GPAT ONLINE CLASSES

In collaboration with A.P govt.

PHARMACEUTICAL
ENGINEERING

Presented by
DR. T.E.GOPALA KRISHNA MURTHY

Professor & Principal
Bapatla College of Pharmacy

Bapatla, Andhra Pradesh.

Topics going to cover in this session

5. Drying

6. Size reduction and size separation

7. Extraction

8. Mixing

Moisture content

• Bound moisture and free moisture

weight of water in samplex100
• % moisture content=

weight of dry sample

• If exactly 5 g of moist sample is brought to a constant dry weight of

4g, calculate loss on drying and moisture content

• Percent MC is more realistic value in determination of dryer load

capacity

• Equilibrium moisture content depends on

– Temperature and humidity of air

– Properties of the material

Mechanism of drying

• Involves both heat and mass transfer

• Rate of evaporation is related to rate of heat

transfer as

dW/d∅=q/ƛ

• The rate equation for mass transfer

dW/d∅=KA (Hs-H g )

Rate of drying & Time of drying

Classification and types of dryers

Tray dryer & Fluidised bed dryer

Freeze dryer

• Pressure 10- 30 N/M2

• Temperature -10 to -300c

• Composed of

– Vacuum drying chamber

– Vacuum source

– Heat source

– Vapour removal source

Stages involved in freeze drying

• Vacuum

• Primary drying

• Secondary drying

Spray drying

• Feed delivery systems

• Atomizer (pneumatic, pressure nozzle, spinning disc)

• 7000 psi and 3,000 to 50,000 rpm

• Heated air supply

• Drying chamber

• Solid- gas separator

• Product collection system

Contents

• Objectives

• Factors affecting size reduction

• Laws governing size reduction

• Classification of mills

• Hammer mill

• Ball mill

• Fluid energy mill or ultra fine grinder or micronizer

• Quadroco mill

• Multi mill

Objectives

• Dissolution and therapeutic efficacy

• Extraction

• Flow ability

• Mixing

• Formulation

Factors affecting size reduction

• Nature of material

– Hardness, toughness, abrasiveness, stickiness, material

structure, bulk density, physiological effect Particle shape,

Polymorphism

• Moisture content

• Temperature

• Feeding rate

• Purity required

Laws governing size reduction
Y

• Griffith Equation T =


D
• Kicks Law E = CIn 1

D2

• Rittinger’s Law E = k1(S2 − S1)

• Bond’s Law Wt1/ D2

 
• Holme’s Equation  1 1

Wt =10Wi − 
 
 D2 D1 

Classification of mills

Hammer mill

• Impact mill using high speed rotor up to 10000 rpm with a peripheral speed

up to 7600 meter per minute

• Dry materials, wet filter press cake, wet granules, ointments and slurries

• Size reduction up to 20 to 40µ

• Circular hole design for fibers and herringbone design for crystalline

materials and continuous operation jump- gap screen for abrasive and

clogging materials.

• Micro pulverizer for nonabrasive materials

Ball mill

• Both wet and dry grinding, up to 10µ

• Pebble, rod mill, tube mill and Hardinge mill

• Sliding, cascading and centrifuging

• The critical speed is n=76.6/D

• Optimum diameter of the ball= D 2
ball =KD (feed particle)

Fluid energy mill or ultra fine grinder
or micronizer

• Air or steam at pressure of 100- 150 psi

• Particle size to 1-20µ

• Feed should be pre milled to 20 to 100 mesh

• Nozzle design and direction of air jets

• Efficiency of air compressors

• Efficiency of filters and separators

Quadro co mill

• Control feed product into upper conical screen chamber

• A rotating impeller calibrates incoming material

• Calibrated product then passes through to the lower chamber

• A second intensifying impeller accelerates the particles.

• Particles are continuously delivered to “action zone” between

screen and impeller

• Particles are size reduced (as fine as 150 micron) and instantly

discharged through screen openings

Multi mill

• Multi mill machines are widely used for

wet and dry granulation, pulverization etc.

• SS beaters having knife and impact edges

rotate within a selected screen

• The material fed in the hopper enters into

the processing chamber where it moves

to the pentery and passes through screen

• Output & quality of final products depend

on (I) shapes of beaters (Knife/ impact

edge) (ii) speed (iii) size of screen

• Theory of Extraction

• Extraction methods

• Equipment for extraction

• Liquid- liquid extraction

– Podbielniak extractor

• Solid- liquid extraction

– Knowledge on botanical structure

– Differences in active constituents

– Different forms of insoluble matter

– Mixture of components

– Microbial growth

Theory of Extraction

Size reduction

Penetration of the drug by solvent

Solution of the soluble matter within the cells

Escape of removable material through the cell walls

Separation of solution and the exhausted drug

Examples

• Sliced/bruised condition for soft drugs such as gention

• Coarse powder for belladonna

• Moderately fine powder for hard and woody drug ipecacuanha

• The cohesive forces of cellulose form micellae

• Vacuum is used to remove air from the pores of the drug

• The solvent would be cheap, non toxic, stable and selective

Extraction methods

• Maceration

• Percolation

• Reserved percolation

• Cover and run down method

• Conical vs cylindrical percolator

• Significance of imbibition in percolation

• Role of filter paper and sand on the surface of packed drug

Equipment for extraction

• Extraction battery

– Represents drug/ solvent ratio 1:1

– If N vessels are used, the drug receives 2N-1 extraction stages

Soxhelt apparatus

Rotocell extractor

Bonotto extractor

• Theory of mixing
• Solid- solid mixing

• Convective mixing
• Shear mixing
• Diffusive mixing

Convective mixing

Shear mixing

Diffusive mixing

Solid- liquid mixing

• Pellet and powder state
• Pellet state
• Plastic state
• Sticky state
• Liquid state

Liquid- liquid mixing

• Bulk transport
• Turbulent mixing
• Laminar mixing
• Molecular diffusion

Laminar mixing Turbulent mixing

Mixing equipment

Solid mixing equipment

• Tumblers/Blenders

• Agitator mixers

• Continuous mixers

Tumblers/Blenders
• Twin- shell (v shape)

• Double cone

• Drum

• Cube and tetrahedral blenders

• Twin shell blender is commonly employed

• Bulk transport and shear

• May consists of baffles and agitator

• Depends on speed of rotation ( 30-100 rpm)

• Rpm depends on size; shape of the tumbler and on the type

of material

Agitator mixers

• Mixing by means of • Fluidized air mixer

moving screws, paddles • RMG
or blades

• Lodge mixer
• Mixing of wet, sticky or

• Diosna mixer granulator
plastic solids

• Gral mixer granulator
• Ribbon mixer/ blender

• Planetary mixer

• Nauta mixer

Continuous mixers

– Zig- zag continuous blender

– Blendex

– Barrel type continuous mixer

Solid – liquid mixing

• Segregation or demixing

• Particle size, shape, density and charge

– Kneaders (Agitator mixers )

– Mills (shear mixers)

– Ultrasonic mixers

Liquid mixing

• Impellers

• Jet mixers

Impellers

• Propellers • Turbines

– Three blade designs is – Radial flow

common – Diffuser ring may be fitted

– Primary effect is axial flow – Deal up to 100 N/m2

– Up to 8000 rpm
• Paddles

– Propeller to container ratio is
• Large surface are with 50

1:20
rpm

– High speed with low viscous

fluids (<5N/m2) • Primarily tangential

Jet mixers

• Air jets

• Liquid jets

– Vortex formation and prevention

• Offset

• Angled

• Side- entering

• Push- pull

• Baffled

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