ERYTHROMYCIN PRODUCTION

Contents
ERYTHROMYCIN PRODUCTION................................................................................................................................1
1.1. Sterilization ..............................................................................................................................................3
1.1.1. Introduction .....................................................................................................................................3
1.1.2. Design conditions ............................................................................................................................3
1.1.3. Energy balance ................................................................................................................................4
1.2. Cooling .....................................................................................................................................................4
1.2.1. Introduction .....................................................................................................................................4
1.2.2. Design conditions ............................................................................................................................5
1.2.3. Energy balance ................................................................................................................................5
1.3. Fermentation ...........................................................................................................................................6
1.3.1. Introduction .....................................................................................................................................6
1.3.2. Design conditions ............................................................................................................................6
1.3.3. Calculation of stoichiometric coefficients .......................................................................................7
.........................................................................................................................................................................7
1.3.4. Mass Balance ...................................................................................................................................8
1.3.5. Energy Balance ................................................................................................................................9
1.3.6. Introduction ...................................................................................................................................11
1.3.7. Design conditions ..........................................................................................................................11
1.3.8. Mass Balance .................................................................................................................................11
1.4. Cooling Unit ...........................................................................................................................................13
1.4.1. Introduction ...................................................................................................................................13
1.4.2. Design conditions ..........................................................................................................................13
1.4.3. Mass Balance .................................................................................................................................14
1.5. Centrifugal Extractor .............................................................................................................................15
1.5.1. Introduction ...................................................................................................................................15
1.5.2. Design conditions ..........................................................................................................................15
1.5.3. Mass balance .................................................................................................................................16
1.6. Re Extraction .........................................................................................................................................17
1.6.1. Introduction ...................................................................................................................................17
1.6.2. Design conditions ..........................................................................................................................18
1.6.3. Mass Balance .................................................................................................................................18
1.7. Crystallization ........................................................................................................................................20
1.7.1. Introduction ...................................................................................................................................20
1.7.2. Design conditions ..........................................................................................................................20
1.7.3. Mass Balance .................................................................................................................................21
8.6.4 Energy Balance .....................................................................................................................................22
...........................................................................................................................................................................25
8.7 Basket centrifugation ............................................................................................................................26
8.7.2 Introduction ...................................................................................................................................26
8.7.2 Design conditions ..........................................................................................................................26
8.7.3 Mass balance .......................................................................................................................................27
a. Fluid Bed Dryer ..........................................................................................................................................28
8.8.1 Introduction ...................................................................................................................................28
 1. Sterilization
1.1.1. Introduction
Sterilization is a heat transfer operation from superheated steam to fermentation media prior to send to the
fermenter. Even though sterilization can be done by filtration, irradiation, sonic vibration or chemical cleansing,
heating is the most widely used sterilization method (Gopalakrishnan & Detchanamurthy, 2011). Superheated
steam is used as heating medium and in this study, it is assumed that steam will only dissipates its latent heat.
Superheated steam at 3 bar and 133.50C is employed.

1.1.2. Design conditions

The assumptions made for the calculations were as follows.

• Heat loss through the sterilizer to the environment is negligible.

• Superheated steam will only dissipate latent heat.
• Heat capacity of Phenoxy acetic acid is similar to water.

Table 7.1: Input conditions to the sterilizer

Mass Inlet Temp. Heat capacity

Component Reference
(kg/batch) (°C) (kJ/kg.K)
Sucrose 342 27 211.3 Boerio-Goates 1991
Ammonia 15.30 27 4.52 Haar and Gallagher 1978
Oxygen 23.33 27 0.92 Air Liquide 2014
Water 635.50 27 4.18

Desired output is to sterilize the media up to 1200C by heat sterilization. Outlet mass is same as inlet.

Latent heat of steam at 3 bar and 133.50C = 2164 kJ/kg (Steam tables)
 1.1.3. Energy balance

mG,1 mSA,1
mG,1 mSA,1
mA,1 mPAA,1
UNIT 1 mA,1 mPAA,1
mO,1
Sterilization mO,1

mS,1 Condensed steam

Superheated steam

Figure 7.1: Block diagram of sterilization

Apply energy balance to the sterilizer,

Heat dissipated by super heated

= Heat absorbed by the media
steam
(𝑚𝐺,1 𝐶𝑃,𝐺 + 𝑚𝑆𝐴,1 𝐶𝑃,𝑆𝐴 + 𝑚𝐴,1 𝐶𝑃,𝐴
𝑚𝑆,1 ℎ𝑓𝑔 =
+ 𝑚𝑃𝐴𝐴,1 𝐶𝑃,𝑃𝐴𝐴 + 𝑚𝑂,1 𝐶𝑃,𝑂 )∆𝑇
(342 × 211.3 + 15.30 × 4.52 + 51.40 × 4.18
𝑚𝑆,1 ℎ𝑓𝑔 = + 23.33 × 0.92
+ 635.50 × 4.18)(120 − 27)
𝑚𝑆,1 ℎ𝑓𝑔 = 2.78 × 106 𝑘𝐽/𝑏𝑎𝑡𝑐ℎ
2.78 × 106
𝑚𝑆,1 = 𝑘𝑔/𝑏𝑎𝑡𝑐ℎ
2164
= 1284.66 𝑘𝑔/𝑏𝑎𝑡𝑐ℎ

2. Cooling
1.1.4. Introduction
Similar to sterilization, cooling is also a heat transfer operation from sterilized media to cooled water. Sterilized
media need to be cooled prior send to the fermenter if not Penicillin production will not occur. Cooled water at
40C will be using to cool the media up to 240C.
 1.1.5. Design conditions
The assumptions made were,

• Heat transfer from environment to cooling water is negligible.

• Heat capacity of Phenoxy acetic acid is similar to water.

Table 7.2: Input conditions to the cooler

Mass Inlet Temp. Heat capacity

Component Reference
(kg/batch) (°C) (kJ/kg.K)
Sucrose 342 120 211.3 Boerio-Goates 1991
Ammonia 15.30 120 4.52 Haar and Gallagher 1978
Oxygen 23.33 120 0.92 Air Liquide 2014
Water 635.50 120 4.18

Desired output is to cool the media up to 240C by cooling water. Outlet mass is same as inlet.

1.

