Variable name Signal type Acquisition system Presence P2O
Digital - Optical OP Digital -
TABLE VIII SENSOR TABLE FOR DIP-COATED PINS ROTATION PROCESS
Actuator Variable name Signal type Acquisition system Engine MD
Digital - Engine MI Digital -
TABLE IX ACTUATOR TABLE FOR DIP-COATED PINS ROTATION PROCESS
5) As can be seen in the black box diagram 24, a presence sensor,
an optical sensor and 2 push buttons are required to control an
engine.
Fig. 24. Dip-coated pins rotation black box diagram
6) The FSM in figure 47 that will control the process has 4 states.
The sub-process leaves the rest state (REST_2), when these
conditions are satisfied: the start button is pressed, an optical
sensor detects the tray with the pins, and the piston is in the
initial position (presence sensor); then a piston is actuated to
hold the tray (HOLD state). Once the tray is clamped (the piston
end position sensor is on) a motor variable is activated which
rotates the system for 1 minute to the right (TURN_RIGHT state).
After that, the same motor is activated to turn left for another
minute (TURN_LEFT state). Subsequently, the motor is switched off
and the piston is brought back to its initial position to release
the tray on the conveyor belt (REST_2 state).
4) Dip-coated pins drying protocol:
1) During this sub-process it is necessary to ensure uniform drying
of the pins covered by the solution to ensure even distribution.
The idea is that the pins are dried while being transported by a
conveyor belt to the next sub-process.
2) The interaction between the operator and the machine is via a
start/stop button located in two places: on the machine interface
screen and on the host computer controller.
3) For correct operation, a weight sensor is required, as well as a
motor to move the conveyor belt.
4) The tables X and XI below shows the sensors and actuators with
their FSM variable name, sensor signal type,and the acquisition
system.
Sensors Variable name Signal type Acquisition system Weight SP
Analogic ADC
TABLE X SENSOR TABLE FOR DIP-COATED PINS DRYING PROCESS
Actuator Variable name Signal type Acquisition system Engine Mbanda
Analogic DCA
TABLE XI ACTUATOR TABLE FOR DIP-COATED PINS DRYING PROCESS
5) As can be seen in the black box diagram 25, a weight sensor and
2 push buttons and an engine are required
Fig. 25. Dip-coated pins rotation black box diagram
6) The FSM in figure 48 that will control the process has 2 states.
Once the start button is pressed and the weight sensor detects a
tray with pins, the conveyor belt is activated (START state), until
the sensor is deactivated (REST_3 state).
5) Demolding protocol:
1) During this sub-process it is necessary to remove the capsules
from the metal pins by hitting a piston on the trays containing the
moulds.
2) The interaction between the operator and the machine is via a
start/stop button located in two places: on the machine interface
screen and on the host computer controller.
3) For correct operation, a weight sensor and two presence sensors
are required, as well as two pistons.
4) The tables XII and XIII below shows the sensors and actuators
with their FSM variable name, sensor signal type,and the
acquisition system.
Sensors Variable name Signal type Acquisition system Weight SPG
Analogic ADC
Presence P3o Digital - Presence P3f Digital -
TABLE XII SENSOR TABLE FOR DEMOLDING PROCESS
Actuator Variable name Signal type Acquisition system Piston P3
Analogic DCA Piston P4 Analogic DCA
TABLE XIII ACTUATOR TABLE FOR DEMOLDING PROCESS
5) As can be seen in the black box diagram 26, a weight sensor, 2
presence sensors,2 push buttons and 2 pistons are required
6) The FSM in figure 49 that will control the process has 3
states.The sub-process starts when the start button is pressed, the
weight sensor detects the tray brought by the conveyor belt and the
clamping piston is in the initial position, activating this piston
to clamp it (HOLD_2 state). Then, when the piston is in the final
position (tray clamped), a piston is activated to give it a stroke
and make the capsules detach from the moulds (HIT state).
D. Drug processing line
1) Grinding:
1) The purpose of this thread is to control and to be able to
monitor the raw material as it’s being grinded, reaching desired
conditions for this process to be executed as well as the next ones
in the production line.
