Department of chemical engineering

MANUFACTURE OF ASPIRIN PROJECT

Addis Ababa Science and Technology University

Faculty of Engineering
Department of Chemical Engineering

A Project submitted by
No Name ID.NO
1 Muluneh Ayalew2413/05
2 Nafyad Tulu2419/05
3 Merga Deresa2298/05
4 Chala Tafa0324/04
5 Obsa Desalegn..2484/05

6.Hiwot Worku.2122/05

SUBMITTED TO: Belachew. Z

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Project on manufacturing of aspirin
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15 May, 201

Table of content..page

1. Acknowledgement.3

2. List of figures

Fig1. BFD for the process6

Fig 2.material balance on CSTR diagram..8

Fig3.material on A diagram8

Fig4.diadram for material balance on mixer.10.

Fig5.diaram for energy balance on mixer.11

Fig6.diagram for energy balance on HE.. 12

3. Introduction ..3

4. General objective of the case stud..5

5. Specific objective of the case stud.................................................................................. ..5.

6. Signification of the case study...........................................................................................5

7. Process calculation and design.5

7.1. Block flow diagram for the process.6

7.2. Material balance on the process...7

7. 3. Energy balance to determine the unknown temperature..11

7.4. The amount of stream and cooling water needed for heat exchanger..13

7.5. Design reactor volume needed to achieve specified conversion13

7.6. The work required for the pump assuming the pump is 85%.....................................14

7.7. Size heat exchanger using approximate value of Uo...................................................14

7.8. An equipment specification list containing the information..15

8. Conclusion.15

9. Recommendation.....16

10.Reference...16

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Acknowledgement

We would like acknowledge our instructor or our teacher Belachew .Z for

giving us more enough time for this case study. We would also like to
acknowledge all of our classmets that participate and give as some hints and
useful idea on this case study

1. INTRODUCTION
Aspirin, or acetylsalicylic acid (ASA) is a salicylate drug, and is generally used as an
analgesic (something that relieves pain without producing anesthesia or loss of consciousness)
for minor aches and pains, to reduce fever (an antipyretic), and also as an anti-inflammatory
drug.Aspirin has also become increasingly popular as an anti-platelet - used to prevent blood
clot formation - in long-term low doses to prevent heart attacks and strokes in high risk
patients. Nowadays, aspirin is often given to patients immediately after a heart attack to
prevent recurrence or cardiac tissue death.

Aspirin is a non-steroidal anti-inflammatory drug (NSAID). Non-steroidal means they are not
steroids, which often have similar effects. It is the most widely used analgesic, and is much
preferred over morphine because it does not involve physiological dependence. . Of all of the
NSAIDs, aspirin is the most widely used since it is inexpensive, easily available and is indicated
in many common conditions such as headache and the common cold. aspirin also has a unique
indication among the family of NSAIDs in that it can reduce the risk of Cardiovascular Disease in
patients with pre-existing Cardiovascular Disease.

Aspirin is also very effective as an antipyretic, or fever-lowering agent and also as an

anti-inflammation agent. It finds wide applications from rheumatism and arthritis to
hangover and the common cold. In spite of extensive research to clarify the mechanism
of the action of aspirin, much of the mystery of its operation still remains. There were,
of course, side effects with salicylic acid as there usually are with all drugs, especially
when they are first introduced. One of these was irritation to the stomach.

The basic structure of acetylsalicylic acid is the benzene ring of six carbon atoms. This
compound is produced by the esterification reaction of salicylic acid with acetic
anhydride as shown by the following the reaction;

Salicylic acid +Acetic anhydride = Acetyl salicylic acid +Acetic acid

MW = 138.1 MW = 102.1 MW=180.2 MW=60.1

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The feedstock to the plant are; solid salicylic acid, acetic anhydride and sulphuric acid
which act as a catalyst. The process main equipments include the feedstock storage
tanks, CSTR reactor, filter, cooler or heat exchanger and centrifugal pump. The acetic
anhydride will serve as both reactant and solvent, a common technique in synthesis.
When all the salicylic acid has been converted to aspirin, water will be added. This
converts any unreacted acetic anhydride to acetic acid; the reaction is shown below.
The reaction is an example of hydrolysis, the splitting (lysis) of a substance with water.