1.1.6. Energy balance

mG,2 mSA,2
mG,2 mSA,2
mA,2 mPAA,2
UNIT 2 mA,2 mPAA,2
mO,2
Cooling mO,2

mCW,2
Cooling water
Figure 7.2: Block diagram for cooling

Apply energy balance to the cooler,

Heat absorbed by cooling water = Heat removed from the media

(𝑚𝐺,2 𝐶𝑃,𝐺 + 𝑚𝑆𝐴,2 𝐶𝑃,𝑆𝐴 + 𝑚𝐴,2 𝐶𝑃,𝐴
𝑚𝐶𝑊,2 𝐶𝑃,𝐶𝑊 ∆𝑇𝐶𝑊 =
+ 𝑚𝑃𝐴𝐴,2 𝐶𝑃,𝑃𝐴𝐴 + 𝑚𝑂,2 𝐶𝑃,𝑂 )∆𝑇
 (342 × 211.3 + 28.81 × 1.34 + 15.30 × 4.52
𝑚𝐶𝑊,2 𝐶𝑃,𝐶𝑊 ∆𝑇𝐶𝑊 = + 51.40 × 4.18 + 23.33 × 0.92
+ 635.50 × 4.18)(120 − 24)
𝑚𝐶𝑊,2 𝐶𝑃,𝐶𝑊 ∆𝑇𝐶𝑊 = 2.86 × 106 𝑘𝐽/𝑏𝑎𝑡𝑐ℎ
2.86 × 106
𝑚𝐶𝑊,2 = 𝑘𝑔/𝑏𝑎𝑡𝑐ℎ
4.18 × (20 − 4)
= 4.28 × 104 𝑘𝑔/𝑏𝑎𝑡𝑐ℎ

3. Fermentation
1.1.7. Introduction
Fermentation is the most important part of the biosynthesis of Erythromycin. Fermentation is conducted in a fed
batch reactor process with Erythromycin erythraea strain at pH 5.5 and 24 0C. The pressure is at ambient
conditions.

1.1.8. Design conditions

Biomass yield per oxygen (𝑌𝐵/𝑂 ) 0.098 g/g

Erythromycin yield per sucrose (𝑌𝐸/𝑆 ) 0.071 g/g

Biomass yield per sucrose (𝑌𝐵/𝑆 ) 0.99 g/g

Conversion 15%

Table 7.3: Properties of components as adapted from Najafpour 2007

Component Molar Mass (kg/kmol)

Erythromycin 734
Water 18
Bio mass 26.02
Glucose 342
Ammonia 17
 1.1.9. Calculation of stoichiometric coefficients

ConsideringGlucose + Ammonia + Oxygen → Erythromycin + Carbon dioxide + Water +Biomass

yield factors
𝑌𝐸/𝐺 = 𝑚𝐸
𝑚𝑆
= 𝑛𝐸 × 𝑀𝐸
𝑛𝑆 × 𝑀𝑆
0.071 = 1 × 734
𝑎 × 342
a = 13.99
Similarly
𝑌𝐵/𝑆 = 𝑚𝐵
𝑚𝑆
0.99 = 𝑑 × 26.02
𝑎 × 342
d = 13a

𝑌𝐵/𝑂 = 𝑚𝐵
𝑚𝑂
0.09 = 26.02 ×𝑑
32 ×𝑐

Applying molar balance to nitrogen

3b = 0.04d + e 𝐸𝑞𝑛 1
Applying molar balance to Carbon
12a = d + 37e + f 𝐸𝑞𝑛 2
Applying molar balance to Hydrogen
22a + 3b = 1.62d + 67e +2g 𝐸𝑞𝑛 3
Applying molar balance to Oxygen
11a + 2c = 0.74d + 13e + g + 2f 𝐸𝑞𝑛 4
By solving equations 1, 2, 3, 4
d = 10.85
b = 0.48
f = 120.04
g = 112.33
c = 109.77

Considering 13.9 moles of glucose as basis

Mass of glucose reacted at 100% efficiency = 13.9 × 𝑀𝑆
= 13.9 × 342
 = 4753.8 g
Mass of Erythromycin formed = 1 × 742 × 15%
= 297.5 g
Mass of Sucrose required per a unit mass of = 4753.8
Erythromycin 297.5

= 15.9 g/g
Annual Erythromycin demand = 3500 kg
Erythromycin produced per batch if 40 = 3500/40
batches are operated
= 87.5 kg
Sucrose required per a batch = 15.9 × 87.5
= 1398.2 kg

Similar to the above calculation the masses of the reactants required, products formed and the reactants remaining per
batch can be calculated

1.1.10. Mass Balance

Table 7.4: Masses of reactants required, remaining and products formed per batch

Input Output (kg/batch)

Component
(kg/batch) Remaining Reactants Products
Sucrose 127.02 19.06 -
Ammonia 15.30 2.30 -
Erythromycin strain 7.71 7.71 -
Oxygen 23.33 3.50 -
Erythromycin - - 87.50
Carbon Dioxide - - 36.96
Water - - 53.51
Bio mass - - 31.01
Total 245.86 245.86

mO,3,O
mCD,3,O mP,3,o mW,3,o
mW,3i mA,3,o mPAA,3,o
mA,7,i mPAA,7,i mSA,3,o mG,3,o mB,3,o
UNIT 3
 Figure 7.3: Block diagram of the fermentation

Biomass composition of final product = 0.045 kg/l water

31.01 0.045 kg/l water
=
𝑉𝑤
𝑉𝑤 = 689 L
Mass of water produced through reaction = 53.50 kg/ batch
53.50
Volume of water produced through reaction =
𝜌𝑤
53.50
=
1
= 53.50 L
Volume of additional water required = 689 - 53.50
= 635.50 L
Mass of additional water required = 635.50 × 1
= 635.50 kg/batch

1.1.11. Energy Balance

Table 7.5: Heat capacity values of reactants and products of fermentation reaction

Component Specific heat (kJ/kg.K)

Erythromycin 142
Biomass 92.05
Erythromycin Strain 4.18
Carbon dioxide 0.8
Oxygen 0.92
Sucrose 211.30
Ammonia 4.52
Water 4.18

The energy balance is based on 1st law of thermodynamics assuming isothermal operation and no net work done.

Energy out = Energy in + generation-consumption-accumulation

𝛿𝑄 = −∆𝐻𝑟𝑥𝑛
−∆𝐻𝑟𝑥𝑛 = ∑ 𝑚𝑝𝑟𝑜𝑑𝑜𝑢𝑡,𝑗 𝐶𝑝𝑗 ∆𝑇 − ∑ 𝑚𝑟𝑒𝑎𝑐𝑡𝑎𝑛𝑡,𝑖 𝐶𝑝𝑖 ∆𝑇

= {87.50 × 142 + 36.96 × 0.86 + 689.00 × 4.18 + 31.01 × 95.15 + 19.06 × 211.30 + 4.32 ×
1.34 + 2.30 × 4.52 + 7.71 × 4.18 + 3.50 × 0.92} − {127 × 211.3 × (24 − 0) + 28.81 × 1.34 × (24 − 0) +
15.30 × 4.52 × (24 − 0) + 51.40 × 4.18 × (24 − 0) + 23.33 × 0.92 × (24 − 0) + 635.50 × 4.18 × (24 −
0)}

= (536794.08 − 716003.45) kJ

=1.79 × 105 kJ

Taking temperature of cooling water at outlet as 23°C, the requirement would be,

𝑄 = 𝑚𝐶𝑝 ∆𝑇

1.79 × 105
𝑚=
4.18 × (23 − 20)

𝑚 = 1.43 × 104 kg/batch

Component kg/batch Component kg/batch

Cooling water 14300 CO2 36.96
Total 14300 Total 36.96

Component kg/batch
Component kg/batch Penicillin
Erythromycin 87.50
Glucose 127.02
1398.2 Bio mass 31.01
Sulfuric 28.81 Glucose 19.06
Ammonia 15.30 Sulfuric 4.32
PA acid
Strain 51.40
7.71 Ammonia 2.30
Oxygen 23.33 PA acid
Strain 7.71
Water 635.50 Oxygen 3.50
Total 881.36 Water 689.00
Total 844.40

Figure 7.4: Summary of mass flow rates of the fermenter

 4. Rotary vacuum filter

1.1.12. Introduction
Rotary vacuum filters use vacuum to drive the liquid (filtrate) through the deposited cake of solids and it is a
continuous process but they have periodically stop to change the filter cloths. Drum filter is made by large hollow
drum around with the filter medium is fitted. This drum is partially submerged in a tank of slurry and filtrate
sucked through the filter cake by inside the drum while wash water is spraying to the drum surface. There are
several methods used for removing deposited cake from drum. They are knives, strings, air jet and wires
(Svarovsky, 1977).

