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Chapter 1
Introduction
Fluconazole is an antifungal triazole drug used in treatment of superficial and systemicfungal infections. In a bulk powder form,it appears as a white crystalline powder. Its
very slightly soluble in water and soluble in alcohol. Its commonly marketed under the
trade names Diflucan and Trican.
(Source: M P Biomedicals)
Formula: C13 H12 F2N6 O
Molecular Mass : 306.271 g/mol.
Structure:
(Source:Murthy et al.,1996)
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Fluconazole was invented by Ken Richardson and received patent number 4404216 on
September 13, 1983.It is a second generation triazole derivative and has been found to be
efficacious against a host of fungal ailments like mucocutaneous
candidiasis,oropharangeal and esophageal candidiasis,isolated pulmonary
cryptococcosis,etc.
Fluconazole is also found to act against following fungal species: Blastomyces
dermatitidis, Histoplasma capsulatum ,Candida spp. (except C.krusei and C.glabrata),
Coccidioidesimmitis ,Trichophytonspp. ,Cryptococcus neoformans ,Epidermophyton spp.
(Source:M P Biomedicals
Longley et al.,(2008).
Pfizer Australia Pty Ltd. Diflucan (Australian Approved Product Information). West
Ryde (NSW): Pfizer Australia; 2004.)
Mechanism of Action
Like other imidazole and triazole class antifungals, fluconazole inhibits the
fungal cytochrome P450 enzyme 14-demethylase. Mammalian demethylase activity is
much less sensitive to fluconazole than fungal demethylase. This inhibition prevents theconversion of lanosterol to ergosterol, an essential component of the fungal cytoplasmic
membrane and subsequent accumulation of 14-methyl sterols. Fluconazole is primarily
fungistatic; however, it may be fungicidal against certain organisms in a dose-dependent
manner, specifically Cryptococcus.
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The data from this as used for registration of the compound with governments for market
approval and fluconazole was marketed as Diflucan in the US and UK and over 30
countries worldwide.
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Physical and Chemical Properties of reactants and products.
A) REACTANTS
1) 2,4-Difluoro-alpha-(1H-1,2,4-triazolyl)acetophenone
CAS No. : 86404-63-9
Chemical Name : 2,4-Difluoro-alpha-(1H-1,2,4-
triazolyl)acetophenone
Synonyms : DFTA;4-Difluoro-2(1h-1;4-triazol-1-
yl)acetophenone;1-(2,4-Difluorophenyl)-2-(1H-
1;Difluoro triazolyl acetophenone;2,4-Difluoro-3-
broMo acetophenone;Voriconazole
CBNumber : CB6684361
Molecular Formula : C10H7F2N3O
Formula Weight : 223.18
MOL File : 86404-63-9.mol
mp : 103-107 C(lit.)
storage temp. : Room temperature.
CAS DataBase Reference : 86404-63-9(CAS DataBase Reference)
Chemical Properties
Pale Yellow Solid
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Usage
Antifungal activity, particularly toward Candida albicans and Candida parapsilosis
2)Trimethylsulfoxonium Iodide
Specifications : Trimethylsulfoxonium Iodide
Product : Trimethylsulfoxonium Iodide
Synonyms : Trimethylsulfoxonium Iodide
CAS NO. : [1774-47-6]
Molecular Formula : C3H9IOS (Trimethylsulfoxonium Iodide)
Molecular Weight : 220.07
Appearance : White to cream coloured crystals.
Solubility : soluble in hot water.
Total Moisture : 0.5% max.
Melting Point : 168' - 172' C
Assay on dry basis : 99% min.
3) 1H -1,2,4-triazole
1,2,4-Triazoles can be prepared using the Einhorn-Brunner reaction or the Pellizzarireaction.[1] The ring structure appears in certain N-heterocyclic carbenes.
Identifiers
CAS number : 288-88-0
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PubChem : 9257
ChemSpider : 8900
ChEBI CHEBI: : 46077
Properties.
Molecular formula : C2H 3N3
Molar mass : 69.0654
Appearance : white solid
Melting point : 120-121
Boiling point : 260
Solubility in water : very soluble
Acidity (pKa) : 2.2
Basicity (pKb) : 10.3
Flash point : 140
Related compounds : 1,2,3-triazole imidazole
B) PRODUCTS:
1)Fluconazole
CAS No. : 86386-73-4
Chemical Name: : Fluconazole
Synonyms : Elazor, Flusol, Zoltec, uk49858, diflucan,
Fluconal, FluMycon,Flunazol,Triflucan.
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CBNumber : CB3740293
Molecular Formula : C13H12F2N6O
Formula Weight : 306.27
MOL File : 86386-73-4.mol
Fluconazole Property
mp : 138-140C
storage temp. : 20C
solubility : DMSO: 5 mg/mL
form : solid
CAS DataBase Reference : 86386-73-4(CAS DataBase Reference)
Safety
Hazard Codes : Xn,Xi
Risk Statements : 22-36/37/38-20/21/22
Safety Statements : 26-36-36/37/39-24/25
RTECS : XZ4810000
Hazardous Substances Data : 86386-73-4(Hazardous Substances Data)
Chemical Properties
White to Off-White Solid
Usage:
Labelled Fluconazole (F421000). Used as an antifungal.
