The document presents a project on the production of L-phenylacetylcarbinol (L-PAC) through fermentation. It includes a literature review on the fermentation process and usage of L-PAC. An economy analysis of the global demand and supply of L-PAC from 2006-2013 is presented. The process description includes fermentation in a bioreactor, centrifugation, precipitation, filtration and drying. Mass and energy balances are calculated for the bioreactor and distillation column. The pressure vessel designs for the bioreactor and distillation column are discussed. Heat exchanger designs and heat integration are analyzed. Control loops for bioreactor level, feed rate and antifoam are proposed. Wastew

1. PRODUCTION OF
L-PHENYLACETYLCARBINOL
Integrated Project
Presentation Group KB1
NAME MATRIC NO.
CHUNG KEN VUI A 98753
LIM KAH HUAY A132816
TEE ZHAO KANG A 132597
SONIA DILIP PATEL A133115
WONG MEI FANG A132213

2. CONTENTS
 Literature Review
 Usage of L-PAC
 Economy Analysis: Production & Demand
 Process Description with PFD
 Calculation of material and energy balance in the
fermentor
 Pressure Vessel Design
 Heat Utility Design and Heat Integration
 Control Dynamic and Process
 Pollution Control and Cleaner Production

3. Literature Review
Glucose
Benzaldehyde
Saccharomyces
cerevisiae
L-PAC
Other products:
Ephedrine,
pseudoephedrine
Pyruvic
acid
Acetaldehyde
Ephedra sinica
Standard microbes for
the fermentation where
ethanol-producers are
preferred (Hagel et al.
2012) and gives
significant yields (Kumar
et al. 2006)
Biotransformation
route remains the
preferred method for
the industry (Shukla &
Kulkarni 2000)
Traditional process to
produce ephedrine that is
no longer preferred due
to tedious and expensive
downstream processes
(Khan et al. 2012)

4. L-PAC: Applications and Usages
MethamphetamineD-pseudoephedrineL-ephedrine
Used as the precursor for the production of these drugs that are known for
the nasal decongestant properties (Oliver et al. 1997, Shukla & Kulkarni
2000)

5. Economy Analysis
Global demand and supply for L-PAC from 2006 to 2013 (reproduced on
MATLAB®)
Source: Nanjing Pharmaceutical Company 2006, China Chemical
Industry News 2012
2006 2007 2008 2009 2010 2011 2012 2013
800
1000
1200
1400
1600
1800
2000
2200
2400
Global Demand and Supply for L-PAC from 2006 to 2013
Year
AmountofL-PAC(in103
kgortonnes)
Demand
Supply
PROPOSED PRODUCTION
Mode of operation: Fed-batch
fermentation
Total demand for L-PAC in
Malaysia in 2013 = 21,000 kg
(Globinmed 2010)
Proposed annual Production:
[L-PAC] = 25% of total demand
= 5,250 kg
Production rate:
[L-PAC] = 5,250kg/150 cycles
= 35 kg per cycle
Bulk price for L-PAC is around
RM312.30 per kg (Balantes
Pharma 2012)

6. Process ProductionProcess Production
Cultivation
of baker’s
yeast
Fermentation
of pyruvic avid
Fermentation
of L-PAC
Centrifugation
and holding
Cold adduction
by precipitation
Rotary filtration
Dissolution of
Adduct
Ethanol
extraction
Distillation and
recovery of
ethanol
Spray Drying

7. Mass Balance
Stoichiometric equation: (Shuler & Kargi 2002)
Calculations are shown for F-102 and F-103 as examples:
Stream In Out
Feed Gas Total Product Gas-off Total
Glucose 72.00 0 72.00 0.66 0 0.66
C7H6O 3.03 0 3.03 0 0 0
NH3 0.50 0 0.50 0 0 0
Biomass 0.36 0 0.36 3.87 0 3.87
L-PAC 0 0 0 35 0 35
N2 0 1620.87 1620.87 0 1620.87 1620.87
CO2 0 0 0 0 14.53 14.53
H2O 458.71 0 458.71 480.54 0 480.54
Ethanol 5.40 0 5.40 5.40 0 5.40
Total 540.00 1620.87 2160.87 525.47 1635.40 2160.87
Comparison with SuperPro® Designer
SuperPro® 533.47 1627.39 2160.86
Error(%) -1.52 0.49 0.00
Mass balance involving F-102 and F-103:

8. Energy Balance
Unit Metabolism
Heat
(kJ)
Agitation Heat
(kJ)
Sensible Heat Heat of
reaction
(kJ)
Energy In
(kJ)
Energy Out
(kJ)
F-102 75789.55 19639.53 8420.09 8587.11 - 95587.10
F-103 3697.05 18613.42 8606.01 8717.42 -23447.99
E-101 - - 60227.89 10037.98 50189.91
The heat balance inside the fermentor (O’Shea 1998):
iCON simulation is also used to calculate the energy balance in distillation column, COL-102.
Stream 47 48 51 In – Out
Energy (W) -11379.47 -3243.51 -5854.92 -2281.04
Utility Condenser Reboiler Change
Energy (W) 264819.45 267100.60 -2281.15

9. Pressure Vessel Design: Internal Pressure
Fermentor, F-102
Specifications and dimensions:
Material = SS 316 or ASME SA-240
Radius of vessel = 0.3545 m
Diameter of vessel = 0.709 m
Height = 1.996 m
Cylindrical shell
Height = 1.418 m
Torispherical heads (Top and Bottom)
Knuckle radius = 0.0425 m
Crown radius = 0.363 m
Height = 0.289 m
Calculated that:
Design pressure = 69.12 psi = 477 kPa
Toverall = 0.14’’
Tmin= 3 mm
Design thickness = 5 mm
MAWP vessel = 98.94 psi

10. Specifications and dimensions:
Material = SS 316 or ASME SA-240
Radius of vessel = 0.25 m
Diameter of vessel = 0.50 m
Height = 3.77 m
Cylindrical shell
Height = 3.52 m
Ellipsoidal heads (Top and Bottom)
Height = 0.125 m
Calculated that:
Design pressure = 20.36psi
Toverall = 5.65mm
Tmin= 3.65mm
Design thickness = 6.35 mm
MAWP vessel = 15psi (Atmospheric pressure)
Pressure Vessel Design: External Pressure
Distillation column, COL-102

11. Properties F-102 C0L-102
Design Pressure, PD (psi) 69.12 20.36
Minimum wall thickness, tmin (mm) 3.00 3.65
Design thickness, tD (mm) 5.00 6.35
MAWP vessel (psi) 98.94 15
Circumferential stress, σ1 (N/mm2) 33.78 3.99
Total longitudinal stress, σ2 (N/mm2) 16.26 - 1.36
Maximum stress intensity, (Δσ)max (N/mm2) 17.52 5.34
Design stress, S (N/mm2) 108.8 132.32
Critical buckling stress,σc (N/mm2) 139.08 247.71
σcompressive (N/mm2) 0.629 4.0345
Skirt thickness, ts (mm) - 10
Design skirt thickness, tD(mm) - 12
Bolt root diameter, (mm) - 10.41
Impeller diameter, Di (m)
Impeller spacing, Hi (m)
Impeller blade length, Li (m)
Impeller blade height, Wi (m)
Location of gas sparger, Hb (m)
0.234
0.468
0.059
0.047
0.117
-
-
-
-
-
Pressure Vessel Design: Summary

12. Heat
Utility
Design
Jacketed
Vessel
into F-102
Cooler E-
101
Jacketed
Vessel
into F-103
Condensor
E-102
Reboiler
E-103
Kettle Reboiler
3.2 mm o.d., 1.9 mm i.d.,
L = 4.8 m, plain U-tubes
Total Condensor
3.2 mm o.d., 1.9 mm i.d., L =
0.508 m, admiralty brass
Dimple Jacket
SS 316, pattern type 1
(100/100) 11 mm, base
length = 63.5 mm
U-tube exchanger
6.35 mm o.d., 2.465 mm i.d.,
L = 6.10 m, cupro-nickel
Jacket with spiral baffle
Stainless steel 316, channel 15 x
200 mm, 6 spirals
Heat Utility Design: Types