1.1.13. Design conditions

The assumptions made were

• 3% filter aid (Shuler and Kargi, 2001)

• 97% yield can achieved (Heinzle et al., 2007)
• 3% of Filter aid goes with biomass

The input mass flow rates to the continuous section as given in table 6.2.
Table 8.1: Input as flow rates to the rotary vacuum filter

Mass flow
Component Phase
rate (kg/day)

Biomass Solid 4.90

Erythromycin Liquid 13.84

Water Liquid 108.98

Glucose Liquid 3.01

Sulfuric Liquid 0.68

Ammonia Liquid 0.36

Erythromycin Strain Liquid 1.22

Total - 133

1.1.14. Mass Balance

mw,4,i mB,4,o
UNIT 5
mt,4,i Filtration mp,4,o

Figure 8.1: Block diagram for vacuum filter

 𝐹𝑖𝑙𝑡𝑒𝑟 𝑎𝑖𝑑(mw,4,i) = 4.90 × 0.03
= 0.15 𝑘𝑔/𝑑𝑎𝑦
𝐼𝑛𝑝𝑢𝑡(mt,4,i) = 133.00𝑘𝑔/day
𝐵𝑖𝑜 𝑚𝑎𝑠𝑠 𝑜𝑢𝑡𝑝𝑢𝑡(mB,4,o) = 𝑆𝑜𝑙𝑖𝑑 𝑠𝑢𝑚 + 𝑙𝑖𝑞𝑢𝑖𝑑 𝑝𝑎𝑟𝑡𝑠
Bio mass + 3% of liquid constituents
= 4.90 + 0.03 × (13.84 + 108.98 + 3.01 + 0.68
+ 0.36 + 1.22)
= 8.75𝑘𝑔/𝑑𝑎𝑦
𝐼𝑛 + 𝐺𝑒𝑛 = 𝑂𝑢𝑡 + 𝐿𝑜𝑠𝑠 + 𝐴𝑐𝑐
mw,4,+mt,4,i = mB,4,o + mp,4,o

mp,4,o = mw,4,i + mt,4,i − mB,4,o

mp,4,o = 0.15 + 133.00 − 8.75
mp,4,o = 124.40 kg/day
 Component kg/day
Penicillin
Erythromycin 13.84 Component kg/day
Water 108.98 Filter aid 0.15
Bio mass 4.90 Total 0.15
Glucose 3.01
Sulfuric 0.68
Ammonia 0.36
PA acid 1.22 Component kg/day
Total 133.00 Penicillin
Erythromycin 13.42
Water 105.85
Glucose 2.92
Sulfuric 0.66
Component kg/day Ammonia
Strain 0.35
Bio mass
Erythromycin 4.90 PA acid 1.18
Penicillin 0.42 Total 124.40
Water 3.27
Filter aid 0.00
Glucose 0.09
Ammonia
Strain 0.01
PA acid 0.04
Sulfuric 0.02
Total 8.75

Figure 8.2: Summary of mass flow rates of the vacuum filter

5. Cooling Unit

1.1.15. Introduction
Cooling is done to enhance the efficiency of Erythromycin purification in the latter stages of the downstream
extraction processes. The inlet to the cooling unit is liquid phase outlet from the vacuum filter. By applying energy
balance the mass flow rate of ammonia is found.

1.1.16. Design conditions

The assumptions are

• 𝐶𝑝 Value of Erythromycin is equal to 𝐶𝑝 value of water.

• There is no energy loss, accumulation or generating.
• Saturated liquid of ammonia at -300 C used as refrigerant and it converts to saturated vapor at -100 C after
passing heat exchanger.

Table 8.2: Properties of the input components

 Inlet Heat Heat
Outlet Mass flow
Component temp. capacity absorbed
0
temp. (0C) rate (kg/day)
( C) (kJ/kg.K) (kJ)
Sucrose 27 0 211.30 13.42 -76586.70
Sulfuric 27 0 1.34 0.66 -24.00
Ammonia 27 0 4.52 0.35 -42.97
Water+Filter aid 27 0 4.18 105.85 -11946.13
Erythromycin 27 0 4.18 13.42 -1515.06
Erythromycin Strain 27 0 4.18 1.18 -133.53
Total - - - 134.90 -90248.39

Data for liquid ammonium used are,

• Inlet temperature of ammonia : -300C

• Outlet temperature of ammonia : -100C
• Enthalpy at the inlet temperature : 44.7 kJ/kg
• Enthalpy at the outlet temperature : 1433.0 kJ/kg

1.1.17. Mass Balance

mA,6 (TA,6,i , hA,6,i ) UNIT 6 mA,6 (TA,6,o , hA,6,0 )

Cooling unit
mp,6 (Tp,6,i , Cpw) mp,6 (Tp,6,0 , Cpw)

Figure 8.3: Block diagram for cooling

Calculation: Apply energy balance to the above unit,

𝐼𝑛 + 𝐺𝑒𝑛 = 𝑂𝑢𝑡 + 𝐿𝑜𝑠𝑠 + 𝐴𝑐𝑐

𝐼𝑛 = 𝑂𝑢𝑡
𝑚𝐴,6 ℎ𝐴,6,𝑜 − 𝑚𝐴,6 ℎ𝐴,6,𝑖 = 90248.39
= 90248.39
𝑚𝐴,6
(ℎ𝐴,6,𝑜 − ℎ𝐴,6,𝑖 )
= 90248.39
𝑚𝐴,6
(1433.00 − 44.70)
𝑚𝐴,6 = 65.01 kg/day
 Component kg/day
Ammonia 65.01
Total 65.01
Component kg/day Component kg/day
Penicillin
Erythromycin 13.42 Penicillin
Erythromycin 13.42
Water 105.85 Water 105.85
Glucose 2.92 Glucose 2.92
Sulfuric 0.66 Sulfuric 0.66
Ammonia 0.35 Ammonia 0.35
PA acid 1.18 PA acid
Strain 1.18
Total 124.40 Total 124.40

Figure 8.4: Summary of mass flow rates of the cooler

6. Centrifugal Extractor
3.

1.1.18. Introduction
A centrifugal extractor, also known as an Annular Centrifugal Extractor (ACE) is used to mix two
immiscible liquids and extract the solute from one liquid phase to another. The separation of phases occurs under
gravity by rotating the mixture by means of a rotor. Heavier phase will move towards the wall of the rotor while
lighter phase remains close to the axis and thereby the separation be done.