Biological Activity
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Triazole antifungal agent. Effective against Candida strains in vitro and in vivo .
Fluconazole Preparation Products And Raw materials
2) Dimethyl Sulphoxide
CAS No. : 67-68-5
Chemical Name : Dimethyl sulfoxide
Synonyms : m176,DMSO,Decap,M 176,Deltan,a10846,
Demeso,DMS70,DMS 90, dms-70
CBNumber CB7854105
Molecular Formula : C2H6OS
Formula Weight : 78.13
MOL File : 67-68-5.mol
mp : 18.4 C
bp : 189 C(lit.)
density : 1.100 g/mL at 20 C
vapor density : 2.7 (vs air)
vapor pressure : 0.42 mm Hg ( 20 C)
FEMA : 3875
refractive index : n20/D 1.479(lit.)
Flash point : 192 F
storage temp. : Store at RT.
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color : clear colourless
FreezingPoint : 18.4
Sensitive : Hygroscopic
Merck : 14,3259
BRN : 506008
CAS DataBase Reference : 67-68-5(CAS DataBase Reference)
NIST Chemistry Reference : Dimethyl sulfoxide(67-68-5)
EPA Substance Registry
System : Methane, sulfinylbis-(67-68-5)
Safety
Hazard Codes : ` Xi
Risk Statements : 36/37/38
Safety Statements : 24/25-37/39-26-36-23
WGK Germany : 1
RTECS : PV6210000
HS Code : 29309070
Hazardous Substances Data : 67-68-5(Hazardous Substances Data)
Chemical Properties
colourless liquid
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General Description
A clear liquid, essentially odorless. Closed cup flash point 192F. Vapors are heavier
than air. Contact with the skin may cause stinging and burning and lead to an odor of
garlic on the breath. An excellent solvent that can transport toxic solutes through the skin.
High vapor concentrations may cause headache, dizziness, and sedation.
Air & Water Reactions
Denser than water and miscible in water.
Reactivity Profile
Dimethyl sulfoxide decomposes violently on contact with many acyl halides, aryl halides
and related compounds such as phenyl and tolyl chloride, acetyl chloride,
benzenesulfonyl chloride, benzoyl chloride, cyanuric chloride, phosphorus chloride,
phosphorus oxychloride, and thionyl chloride [Chem. Eng. News 35(9):87 (1957)].
Reacts, possibly violently, with iodine pentafluoride [Chem. Eng. News 47(12):,
109(1969)]. Vacuum distillation from anhydrous magnesium perchlorate led to an
explosion [MCA Case History 1187(1966)]. Violently reactive with fluorinating agents
such as silver fluoride [Chem. Eng. News 44(24):7(1956)]. Can explode with sodium
hydride [Chem. Eng. News 44(24):7(1966)]. Mixture with methyl bromide resulted in an
explosion that shattered the apparatus [NFPA 491M, 1991]. Forms salts with perchloric
acid that are explosive when dry [Chem. Abst. 44:p3935d (1950)]. Decomposes when
heated above normal boiling point.
Health Hazard
Slight eye irritation.
Fire Hazard
Special Hazards of Combustion Products: Sulfur dioxide, formaldehyde, and methyl
mercaptan can form
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Biological Activity
Solvent with wide ranging applications in biological research.
3) Sodium Iodide
CAS No. : 7681-82-5
Chemical Name : Sodium iodide
Synonyms : Ioduril,Soiodin,Anayodin,jodidsodny,
Jodid sodny sodiumiodine;natriiiodidum;
SODIUM IODIDE;Sodium iodine
CBNumber : CB6170714
Molecular Formula : INa
Formula Weight : 149.89
MOL File : 7681-82-5.mol
Sodium iodide Property
mp : 661 C(lit.)
bp : 1300 C
density : 3.66
vapor density : >1 (vs air)
refractive index : 1.7745
Fp : 1300-1304C
storage temp. : Store at RT.
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form : beads
Water Solubility : 184 g/100 mL (25 C)
Sensitive : Hygroscopic
Merck : 14,8631
CAS DataBase Reference : 7681-82-5(CAS DataBase Reference)
NIST Chemistry Reference : Sodium iodide(7681-82-5)
EPA Substance Registry System : Sodium iodide (NaI)(7681-82-5)
Safety
Hazard Codes : Xi
Risk Statements : 36/38-36/37/38
Safety Statements : 26
WGK Germany : 1
RTECS : WB6475000
F : 8
HS Code : 28276000
Hazardous Substances Data : 7681-82-5(Hazardous Substances Data)
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Chapter 4
Methods of manufacture
Several methods for the synthesis of Fluconazole are reported in the literature. Some
prominent ones are listed below:
4.1.1 Synthesis of Fluconazole starting from 1,3-Difluorobenzene.
It comprises of the following steps:
Fluconazole
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4.2.2 Synthesis of Fluconazole from 2,4-Difluoro-2-(1H-1,2,4-Triazole-1 yl) Acetophenone.
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The above process (2) ,(i.e. the synthesis of Fluconazole from 2,4-Difluoro-alpha-(1H-
1,2,4-triazolyl)acetophenone, Tri Methyl Sulphoxinium Iodide and 1H-1,2,4-Triazole)
has been selected in Polydrug Laboratories Pvt.Ltd because:
The process (1) of manufacturing Fluconazole from 1,3-Difluorobenzene has very low
overall yield of only 4-8 % of Fluconazole.