13. Figure 6.7 Heat Cascade
18.67
0
-23.97
0
-261
18.67
0
-23.97
0
-261
Start with
0 kW
Start with
18.67 kW
107.6
97.05
72
25
20
-5
∆Tmin = 20°C
-18.67
-18.67
5.3
5.3
266.3
0
0
42.64
42.64
303.64
QHmin = 18.67 kW
1
2
3
4
5
QCmin = 303.64 kW
Heat Utility Design: Heat Integration

14. Before After
Total energy required 303.64kW 303.64kW
Total energy recovery 0%
Table 6.10 Total energy requirement
Figure 6.8 Grid Representative
20
48
55
30°C
82°C
97.6°C
35°C
Cp
pinch
1.77
0.51
10.44
∆Habove pinch (kW)
0
0
18.67
5°C
87.05°C
107.5°C
107.5°C
∆Hbelow pinch (kW)
261
23.97
0
Heat Utility Design: Heat Integration

15. Properties Jacketed
Vessel
F-102
Cooler
E-101
Jacketed
Vessel
F-103
Condensor
E-102
Reboiler
E-103
Heat load, Q (kW) 1.106 14.21 0.271 0.0444 2.71
Uestimate (W/m2 720 550 550 650 850
Area required (m2) 9.30 0.0014 0.1909
Area of channel (m2) 3 x 10-3 1.86 x 10-3
hj (W/m2°C) 1661.41 - 967.6 - -
hff,v (W/m2°C) 3785 - 3785 - -
hff,j (W/m2°C) 4000 - 5000 - -
∆wall (m) 0.003 - 0.003 - -
hv (W/m2°C) 13203.13 - 10562.73 - -
hnb (W/m2°C) - - - - 2528.69
hc (W/m2°C) - - - 1000 -
ut (m/s) - 0.57 - 2.68 -
hi (W/m2°C) - 3557.38 - 16243.92 -
us (m/s) - 0.18 - 50.35 2.08
hs (W/m2°C) - 3715.34 - - -
Ucalculated (W/m2°C) 726.81 473.47 562.93 649.99 863.56
∆Ps (kPa) - 36.66 - 52.29 2.09
∆Pt (kPa) 0.805 30.14 0.178 50.05 -
Heat Utility Design: Summary

16. Process Dynamic & Control: Modeling
Fermentor, F-103
The mathematical models that are used for F-103:
1. (Rate of accumulation) = (Rate in) + (Rate of formation)
2. For component balance – cell:
3. For component balance – product:
4. For component balance – substrate:
SK
S
X
dt
dX
s
max
XY
dt
dP
XP /
dt
SSd
Y
X f
SP /

17. PD&C: Degree of Freedom
Degree of Freedom analysis
Number of variables = 10
Number of equation = 4 (as in previous slide)
Degree of freedom:
Variables to be controlled:
Revised degree of freedom:
Hence, 3 control loops are to be designed
- Level, flow rate into the fermentor, antifoam
PXSSFYYVKN fSXXPSV ,,,,,,,,, //max
6410F
EVF
N
NNN
SKV ,, max
336FN

18. LT
LC
Sensor – Differential
pressure
Signal type – Pneumatic
Valve – Diaphragm Source: Smith & Corripio 2006
Level sensor detects
difference in pressure
caused by hydrostatic
head
Sends pneumatic
signal to the
transmitter
Transmitter
directs the signal
to the level
controller
Controller calculates
the necessary
correction needed
Controller sends
signal to the
diaphragm valve
located at the output
of F-103
Diaphragm valve
moves the
diaphragm to open
or close the area of
flow
PD&C: Level Control Loop