Acetic anhydride + Water = 2 Acetic Acid

Aspirin is not very soluble in water, so it crystallizes as the solution cools. It is then
isolated by vacuum filtration. Most of the acetic acid is removed by the filtration, but
enough remains to heavily contaminate the product. Often when a solid product is
expected and one of the reactants is a liquid and the other is a solid, it is easier to
achieve a good separation of the excess reactant from product if the liquid rather than
the solid reactant is used in excess. In this reaction,salicylic acid and aspirin are both
solids and acetic anhydride is a liquid so acetic anhydride is used in excess.At elevated
temperatures in the presence of even trace amounts of water, Equation above may be
reversed in a process called hydrolysis, which results in production of salicylic acid and
acetic acid (a reversal of the esterification process).

There are many brands of aspirin, but most of these are about the same, the major
difference being the purity of the product. It costs more to remove the unreacted
salicylic acid and acetic anhydride and the acetic acid by washes and recrystallizations.
However, the drug laws require conformity here, so aspirin is aspirin regardless of the
source. We are using acetic anhydride in this case study and not the more abundant and
less costly acetic acid. The reason is that salicylic acid has both a phenolic group and a
carboxylic group. The phenolic group of one salicylic acid molecule could react with the
carboxylic acid group of another salicylic acid molecule to produce a dimer side-product
and not the desired aspirin product. To minimize the production of the dimer side-
product, acetic anhydride is used because it is more reactive than acetic acid and
minimizes the amount of dimer side-product by quickly consuming the salicylic acid
before much can react with itself.

Aspirin is an analgesic (painkiller), an antipyretic (fever reducer), and an anti-

inflammatory agent. It is the premier drug for reducing fever, a role for which it is
uniquely suited. As an antiinflammatory,it has become the most widely effective
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treatment for arthritis. Patients suffering from arthritis must take so much aspirin (up to
four grams per day) that gastric problems may result. For this reason, aspirin is often
combined with a buffering agent. Bufferin is an example of such a preparation.The
ability of aspirin to diminish inflammation is apparently due to its inhibition of the
synthesis of prostaglandins, a group of C-20 molecules that enhance inflammation.
Aspirin alters the oxygenase activity of prostaglandin synthetase by moving the acetyl
group to a terminal amine group of the enzyme.

2.GENERAL OBJECTIVES OF THE CASE STUDY

The general objective of this case study is to design a manufacturing facility that has a
best capacity of producing aspirin.
To design and evaluate the performance of the crystalliser or cooler(heat exchanger) in
manufacturing facility by evaluating of the crystallisation process

3.SPECIFIC OBJCTIVE OF THE CASE STUDY

To evaluate the aspirin manufacturing process

To develop a case study plan and draw BFD for process
To evaluate the different process units
To design and draw the reactor, cooler or crystalliser unit
To calculate the mass balance for the each unit processes
To calculate the energy balance for each units
To design the control and instrumentation system for each units
To design and draft the piping and instrumentation diagram for the crystalliser

4. SIGNIFICANCE OF THE CASE STUDY

The significance of aspirin lies in the development of a compound into a useful drug. Turning a
chemical into a drug calls for extensive research to identify its potential applications and markets,
evaluate its clinical effects, optimize its properties, and design efficient manufacturing processes. Aspirin
is used to reduce fever and relieve mild to moderate pain from conditions such as muscle aches,
toothaches, common cold, and headaches. It may also be used to reduce pain and swelling in conditions
such as arthritis. It works by blocking a certain natural substance in your body to reduce pain Turning a
chemical into a drug calls for extensive research to identify its potential applications and markets,
evaluate its clinical effects, optimize its properties, and design efficient manufacturing processes and
swelling and a low dose of aspirin to prevent blood clots. This effect reduces the risk of stroke and heart
attack. aspirin can also used as an analgesic and an antipyretic.

