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
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)
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
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
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.
12. Mohamad Sulong, Astimar A. Aziz & AB Gapor Md. Top 2008 Bio-Fertiliser from palm Oil Biomass and POME Solids by Mobile Composter.
MPOB Information Series. ISSN 1511-7871
13. Nanjing Pharmaceutical Company. 2006. Ephederine and Mongolia Shengle Pharmaceutical Research Report.
http://wenku.baidu.com/view/dfcea5254b35eefdc8d3331a.html [16 March 2013].
14. Oliver, A.L., Roddick, F.A., & Anderson, B.N. 1997. Cleaner production of phenylacetylcarbinol by yeast through productivity improvements
and waste minimisation. Pure & Applied Chemistry 69(11): 2371-2385.
15. Shukla, V.B. & Kulkarni, P.R. 2000. L-phenylacetylcarbinol (L-PAC) biosynthesis and industrial applications. World Journal of Microbiology
and Biotechnology 16(7): 499-506.
16. Smith, C.A. & Corripio, A.B. 2006. Principles andPractice of Automatic Process Control. Third edition. New Jersey: John Wiley & Sons.
17. Towler, G. & Sinnott, R. 2013. Chemical Engineering Design: Principles, Practice and Economics of Plant and Process Design. Second
edition. London: Butterworth-Heinemann.
18. Tripathi, C.M., Agarwal, S.C. & Basu, S.K. 1997. Production of L-Phenylacetylcarbinol by fermentation. Journal of Fermentation and
Bioengineering 84: 487-492.