19. • Based on the Environment Quality (Amendment) Act 2012:
1. Environmental Quality (Clean Air) (Amendment) Regulations 2000
2. Environmental Quality (Industrial Effluent) Regulations 2009
3. Environmental Quality (Scheduled Wastes) (Amendment) Regulations 2007
4. Environmental Quality (Sewage) Regulations 2009
(Source: DOE 2013)
Pollution Control and Cleaner Production
(1)
Unit
(2)
Standard A
(3)
Standard B
Chemical Oxygen Demand mg/L 80 200
Temperature 0C 40 40
pH value - 6.0-9.0 5.5-9.0
BOD5 at 200C mg/L 20 50
Suspended solid mg/L 50 100
Phenol mg/L 0.001 1.0
Ammoniacal Nitrogen mg/L 10 20
Formaldehyde
Colour
mg/L
ADMI*
1.0
100
2.0
200
Discharge Limit according EQ(IE)R 2009
(Source: Taken and Modified from Department of Environment 2013)

20. PC&CP: Wastewater Treatment Plant
Overall Diagram for Modified WWTP
Stream Q Q + Qr Q - Qw Qu Qr Qw
Flow rate (m3/d) 13.15 14.77 9.37 5.40 1.62 3.78
S, BOD(mg/L) 14062.86 18 18 - - -
X, SS (mg/L) 0 9410.06 45 9365.06 9365.06 9365.06
Mass Balance for Modified WWTP
Equation used (Michael & David 2011):
X = 9410.06 mg/L V = 56.46m3 θc = 14.83 days O2 = 4471.20 kg/day

21. References
1. Bukhari, A. A. 2012. Part I: Treatment of Pharmaceutical Wastewater. Pharmaceutical Waste Treatment and Disposal Practices. KFUPM
2. Cheresources. 2010. Jacketed vessel design forum. http://www.cheresources.com/content/articles/heat-transfer/jacketed-vessel-design [29
April 2013].
3. China Chemical Industry News. 2012. Synthetic Ephederine from Zhejiang Achievements Conversion Award.
http://www.39kf.com/my/tag_1_32032a-24892a-24901/ [16 March 2013].
4. Department of Environment Malaysia. 2011. Legistration, acts, regulation & order. http://www.doe.gov.my/portal/legislation-actsregulation-
order/ [3 April 2013]
5. Geankoplis, C.J. 2003. Transport Processes and Separation Process Principles: Includes Unit Operations. Fourth Edition. New Jersey:
Prentice Hall.
6. Globinmed. 2010. Ephedrine and its salt. Price range by year from 2000 to 2007.
http://www.globinmed.com/index.php?option=com_content&view=article&id=81286:ephedrine-a-its-salts--price-values-by-year-from-2000-
to-200&catid=45&Itemid=137
7. Hagel, J.M., Krizevski, R., Marsolais, F., Lewinsohn, E. & Facchini, P.J. 2012. Biosynthesis of amphetamine analogs in plants. Trends in
Plant Science 17(7): 404-412.
8. Khan, M. A., Ul-Haq, I., Javed, M. M., Qadeer, M.A., Akhtar, N. & Bokhari, S.A.I. 2012. Studies on the Production of L-Phenylacetylcarbinol
by Candida Utilis in Shake Flask. Pak J. Bot. 44: 361-364.
9. Kostraby, M.M. 1999. The yeast mediated synthesis of the L-ephedrine precursor, L-phenylacetylcarbinol, in an organic solvent. Thesis
Doctor of Philosophy, School of Life Sciences and Technology, Victoria University of Technology.
10. Kumar, M.R., Chari, M.A. & Narasu, M.L. 2006. Production of L-phenylacetylcarbinol (L-PAC) by different novel strains of yeasts in
molasses and sugar cane juice as production medium. Research Journal of Microbiology 1(5): 433 – 437.
11. McKetta, J.J.. 1991. Heat Transfer Design Methods. New York: Marcel Dekker, Inc.
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MPOB Information Series. ISSN 1511-7871
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http://wenku.baidu.com/view/dfcea5254b35eefdc8d3331a.html [16 March 2013].
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22. THANK YOU