The other major process used in manufacture of Fluconazole requires reactant which is
produced by reaction of 1,3-ditriazole acetone with the corresponding Grignard of
Difluorobenzene. However, the solvents used in both lithiation and Grignard reactions
are extremely flammable and hazardous. The reagents and solvents are dangerous to
handle in large quantities,hence this method is not very attractive for large scale
commercial production.
Thus, in comparison to these methods,the method employed in Polydrug Laboratories
Pvt. Ltd. Utilises materials which are readily available commercially,easily
handled,relatively inexpensive and relatively safe to use.
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Material Balance?
Energy balance?
Thermodynamic feasibility?
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Chapter
Energy Balance
One of the most important parameters in a chemical industry is the temperature at whichchemical reaction is carried out.Thus depending upon whether the reaction is
endothermic or exothermic,heat is either absorbed or evolved.Thus we provide cooling
utilities to keep the reaction constant in an exothermic reaction and heating utilities to
keep the reaction temperature constant in an endothermic reaction.
In our process for manufacture of Fluconazole, heat is liberated by the following
reaction.
DFTA + TMSI + 1 H-1,2,4Triazole
Fluconazole + DMSO + NaI
As we know, heat of reaction ( HR) is calculated as follows :
HR= (HR)298+ CP dT
where CP = (CP) PRODUCTS - (CP) REACTANTS
But (CP) PRODUCTS = (CP) REACTANTS
Thus, HR= (HR)298
We use Joback group contribution theory to calculate the Standard Heat of Formation of
each reaction species and product species and then we proceed to calculate the overall
Heat of Reaction .
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A)2,4-Difluoro-2-(1H-1,2,4-Triazole-1 yl) Acetophenone.
Functional Group No of groups (Hj)298 Hj
=N- (ring) 3 55.52 166.56
F- 2 -251.9 -503.8
=CH- (ring) 5 2.09 10.45
=C= (ring) 3 46.43 139.29
=C= (non ring) 1 83.99 83.99
O= (non ring) 1 -247.6 -247.6
=CH2 (non ring) 1 -20.64 -20.64
Hence, H (DFTA) = , Hj + 68.29
= -293.46 kcal/mol
B)Trimethyl Sulphoxinium IodideFunctional Group No of groups (Hj)298 Hj
-CH3 (non ring) 3 -76.45 -229.35
I- 1 21.06 21.06O= (any other) 1 -247.6 -247.6
1 41.87 41.87
Hence, H (TMSI) = Hj + 68.29
= -345.73 kcal/mol
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C)1H-1,2,4-Triazole
Functional Group No of groups (Hj) 298 Hj
-N= (ring) 2 55.52 111.04
=NH (ring) 1 31.65 31.65
-CH= (ring) 2 2.09 4.18
Hence, H (1H-1,2,4-Triazole) = Hj + 68.29
= 215.16 kcal/mol.
D) Fluconazole
Funtional Group No of groups Hj298 Hj
F- 2 -251.9 -503.8
=N- (ring) 6 55.52 333.12
=C= (non ring) 1 82.23 82.33
OH- 1 -208 -208
=CH2 (non ring) 2 -20.64 -41.28
=CH- (ring) 7 2.09 14.63
=C= (ring) 3 46.43 139.29
Hence, H (Fluconazole) = Hj + 68.29
= -115.52 kcal/mol
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E) Dimethyl Sulphoxide
Functional Group No of groups Hj298 Hj
-CH3 2 -76.45 -152.9
-S- 1 41.87 41.87
O= 1 -247.6 -247.6
Hence, H(DMSO) = Hj + 68.29
= -290.34 kcal/mol.
F) Sodium Iodide
H ( NaI) = -68.784 kcal/mol.
Thus, HR = HPRODUCTS - HREACTANT
= [HFLUCONAZOLE+HDMSO+HNAI]
- [ HDFTA+HTMSI+HTRIAZOLE]= -474.644 - [-424.03]
= -50.614 Kcal/ kmol.
Thus, Reaction is exothermic. We provide cooling utility i.e. cooling water to keep
temperature constant.
Heat evolved by chemical reaction = Heat gained by cooling water
H = m * Cp * ( T inT out) .. ( 1 )
Where, Tin = 5C.
= 278 K
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Cp = 4.187 KJ/ Kg K.
Lets Tout = 303 K
H = (Kmole of DFTA reacted) * (HRin KJ/Kmol)
= 0.966 * ( - 50.614 * 4.187)
= -204.71 * 10 ^ 3 KJ
Thus, from above equation ( 1 ), value of mass of water required per batch can be
obtained.
Thus, m = 1955.67 kg per batch
m = 1.956 tons per batch
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Chapter
Equipment Design
Density of DFTA = 1390 kg/m3
Density of H20 = 1000 kg/m3
Density of 1 H-1,2,4-Triazole = 1394 kg/m3
Density of NaOH = 2130 kg/m3
Density of TMSI = 1390 kg/m
3
Volume of DFTA = 400/1390
= 0.288 m3
Volume of NaOH = 160/2130
= 0.075 m3
Volume of H2O = 6000/1000
= 6 m3
Volume of TMSI = 400/1399
= 0.286 m3
Volume of 1 H-1,2,4-Triazole = 160/1394
= 0.115 m3
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Total Volume = Vol ( DFTA ) + Vol ( NaOH) + Vol ( H2O) + Vol (TMSI) +
Vol ( 1 H-1,2,4-Triazole)
Total Volume = 6.764 m3
This is the Hold up volume. Holdup volume is generally 75 % of the Total volume.
