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BP304T - Pharmaceutical Engineering: Unit I

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PART 1: FLOW OF FLUIDS

What is a Fluid?

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Types of Manometers

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Reynolds Number (Re)

Re = (ρ × v × D) / μ

• ρ = density of fluid (kg/m³)
• v = velocity of fluid (m/s)
• D = diameter of pipe (m)
• μ = dynamic viscosity (Pa·s)

• Re < 2100 → Laminar (streamline) flow - fluid moves in parallel layers, no mixing between layers
• Re = 2100-4000 → Transitional flow
• Re > 4000 → Turbulent flow - fluid moves in an irregular, chaotic pattern with eddies

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Bernoulli's Theorem

1. Pressure energy = P/ρ
2. Kinetic energy = v²/2
3. Potential energy = gh

P/ρ + v²/2 + gh = constant

Pressure head + Velocity head + Datum head = Constant

• Design of fluid transport systems (pipes, pumps)
• Basis for flow measurement devices (orifice meter, venturi meter, pitot tube)
• Explaining flow through constrictions in pipelines

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Energy Losses in Fluid Flow

1. Friction losses (major losses) - due to viscosity of fluid against pipe walls (Darcy-Weisbach equation)
2. Minor losses - due to:
   • Sudden enlargement or contraction of pipe
   • Bends, elbows, valves, fittings
   • Entrance and exit losses

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Flow Measurement Devices

1. Orifice Meter

• Principle: A circular plate with a central hole (orifice) is placed in the pipe. Flow creates a pressure drop across it. By measuring this pressure drop, flow rate is calculated (Bernoulli's theorem).
• Construction: Flat plate with beveled-edge circular hole, fitted between flanges.
• Merits: Simple, cheap, no moving parts.
• Demerits: High permanent pressure loss, susceptible to wear, not suitable for slurries.

2. Venturi Meter

• Principle: Based on Bernoulli's theorem. The pipe converges to a throat (narrower section), then diverges. The pressure difference between inlet and throat gives the flow rate.
• Construction: Converging section + cylindrical throat + diverging section (recovery cone).
• Merits: Low pressure loss (about 10-20% of differential), accurate, suitable for large flows.
• Demerits: Expensive, requires long installation space.

3. Pitot Tube

• Principle: Measures the velocity of fluid at a point. One tube faces the flow (stagnation pressure) and one is perpendicular (static pressure). The difference = velocity head.
• Construction: Two concentric tubes - inner tube faces upstream, outer tube has side holes.
• Merits: No pressure loss, simple, can measure velocity profile across the pipe.
• Demerits: Measures only point velocity (not average), not suitable for dirty/corrosive fluids.

4. Rotameter (Variable Area Meter)

• Principle: A float rises inside a tapered (wider at top) vertical tube. The float rises until the upward drag force equals its weight. The position of float indicates the flow rate.
• Construction: Vertical tapered glass tube, float (plummet) inside.
• Merits: Direct reading, constant and small head loss, wide range of flow rates, suitable for corrosive liquids (glass/PTFE).
• Demerits: Must be vertically mounted, not suitable for opaque fluids (unless special design), fragile (glass).

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PART 2: SIZE REDUCTION

Definition

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Objectives of Size Reduction

1. Increases surface area - faster dissolution rate (e.g., micronized griseofulvin shows ~5x better absorption)
2. Produces narrow particle size range - improves mixing uniformity
3. Required for pharmaceutical suspensions - reduces sedimentation rate
4. Required for capsules, suppositories, ointments, insufflations - particles must be below 60 µm
5. Improves extractability of plant drugs

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Mechanisms of Size Reduction

1. Impact - particle is hit by a fast-moving object (e.g., hammer mill)
2. Attrition - particle is rubbed between surfaces (e.g., fluid energy mill)
3. Compression (crushing) - particles are compressed between two surfaces
4. Cutting - particles are sheared by a sharp blade

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Laws Governing Size Reduction

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Factors Affecting Size Reduction

1. Hardness of the material
2. Toughness - resistant to fracture
3. Stickiness - sticky materials clog mills
4. Softening/melting temperature - heat generated during milling can melt low-melting materials
5. Moisture content - wet materials are tough and sticky
6. Particle size required - finer the product, more energy needed
7. Fibrous nature - difficult to reduce by impact

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Size Reduction Equipment

1. Hammer Mill

• Principle: Impact
• Construction: Rotor with swinging hammers attached, surrounded by a metal casing; screen at bottom controls particle size.
• Working: Material is fed in, hammers impact particles at high speed, broken particles exit through the screen.
• Uses: Dry granulation, milling of crude drugs, starch, sugar.
• Merits: Versatile, high capacity, easy to clean.
• Demerits: Not suitable for hard abrasive materials; generates heat; not for sticky materials.

2. Ball Mill

• Principle: Impact + attrition
• Construction: Horizontal rotating cylinder filled with balls (steel or porcelain), 30-50% of cylinder volume.
• Working: As the cylinder rotates, balls cascade and grind the material between them. Critical speed = speed above which balls stick to wall without grinding.
• Uses: Very fine grinding of hard materials; pharmaceutical suspensions; pigments.
• Merits: Can operate in closed circuit; suitable for hard materials; can work in sterile conditions (sealed).
• Demerits: Slow, noisy, generates heat, not for sticky or heat-sensitive materials.