2) This process can be described as the transformation of raw
material to a grinded pharmaceutic acomplishing quality measures
and practicality, alining with the gen- eral process’ goals, which
is reach a capsuled pharma- ceutic of high quality and
reliability.
3) The operator at this point of the production line can in- teract
with this thread through a start/stop button located in 2
intefaces, the one located at this stage’s machine interface, as
well as the main computer controller.
4) For this thread to achieve a high fluency level, it’s imperative
for the production line to always have raw material ready to fill
the grinding machine with, as well as ensure through sensor
monitoring that the tem- perature reaches the desired value every
time for the grinding to be of high quality.
5) The following data tables XIV and XV show all the sensors and
actuators with their respective FSM variable name, sensor signal
type, acquisition system and the PLC they belong to.
Fig. 26. Dip-coated pins rotation black box diagram
Sensor Variable name Signal type Acquisition system Temperature
grinding.temp Analogic ADC
Speed grinding.speed Analogic ADC Level grinding.maxLevel Digital -
Level grinding.minLevel Digital -
TABLE XIV SENSOR TABLE FOR GRINDING PROCESS
Actuator Variable name Signal type Pneumatic actuator AC
Digital
Container door PR Digital TABLE XV
ACTUATOR TABLE FOR GRINDING PROCESS
6) The black box diagram in figure 27 shows all inputs and outputs
of this grinding process.
Fig. 27. Grinding black box diagram
7) The FSM of the grinding process has 4 states, which are: E1, E2,
E3, E4. Aditionally, it has a timer that allows the proper
functioning of it’s actuators. The illustration of the FSM is
represented on figure 50
2) Sifting and Drying: 1) This thread consists in having the
grinded raw material
undergo a Sieving process, which is a systematized filter
responsible of ensuring that the raw material is pulverized, clean,
and dry. After the Mixing process, it then goes through the Drying
process.
2) This thread can be described as the proper adaptation of the raw
material and conditioning of it for a better quality final product,
it being the hard capsules.
3) The operator interacts with this thread with an auto- mated
start/stop system located at the main computer’s interface, as well
as the machine’s interface.
4) For the correct functioning of this thread, many com- ponents
must be considered:
• Humidity measurement: Through sensors the hu- midity in the
environment and in the process will be monitored, which will have a
maximum degree of humidity, and that is when the sensors will send
start signals to the fan or extractor, in order to keep the product
fresh.
• Temperature measurement: Thermal sensors will be strategically
located, continuously monitoring the temperature of the environment
and raw material given the ventilation system developed to keep the
product at temperature conditions specified by the producer, and
will be activated by analog signals.
• Air Flow measurement: By means of an electronic system, the
ventilation process will be regulated, calculating the RPM of the
blades necessary to keep the place cool and optimize energy.
5) The following data tables XVI and XVII show all sen- sors and
actuators associated with the respective FSM variable name, sensor
signal type, acquisition system and the PLC they belong to.
Sensor Variable name Signal type Acquisition system Flow SFC
Analogic ADC
Humidity SH Analogic ADC Temperature ST Analogic ADC
Air flow SFA Analogic ADC Humidity SRPM Analogic ADC
TABLE XVI SENSOR TABLE FOR PACKAGING PROCESS
Actuator Variable name Signal type Vibrator Vibrator Digital
Extractor Extractor Digital
Electric resistance Resistance Digital Regulator Regulator Analogic
Extractor Engine Digital Indicator Indicator Analogic
TABLE XVII ACTUATOR TABLE FOR PACKAGING PROCESS
6) The black box diagrams in figures 28 and 29show all inputs and
outputs of this thread.
Fig. 28. Sifting black box diagram
Fig. 29. Drying black box diagram
7) The FSM of the Sieving and Drying process which can be seen on
figure 51 has states which allow to control the whole manufacturing
process of the tablets. The
states are: . In addition, it has timers that allow its actuators
to operate properly.
3) Mixing: 1) The goal of the mixing process is to ensure all
chemical
components are mixed to create the capsule content. 2) The mixing
process can be divided in four different sub
process: • Raw material reception: It is about separated the
materials in different tanks, depending on its char-
acteristics.