5. PROCESS CALCULATION AND DESIGN

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5.1. BLOCK FLOW DIAGRAM FOR THE PROCESS

Fig1. BFD for the process

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5.2. perform material balance on the process,one unit at a time,to determine

the component flows for each streams

To do material balance let us change volumetric flow rate to mole or mass flow
rate

A+B=C+D XA=0.995

mA=2000Kg/hr,Q=FvB=5000L/hr ,from Row=mB/FvB

mB= B *FvB=1.08*0.001Kg/10^3=1.08Kg/L

mB= B*QB= B *FvB=5000Kg/hr*1.05Kg/L=5400Kg/hr

Fvcatalyst=Qcatalyst=1250L/hr

mcatalyst= catalyst*Qcatalyst=1.68*1250=2100Kg/hr

And for CSTR,(-ra) interms of CA is,

(-rA)=KCA, but CA=FA/FVf=FA,o(1-XA)/Fv,o(1+EXA) for constant volumetric flow

rate.

FA,o/Fv,o=CA,o

Therefore CA=CA,o(1-XA)/(1+XA) but =UYA=(U product

Ureactant)*YA,o/(UA)=0

Therefore CA=CA,o(1-XA)/1

(-ra)=KFA,o(1-XA)/FV,o(1+0XA)=KFA,o(1-XA)/FV,o

FA,o=mA/MwA=2000Kg/hr/(138.1Kg/Kmol)=14.48kmol/hr

FVoA=mA/A=2000kg/hr/(1.44kg/L)=1388.89L/hr

-rA =(0.5*3600/hr)*14.48kmol/hr*(1-0.995)/(1388.89L/hr)

-rA=0.0938kmol/Lhr

Then reactor volume is given by;

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V=(FA,o-FA)/(-rA)

V=(FAO-FAO(1-XA))/-rA=(FAO-FAO + FAOXA)/-Ra

V=FAOXA/-rA
rA =14.48kmol/hr*0.995/0.9938kmol/Lhr =153.6

A. Over all material balance on CSTR

Fig 2.material balance on CSTR diagram

Input output + generation = accumulation

Steady state accumulation=0

Generation=0

Input output + generation = accumulation

Then input=output

mA1 + mB+ mcatalyst = mcatalyst + mt ,where mB1 +mB=mt = 7400kg/hr

B.Material balance on A

mA2

mA1 XA=0.005

Fig3.material on A diagram

Input=output

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mA,1=mA,2

mA,2=mA,1*0.005=2000Kg/hr*0.005=10Kg/hr

or from stoichiometry

FA,2=FA,o(1-XA) mA,2/MwA=(mA,o/MwA)*(1-XA)

mA,2=2000*(1-0.995)=10Kg/hr

FB=FB,o-FA,o XA mB/MwB=(mB,o/MwB)-
(mA,o/MwA)X

mB/MwB=(5400/102.1)-(2000/138)*(0.95)

mB2=3928.2Kg/hr

Fc=Fc,o+FA,O XA, wher FC,o=0

mC,o/Mwc=(mA,O/MWA)*XA
mC=(2000/138.1)*0.995*180.2=2596.65Kg/hr

FD=FDO+FA,O*XA mD/MWD=(mAO/MWD)XA

mD=(2000/138.1)*0.995*60.1=865.8Kg/hr

mt=mi=7400kg/hr

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C. Material balance on mixer

mH2O=22000L/hr*1kg/L

mH2O in=22000kg/hr mC=mH2O=22000kg/hr

Mt=7400 mA=10

mA2=mA1 mB2=0

mB2= mC=2596.65

mC=mC1 mD=?

