Pharmaceutical Processing

(Acetaminophen)
Group Members :

Syahirah Bt. Harun 2010141155
Siti Zakiah Bt. Razali 2010189203
Norsolehah Bt. Hanafiah 2010305937
Mohd Ridzuan B. Mohatar 2010167473
Siti Norfasha Bt. Abu Bakar 2010564757
Nurrul Shafiqah Bt. Mahamad Taib 2010122259
Hopper Design
Temporary storage
Weigh hopper
Measure weight of Paracetamol to be mixed in
the tumble blender

Details of Paracetamol
Parameter Value
Particle size (m) 78.52
Bulk density, b (kg/m) 768.3
Particle density, p (kg/m) 1290
Angle of repose, ( ) 35.6
Effective angle of internal friction, ( ) 39.2
Unconfined Yield Stress, y (Pa) 1720
Compacting Stress, c (Pa) 18100
Flow Factor, ff 7
Shape factor, m 1
Material Stainless steel 304
= 0.001

2
0.005

+ 1.6251
= 10.6
10.6 = 0.001

2
0.005

+ 1.6251

= 25
Thus,
Angle of wall friction , w = 25
Thus,
Semi included angle, = 17.63
= 0.0122

2
0.9024

+ 47.814
= 17.63
Determining the crit

(Pa)

(Pa)
4383 688
6243 889
8065 969
10383 1240

=
1

= 0.1429

crit = 873.7113 Pa
0
500
1000
1500
2000
2500
0 2000 4000 6000 8000 10000 12000 14000
Powder Flow Function
= 2 +

60

= 2 +
17.63
60

= 2.758
=
()

=
(2.2938)(873.7113)
(768.3)(9.81)

= 0.1981
0.2
Mass we want to store in the hopper;
m = 30 kg
bulk density of the hopper;

B
= 768.3 kg/m
3

The minimum volume of the hopper is;
=

=
30
768.3 /
3


V = 0.039 m
3


V = 0.262 H (D
1
2
+ D
2
2
+ D
1
D
2
)
0.039 = 0.262 H (D
1
2
+ D
2
2
+ D
1
D
2
)
For a silo ;
H > 1.5 D
Thus;
0.039= 0.393D
1
(D
1
2
+ D
2
2
+ D
1
D
2
)
D
2
= 0.2 m
0.039 = 0.393D
1
(D
1
2
+ 0.2
2
+ 0.2D
1
)
0.039= 0.393 D
1
3
+ 0.01572D
1
2
+ 0.0786D
1
)
D
1
= 0.32 m
H = 1.5(0.32)
= 0.48 m






Note that, the relation of H is from volume of
particle occupied. Thus, H is the height of
particle bed.
To ensure mass flow,
Height of particle must at least 0.75 of hoppers
height. Thus, HH
H = 0.75HH
HH = 0.64 m

Mixing
Characteristics of particles to be mixed
Paracetamol
Particle size = 78.52 m
Density, p = 1290 kg/m3

Starch1500
Particle size = 70.10 m
Density, p = 1005 kg/m3
With a ratio of:
Paracetamol : starch 1500
5.67 : 1
Why starch1500 is chosen?
Multifunctional excipient
Yield excellent content uniformity

Mixer
Tumbler mixer
Most commonly used in pharmaceutical industry
Allows for close quality control
Gentle mixing
Easy to clean

In-bin blending
Elimination of a transfer step from blender to
container
Elimination of cleaning step between different batches
Segregation
The main factor;
Size difference


Even a small size difference significant rise
to segregation

Paracetamol Starch1500
78.52 m 70.10 m
Standard Deviation
For paracetamol;
SD = 1.0 (taken from journal)

The lower the SD value, the better the quality of
the mixture


Fluid bed spray granulator
High shear granulator
Single-pot granulator
Precision-granulator
Melt granulator

Video

The purpose of granulation process

To improve powder flow.
To improve compressibility.
To reduce fines.
To control the tendency of powders to
segregate.
To control density.
To capture and fuse small quantities of active
material.
Precision-granulator
Liquid
addition
Inlet temperature 60
o
C
Air pressure 0.3 bar
Air flow volume rate 111/143m
3
/h
Drying
Inlet temperature 80
o
C
Air flow volume rate 80m
3
/h
Dried to LOD(loss of drying)<2% and bed temperature >50
o
C
Size analysis
By sieving
Process name : Sonic sifter, ATM
Result after granulation.

Response Variable Low High

Mean
Maximum granule moisture (% L.O.D.) 4.1 27.6

15.85
Granule flowability (g/sec.) 2.68 9.44

6.06
Mean granule size (microns) 136.7 922.1

529.4
Bulk density (g/cm3) 0.340 0.569

0.4545
Tablet hardness at 15KN force (kp) 8.2 20.0

14.1
Product Bed Temperature C 19 32

25.5
*The result above is taken from the experiment of granulation of the paracetamol in range of experimental
conditions (binder solid, atomizing air pressure, inlet air temperature, and fluid delivery) and for the next
process, which is the design of the fluid-bed dryer, the mean value will be used.
PNEUMATIC TRANSPORT
GAS (NITROGEN)
PARTICLE
(PARACETAMOL)
PIPE
Viscosity, = 1.6629 x 10
-5
Pa.s
Density,
f
= 1.153 kg/m
3

Vol. flowrate = 5.98 x 10
-3
m
3
/s
Particle size, X
p
= 529.4 m
Mass flowrate,M
p
= 0.1kg/sec
Density ,
p
= 1236.5 kg/m
3

Diameter pipe, D = 0.05 m
Length, Lv = 1.5m
Length, L
H
= 1m
Pneumatic
transport here!
PNEUMATIC TRANSPORT
1.5m
1m
PNEUMATIC TRANSPORT
Gas velocity horizontal ( Usalt )

= 10.96 m/s


Superficial velocity, U =Usalt x 1.5
= 10.96 x 1.5
= 16.44 m/s

Total Pressure drop, = + +

Horizontal pressure drop = term 1 + term 2 + term 3 + term 4

=


= 156.39 + 323.91 + 77.74 + 285.45

= 843.49 Pa
PNEUMATIC TRANSPORT
Vertical pressure drop = term 3 + term 4 + term 5 + term 6



= 428.17 + 60.99 + 47.27 + 14.65

= 551.084 Pa

Pressure drop for bend (1 bend)

Pressure loss across each 120 bend equivalent to 7.5 m of vertical pipe.

= 367.39 Pa/m


Pressure drop across 1 bend of 120 = 1 x 367.39 x 7.5

= 2755.43 Pa

Total pressure drop, = 843.49 + 551.08 + 2755.43 = 4150 Pa
PNEUMATIC TRANSPORT
The power required for the pump is:

Power = Q x
= (0.0323) x 4150
= 134.05 watt


FLUIDIZATION
Properties known:
Granule Air Tower dimension
(Vanguard Pharmaceutical
Machinery, Inc USA)
p = 1236.54 kg/m f = 1.2 d = 0.86 m
b = 454.5 kg/m f = 18.4x10Pa.s H = 2.52 m
dp = 529.4 m
m = 30kg
Power consumption for the air supply;
Power = QP

When, U = 0.1331 m/s

Q = Velocity x area
= 0.1331 x 0.5809
= 0.0773 m
3
/s

Power = 0.0773 x 506.14
= 39.13 W