• Weighing: This process is about measuring the weights of the
different materials to conform the mix wished to produce the
capsule content
• Mixing: It is about mixing all the liquid and hard materials
together for a period on a heated tank in order to allow the
reagents to produce the desired mix. It is important to control the
speed of the tank and the temperature.
• Transport: It is the process after the mixing, it is desired to
transport the final mix to the drying zone.
3) This process begins when the machine sensor detects that there
are materials coming to the tanks and the operator press the start
button on the screen in the controller room.
4) It is required to ensure constant flow of material to be mixed
and energy to operate the machine and to communicate the
information to the controller room.
5) The tables XVIII and XIX below shows all sensors and actuators
that control the mixing process
Sensor Variable name Signal type Acquisition system Level N1
Digital - Level N2 Digital -
Temperature tem Analogics ADC Presence p1 Digital -
TABLE XVIII SENSOR TABLE FOR MIXING PROCESS
Actuator Variable name Signal type Conveyor Belt mt Digital
Valve val Analogic Heat resistance r Analogic
Engine tank mb Digital Piston P Digital
TABLE XIX ACTUATOR TABLE FOR MIXING PROCESS
6) The black box diagram en figure 30 shows all inputs and outputs
of the mixing process
Fig. 30. Mixer black box diagram
7) The FSM of the mixing process has 6 states, which are: rest,
solid material filling, heating, liquid material filling, stirring
and tank emptying. It also has 3 timers to control the actions of
the actuators.The ilustration of the FSM is represented on figure
52
E. Blistering
1) We want to control a blister machine . 2) This system has 8
processes, they are:
• Repose: when the machine is deactivated until a person press the
start button.
• Unwrap: The blister machine uses a motor that helps to unwrap the
film paper used to cover the capsules.
• Heating: This process uses a resistance in order to heat the film
paper.
• Molding: The film is preheated to have the nec- essary
temperature to make the pressing process easier.
• Fill: Here we can seal the capsules in the plastic
containers.
• Cutting: Is the final process where the blister ma- chine cut and
separate the capsules.
• Transport: After 100 blisters is cut, they go to the next process
that is packaging.
3) The machine-man interaction is in the moment when a person
presses the start button to turn on the machine.
4) Requirements
• Raw matter:
• Materials:
– Shears – puncture – Roller – Conveyor band
5) The table XX and XXI below describe the sensors and actuators
used on the blistering FSM that help to describe each state in
order to control the process.
Sensor Variable name Signal type Acquisition system Position SP
Digital - Counting SK Digital - Presence SP3 Digital - Pressure
SPRE Digital - Presence SB Digital - Pressure SP4 Digital -
Open/close SP5 Digital - Temperature ST Analogic ADC
TABLE XX SENSOR TABLE FOR BLISTERING PROCESS
6) The black box diagram in figure 31 shows all inputs and outputs
of this blistering process.
Actuator Variable name Acquisition system Conveyor band engine MB
DCA
Unwrapping engine MD - Electric resistance R -
Thermoformed engine MT - Guillotine engine MG DCA Hydraulic piston
MH DCA Open/close piston PI - Open gate engine MC -
TABLE XXI ACTUATOR TABLE FOR BLISTERING PROCESS
Fig. 31. Blistering black box diagram
7) One of the most important FSM in the blister process is the
molding stage, it is where the capsule content and capsules will be
place together and formed In order to carry out this process, it is
necessary to have a previous heating (previous state to molding) to
bring the film to an optimum temperature so that this process can
be carried out; after the film is formed, it is possible to
continue with the filling state, which consists of depositing the
finished hard gelatin capsule in the respective containers and thus
continue with the other states of the process. The FSM that control
the blister machine are separated in 8 different FMS as they can be
see on figures from 54,55,56 and 57, each of them represent one of
the operations that the machine makes.
F. Encapsulation
1) The objective of this process is to join the capsule mix from
the main line production with the hard gelatin capsules line.
2) This process can be divided in four sub process: • The capsule
placement: It is about receiving the
gelatin capsules and place them on an assembly matrix
• Medicine filling: It is about filling the first half of the
capsule with the medicine which is on the assumably matrix.