1.1.19. Design conditions

Assumptions are,

• No material generation, loss or accumulation of the system

• Water and butyl acetate are immiscible
• Only Erythromycin is extracted into butyl acetate

Table 8.4: Input mass flow rates to the centrifugal extractor

Component Mass flow rate (kg/day)

Erythromycin 13.42
Water 105.85
Glucose 2.92
Ammonia 0.35
Erythromycin strain 1.18
Sulfuric acid 0.67
Total 124.40
 • Extraction yield = 90% ( Najafpour 2007)
• Equilibrium constant of Erythromycin
in butyl acetate: water
= 25(Chemical Engineering II 2007)

1.1.20. Mass balance

Raffinate
(Aqueous phase) Extract
mWP,8,o (Organic phase)
xP,WP,8,o xW,8,o mOP,8,o
xG,8,o xA,8,o xP,OP,8,o
xPAA,8,o xSA,8,o xBA,8,o
UNIT 8

Feed Centrifugal
(Aqueous phase) Extractor
mWP,8,I xP,WP,8,i Solventm
xW,8,i xG,8,i OP,8,i
xA,8,I xPAA,8,i
xSA,8,i
Figure 8.7: Block diagram for centrifugal extraction

Apply mass balance to Erythromycin,

In + Gen = Out + Loss+ Acc

From above assumptions Gen = Loss = Acc = 0.

Therefore,

𝑚𝑊𝑃,8,𝑖 𝑥𝑃,𝑊𝑃,8,𝑖 = (𝑚𝑊𝑃,8,𝑜 𝑥𝑃,𝑊𝑃,8,𝑜 ) + (𝑚𝑂𝑃,8,𝑜 𝑥𝑃,𝑂𝑃,8,𝑜 )

(𝑚𝑊𝑃,8,𝑜 𝑥𝑃,𝑊𝑃,8,𝑜 ) + (𝑚𝑂𝑃,8,𝑜 𝑥𝑃,𝑂𝑃,8,𝑜 ) = 124.40 × 0.11

(𝑚𝑊𝑃,8,𝑜 𝑥𝑃,𝑊𝑃,8,𝑜 ) + (𝑚𝑂𝑃,8,𝑜 𝑥𝑃,𝑂𝑃,8,𝑜 ) = 13.42 𝑘𝑔/𝑑𝑎𝑦

For 90% yield,

(𝑚𝑂𝑃,8,𝑜 𝑥𝑃,𝑂𝑃,8,𝑜 ) = 0.9 × (𝑚𝑊𝑃,8,𝑖 𝑥𝑃,𝑊𝑃,8,𝑖 )

= 0.9 × 13.42
= 12.08 𝑘𝑔/𝑑𝑎𝑦
Therefore,

𝐴𝑚𝑜𝑢𝑛𝑡 𝑜𝑓 𝐸𝑟𝑦𝑡ℎ𝑟𝑜𝑚𝑦𝑐𝑖𝑛 𝑖𝑛 𝑤𝑎𝑡𝑒𝑟 𝑝ℎ𝑎𝑠𝑒 𝑜𝑢𝑙𝑡𝑒𝑡 = 13.42 − 12.08

= 1.34 𝑘𝑔/𝑑𝑎𝑦
𝑂𝑢𝑡𝑙𝑒𝑡 𝑚𝑎𝑠𝑠 𝑓𝑙𝑜𝑤 𝑟𝑎𝑡𝑒 𝑜𝑓 𝑤𝑎𝑡𝑒𝑟 𝑝ℎ𝑎𝑠𝑒 = 1.34 + 105.85 + 2.92 + 0.35 + 1.18
+ 0.67
𝑚𝑊𝑃,8,𝑜 = 112.32 𝑘𝑔/𝑑𝑎𝑦
1.34
𝑥𝑃,𝑊𝑃,8,𝑜 =
112.32
= 0.01
For the equilibrium of outlet streams,
 𝑀𝑎𝑠𝑠 𝑓𝑟𝑎𝑐𝑡𝑖𝑜𝑛 𝑜𝑓 𝐸𝑟𝑦𝑡ℎ𝑟𝑜𝑚𝑦𝑐𝑖𝑛 𝑖𝑛 𝑜𝑟𝑔𝑎𝑛𝑖𝑐
𝑝ℎ𝑎𝑠𝑒
= 25
𝑀𝑎𝑠𝑠 𝑓𝑟𝑎𝑐𝑡𝑖𝑜𝑛 𝑜𝑓 𝐸𝑟𝑦𝑡ℎ𝑟𝑜𝑚𝑦𝑐𝑖𝑛 𝑖𝑛 𝑤𝑎𝑡𝑒𝑟
𝑝ℎ𝑎𝑠𝑒
(𝑥𝑃,𝑂𝑃 )8,𝑜
= 25
(𝑥𝑃,𝑊𝑃 )8,𝑜

𝑥𝑃,𝑂𝑃,8,0 = 25 × 0.01
= 0.25

𝑀𝑎𝑠𝑠 𝑓𝑟𝑎𝑐𝑡𝑖𝑜𝑛 𝑜𝑓 𝐸𝑟𝑦𝑡ℎ𝑟𝑜𝑚𝑦𝑐𝑖𝑛 𝑖𝑛 𝑜𝑟𝑔𝑎𝑛𝑖𝑐 𝑀𝑎𝑠𝑠 𝑓𝑙𝑜𝑤 𝑟𝑎𝑡𝑒 𝑜𝑓 𝐸𝑟𝑦𝑡ℎ𝑟𝑜𝑚𝑦𝑐𝑖𝑛

= 𝑀𝑎𝑠𝑠 𝑓𝑙𝑜𝑤 𝑟𝑎𝑡𝑒 𝑜𝑓
𝑝ℎ𝑎𝑠𝑒 (𝐸𝑟𝑦𝑡ℎ𝑟𝑜𝑚𝑦𝑐𝑖𝑛 + 𝑠𝑜𝑙𝑣𝑒𝑛𝑡)
12.08
0.25 =
12.08 + (𝑚𝑂𝑃 )8,𝑜
𝑚𝑂𝑃,8,𝑜 = 28.35 𝑘𝑔/𝑑𝑎𝑦

Component kg/day Component kg/day

Butyl acetate 28.35 Penicillin
Erythromycin 13.42
Total 28.35 Water 105.85
Component kg/day Glucose 2.92
Penicillin
Erythromycin 12.08 Ammonia 0.35
Butyl acetate 28.35 PA acid
Strain 1.18
Total 40.44 Sulfuric acid 0.67
Total 124.40

Component kg/day
Penicillin
Erythromycin 1.34
Water 105.85
Glucose 2.92
Ammonia
Strain 0.35
PA acid 1.18
Sulfuric acid 0.67
Total 112.32

Figure 8.8: Summary of mass flow rates of the extractor

7. Re Extraction
1.1.21. Introduction
Erythromycin in the organic phase has to be re extracted into an aqueous phase in order to form the Erythromycin
thiocyanate which can then be precipitated. Re extraction is done at neutral pH where Erythromycin is more
soluble in water than in that of organic fluids (Najafpour 2007). The extraction is single stage where a mixer and
settler mechanism will be employed assuming that butyl acetate and water are immiscible.
 1.1.22. Design conditions
pH of solvent (Distilled water) =7

