PRODUCTION OFL-PHENYLACETYLCARBINOLIntegrated ProjectPresentation Group KB1
CONTENTS Literature Review Usage of L-PAC Economy Analysis: Production & Demand Process Description with PFD Calculat...
Literature ReviewGlucoseBenzaldehydeSaccharomycescerevisiaeL-PACOther products:Ephedrine,pseudoephedrinePyruvicacidAcetald...
L-PAC: Applications and UsagesMethamphetamineD-pseudoephedrineL-ephedrineUsed as the precursor for the production of these...
Economy AnalysisGlobal demand and supply for L-PAC from 2006 to 2013 (reproduced onMATLAB®)Source: Nanjing Pharmaceutical ...
Process ProductionProcess Production
Mass BalanceStoichiometric equation: (Shuler & Kargi 2002)Calculations are shown for F-102 and F-103 as examples:Stream In...
Energy BalanceUnit MetabolismHeat(kJ)Agitation Heat(kJ)Sensible Heat Heat ofreaction(kJ)Energy In(kJ)Energy Out(kJ)F-102 7...
Pressure Vessel Design: Internal PressureFermentor, F-102Specifications and dimensions:Material = SS 316 or ASME SA-240Rad...
Specifications and dimensions:Material = SS 316 or ASME SA-240Radius of vessel = 0.25 mDiameter of vessel = 0.50 mHeight =...
Properties F-102 C0L-102Design Pressure, PD (psi) 69.12 20.36Minimum wall thickness, tmin (mm) 3.00 3.65Design thickness, ...
HeatUtilityDesignJacketedVesselinto F-102Cooler E-101JacketedVesselinto F-103CondensorE-102ReboilerE-103Kettle Reboiler3.2...
Figure 6.7 Heat Cascade18.670-23.970-26118.670-23.970-261Start with0 kWStart with18.67 kW107.697.05722520-5∆Tmin = 20°C-18...
Before AfterTotal energy required 303.64kW 303.64kWTotal energy recovery 0%Table 6.10 Total energy requirementFigure 6.8 G...
Properties JacketedVesselF-102CoolerE-101JacketedVesselF-103CondensorE-102ReboilerE-103Heat load, Q (kW) 1.106 14.21 0.271...
Process Dynamic & Control: ModelingFermentor, F-103The mathematical models that are used for F-103:1. (Rate of accumulatio...
PD&C: Degree of FreedomDegree of Freedom analysisNumber of variables = 10Number of equation = 4 (as in previous slide)Degr...
LTLCSensor – DifferentialpressureSignal type – PneumaticValve – Diaphragm Source: Smith & Corripio 2006Level sensor detect...
• Based on the Environment Quality (Amendment) Act 2012:1. Environmental Quality (Clean Air) (Amendment) Regulations 20002...
PC&CP: Wastewater Treatment PlantOverall Diagram for Modified WWTPStream Q Q + Qr Q - Qw Qu Qr QwFlow rate (m3/d) 13.15 14...
References1. Bukhari, A. A. 2012. Part I: Treatment of Pharmaceutical Wastewater. Pharmaceutical Waste Treatment and Dispo...
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L-Phenylacetylcarbinol presentation

  1. 1. PRODUCTION OFL-PHENYLACETYLCARBINOLIntegrated ProjectPresentation Group KB1
  2. 2. CONTENTS Literature Review Usage of L-PAC Economy Analysis: Production & Demand Process Description with PFD Calculation of material and energy balance in thefermentor Pressure Vessel Design Heat Utility Design and Heat Integration Control Dynamic and Process Pollution Control and Cleaner Production
  3. 3. Literature ReviewGlucoseBenzaldehydeSaccharomycescerevisiaeL-PACOther products:Ephedrine,pseudoephedrinePyruvicacidAcetaldehydeEphedra sinicaStandard microbes forthe fermentation whereethanol-producers arepreferred (Hagel et al.2012) and givessignificant yields (Kumaret al. 2006)Biotransformationroute remains thepreferred method forthe industry (Shukla &Kulkarni 2000)Traditional process toproduce ephedrine that isno longer preferred dueto tedious and expensivedownstream processes(Khan et al. 2012)
  4. 4. L-PAC: Applications and UsagesMethamphetamineD-pseudoephedrineL-ephedrineUsed as the precursor for the production of these drugs that are known forthe nasal decongestant properties (Oliver et al. 1997, Shukla & Kulkarni2000)