Hence , Total Volume = 9.019 m3
Concentration in Feed = Moles / Volume
= Mass / ( Molecular weight * Volume)
Thus,
C ( DFTA) = 400/ ( 223 * 6.764 )
= 0.265 kmol/m3
C ( TMSI) = 400/( 220 * 6.764 )
= 0.2688 kmol/ m3
C ( NaOH) = 160/ ( 40 * 6.764)
= 0.591 kmol/m3
C ( 1 H-1,2,4-Triazole) = 160/ ( 69 * 6.764)
= 0.343 kmol/m3
Also, Total Volume = ( / 4) * D2 H
Generally, D= 0.8 H
Thus, 9.019 = (/4) * (0.8 H) * H
Thus, H = 2.618 m
D = 2.094 m.
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Chapter
Mechanical Design
Design Pressure = 3 kg/ cm2
= 0.3 N/ mm2
A)Thickness of Shell :ts = ( P * di ) / ( 2 f JP ) + c
= ( 0.3 * 2094) / ( 2 * 110 * 0.85 - 0.3) + 2
= 5.36 mm.
Take ts = 6 mm
Now, lets check if the resultant stress allows for thickness obtained from above
calculation.
Calculation for the resultant/ equivalent stress for cylindrical vessel under combined
loadings.
1) Circumferential stressft = P ( Di + t) / ( 2 t)
= ( 0.3 * (2094 + 6) ) / ( 2 * 6 )
ft = 52.5 N/ mm2
2) Stresses in axial direction.
a) Due to internal pressure:
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fL1 = P ( Di + t) / ( 4 t )
fL1 = 26.25 N/ mm2
b) Due to weight of the vessel and its contents for vertical vessel.
fL2 = W/ ( * ( Di + t) t )
Here, W is the total weight of the vessel alongwith its contents, fittings,auxialliary
equipments , etc. It is expressed in Newtons. Also W is obtained by increasing
the weight of the vessel and its contents by 10 to 15 % , to take care of the weight
due to various fittings and auxiliary equipments.
Let Wo be the weight of the vessel.
Wo = density * volume * 9.81
= 8000 * 9.019 * 9.81
= 707811.12 N
Thus, W = Wo + 0.15 W
W = 813982.79 N
fL2 = ( 813982.79) / ( * (2094 + 6 ) * 6 )
fL2 = 20.56 N/ mm2
c) Due to wind load.
fL3 = 0 ( No wind Load )
Thus resultant stress in the longitudinal direction :
fLR = fL1 + fL2 + f L3
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= 26.25 + 20.56
fLR = 46.81 N/mm2
3) Torsional stress
Torque on vessel = 37 kN m
= 37 * 10 ^ 6 N mm
Stress due to torque ( fs ) = 2 T / ( * Di * t * (Di + t))
= ( 2 * 37 * 10 6 ) / ( * 2094 * 6* 2100)
fS = 0.893 N / mm2
Resultant stress i.e. fR = ( fT2fT * fLR+ fLR
2+ 3 fs
2)
fR = ( 52.5252.5 * 46.81 + 46.82 + 3* 0.8932)
Hence , fR = 58.69 N / mm2
As this resultant stress is less than the permissible stress of 110 N/mm2 that we utilized
earlier, the thickness obtained is satisfactory and design is safe.
Thus, including corrosion allowance of 2 mm , take shell thickness ts = 8 mm.
Outer diameter of shell = inner diameter + 2 tS
= 2094 + 16
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= 2110 mm.
Design Procedure is applicable to shell having ratio of (Do/ Di) < 1.5
Here, (Do/ Di) = 2110/ 2094
= 1.008
Hence, (Do/ Di) < 1.5
Hence, procedure holds for good design.
B)Design for HeadFor flanged and shallow dished head :
Th = ( P Rc W ) / ( 2 f J)
Where, Rc = Crown radius
= 2094 mm
W = stress intensification factor
W = (1/4) * ( 3 + ( Rc / Rk ) )
But, Rk = 6 % of Rc
Rk = 0.06 * 2094
= 125.64 mm.
W = (1/4) * ( 3 + ( 2094 / 125.64 ))
W = 1.77
J = 1 ( for head )
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Thus , we have Th = ( 0.3 * 125.64 * 1.77 ) / ( 2 * 110 * 1)
Th = 0.303 mm.
Including corrosion allowance of 2 mm,
Th = 3 mm.
We take Th as 8 mm as its thickness of shell.
C) Jacket Design
We use conventional or Plain jacket.
a) Jacket shell thickness for internal pressure.Dij = Dso + 1.2
= 2230 mm.
t rj = ( Pj Dij ) / ( 2 f JPj)
Design Pressure = 6 kg/ cm2
= 0.6 N/ mm2
trj = ( 0.6 * 2230 ) / ( 2 * 110 * 0.850.6 )
trj = 7.178 mm
Including corrosion allowance
take trj = 10 mm.