Temperature of solvent = 5 0C

The percentage Erythromycin recovery from re extraction = 90% ( Najafpour 2007)

Distribution coefficient of Erythromycin in Butyl acetate and

water at pH7 = 0.1 (Chemical Eng. II, 2007)

Table 8.5: Input mass flow rates to the re extractor

Component Mass flow rate (kg/day)

Erythromycin 12.08
Butyl acetate 28.35
Total 40.44

1.1.23. Mass Balance

Raffinate Extract
(Organic Phase)
(Aqueous phase)
mBA,9,o mP,OP,9,o
mW,9,o mP,AP,9,o

UNIT 9
Feed
Re extraction Solvent
(Organic Phase)
mW,9,i
mBA,9,i mP, OP,9,i

Figure 8.9: Block diagram of re extraction

Applying mass balance to Erythromycin

Mass of Erythromycin in feed = Mass of Erythromycin in raffinate
+
 Mass Erythromycin of in extract
𝑚𝐸,𝑂𝑃,9,𝑖 = 𝑚𝐸,𝑂𝑃,9,𝑜 + 𝑚𝐸,𝐴𝑃,9,𝑖
Considering extraction efficiency
𝑚𝐸,𝐴𝑃,9,𝑜 = 𝑚𝐸,𝑂𝑃,9,𝑖 × 90%
= 12.08 × 90%
= 10.87 kg/day
Therefore 𝑚𝐸,𝑂𝑃,9,𝑜 = 12.08 - 10.87
= 1.21 kg/day
Since water and butyl acetate are immiscible
𝑚𝐵𝐴,9,𝑖 = 𝑚𝐵𝐴,9,𝑜
𝑚𝐵𝐴,9,𝑜 = 28.35 kg/day
Since the extract and the raffinate are in equilibrium
(𝑥𝑝 )𝑂𝑃 = Distribution Coefficient
(𝑥𝑝 )𝐴𝑃
𝑚𝐸,𝑂𝑃,9,𝑜 = 0.1
𝑚𝐸,𝑂𝑃,9,𝑜 + 𝑚𝐵𝐴,9,𝑜
⁄ 𝑚𝐸,𝐴𝑃,9,𝑜
𝑚𝐸,𝐴𝑃,9,𝑜 + 𝑚𝑊,9,𝑜
1.21 = 0.1
1.21 + 28.35⁄
10.87
10.87 + 𝑚𝑊,9,𝑜
𝑚𝑊,9,𝑜 = 15.73kg/day
Since water and butyl acetate are immiscible
𝑚𝑊,9,𝑖 = 𝑚𝑊,9,𝑜
𝑚𝑊,9,𝑖 = 15.73kg/day

Component kg/day
Penicillin
Erythromycin 12.08
Butyl acetate 28.35
Total 40.44

Component kg/day
Water 15.73
Total 15.73 Component kg/day
Penicillin
Erythromycin 10.87
Water 15.73
Total 26.61

Component kg/day
Penicillin
Erythromycin 1.21
Butyl acetate 28.35
Total 29.56
 Figure 8.10: Summary of mass flow rates of the re extractor

8. Crystallization

1.1.24. Introduction
In precipitation, the Crystallization is reacted with NaOH in a mixer settler equipment, where the following
reaction takes place.

Erythromycin + Sodium thiocyanate

Erythromycin Thiocyanate + Sodium
Hyrodxide

(Peterfi et al 1999)

Due to the high concentration of Erythromycin formed, it precipitates until the dissolved concentration of
Erythromycin thiocyanate is equal to the critical concentration of precipitation at the relevant temperature.

4.

1.1.25. Design conditions

Table 8.6: Input mass flow rates to the precipitator and densities adapted from

Component Mass flow rate (kg/day) Density /(kg/L)

Erythromycin thiocyanate 10.87 3.42
Water 15.73 1.00
Total 26.61 -

• Operation temperature = 5 0C (Heinzel et al 2006)

• Critical solubility of Erythromycin salt at 50C = 0.0502mol/L (Peterfi et al 1999)

Table 8.7: Molar masses of different components

Component Molar mass/(kg/kmol)

Erythromycin 742
Water 18
Erythromycin thiocyanate 98
Sodium thiocyanate 39
 1.1.26. Mass Balance

nPA,10,i
VPA
nPI,10,o n,W,10,o
nP,10,i
nA,10,o nK,10,o
nW,10,i UNIT 10
nPP,10,o nAA,10,o
Vi Precipitation
Vo
Figure 8.6: Block diagram for precipitation

Volume calculation

𝑉𝑖 = 𝑉𝐸,𝑖 + 𝑉𝑊,𝑖
= 𝑚𝐸,10,𝑖 𝑚𝑊,10,𝑖
+
𝜌𝐸 𝜌𝑊
= 10.87 15.73
+
3.42 1.00
= 18.91 L/ day
= 𝑚𝐸,10,𝑖
𝑛𝐸,10,𝑖
𝐸
= 10.87 × 1000
742
= 31.07 mol/day
From stoichiometry
𝑛𝐸,10,𝑖 ∶ 𝑛𝐸𝑇,10,𝑖 = 1:1
Therefore 𝑛𝐸𝑇,10,𝑖 = 31.07 mol/day
Erythromycin formed 𝑛𝐸 = 31.07 mol/day

The above calculated value exceeds the critical concentration at precipitation. Therefore,
precipitation takes place
Concentration of dissolved =
Erythromycin salt leaving the 0.0502 mol/L (Critical concentration)
precipitator
The above concentration is equal to the concentrations of sodium and Erythromycin ions dissolved
Therefore 𝑛𝐸𝐼,10,0 = 0.0502 × 𝑉𝑊
For the above calculation, the volume of the exit stream is assumed to be equal to the volume of
the water input, since a majority of Erythromycin precipitates reducing the liquid volume in the
precipitator
𝑛𝐸𝐼,10,0 = 0.0502 × 15.73
= 0.79 mol/Day
Applying molar balance to
Erythromycin
 = 𝑀𝑜𝑙𝑒𝑠 𝑜𝑓 𝐸𝑟𝑦𝑡ℎ𝑟𝑜𝑚𝑦𝑐𝑖𝑛
[ ]
𝑀𝑜𝑙𝑒𝑠 𝑜𝑓 𝐸𝑟𝑦𝑡ℎ𝑟𝑜𝑚𝑦𝑐𝑖𝑛 𝑠𝑎𝑙𝑡 𝑝𝑟𝑒𝑐𝑖𝑝𝑖𝑡𝑎𝑡𝑒𝑑
[ ]
𝑖𝑛𝑝𝑢𝑡 𝑀𝑜𝑙𝑒𝑠 𝑜𝑓 𝐸𝑟𝑦𝑡ℎ𝑟𝑜𝑚𝑦𝑐𝑖𝑛
+[ ]
𝑑𝑖𝑠𝑠𝑜𝑙𝑣𝑒𝑑
𝑛𝐸𝑇,10,𝑖 = 𝑛𝐸,10,𝑜 + 𝑛𝐸𝐼,10,0
𝑛𝐸𝑇,10,𝑜 = 𝑛𝐸,10,𝑖 − 𝑛𝐸𝐼,10,0
= 31.07 – 0.79
= 30.28 mol/day