mD2= mH2O=2180.32

mH2O= Fig4.diadram for material balance on mixer

Rxn is B+H2O 2D ;Limiting reactant is B,

From stiochiometry for each component of mixiture
FH2O out= FH2On i FBOXB
mH2O/MWH2O=mH2O/MWH2O-(MBO/MWB)XA=22000/18-3929/102.1
mH2O=(22000/18-3929/02.1)*18=21307.32Kg/hr
For D; FD=FDO+2FBOXB
mD/MWD=MD/MWD+2(3929/102.1)
mD=(865.8/60.1+2(3929/102.1)60.1=5489.28Kg/hr
Or
Input =out put

mA2+mB2+mC+D1+H2O=mA2+mC+D2+H20+D1

mB2+m1H2O=D2+m2H2O

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3929+22000=D2+21307.32

D2=4621.68

mD=mD1+mD2=865.2+4621.68=5486.86

5. 3.perform energy balance to determine the unknown temperature

A.Energy Balance on CSTR

FTcpdT+Hr(rv)=UA(TS-T)

Hr(rv)=UA(TS-T)=Q

-85000J/mol*(0.0935)*153lit=Q

Q=85000J/mol*93.8mol/lit*hr*153lit=338.8KJ/hr

B.Energy balance on mixer

CP=4.184 T=25oc

mH2O=22000kg/hr

mt= mt=

T =70oc Tx=?

Cp=1.67 Cp=3.41

Fig5.diaram for energy balance on mixer

Accumulation=input-output+ generation

Input=output

HF+Q=HE

Q=HE-HF=-FcpdT-Hr(rv)

Hr(rv)=0,Therefore, Q= -FTcpdT

For Water, water gains heat, Q is +ve

Q=-FT2CP2(Tx-250c) (1)

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Energey balance on reactor outlet.

Q=-FT1CP1(TX-70OC) (2) Equating Equations (1)&(2)

FT2cp2(TX-25OC)=-FT1cp1(TX-70OC)

22000*4180(Tx-25OC)/(22000*4180)=-7400*1670(TX-70OC)/22000*4180

(Tx-25OC)=0.134(70OC-Tx)

Tx-25OC =0.134(70OC)-0.134Tx

Tx+0.134Tx=9.407+25

1.134Tx/1.134=34.4/1.134

Tx=30.34oc

then Q=22000*4180(30.34-25) =13.4KJ/Sec

Or Q=7400*1670(30-70)oc=136.4KJH/Sec

C.Energy balance on heat exchanger

T=18oc mc=mH2o=cold water

m Thi

Thi=30oc mt Tce The

Cp=3.41 The=25oc Tci

mt= Tce=? cp=3.41cc

mc=mh=? For counter flow HE;T1=Thi-Tce

5=30.4-Tce

Fig6.diagram for energy balance on HE Tce=30.4-5=25.4oc

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5.4.The amount of stream and cooling water needed for heat exchanger can be
calculated from energy balance on HE as follow

assuming the maximum of

Tce return is=400c

Q= mhtCph(Thi-The)

Mtcph(30.4-25)=17.16kJ/S

For cold Q=mhcph(Thi-The)=mccpc(Tce-Tci)

mc = Q/cpc(Tce-Tci) =17.16KJ/s/(4.18*(25.4-18)0c)=0.55kg/hr

5.5.Design the reactor-determine reactor volume needed to achieve specified

conversion

Volume can be calculate from reaction rate:

(-rA)=KCA, but CA=FA/FVf=FA,o(1-XA)/Fv,o(1+XA) for constant volumetric flow

rate, FA,o/Fv,o=CA,o

=UYA=(U product Ureactant)*YA,o/(UA)=0

(-ra)=KFA,o(1-XA)/FV,o(1+0XA)=KFA,o(1-XA)/FV,o

FA,o=mA/MwA=2000Kg/hr/(138.1Kg/Kmol)=14.48kmol/hr

FVoA=mA/A=2000kg/hr/(1.44kg/L)=1388.89L/hr

-rA =(0.5*3600/hr)*14.48kmol/hr*(1-0.995)/(1388.89L/hr)

-rA=0.0938kmol/Lhr

Then reactor volume is given by; V=(FA,o-FA)/(-rA)