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b) Jacket Closer ThicknessIt should be the higher value of the following :
i) trc = 2 * t rj= 2 * 10
trc = 20 mm
ii) trc = 0.866 * Wj ( Pj / f )Here, Wj = Jacket width
But, Jacket width = ( Inside dia. Of JacketOutside dia. Of vessel) / 2
Wj = (22302110 ) / 2
Wj = 60 mm.
Thus, trc = 0.866 * 60 * ( 0.6 / 110 )
trc = 3.84 mm
Hence, take higher value of trc , i.e. trc = 20 mm.
Design of jacket torispherical end for internal jacket pressure
Thickness of jacket head:
thj = (P Rc W) / ( 2 f J )
= ( 0.6 * 2230 * 1.77 ) / (2 * 110 * 1)
thj = 1.076 mm.
Thus, we use 5 mm thickness for jacket torispherical end.
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Diameter of gasket at load reaction ( G ) = Go2 b
= 2151.25 - 2 ( 7 )
G = 2137.25 mm.
II) Design of Bolt :
Bolt load under atmospheric condition :
Wm1 = G b y
= * 2137.25 * 7 * 11
Wm1 = 517006.41 N
Bolt load under operating conditions :
Wm2 = G * 2b * m * p + ( /4) G2
* P
Wm2 = 1132672.07 N
As Wm2 > Wm1, we take this value.
Hence, area of bolt required is Ab = Wm / ( fb ) = ( 1132672.07 / 53)
Ab = 21371.17 mm2
But, Ab = n * ( /4 ) * db2
Where, n = no. of bolts.
n = G/ 25 = 2137.25/ 25
n = 86
Take n = 88 ( multiple of 4 )
Thus db = ( (4 * ) / ( A/ n ))
db = 17.58 18 mm.
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Use M18 * 2 bolts, 88 numbers.
Bolt circle diameter (B) = Go + 2 db +12
B = 2151.25 + 2 (18) + 12
B = 2199.25 mm
Thus, B = 2200 mm.
Actual bolt spacing required bs = B/ n
= ( * 2200 ) / 88
bs = 78.54 mm
III) Design of FlangeOutside diameter of the flange Dfo = B + 2 db+ 12
= 2200 + 2 ( 18) + 12
Dfo = 2248 mm.
k = 1 / ( 0.3 + 1.5 Wm hG / (HG) )
where, Wm = Max bolt load
= 1132672.07 N
hG = (B - G) / 2
= ( 22002137.25) / 2
hG = 31.38 mm.
H = (/4) * G 2 P
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H = 1076271.37
Thus, k = 3.0943
Thickness of flange tf = G ( P/ k f)
tf = 2137.25 ( 0.3 / ( 3.0943 * 110 ))
Thus, tf = 63.45 mm 65 mm.
E)Nozzle Reinforcement DesignDesign Pressure = 0.3 N / mm
2
Diameter of nozzle = 100 mm.
Material of nozzle is same as that of reactor.
Thickness of nozzle ( tn) = P Di / ( 2f JP)
tn = ( 0.3 * 100 ) / ( 2 * 110 * 1- 0.3)
tn = 0.1365 mm.
1 mm.
Horizontal diameter for compensation
AB = 2 Dn
= 2 * 100
= 200 mm
Vertical Diameter for Compensation.
We take the greater value of the following:
i) AD = 6 * tn
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= 6 * 3 = 18 mm.
ii) AD = 3.5 * ts + 2.5 tn
= 3.5 * 8 + 2.5 * 3
AD = 35.5
Take greater value , i.e. AD = 35.5
Area of Compensation = 100 * 8
= 800 mm2
Area of compensation provided by head = Din* ( tsts )
Ah = 100 * (8-6)
= 200 mm2
Area of compensation provided by nozzle = 2 Ht * ( tntn c)
Where, Ht = 2.5 * ts
= 2.5 * 8 = 20 mm.
tn = 3
tn = 0.1365
Thus, Ao = 2 * 20 * ( 3- 0.13650 )
Ao = 114.54 mm2
Nozzle does not project inside the vessel. Thus, H2 and At =0.
Total area of compensation available = An + Ao + At
= 200 + 114.54 + 0
= 314.54 mm2
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Hence, as the area of compensation required is 300 mm2
and 314.54 mm2
is already
available, no ring is required.
Design For Agitator
Power required for agitator (P) = (Np * * N ^3 * Da^5) / (gc * 75)
Where , N = 10 rpm
= 0.1667 rps
gc = 9.81 m/ sec2
Agitator Diameter (Da) = 1.01 m
To find density of reaction mixture ( )
Density of fluid entering the reactor = Mass / Volume
Where, Mass = Mass ( Reactants + Water)
Volume = Volume (Reaction Mixture )
Total mass of reactants = ( 400 kg DFTA + 400 kg TMSI
+ 160 kg 1 H-1,2,4-Triazole
+ 160 kg NaOH )
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Total mass of reactants = 1120 kg.
Mass of Water = 6000 kg
Thus, total mass = 7120 kg.