𝑚𝐸,10,𝑜 = 𝑛𝐸,10,𝑜 × 𝑀𝐸
= 30.28 ×742
1000

= 21.75 kg/day

Applying mass balance to water

𝑊𝑎𝑡𝑒𝑟 𝑖𝑛𝑝𝑢𝑡 𝑓𝑟𝑜𝑚 =
[ ]
𝑟𝑒 𝑒𝑥𝑡𝑟𝑎𝑐𝑡𝑜𝑟
𝑊𝑎𝑡𝑒𝑟 𝑐𝑜𝑛𝑡𝑒𝑛𝑡 [𝑊𝑎𝑡𝑒𝑟 𝑜𝑢𝑡𝑝𝑢𝑡]
+[ 𝑖𝑛 ]
𝑁𝑎𝑂𝐻
But
𝑊𝑎𝑡𝑒𝑟 𝑐𝑜𝑛𝑡𝑒𝑛𝑡 =
𝑖𝑛 𝑚𝑁𝑎𝑂𝐻 ,10,𝑖 × (1 − 𝑃𝑢𝑟𝑖𝑡𝑦)
𝑁𝑎𝑂𝐻
= 3.11× (1-0.98)
= 0.06

Therefore 𝑚𝑤,10,0 = 𝑚𝑤,10,𝑖 + 0.06

= 15.73 + 0.06
= 15.79 g/day

5. 8.6.4 Energy Balance

Prediction of Formation Enthalpy

According to Perry RH 1934, the heat of formation at the standard conditions is given by the following equation.

∆Hf298 = 68.29 ∑ni=1 Ni∆Hi Equation 1

Where

∆Hf298 = Enthalpy of formation at 298 K in kJ/mol

n = Number of different atomic groups contained in the molecule
Ni = Number of atomic group i contained in the molecule
∆Hi = Numerical value of atomic group i obtained from the Table 8.8
With reference to Perry RH 1934 and considering the molecular structure of Erythromycin as per Figure 1.1 the
following table gives the data regarding heat of formation.

Table 8.8: ∆Hi of different atomic groups

Type of the group Number of Groups ∆𝐇𝐢

2 -76.45
1 -20.64

2 29.89

2 82.23

1 -426.72
1 41.87
2 123.34
1 -138.16

2 -133.22

From equation 1
∆Hf298 of Erythromycin = 68.29 + (2 × −76.45) + (−20.64) + (2 × 29.89)

+(2 × 82.23) + (−426.72) + (41.87) + (2 × 123.24)

+(138.16) + (2 × −133.22)
= -360.78 kJ/mol
Similarly
∆Hf298 of Erythromycin thiocyanate = -722.6 kJ/mol
∆Hf298 of Sodium thiocynatae = -523.9 kJ/mol
∆Hf298 of NaOH = -483.88 kJ/mol

Prediction of the Specific heat capacity

From Hurst and Harrison Method as per Perry RH 1934, the specific heat of a constituent can be predicted from
the following equation.

Cp = ∑ni Ni∆Ei Equation 2

Where
Cp = Molar heat capacity of the component at 298 K in J/mol.K
N = Number of different atomic groups contained in the molecule
 Ni = Number of atomic group i contained in the molecule
∆Ei = Numerical value of atomic group i obtained from the Table 8.9

Table 8.9: Data of different atomic groups

Atom Number of atoms ∆𝐄𝐢

C 16 10.89
H 18 7.56
O 5 13.42
N 2 18.74
S 1 12.36

From equation 2
Cp of Erythromycin at 298 K = (16 × 10.89) + (187.56) + (5 ×13.42) + (2× 18.74) +
(12.36)
= 427.26 J/mol.K

Similarly
Cp of NaOH at 298 K = 109.38 J/mol. K
Cp Erythromycin thiocyanate at 298 = 448.48 J/mol.K
K
Cp of Sodium thiocyanate at 298 K = 123.1 J/mol.K

Heat of reaction ∆Hr = ∆HfProducts − ∆Hfreactants

(Sinnot RK 2005)

∆Hr of the above reaction at 298 K = [(−523.9 ) + (−483.88)] − [(−360.78 ) + (−722.6 )]

(∆Hf values are predicted above)

= 75.6 kJ/mol

Heat of reaction at 5 0C ∆Hr278K = 278

∆Hr298K + ∫ ∇Cp dt
298
Where
∇Cp = CpProducts − CpReactants
(Perry RH 1934)

Since the solubility of Erythromycin salt produced is very less, it could be assumed that the entire salt is in solid
form. In addition, the specific heat capacities of solids and liquids remain constant near the critical temperature
of 273 K( Sinnot RK 2005). Therefore it could be assumed that the Cp values remain constant.

278
Heat of reaction at 5 0C ∆Hr278K = 75.6 +∫298 [(448.48 + 123.1) − (109.38 + 437.26)] × 10−3 dt

(Cp values are predicted above)

 = 74.9 kJ/mol
Erythromycin thiocyanate formed = 31.07 mol/day
Heat absorbed during precipitation = (74.9 ×31.07)
= 2327 kJ/day

From the above calculation, it could be seen that the precipitation of the Erythromycin salt is an endothermic
reaction which absorbs heat. Since precipitation should be carried out at 50C or below that temperature, cooling
water has to be provided in order to maintain the temperature. The heat absorbed by the reaction will result in
reducing the temperature of cooling water further.

Assuming that

Cp of cooling water = 4.18 kJ/kg.K

Inlet temperature of cooling water = 50C
Outlet temperature of cooling water = 10C
Mass of cooling water required = 2327
4.18 × (5 − 1)
= 139.17 kg/day

Component kg/batch
Cooling water 139.17
Component kg/day Total 139.17
PP
NaOH 3.11
Total 3.11

Component kg/day
Potassium
Sodium ions ions 0.03
Component kg/day
Penicillin
Erythromycinions
ions 0.28
Penicillin
ETC 10.87
Water 15.79
Water 15.73
Acetic
ETC acid 1.86
SubTotal 26.61
Pen-COOK
Erythromycin preci. 11.75
Total 29.71

Figure 8.7: Summary of mass flow rates of the precipitator

 9. Basket centrifugation

8.7.2 Introduction
Basically basket centrifugation is an equipment use centrifugal force to separate solid particles from liquid.
Centrifugation is a process, which solid particles are sediment and separated from a liquid using centrifugal force
as a driving force. Depending on the rotational speed and distance from the axis of rotation, the centrifugal force
can be many times greater than the force of gravity, allowing even very small particles or particles slightly denser
than the fluid to settle. Operations such as cake filtration, centrifugation, and bed drying are commonly employed
for this purpose (Bloch & Soares 1998).

8.7.2 Design conditions

The assumptions made were,

• Assume isothermal operation.

• Assume there are no accumulation, spill and leakage in the system.
• Assume there is no chemical reaction taking place.
• Assume that the final moisture content is 9 % wet basis.
• Assume there is no need a washing stage because required amount of water for washing is less than water
entering at the inlet.