3. Fluid Energy Mill (Jet Mill)

• Principle: Attrition + impact between particles
• Construction: Loop-shaped chamber; high-pressure jets of air/gas at points around the loop.
• Working: Compressed gas at high velocity (300-500 m/s) carries particles around the loop, particles collide with each other and with the walls, achieving ultra-fine grinding. Classifier built in - only fine particles exit.
• Uses: Micronization of steroids, antibiotics, cytotoxics; heat-sensitive materials.
• Merits: Produces ultra-fine particles (1-10 µm); no heat generation (gas expands and cools); sterile milling possible.
• Demerits: High energy consumption; not for hard abrasive materials; expensive.

4. Edge Runner Mill (Roller Mill)

• Principle: Compression + attrition
• Construction: Heavy cylindrical runners (rollers) rotating on a flat circular bed (pan).
• Working: Material placed on the pan is ground by the weight and rotation of the rollers.
• Uses: Wet grinding; ointments; pigments; soft materials.
• Merits: Suitable for wet or dry grinding; good for pastes.
• Demerits: Slow; limited to moderate fineness; not for hard materials.

5. End Runner Mill

• Principle: Compression + attrition
• Construction: Vertical pestle rotating in a mortar-shaped bowl.
• Working: Rotating pestle grinds material against the mortar bowl.
• Uses: Small-scale grinding of hard brittle materials; similar to edge runner but vertical orientation.
• Merits: Suitable for small batches.
• Demerits: Slow; limited capacity.

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PART 3: SIZE SEPARATION

Definition

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Objectives of Size Separation

1. After size reduction, particles vary widely in size - separation produces uniform fractions
2. Tablet granulation requires granules within a narrow size range
3. Quality control tool for raw material analysis
4. Determines particle size distribution for capsule and tablet production
5. Optimizes process conditions (method of agitation, milling time)

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Official Standards for Powders

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Size Separation Equipment

1. Sieve Shaker

• Principle: Mechanical agitation to separate particles through sieves of different mesh sizes.
• Construction: Set of sieves (coarsest at top, finest at bottom) mounted on a mechanical shaker.
• Working: Sample placed on the top sieve; machine vibrates for set time; particles pass through progressively finer meshes; each fraction is collected and weighed.
• Uses: Particle size analysis; quality control; production of uniform powder fractions.
• Merits: Simple, cheap, can analyze multiple size fractions simultaneously.
• Demerits: Slow; not suitable for moist or sticky materials; limited for very fine powders.

2. Cyclone Separator

• Principle: Centrifugal force
• Construction: Cone-shaped chamber with tangential inlet at top; central outlet tube at top for fine particles; coarse particle exit at bottom.
• Working: Air-particle mixture enters tangentially at high velocity, creating a spinning vortex. Coarse particles move to the wall and fall to the bottom (outer vortex); fine particles remain in inner vortex and exit from the top.
• Uses: Separates fine particles from air streams; used with fluid energy mills.
• Merits: No moving parts; continuous operation; handles large volumes.
• Demerits: Not effective for very fine particles (<5 µm); efficiency decreases with smaller particle size.

3. Air Separator

• Principle: Combination of centrifugal force + air current
• Construction: Rotating impeller inside a casing; adjustable air flow.
• Working: Ground material enters; rotating air current separates fine particles (carried by air upward) from coarse particles (fall down for regrinding). The cut size is controlled by changing the air speed and rotor speed.
• Uses: Closed-circuit operation with mills; classification of fine powders.
• Merits: Continuous; adjustable cut size.
• Demerits: Requires air handling equipment; not for very cohesive materials.

4. Bag Filter

• Principle: Filtration of fine particles from air using fabric bags.
• Construction: Collection of fabric bags inside a casing; cleaned by shaking or reverse air pulse.
• Working: Air containing fine particles passes through the bags; particles are trapped on the fabric surface; cleaned bags release particles into a collection hopper.
• Uses: Collecting fine dust from milling and drying operations; pollution control.
• Merits: Very efficient for fine particles; can recover valuable material.
• Demerits: Requires regular cleaning/replacement of bags; high pressure drop.

5. Elutriation Tank

• Principle: Separation by upward moving air/water current (counter-current)
• Construction: Vertical cylindrical tank; inlet at bottom for fluid (air or water); overflow at top.
• Working: Fluid rises upward; fine particles (terminal velocity < fluid velocity) are carried upward and overflow; coarse particles (terminal velocity > fluid velocity) settle at the bottom. By adjusting fluid velocity, particles of different sizes can be separated.
• Uses: Separation of light fine particles from heavy coarse ones; wet classification.
• Merits: Gentle on fragile particles; no moving parts.
• Demerits: Requires large volumes of fluid; slow process.

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Quick Revision Summary

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• Pharmaceutical Engineering by C.V.S. Subrahmanyam et al. (Vallabh Prakashan)
• Unit Operations of Chemical Engineering by McCabe & Smith
• Lachman/Lieberman's Theory and Practice of Industrial Pharmacy
• Introduction to Chemical Engineering by Badger & Banchero

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Flow Measurement Devices — Comparison Table

Table 1: Basic Specifications

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Table 2: Technical Performance

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Table 3: Physical Characteristics

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Table 4: Cost Parameters

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Table 5: Pharmaceutical Industry Suitability

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Table 6: Merits vs. Demerits at a Glance

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Selection Guide for Pharmaceutical Engineering

Need high accuracy in large pipeline?          → Venturi Meter
Budget constrained, moderate accuracy?         → Orifice Meter
Measuring air/gas velocity in ductwork?        → Pitot Tube
Small flow, sterile or corrosive fluid?        → Rotameter
Need widest measurable range (turndown)?       → Rotameter
Permanent pressure loss is a concern?         → Venturi or Pitot Tube