  5. 5. Economy AnalysisGlobal demand and supply for L-PAC from 2006 to 2013 (reproduced onMATLAB®)Source: Nanjing Pharmaceutical Company 2006, China ChemicalIndustry News 20122006 2007 2008 2009 2010 2011 2012 201380010001200140016001800200022002400Global Demand and Supply for L-PAC from 2006 to 2013YearAmountofL-PAC(in103kgortonnes)DemandSupplyPROPOSED PRODUCTIONMode of operation: Fed-batchfermentationTotal demand for L-PAC inMalaysia in 2013 = 21,000 kg(Globinmed 2010)Proposed annual Production:[L-PAC] = 25% of total demand= 5,250 kgProduction rate:[L-PAC] = 5,250kg/150 cycles= 35 kg per cycleBulk price for L-PAC is aroundRM312.30 per kg (BalantesPharma 2012)
  6. 6. Process ProductionProcess Production
  7. 7. Mass BalanceStoichiometric equation: (Shuler & Kargi 2002)Calculations are shown for F-102 and F-103 as examples:Stream In OutFeed Gas Total Product Gas-off TotalGlucose 72.00 0 72.00 0.66 0 0.66C7H6O 3.03 0 3.03 0 0 0NH3 0.50 0 0.50 0 0 0Biomass 0.36 0 0.36 3.87 0 3.87L-PAC 0 0 0 35 0 35N2 0 1620.87 1620.87 0 1620.87 1620.87CO2 0 0 0 0 14.53 14.53H2O 458.71 0 458.71 480.54 0 480.54Ethanol 5.40 0 5.40 5.40 0 5.40Total 540.00 1620.87 2160.87 525.47 1635.40 2160.87Comparison with SuperPro® DesignerSuperPro® 533.47 1627.39 2160.86Error(%) -1.52 0.49 0.00Mass balance involving F-102 and F-103:
  8. 8. Energy BalanceUnit MetabolismHeat(kJ)Agitation Heat(kJ)Sensible Heat Heat ofreaction(kJ)Energy In(kJ)Energy Out(kJ)F-102 75789.55 19639.53 8420.09 8587.11 - 95587.10F-103 3697.05 18613.42 8606.01 8717.42 -23447.99E-101 - - 60227.89 10037.98 50189.91The 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 – OutEnergy (W) -11379.47 -3243.51 -5854.92 -2281.04Utility Condenser Reboiler ChangeEnergy (W) 264819.45 267100.60 -2281.15
  9. 9. Pressure Vessel Design: Internal PressureFermentor, F-102Specifications and dimensions:Material = SS 316 or ASME SA-240Radius of vessel = 0.3545 mDiameter of vessel = 0.709 mHeight = 1.996 mCylindrical shellHeight = 1.418 mTorispherical heads (Top and Bottom)Knuckle radius = 0.0425 mCrown radius = 0.363 mHeight = 0.289 mCalculated that:Design pressure = 69.12 psi = 477 kPaToverall = 0.14’’Tmin= 3 mmDesign thickness = 5 mmMAWP vessel = 98.94 psi
  10. 10. Specifications and dimensions:Material = SS 316 or ASME SA-240Radius of vessel = 0.25 mDiameter of vessel = 0.50 mHeight = 3.77 mCylindrical shellHeight = 3.52 mEllipsoidal heads (Top and Bottom)Height = 0.125 mCalculated that:Design pressure = 20.36psiToverall = 5.65mmTmin= 3.65mmDesign thickness = 6.35 mmMAWP vessel = 15psi (Atmospheric pressure)Pressure Vessel Design: External PressureDistillation column, COL-102
  11. 11. Properties F-102 C0L-102Design Pressure, PD (psi) 69.12 20.36Minimum wall thickness, tmin (mm) 3.00 3.65Design thickness, tD (mm) 5.00 6.35MAWP vessel (psi) 98.94 15Circumferential stress, σ1 (N/mm2) 33.78 3.99Total longitudinal stress, σ2 (N/mm2) 16.26 - 1.36Maximum stress intensity, (Δσ)max (N/mm2) 17.52 5.34Design stress, S (N/mm2) 108.8 132.32Critical buckling stress,σc (N/mm2) 139.08 247.71σcompressive (N/mm2) 0.629 4.0345Skirt thickness, ts (mm) - 10Design skirt thickness, tD(mm) - 12Bolt root diameter, (mm) - 10.41Impeller diameter, Di (m)Impeller spacing, Hi (m)Impeller blade length, Li (m)Impeller blade height, Wi (m)Location of gas sparger, Hb (m)0.2340.4680.0590.0470.117-----Pressure Vessel Design: Summary
  12. 12. HeatUtilityDesignJacketedVesselinto F-102Cooler E-101JacketedVesselinto F-103CondensorE-102ReboilerE-103Kettle Reboiler3.2 mm o.d., 1.9 mm i.d.,L = 4.8 m, plain U-tubesTotal Condensor3.2 mm o.d., 1.9 mm i.d., L =0.508 m, admiralty brassDimple JacketSS 316, pattern type 1(100/100) 11 mm, baselength = 63.5 mmU-tube exchanger6.35 mm o.d., 2.465 mm i.d.,L = 6.10 m, cupro-nickelJacket with spiral baffleStainless steel 316, channel 15 x200 mm, 6 spiralsHeat Utility Design: Types
  13. 13. Figure 6.7 Heat Cascade18.670-23.970-26118.670-23.970-261Start with0 kWStart with18.67 kW107.697.05722520-5∆Tmin = 20°C-18.67-18.675.35.3266.30042.6442.64303.64QHmin = 18.67 kW12345QCmin = 303.64 kWHeat Utility Design: Heat Integration