Table 8.10: Inlet conditions to the basket centrifugal seperator

Component Inlet mass flow (kg/day)
Erythromycin salt 11.75
Erythromycin
0.28
thiocyanate
Sodium thiocyanate 1.86
Water 15.79
Total 29.71
6.

• Moisture content of final separated

= 9 – 25 % dry basis (Filorikyan & Vylinkina 1969)
solid

• Yield = 99% (Heinzle.E 2006)

 • Molar mass of Erythromycin = 742 kg/kmol
• Molar mass of Erythromycin
= 793 kg/kmol
thiocyanate
• Molar mass of sodium thiocyanate = 81 kg/kmol

7. 8.7.3 Mass balance

m11,i m11,o
UNIT 11
xP,11,i xP,11,o
Basket Centrifugation
xW,11,i xW,11,o

m11,e

xP,11,e
Figure 8.8: Block diagram for basket centrifugation

Apply mass balance

𝑚𝑖𝑛 + 𝑚𝑔𝑒𝑛 = 𝑚𝑜𝑢𝑡 + 𝑚𝑎𝑐𝑐 + 𝑚𝑙𝑜𝑠𝑠

From above assumptions
m gen= 0 , m acc =0, m loss = 0
Therefore
𝑚𝑖𝑛 = 𝑚𝑜𝑢𝑡

Mass of Erythromycin crystals in outlet = 11.75 x 0.99

= 11.63 kg /day

mass of water in crystals = 11.63 x 0.09

= 1.05 kg/day

Total mass balance

0.03 + 0.28 + 15.79 + 1.89 + 11.75 = 11.63 + 1.05 + 𝑚11,𝑒
𝑚11,𝑒 = 17.04 kg/day

Total water balance

[Mass of inlet water with crystals] = [Mass of outlet water with crystals]+[Mass of
effluent water]

15.79 = 1.05 + 𝑚𝑊,11,𝑒

 𝑚𝑊,11,𝑒
Total Erythromycin balance
[mass of Erythromycin in Erythromycin salts
at inlet] + [mass of Erythromycin thiocyanate
at inlet]
= 14.74 𝑘𝑔/𝑑𝑎𝑦
= [mass of Erythromycin in Erythromycin salts at
outlet] + [mass of Erythromycin thiocynate at outlet]

349 349
11.75 x + 0.28 = 11.63 x + 17.04 x Xp,11e
388 388
Xp,11e = 0.02

10. Fluid Bed Dryer

8. Introduction

Drying of pharmaceutical is one of the most sophisticated and expensive process in drying technology, because
pharmaceuticals are often heat sensitive materials, oxidation of the product can take place in presence of normal
atmosphere, and the contamination of the product must be severely avoid. Fluid bed dryers are more commonly
used for drying of Erythomcyin crystals in pharmaceutical industry.
The Erythromycin crystals are fluidized by using hot air and heat transfer and mass transfer occur simultaneously
inside the fluidized bed column. Dried product is taken out from the bottom of the dryer after it comes to desired
condition.

8.8.1 Design conditions

Wet solid at 5 0𝐶 is fed to the fluid bed dryer which contains 9% moisture on dry basis and it should be reduced
to 0.5% moisture on dry basis. 11.63 kg of Erythromycin crystals is the throughput per batch. It is essentially to
obtain a temperature for dried Erythromycin crystals which is below the denaturation temperature of
Erythromycin (130 0𝐶 ) crystals.

The assumptions are,

• Amount of dust Erythromycin in outlet gas stream is negligible. Therefore, amount of inlet feed Erythromycin
crystals is equal to amount of outlet dried penicillin Erythromycin. There is no water loss.
• It is essentially assumed that the final solid temperature only rises up to dry bulb temperature of outlet gas
stream.
• Heat loss from the wall is taken as 5% of the enthalpy of inlet air (Mujudar, 2004).

The required data are,

• Specific heat capacity of Erythromycin

crystal = 0.85 kJ/kg.K
 • Average Specific heat capacity of water = 4.2 kJ/kg.K

• Specific heat capacity of air = 1 kJ/kg.K

2370 kJ/kg (Mujudar, 2004)
• Latent heat of vaporization of water =

8.8.2 Mass and energy balance calculations

𝐺𝑔 , 𝑌𝑜𝑢𝑡

UNIT 12

𝐹𝑠,𝑜𝑢𝑡 , 𝑋𝑜𝑢𝑡 Fluid Bed 𝐹𝑠,𝑖𝑛 , 𝑋𝑖𝑛

Dryer

𝐺𝑔 , 𝑌𝑖𝑛
Figure 8.10: Mass balance for the fluid bed dryer

Notation:
Gg – Mass of dry air
Fs – Mass of dry Erythromycin

Mass balance for continuous fluid bed dryer –well mixed

Water balance for the dryer

Amount of water removed form the solids = Total additional moisture in outlet gas stream

𝐹𝑠 (𝑋𝑖𝑛 − 𝑋𝑜𝑢𝑡 ) = 𝐺𝑔 (𝑌𝑖𝑛 − 𝑌𝑜𝑢𝑡 )

11.6 (0.09 − 0.005) = 𝐺𝑔 (𝑌𝑜𝑢𝑡 − 0.005)

11.63(0.09 − 0.005)
𝐺𝑔 =
( 𝑌𝑜𝑢𝑡 − 0.005)

(0.9885 + 𝐺𝑔 0.005)
𝑌𝑜𝑢𝑡 =
𝐺𝑔
Heat balance for continuous fluid bed dryer –well mixed

𝐸𝑛𝑒𝑟𝑔𝑦 𝐸𝑛𝑒𝑟𝑔𝑦 𝐸𝑛𝑒𝑟𝑔𝑦 𝐸𝑛𝑒𝑟𝑔𝑦

𝐸𝑛𝑒𝑟𝑔𝑦
𝑖𝑛 𝑡ℎ𝑒 𝑖𝑛 𝑡ℎ𝑒 𝑖𝑛 𝑡ℎ𝑒 𝑖𝑛 𝑡ℎ𝑒
[ ]+ [ ] = [ ]+ [ ] + [ 𝑙𝑜𝑠𝑠 𝑓𝑟𝑜𝑚]
𝑖𝑛𝑝𝑢𝑡 𝑎𝑖𝑟 𝑖𝑛𝑝𝑢𝑡 𝑠𝑜𝑙𝑖𝑑 𝑜𝑢𝑡𝑝𝑢𝑡 𝑎𝑖𝑟 𝑜𝑢𝑡𝑝𝑢𝑡
𝑡ℎ𝑒 𝑤𝑎𝑙𝑙
𝑠𝑡𝑟𝑒𝑎𝑚 𝑠𝑡𝑟𝑒𝑎𝑚 𝑠𝑡𝑟𝑒𝑎𝑚 𝑠𝑜𝑙𝑖𝑑 𝑠𝑡𝑟𝑒𝑎𝑚