• Capsule sealing: The purpose of the process is to seal both ends
of the capsule with its content inside it.
• Transport: After the medicine and the capsule are shaped, they
are sent to the blister process using a transport band.
3) This process works by pressing the start button from the control
room and when the sensors of both hoppers, one for the medicine and
one for the capsule are active.
Meaning that there are enough material to make a run of the
process.
4) For this process it is needed to ensure a constant flow of
capsules and medicine to operate the encapsulation operation.
5) The tables XXII and XXIII below show all the sensor, its
variable names and the actuators used to control the encapsulation
process.
Sensor Variable name Signal type Acquisition system Level N1
Digital - Level N3 Digital -
Presence C1 Digital - Presence C2 Digital - Presence C3 Digital -
Position S1 Digital - Position S2 Digital -
TABLE XXII SENSOR TABLE FOR ENCAPSULATION PROCESS
Actuator Variable name Signal type Acquisition system Piston p1
Digital DCA Piston p4 Digital DCA Piston p5 Digital DCA
Conveyor Belt m1 Digital - Conveyor Belt m2 Digital -
TABLE XXIII ACTUATOR TABLE FOR ENCAPSULATION PROCESS
6) The figure 32 below shows all inputs and outputs on the
encapsulation machine.
Fig. 32. Mixer black box diagram
7) The FSM of the encapsulation process which can be seen on figure
53 has 6 states which allow to control the whole manufacturing
process of the tablets. The states are: resting, capsule emptying,
powder emptying, transport, sealing, capsule emptying. In addition,
it has timers that allow its actuators to operate properly.
G. Packaging
1) The goal of this process is to settle the blistered capsules
into their individual boxes, for further preparation to be
dispatched to clients, ensuring each individual package has a valid
bar code.
2) this thread describes as the process in which every individual
blistered capsule pack is set into its own package at a constant
rate.
3) For the operator to interact with this part of the pro- cess, he
will have available a start/stop button at the
machine’s interface, as well as at the main computer
interface.
4) For the correct execution of this thread, there must be a
constant flow of blistered capsule packs at the start of this
process’ cycle. Also, the pistons used for the mechanism of
inserting the capsule packs to their individual packages must be
rightfully calibrated so it guarantees the process’ purpose
fulfilling.
5) The following data tables XXIV and XXV show all sensors and
actuators associated with the respective FSM variable name, sensor
signal type, acquisition system and the PLC they belong to.
Sensor Variable name Signal type Acquisition system Presence
packaging.presence Digital - Optical packaging.barCode Digital
-
Presence packaging.finalPistonPos Digital - TABLE XXIV
SENSOR TABLE FOR PACKAGING PROCESS
Actuator Variable name Signal type Conveyor Belt B Digital
Piston P1 Digital Piston P2 Digital
TABLE XXV ACTUATOR TABLE FOR PACKAGING PROCESS
6) The black box diagram in figure 33 shows all inputs and outputs
of this grinding process.
Fig. 33. Packaging black box diagram
7) The FSM of the Packaging process which can be seen on figure 58
has 4 states which allow to control the whole packaging process of
the tablets. The states are: E1, E2, E3, E4. In addition, it has a
counter that allows its actuators to operate properly.
H. Palletizing
1) This thread’s purpose, being the last one on the pro- duction
line, is to culminate all the process with the palletizing of the
boxes filled with packaged capsules to deady them for
dispatch.
2) This process can be described as the preparation of boxes with
capsules to be dispatched to clients. Being this the last thread in
the process, it represents the culmination of the automated capsule
manufacturing process.
3) The operator interacts with this thread through a start/stop
button located at the main computer interface, as well as at the
stage’s machine interface.
4) For the right functioning of this thread, the previous thread,
packaging, must have boxes filled with packaged capsules ready to
be placed on the palletizing machine
for the culmination of the process, considering at the end of the
line there will be an operator reveiving the boxes and readying
them for palletizing.
5) The following data tables XXVI and XXVII show all sensors and
actuators associated with the respective FSM variable name, sensor
signal type, acquisition system and the PLC they belong to.