Volume of water fed = 6000/ 1000
= 6 m3
Volume of DFTA fed = Mass/ Volume
= 400/1390
Volume of DFTA fed = 0.288 m3
Similarly,
Volume of NaOH fed = 160/2130
= 0.075 m3
Volume of TMSI = 400/ 1399
= 0.286 m3
Volume of 1 H-1,2,4-Triazole = 160/ 1394
= 0.115 m3
Thus, Total Volume of Reaction Mixture = Volume ( water +reactants )
= 6 + ( 0.764)
Hence, density of reaction mixture () = 7120 kg/ 6.764 m3
= 1052.63 kg/m3
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To find Power number
Power number ( Np) can be approximated from a graph of log ( Np) v/s log ( NRe)
NRe is Reynolds number.
But, Nre = ( N Da^5 ) /
Let N = 10 rpm for highly viscous fluid.
The value of of reaction mixture is taken as the viscosity of Fluconazole
suspension in water as gel.
Thus , = 103.96 pascal sec.
Hence , Nre = 1052.63 * 0.1667 * ( 1.01 )^5 / 103.96
Nre = 2
From log Np v/s log Nre graph, Np = 28
Hence , Power required for agitator ( P) = (Np * * N ^3 * Da^5) / ( gc * 75 )
P = 0.196 hp
Considering 10 % gland losses and 20 % transmission losses ,power required is 0.259 hp.
Select 0.5 hp motor.
1) Shaft designRated Motor torque ( Tr) = ( P * 4500) * 10 ^4 / ( 2 N ) N mm.
= (0.5 * 4500) * 10 ^4 / ( 2 * 10)
Tr = 358098.62 N mm
Maximum Torque (Tm) = 1.5 Tr
= 537147.93 N mm.
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a) But, Tm = ( / 16 ) * fs * d ^3Where, fs = 125 N/ mm
2for SS 316.
Thus, 537147.93 = (/16) * 125 * d ^3
d = 27.97 mm.
b) This Tm is resisted by the Fm which acts at 75 % of max radius of
impeller.
Thus, Fm = Tm / ( 0.75 * Rb)
Where, Rb = radius of blade in mm.
= 505 mm
Fm = 1418.21 N
But, Mm = Fm * L
Where L is shaft length between agitator and bearing.
Mm = 1418.21 * 900
Mm = 1276389 N mm
Also, Mm = ( / 32) * fb * d^3
Where, fb = bending stress
fb = 230 N/ mm2
for S.S.
Hence, 1276389 = ( / 32) * 230 * d ^ 3
d = 38.38 mm.
Also, by maximum shear stress theory, Equivalent twisting moment ( Te) is given as :
Te = ( Mm2 + Tm2 )
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Te = ( 1276389 ^ 2 + 537147.93 ^ 2)
Te = 1.38 * 10 ^ 6 N/ mm2
But, Te = ( / 16) * fs * d^3
d = 38.31 mm.
Also, by maximum normal stress theory , Equivalent Bending moment ( Me) :
Me = (1/2) * ( Mm + ( Mm ^ 2 + Tm ^ 2))
Me = 1.33 * 10 ^ 6 N/ mm2
Also, Me = ( / 32) * fb * d ^3
1.33 * 10 ^ 6 = ( / 32) * 230 * d ^ 3
d = 38.91 mm.
Thus, we obtained 4 values of shaft diameter ( d) . We select the highest value , i.e.
d = 38.91 mm Or d 40 mm.
Hence, actual value of shaft diameter = 70 2 mm is adequate.
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Design of Centrifuge
Top discharge with hydraulic power pack arrangement for lifting bag and lid.
Basket Diameter D = 1210 5 mm
Thickness of basket = 6 1 mm.
Overall Height of basket = 1650 mm.
The overall dimensions of the basket are as follows:
1210 mm * 500 mm * 6 mm
Diameter Height Thickness
Now, let us find out if this thickness provided is adequately safe for operation at a
particular rpm.
Let = 750 rpm
= 78.54 rad / sec
Let the solid cake obtained have a thickness of 100 mm.
Pressure exerted ( Pc) by the solids on the wall of the basket is given by:
Pc = 0.5 * * ^2 * ( b2a 2)
Where, = density of solids.
= angular velocity.
b = radius of basket.
a = radius of inner surface of solids
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a = radius of basketthickness of solid layer
= 0.605 - 0.1
a = 0.505 m
= 78.54 rad / sec
To find density of solids ( ) :
i) Density of each speciesDensity of Fluconazole = 1490 kg/ m
3
Density of TMSI = 1399 kg/ m3
Density of NaOH = 2130 kg/m3
Density of DFTA = 1390 kg/m3
Density of 1H-1,2,4-Triazole = 1394 kg/m3
Density of DMSO = 1100 kg/m3
Density of NaI = 3670 kg/m3
ii) No. of moles of each species in centrifuge:Kmol of Fluconazole = 0.947
Kmol of NaI = 0.947
Kmol of DMSO = 0.947
Kmol of DFTA = 0.827
Kmol of TMSI = 0.844
Kmol of 1H-1,2,4- Triazole = 1.344
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iii) Mass of each species in centrifuge = kmol * molecular weight.mass of Fluconazole = 0.947 * 306
= 289.78 kg.
mass of NaI = 0.947 * 150
= 142.05 kg.
mass of DMSO = 0.947 * 78
= 73.87 kg.
mass of DFTA = 0.827 * 223
= 184.421 kg.
mass of TMSI = 0.844 * 220
= 185.68 kg.
mass of 1 H1,2,4-Triazole = 69 * 1.344
= 92.72 kg.
mass of NaOH = 122.12 kg.
iv) Mass fraction of each speciesFluconazole = 0.265
NaI = 0.13
DMSO = 0.067
DFTA = 0.169
TMSI = 0.17
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1 H-1.2.4-Triazole = 0.088
NaOH = 0.111
Hence, density of solids = average density of solids in the product mixture in
centrifuge.
i.e. = i xi
thus, = 1773.31 kg/m3
Hence, Pc = 0.5 * 1773.31 * ( 78.54) ^ 2 * (0.6^2 -
0.505 ^2)
Pc = 5.74 * 10^ 5 N / mm2.