  14. 14. Before AfterTotal energy required 303.64kW 303.64kWTotal energy recovery 0%Table 6.10 Total energy requirementFigure 6.8 Grid Representative20485530°C82°C97.6°C35°CCppinch1.770.5110.44∆Habove pinch (kW)0018.675°C87.05°C107.5°C107.5°C∆Hbelow pinch (kW)26123.970Heat Utility Design: Heat Integration
  15. 15. Properties JacketedVesselF-102CoolerE-101JacketedVesselF-103CondensorE-102ReboilerE-103Heat load, Q (kW) 1.106 14.21 0.271 0.0444 2.71Uestimate (W/m2 720 550 550 650 850Area required (m2) 9.30 0.0014 0.1909Area of channel (m2) 3 x 10-3 1.86 x 10-3hj (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) - - - - 2528.69hc (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 2.08hs (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. 16. Process Dynamic & Control: ModelingFermentor, F-103The 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:SKSXdtdXsmaxXYdtdPXP /dtSSdYX fSP /
  17. 17. PD&C: Degree of FreedomDegree of Freedom analysisNumber of variables = 10Number 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, antifoamPXSSFYYVKN fSXXPSV ,,,,,,,,, //max6410FEVFNNNNSKV ,, max336FN
  18. 18. LTLCSensor – DifferentialpressureSignal type – PneumaticValve – Diaphragm Source: Smith & Corripio 2006Level sensor detectsdifference in pressurecaused by hydrostaticheadSends pneumaticsignal to thetransmitterTransmitterdirects the signalto the levelcontrollerController calculatesthe necessarycorrection neededController sendssignal to thediaphragm valvelocated at the outputof F-103Diaphragm valvemoves thediaphragm to openor close the area offlowPD&C: Level Control Loop
  19. 19. • Based on the Environment Quality (Amendment) Act 2012:1. Environmental Quality (Clean Air) (Amendment) Regulations 20002. Environmental Quality (Industrial Effluent) Regulations 20093. Environmental Quality (Scheduled Wastes) (Amendment) Regulations 20074. Environmental Quality (Sewage) Regulations 2009(Source: DOE 2013)Pollution Control and Cleaner Production(1)Unit(2)Standard A(3)Standard BChemical Oxygen Demand mg/L 80 200Temperature 0C 40 40pH value - 6.0-9.0 5.5-9.0BOD5 at 200C mg/L 20 50Suspended solid mg/L 50 100Phenol mg/L 0.001 1.0Ammoniacal Nitrogen mg/L 10 20FormaldehydeColourmg/LADMI*1.01002.0200Discharge Limit according EQ(IE)R 2009(Source: Taken and Modified from Department of Environment 2013)
  20. 20. PC&CP: Wastewater Treatment PlantOverall Diagram for Modified WWTPStream Q Q + Qr Q - Qw Qu Qr QwFlow rate (m3/d) 13.15 14.77 9.37 5.40 1.62 3.78S, BOD(mg/L) 14062.86 18 18 - - -X, SS (mg/L) 0 9410.06 45 9365.06 9365.06 9365.06Mass Balance for Modified WWTPEquation used (Michael & David 2011):X = 9410.06 mg/L V = 56.46m3 θc = 14.83 days O2 = 4471.20 kg/day
  21. 21. References1. Bukhari, A. A. 2012. Part I: Treatment of Pharmaceutical Wastewater. Pharmaceutical Waste Treatment and Disposal Practices. KFUPM2. Cheresources. 2010. Jacketed vessel design forum. http://www.cheresources.com/content/articles/heat-transfer/jacketed-vessel-design [29April 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=1377. Hagel, J.M., Krizevski, R., Marsolais, F., Lewinsohn, E. & Facchini, P.J. 2012. Biosynthesis of amphetamine analogs in plants. Trends inPlant 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-Phenylacetylcarbinolby 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. ThesisDoctor 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 inmolasses 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 1511-787113. 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 improvementsand 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 Microbiologyand 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. Secondedition. London: Butterworth-Heinemann.18. Tripathi, C.M., Agarwal, S.C. & Basu, S.K. 1997. Production of L-Phenylacetylcarbinol by fermentation. Journal of Fermentation andBioengineering 84: 487-492.
  22. 22. THANK YOU

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