Sensor Variable name Signal type Acquisition system Pressure
palletizing.pressure1 Digital - Pressure palletizing.pressure2
Digital - Presence palletizing.presence1 Digital - Presence
palletizing.presence2 Digital -
Level palletizing.level Digital - Speed palletizing.speed Analogic
ADC
TABLE XXVI SENSOR TABLE FOR PALLETIZING PROCESS
Actuator Variable name Signal type Conveyor Belt B Digital
Piston P Digital Stop T Digital
TABLE XXVII ACTUATOR TABLE FOR PALLETIZING PROCESS
6) The black box diagram in figure 34 shows all inputs and outputs
of the Palletizing thread.
Fig. 34. Palletizing black box diagram
7) The FSM of the Palletizing process which can be seen on figure
59 has 4 states which allow to control the whole palletizing
thread. The states are: ReposoPalet, Start, PistonPush, PlatFinal.
In addition, it has a timer and a counter that allow its actuators
to operate properly.
VI. IMPLEMENTATION
A. FSM’s in MATLAB Simulink
The FSMs shown earlier in the protocols were modelled in simulink,
using dashboard elements such as lamps, push bottoms, slider
switches and displays. With the simulations, it was possible to
determine whether the proposed FSMs were functional for the
automatizing. All implementations can be found in the annexes.
However, in order to exemplify the simulation, the demolding
process simulation will be explained (figure 35). The buttons on
the left are pressed to start or stop the process, while the
switches represent whether the sensors are on or off, these are
connected to the FSM, generating transitions between states
depending on the conditions. On the other hand, on the right side
are the displays connected to the lamps to show when the respective
actuators are switched on or off.
Fig. 35. Demolding implementation
B. HMI
1) Storage process: Figure 36 shows the main indicators of the raw
material storage process. The diagram has start and stop buttons
that control the status of the process as a precautionary measure.
The diagram is shown in the actuators section, where there is an
icon for each actuator and an LED light that indicates whether they
are active at that moment, such as the conveyor belt, an industrial
fan and a motor. Likewise, there is a sensor tab on the upper right
side in case you need to monitor them.
Fig. 36. Human machine interface in the storage process
2) Grinding: This man-machine diagram 37 shows the main indicators
of the milling process. The diagram has start and stop buttons that
control the status of the process as a precautionary measure. The
diagram is shown in the actuators section, where there is an icon
of each actuator and a led light that indicates if they are active
at that moment, such as a pneumatic actuator and the grinding
vessel gate. Likewise, there is a sensor tab on the upper right
side in case you need to monitor them.
Fig. 37. Human machine interface in the grinding process
3) Sifting and Drying: Continuing with the general pro- cess order,
Figure 38 shows the main indicators of the sieving and drying
processes. The diagram has start and stop buttons that control the
status of the process as a precautionary measure. The diagram is
shown in the actuators section, where there is an icon for each
actuator and an LED light that indicates whether they are active at
that moment, such as an electric resistance, a three-phase motor
and an extractor. Likewise, there is a sensor tab on the upper
right side in case you need to monitor them.
Fig. 38. Human machine interface in the sifting and drying
process
4) Mixing: The IHM diagram 39 process shows the main indicators of
the mixing process. The diagram has start and stop buttons that
control the status of the process as a precautionary measure. The
diagram is shown in the actuators section, where there is an icon
of each actuator and an LED light that indicates if they are active
at that moment, such as an industrial fume extractor, a conveyor
belt, pistons, an electric resistance and an industrial hopper.
Likewise, there is a sensor tab on the upper right side in case you
need to monitor them.
Fig. 39. Human machine interface in the mixing process
5) Encapsulation and capsule manufacturing line: In the capsule
encapsulation and manufacturing sub-process, the human-machine
interface 40 consists of a platform that dis- plays the process
live. The diagram has start and stop buttons that control the
status of the process as a precautionary measure. The diagram is
shown in the actuators section, where there is an icon of each
actuator and a led light that indicates if they are active at that
moment, such as pistons and a conveyor belt. Likewise, there is a
sensor tab on the upper right side in case you need to monitor
them.