Also, stress ( f) in the basket walls is given as:
f = ( b/ )* ( Pc + m * * b * ^ 2)
But, f = 110 N/ mm2
for SS 316
Above equation has only one unknown i.e. . Thus by substituting the values ofthe other variables in the above equation, we have
110 * 10 ^6 = (0.605/ ) * ( 5.74* 10 ^ 5 + ( 2.99 * 10^7))
Thus, = 3.78 mm
The minimum thickness of centrifuge required to have safe design is 3.78 mm.
But , the actual thickness is 6 mm.
Hence, our design is safe.
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Fluconazole MSDS
Section 1
Chemical Product and Company Identification
Product Name : Fluconazole
Catalog Codes : SLF1666
CAS# : 86366-73-4
RTECS : XZ4810000
TSCA : TSCA 8(b) inventory: No products were found.
CI# : Not available.
Synonym : Fluconazole; Diflucan
Chemical Name : 2,4-Dfluoro-alpha, alpha-1-bis(1H-1,2,4-
triazol-1-ylmethyl)benzyl A
1H-1,2,4-Triazole-1-ethanol,alpha-
(2,4-difluorophenyl)-alpha-(1H-1,2,4-
triazol-1-ylmethyl)- l c o h o l o r
Chemical Formula : C13-H12-F2-N6-O
Contact Information : Sciencelab.com, Inc.14025 Smith Rd.
Houston, Texas 77396 US Sales: 1-800-901-7247
International Sales: 1-281-441-4400
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Section 2
Composition and Information on Ingredients
Name CAS # % by Weight
Fluconazole 86366-73-4 100
Toxicological Data on Ingredients: Fluconazole: ORAL (LD50): Acute: 1271 mg/kg
[Rat]. 1408 mg/kg [Mouse].
Section 3
Hazards Identification
Potential Acute Health Effects : Slightly hazardous in case of skin
Contact (irritant), of eye contact
(irritant), of ingestion, of inhalation.
CARCINOGENIC EFFECTS : Not available.
MUTAGENIC EFFECTS : Not available.
TERATOGENIC EFFECTS : Classified.POSSIBLE for human.
DEVELOPMENTAL TOXICITY : Not available. Repeated or prolonged
exposure is not known to aggravate
medical condition.
Section 4
First Aid Measures
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Eye Contact:
Check for and remove any contact lenses. In case of contact , immediately flush eyes
with plenty of water for atleast 15 minutes. Get medical attention if irritation occurs.
Skin Contact:
Wash with soap and water. Cover the irritated skin with an emollient. Get medical
attention if irritation develops.
Serious Skin Contact: Not available.
Inhalation:
If inhaled, remove to fresh air. If not breathing, give artificial respiration. If breathing is
difficult, give oxygen. Get medical attention.
Serious Inhalation: Not available.
Ingestion:
Do NOT induce vomiting unless directed to do so by medical personnel. Never give
anything by mouth to an unconscious person. If large quantities of this material are
swallowed, call a physician immediately. Loosen tight clothing such as a collar, tie, belt
or waistband.
Serious Ingestion : Not available.
Section 5:
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Fire and Explosion Data
Flammability of the Product : May be combustible at high temperature.
Auto-Ignition Temperature : Not available.
Flash Points : Not available
Flammable Limits : Not available.
Products of Combustion : These products are carbon oxides (CO, CO2)
Nitrogen oxides ( NO,NO2), halogenated
compounds.
Fire Hazards in Presence
of Various Substances : Slightly flammable to flammable in
presence of heat. Non flammable in
presence of shocks.
Explosion Hazards in Presence
of Various Substances : Risks of explosion of product in presence
of mechanical impact : not available.
Risks of explosions of the product in
Presence of static discharge : not available.
Fire fighting Media and instructions : SMALL FIRE: Use DRY chemical powder.
LARGE FIRE: Use water spray,
fog or foam. Do not use water jet.
Special Remarks on Fire Hazards : Not available.
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Special Remarks on Explosion Hazards : Not available.
Section 6:
Accidental Release Measures
Small Spill:
Use appropriate tools to put the spilled solid in a convenient waste disposal container.
Finish cleaning by spreading water on the contaminated surface and dispose of according
to local and regional authority requirements.
Large Spill:
Use a shovel to put the material into a convenient waste disposal container. Finish
cleaning by spreading water on the contaminated surface and allow to evacuate through
the sanitary system.
Section 7:
Handling and Storage
Precautions:
Keep locked up.. Keep away from heat. Keep away from sources of ignition. Empty
containers pose a fire risk, evaporate the residue under a fume hood. Ground all
equipment containing material. Do not ingest. Do not breathe dust. Wear suitable
protective clothing. If ingested, seek medical advice immediately and show the container
or the label.
