Acetaminophen Production

Particle Technology Pharmaceutical Processing

(Acetaminophen)

Group Members :

Syahirah Bt. Harun 2010141155

Siti Zakiah Bt. Razali 2010189203Norsolehah Bt. Hanafiah 2010305937Mohd Ridzuan B. Mohatar 2010167473Siti Norfasha Bt. Abu Bakar 2010564757Nurrul Shafiqah Bt. Mahamad Taib 2010122259

Hopper Design

Temporary storage Weigh hopper Measure weight of Paracetamol to be mixed in

the tumble blender

Details of ParacetamolParameter Value

Particle size (μm) 78.52

Bulk density, ρb (kg/m³) 768.3

Particle density, ρp (kg/m³) 1290

Angle of repose, ϴ ( ˚) 35.6

Effective angle of internal friction, δ ( ˚) 39.2

Unconfined Yield Stress, σy (Pa) 1720

Compacting Stress, σc (Pa) 18100

Flow Factor, ff 7

Shape factor, m 1

Material Stainless steel 304

− 𝑓𝑓 =−0 .001𝛿𝑤2 −0 .005𝛿𝑤+1 .6251

Thus, Angle of wall friction , Φw = 25˚

Thus, Semi included angle, ϴ = 17.63

−𝜃=−0.0122 𝛿𝑤2 −0.9024 𝛿𝑤+47.814

𝜃=17.63 ˚

Determining the σcrit

(Pa) (Pa) 4383 6886243 8898065 969

10383 1240

σcrit = 873.7113 Pa0 2000 4000 6000 8000 10000 12000 14000

0

500

1000

1500

2000

2500

Powder Flow Function

Mass we want to store in the hopper;m = 30 kg

bulk density of the hopper;ρB = 768.3 kg/m3

The minimum volume of the hopper is;

V = 0.039 m3

V = 0.262 H (D12 + D22 + D1D2)0.039 = 0.262 H (D12 + D22 + D1D2)For a silo ; H > 1.5 DThus;0.039= 0.393D1 (D12 + D22 + D1D2)D2 = 0.2 m0.039 = 0.393D1 (D12 + 0.22 + 0.2D1)0.039= 0.393 D13+ 0.01572D12 + 0.0786D1)D1 = 0.32 mH = 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 hopper’s height. Thus, HH

H = 0.75HH HH = 0.64 m

Mixing

Characteristics of particles to be mixed

• ParacetamolParticle size = 78.52 mDensity, p = 1290 kg/m3

• Starch1500 Particle size = 70.10 mDensity, p = 1005 kg/m3

With a ratio of:Paracetamol : starch 1500

5.67 : 1

Why starch1500 is chosen?

Multifunctional excipientYield excellent content uniformity

Mixer

• Tumbler mixerMost commonly used in pharmaceutical industry

Allows for close quality controlGentle mixingEasy to clean

• In-bin blendingElimination of a transfer step from blender to

containerElimination 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

Granulation process

Fluid bed spray granulatorHigh shear granulatorSingle-pot granulatorPrecision-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 oC• Air pressure 0.3 bar• Air flow volume rate 111/143m3/h

Drying

• Inlet temperature 80 oC• Air flow volume rate 80m3/h• Dried to LOD(loss of drying)<2% and bed temperature >50oC

Size analy

sis

• 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, µ = 1.6629 x 10-5 Pa.s

• Density, ρf = 1.153 kg/m3

• Vol. flowrate = 5.98 x 10-3 m3/s

• Particle size, Xp = 529.4 µm

• Mass flowrate,Mp = 0.1kg/sec

• Density , ρp = 1236.5 kg/m3

• Diameter pipe, D = 0.05 m• Length, Lv = 1.5m

• Length, LH = 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/m³ f = 1.2 d = 0.86 m

b = 454.5 kg/m³ f = 18.4x10⁻⁶Pa.s H = 2.52 m

dp = 529.4 m

m = 30kg

Power consumption for the air supply;Power = QΔP

When, U = 0.1331 m/s

Q = Velocity x area = 0.1331 x 0.5809 = 0.0773 m3/s

Power = 0.0773 x 506.14= 39.13 W

Q & A Session