Fig. 40. Human machine interface in the encapsulation and capsule
manufacturing process
6) Blistering: Figure 41 shows the main indicators of the
blistering process. The diagram has start and stop buttons that
control the status of the process as a precautionary measure. The
diagram is shown in the actuators section, where there is an icon
for each actuator and an LED light that indicates whether they are
active at that moment, such as a motor, an electric resistance,
pistons and a conveyor belt. Likewise, there is a sensor tab on the
upper right side in case you need to monitor them.
Fig. 41. Human machine interface in the blistering manufacturing
process
7) Packaging and palletizing: Finally, Figure 42 shows the main
indicators of the packaging and palletizing pro- cesses. The
diagram has start and stop buttons that control the status of the
process as a precautionary measure. The diagram is shown in the
actuators section, where there is an icon for each actuator and an
LED light that indicates whether they are active at that moment,
such as conveyor belts, pistons and a stopper. Likewise, there is a
sensor tab on the upper right side in case you need to monitor
them.
Fig. 42. Human machine interface in the packaging and palletizing
manufacturing process
VII. CONCLUSIONS
• The automation of a production process such as the manufacture of
gelatin capsules is useful to reduce costs, achieve the high
quality standards for medicines, increase the productivity of the
plant in order to be a more competitive company in the
market.
• The manufacturing process of hard gelatin capsules filled with
powdered drug formulations was automated to ensure high quality
with an adequate production volume to meet demand.
• Accurate dosing that met international standards was achieved
through the use of appropriate sensors for critical variables and
effective control of the actuators.
• Optimal and detailed protocols were designed and all
sub-processes were successfully completed.
• Functional FSM were developed and implemented in MATLAB Simulink
for each sub process.
• Appropriate sensors were used to monitor the critical variables
of each sub process and logic control was applied to ensure correct
operation of the actuators.
REFERENCES
[2] COSHH essentials: easy steps to control chemicals. (2003).
Tamizado [Conjunto de datos]. Recuperado de: https:
//www.insst.es/documents/94886/123995/FCAQ+218+
Tamizado/0210d165-b156-4f64-b8d7-9a04f2833c94
[3] GALAXIE Proceso de Secado spray. (2012, 11 noviembre). [Archivo
de vídeo]. Recuperado de: https://www.youtube.
com/watch?v=3DZr5cOgWEg
[4] "Manufacturing of shells of hard capsules". Tips and Tricks by
AMB, 30 de abril, 2020 [Video en línea]. Disponible en:
https://www.youtube.com/watch?v=tAGvds2kH7s&
list=PL86iM_uM6cprW0EHx9tUdm4OnsGN8PTqx&index=3
[5] "Empty capsules making machines production line from A to Z
pharmaceutical pills manufacturing line". Jack Du, 7 de marzo, 2013
[Video en línea]. Disponible en: https://www.
youtube.com/watch?v=9XMMMmxWoqw&list=PL86iM_
uM6cprW0EHx9tUdm4OnsGN8PTqx&index=10&t=272s
[6] "Hard Capsules Production Line". Adam Zhao, 19 de marzo, 2018
[Video en línea]. Disponible en:
https://www.youtube.com/watch?v=IDtNhL7z06M&list=PL86iM_u
M6cprW0EHx9tUdm4OnsGN8PTqx&index=5&t=34s
[7] Capuge. (May 25, 2017). Oportunidades emergentes en el mercado
de cápsulas vacías [Entrada de blog]. Recuperado de
https://www.youtube.com/watch?v=bP9grhXLC_Q&ab_
channel=LELYMELIZAHIDALGOSANCHEZ
[8] WDSrx.(april 28, 2016) 3PL Pharmaceutical Warehousing and Dis-
tribution [Video en línea]. Recuperado de https://youtu.be/
oYZ-RucaiIM
[9] WWITRON Logistik & Informatik GmbH.(March 29, 2017) The
Warehouse of the Future [Video en línea]. Recuperado de https:
//youtu.be/bn5jjVKhFUs
[10] BANDICAM.(July 9, 2018) Blistering process [Video en línea].
Recuperado de https://www.youtube.com/watch?v=
bP9grhXLC_Q&ab_channel=LELYMELIZAHIDALGOSANCHEZ