Storage:
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Keep container tightly closed. Keep container in a cool, well-ventilated area. Do not store
above 25C (77F).
Section 8:
Exposure Controls/Personal Protection
Engineering Controls:
Use process enclosures, local exhaust ventilation, or other engineering controls to keep
airborne levels below recommended exposure limits. If user operations generate dust,
fume or mist, use ventilation to keep exposure to airborne contaminants below the
exposure limit.
Personal Protection:
Safety glasses. Lab coat. Dust respirator. Be sure to use an approved/certified respirator
or equivalent. Gloves.
Personal Protection in Case of a Large Spill:
Splash goggles. Full suit. Dust respirator. Boots. Gloves. A self contained breathing
apparatus should be used to avoid inhalation of the product. Suggested protective
clothing might not be sufficient; consult a specialist BEFORE handling this product.
Exposure Limits:
Not available.
Section 9:
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Stability and Reactivity Data
Stability : The product is stable.
Instability Temperature : Not available.
Conditions of Instability : Excess heat.
Incompatibility with various
Substances : Not available.
Corrosivity : Not available.
Special Remarks on Reactivity : Not available.
Special Remarks on Corrosivity : Not available.
Polymerization : Will not occur.
Section 11:
Toxicological Information
Routes of Entry : Inhalation. Ingestion.
Toxicity to Animals : Acute oral toxicity (LD50): 1271 mg/kg
[Rat].
TERATOGENIC EFFECTS : Classified POSSIBLE for human.
Other Toxic Effects on Humans : Slightly hazardous in case of skin contact
(irritant), of ingestion, of inhalation.
Special Remarks on Toxicity to Animals :
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Not available.
Special Remarks on Chronic Effects on Humans:
May cause birth defects (teratogenic). There are no adequate and well controlled studies
of pregnant women. There have been reports of multiple congenital abnormalities in
infants whose mothers wre being treated for 3 or more months with high doses (400-800
mg/day). Excreted in maternal milk in human.
Special Remarks on other Toxic Effects on Humans:
Acute Potential Health Effects: Skin: Eyes: May cause eye irritation. Inhalation: May
cause respiratory tract irritation. Ingestion: May cause gastrointestinal tract irritation with
nausea, vomiting, abdominal pain, diarrhea, dyspepsia, and tast perversion. May also
affect behavior/central nervous system (headache, dizziness, seizures), metabolism
(Hypercholesterolemia, Hypertriglyceridemia, Hypekalemia), liver, blood (leukopenia,
neutropenia, agranulocytosis, thrombocytopenia), and cardiovascular system. Other
symptoms may include skin rashes, exfoliative skin disorders such as Stevens-Johnson
syndrome and toxic epidermal necrolysis and alopecia. Anaphylaxis in rare cases has
been reported. Clincally or potentially significant drug interactioins between Fluconazole
and the follwoing agents/classes have been observed: Oral hypoglycemics, Coumarin-
type anticoagulants, Phenytoin, Cyclosporine, Rifampin, Teheophylline, Terfenadine,
Cisapride, Astemizole, Rifabutin, Tacrolimus.
Section 12:
Ecological Information
Ecotoxicity : Not available.
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BOD5 and COD : Not available.
Products of Biodegradation : Possibly hazardous short term degradation
products are not likely. However,
long term degradation products may arise.
Toxicity of the Products
of Biodegradation : The products of degradation are as toxic as
the product itself..
Special Remarks on the Products
of Biodegradation : Not available.
Section 13:
Disposal Considerations
Waste Disposal:
Waste must be disposed of in accordance with federal, state and local environmental
control regulations.
Section 14:
Transport Information
DOT Classification : Not a DOT controlled material (United
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States)
Identification : Not applicable.
Special Provisions for Transport : Not applicable
Section 15:
Other Regulatory Information
Federal and State Regulations : TSCA 8(b) inventory:
No products were found.
Other Regulations : Not available.
Other Classifications : WHMIS (Canada): Not controlled under
WHMIS (Canada).
DSCL (EEC) : R22- Harmful if swallowed. R63-Possible
risk of harm to the unborn child.
S2- Keep out of the reach of children. S46-
If swallowed, seek medical advice
immediately and show this container or
label.
HMIS (U.S.A.)
Health Hazard : 1
Fire Hazard : 1
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Reactivity : 0
Personal Protection : E
National Fire Protection Association (U.S.A.)
Health : 1
Flammability : 1
Reactivity : 0
Specific hazard:
Protective Equipment:
Gloves. Lab coat. Dust respirator. Be sure to use an approved/certified respirator or
equivalent. Safety glasses.
Section 16:
Other Information
References : Not available.
Other Special Considerations : Not available.
Created : 10/09/2005 05:33 PM
Last Updated : 06/09/2012 12:00 PM
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Uses
Fluconazole has a variety of applications, especially in severely immunocompromised
patients. This includes:
For treatment of systemic Candida infections.
For Treatment of Oropharangeal and esophageal Candidiasis in patients with advance
HIV infection.
For treatment of Isolated Pulmonary Cryptococcosis.
As a prophylactic drug in patients having undergone bone marrow transplants.
For treatment of Hematogenous Candidiasis in Cancer patients.
As an antifungal remedy formulation for external application.
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