𝐹𝑠 𝐻𝑠,𝑖𝑛 + 𝐺𝑔 𝐻𝑔,𝑖𝑛 = 𝐹𝑠 𝐻𝑠,𝑜𝑢𝑡 + 𝐺𝑔 𝐻𝑔,𝑜𝑢𝑡 + 𝑄𝑤

Enthalpy
for solid inlet and outlet can be obtained from following equations respectively

𝐻𝑠,𝑖𝑛 = (𝐶𝑝𝑠 + 𝑋𝑖𝑛 𝐶𝑙 )𝑇𝑠,𝑖𝑛

𝐻𝑠,𝑜𝑢𝑡 = (𝐶𝑝𝑠 + 𝑋𝑜𝑢𝑡 𝐶𝑙 )𝑇𝑠,𝑜𝑢𝑡

Enthalpy for gas inlet and outlet can be obtained from following equations respectively

𝐻𝑔,𝑖𝑛 = (𝐶𝑝𝑔 + 𝑌𝑖𝑛 𝐶𝑙 )𝑇𝑔,𝑖𝑛 + 𝜆𝑌𝑖𝑛

𝐻𝑔,𝑜𝑢𝑡 = (𝐶𝑝𝑔 + 𝑌𝑜𝑢𝑡 𝐶𝑙 )𝑇𝑔,𝑜𝑢𝑡 + 𝜆𝑌𝑜𝑢𝑡

Since 𝑄𝑤 = 0.05𝐺𝑔 𝐻𝑔,𝑖𝑛 above equation can be simplified as follows

𝐹𝑠 𝐻𝑠,𝑖𝑛 + 𝐺𝑔 𝐻𝑔,𝑖𝑛 = 𝐹𝑠 𝐻𝑠,𝑜𝑢𝑡 + 𝐺𝑔 𝐻𝑔,𝑜𝑢𝑡 + 0.05 𝐺𝑔 𝐻𝑔,𝑖𝑛

𝐹𝑠 𝐻𝑠,𝑖𝑛 + 0.95 𝐺𝑔 𝐻𝑔,𝑖𝑛 = 𝐹𝑠 𝐻𝑠,𝑜𝑢𝑡 + 𝐺𝑔 𝐻𝑔,𝑜𝑢𝑡

Finding enthalpy of inlet and outlet for both streams

𝐻𝑠,𝑖𝑛 = (𝐶𝑝𝑠 + 𝑋𝑖𝑛 𝐶𝑙 )𝑇𝑠,𝑖𝑛

𝐻𝑠,𝑖𝑛 = (0.85 + 0.09 × 4.2)5

𝐻𝑠,𝑖𝑛 = 6.14 𝐾𝐽/𝑘𝑔

For outlet solid enthalpy

𝐻𝑠,𝑜𝑢𝑡 = (𝐶𝑝𝑠 + 𝑋𝑜𝑢𝑡 𝐶𝑙 )𝑇𝑠,𝑜𝑢𝑡

𝐻𝑠,𝑜𝑢𝑡 = (0.85 + 0.005 × 4.2)28

𝐻𝑠,𝑜𝑢𝑡 = 24.39 𝑘𝐽/𝑘𝑔

For inlet gas enthalpy

𝐻𝑔,𝑖𝑛 = (𝐶𝑝𝑔 + 𝑌𝑖𝑛 𝐶𝑙 )𝑇𝑔,𝑖𝑛 + 𝜆𝑌𝑖𝑛

 𝐻𝑔,𝑖𝑛 = (1 + 0.005 × 4.2) 67 + 2370 × 0.005

𝐻𝑔,𝑖𝑛 = 80.26 𝑘𝐽/𝑘𝑔

For outlet gas enthalpy

𝐻𝑔,𝑜𝑢𝑡 = (𝐶𝑝𝑔 + 𝑌𝑜𝑢𝑡 𝐶𝑙 )𝑇𝑔,𝑜𝑢𝑡 + 𝜆𝑌𝑜𝑢𝑡

Substitute for 𝑌𝑜𝑢𝑡 in terms of Gg

(0.9885+ 𝐺𝑔 0.005) (0.9885+ 𝐺𝑔 0.005)

𝐻𝑔,𝑜𝑢𝑡 = {1 + 4.2 × } 28 + 2370 ×
𝐺𝑔 𝐺𝑔

116.25 +𝐺𝑔 0.588 2342.86+11.85𝐺𝑔

𝐻𝑔,𝑜𝑢𝑡 = {28 + ( )} + ( )
𝐺𝑔 𝐺𝑔

Substituting all values for following equation

𝐹𝑠 𝐻𝑠,𝑖𝑛 + 0.95 𝐺𝑔 𝐻𝑔,𝑖𝑛 = 𝐹𝑠 𝐻𝑠,𝑜𝑢𝑡 + 𝐺𝑔 𝐻𝑔,𝑜𝑢𝑡

11.63 × 6.14 + 0.95 × 𝐺𝑔 × 80.26 = 11.63 × 24.39 + 40.438 𝐺𝑔 + 2459.1

𝐺𝑔 = 76.01 𝑘𝑔
Absolute humidity at inlet

(0.9885 + 76.01 × 0.005)

𝑌𝑜𝑢𝑡 =
76.01

Enthalpy of outlet gas stream 𝑌𝑜𝑢𝑡 = 0.018 𝑘𝑔/𝑘𝑔

116.25 +76.01×0.588 2342.86+11.85×76.01

𝐻𝑔,𝑜𝑢𝑡 = {28 + ( )} + ( )
76.01 76.01

𝐻𝑔,𝑜𝑢𝑡 = 72.79 𝑘𝐽/𝑘𝑔

Amount of water removed = 𝐹𝑠 (𝑋𝑖𝑛 − 𝑋𝑜𝑢𝑡 )

= 11.63(0.09 − 0.005)

= 0.9885 kg

Amount of inlet water in solid stream = 11.63 × 0.09

= 1.0467 kg

Amount of water in outlet solid stream = (1.0467 -0.9885)

= 0.0582 kg

Total energy in input air stream = 𝐺𝑔 𝐻𝑔,𝑖𝑛

 = 76.01 × 80.26

= 6100.36 kg

Total energy in output air stream = 𝐺𝑔 𝐻𝑔,𝑜𝑢𝑡

= 76.01 × 72.79

= 5532.82 kJ

Total energy in input solid stream = 𝐹𝑠 𝐻𝑠,𝑖𝑛

= 11.63 × 6.14

= 71.40 kJ

Total energy in output solid stream = 𝐹𝑠 𝐻𝑠,𝑜𝑢𝑡

= 11.63 × 24.39

= 283.63 kJ

Total energy loss = 355.31 kJ

This calculation is done as a trial and error method by changing the inlet and out temperature of air stream to
satisfy with required energy to remove water from Erythromycin crystals. Then, finally it is obtained 67 0𝐶 as
inlet temperature and 28 0𝐶 as outlet temperature.

Component kg/day
Hot air 76.01
Total 76.01

Component kg/day Component kg/day

Penicillin crystals 11.63
Erythromycin Penicillin crystals 11.63
Erythromycin

Water 1.05 Water 0.06

Total 12.68 Sub total 11.69

Component kg/day
Hot air 76.01
Water 0.99
Total 77

Figure 8.11: Summary of mass flow rates of the dryer

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