Final Project Black Book

7/30/2019 Final Project Black Book

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SSJCOE Manufacture of Fluconazole

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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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Molecular Formula : C13H12F2N6O



Fluconazole Property

mp : 138-140C

storage temp. : 20C

solubility : DMSO: 5 mg/mL

form : solid


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



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


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


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


Molecular Formula : INa



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


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



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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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Documents

Final Project Black Book