V=(FAO-FAO(1-XA))/-rA=(FAO-FAO + FAOXA)/-rA

V=FAOXA/-rA =14.48kmol/hr*0.995/0.9938kmol/Lhr =153.6 L

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5.6. Determine the work required for the pump assuming the pump is 85%
Assumption

The pipe in the pump is smooth

The suction and discharge pipe has equal diameter
The suction occurs at atmospheric pressure
There is no potential difference between the suction and discharge pipes
The pipe in the pump is smooth
The suction occurs at atmospheric pressure

From General Bernoullis equation

Specific work (Y) = (Pd-Ps)/ + (vd2-vs2)/2 + eg + Hf

But because of the above assumptions

Y= (Pd-Ps)/

Pd = the final pressure + pressure drop in heat exchanger + pressure drop in

filtration sequence

Pd = 14psi + 22psi +260psi = 296.69psi

Y= (296.69-14.69)/

Where density is the average density of components in the mixture

= (1440 +1680 + 1350 +1050 + 1000)/ 5 = 1304kg/m3

Y = 282psi/1304kg/m3 =1944.32kPa/1304kg/m3 =1.491kj/kg

W=Y*M =1.491kJ/Kg * 7400 Kg/hr = 3064.83 watt

Nb (brake power) = N (useful power)/ = 3064.83watt/0.85

Nb = 3605.68 watt = 4.8353 horse power

5.7. Size heat exchanger using approximate value of Uo.

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Q = Uo A Tm
But Tm= (T1 -T2) / In(T1/T2)

Tm = -2 / In (5/7)
Tm = 5.95

Uo A = Q / Tm
UoA = 17.6kw / 5.950c
UoA = 2.89kw/oc

A=2.89KW/oc/(Uo)

Uo is the average heat transfer coefficient of the mixture

5.8. complete an equipment specification list containing the following
information;
For Pump: the required horsepower is =

For heat exchanger: heat duty (Q) =17.16KJ/se Area= 2.89kw/oc/(Uo)

cooling water (mc)=0.55kg/

For CSTR: volume= 153.6 liter, heat duty= 338.8kJ/hr

6. Conclusion

We can conclude that aspirin has been and will be the drug of choice for the
long-term oral treatment of platelet hyperactivity, most notably in the
secondaryprevention of myocardial infarction. We can also conclude that aspirin
is also the basic antiplatelet agent for all kinds of acute disease that may cause
plateletdependent thrombotic vessel occlusion and it can be produced by the
esterification reaction of salicylic acid with acetic anhydride using phosphoric acid
as a catalyst. The other thing that we can conclude is that the performance and
aspirin manufacturing process can be evaluated and designed using the energy
and mass balance on different unit operation and the design parameter like size,
volume, time which directily influence the cost of and quality. There are rating
and sizing problem during heat exchanger and generally all parameter calculated
above affect the rate of production of aspirin.

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7. Recommendation
There is no elevation given between CSTR and mixer in this case study. As a result
it is difficult to discharge the output from CSTR to mixer. Therefore we
recommended that there must be the elevation between reactor and mixer to
carry out the design for this case study. There is some amount of aspirin that lost
with by products and our product aspirin has some negative side effects. So we
recommended that aspirin that lost with by product should be saved and the
product quality should be increased and the aspirin side effect should be
minimized.

8. References
Ende, D. J, 2011. Chemical Engineering in the Pharmaceutical Industry: R&D to Manufacturing. New
York: John Wiley and Sons.

Sinnott, R. K., & Towler, G, 2009. Chemical engineering design. New York: Elsevier.

CHEMICAL REACTION ENGINEERING, O.LEVENSPIEL,3rd edition.

ELEMENTS OF CHEMICAL REACTION ENGINEERING,FOGLER ,4TH edition

Perry chemical engineering handbook-1999

ELEMENTARY PRINCIPLE OF CHEMICAL ENGINEERING.

Sadik, heat exchanger text book.

Fundamental of chemical engineering text book.

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