Clarification

│
├── Definition
│ - Removal or separation of solid from liquid or fluid from another fluid
│ - Fluid includes both liquids and gases
│
├── Techniques
│ ├── Filtration
│ │ - Process of separating particles from liquid using permeable material
│ │ - Porous medium known as filter traps particles, allowing liquid to pass
│ │ - Mixture forced through filter, solids retained as residue, liquid as filtrate
│ │ - Recovery of solids called cake filtration
││
│ └── Centrifugation
│ - Separates fluid from fluid or collects solid as product
│
└── Output
- Residue: Solids retained on filter
- Effluent/Filtrate: Clarified liquid discharged from filter

Filtration Applications
├── Clarification
│ - Improve product appearance
│ - Provide "sparkle" or "brightness"
│
├── Irritant Removal
│ - Eliminate potential irritants from formulations
│ - Ensure safety for mucous membrane applications
│
├── Solid Material Recovery
│ - Obtain desired solid material from suspension or slurry
│ - Recover drug or excipient after crystallization
│
├── Water Production
│ - Produce pharmaceutical-grade water
│ - Ensure water quality meets standards
│
├── Sterility Specification
│ - Achieve sterility by removing microorganisms
│ - Utilize sterile or aseptic filtration
│
├── Sterilization
│ - Sterilize solutions and suspension vehicles
│ - Preserve chemically or physically unstable products
│
├── Microorganism Detection
│ - Analyze filters to detect microorganisms
│ - Assess efficacy of preservatives
│
└── Advanced Techniques
- Nanofiltration
- Ultrafiltration
- Microfiltration
- Recover colloidal delivery systems
- From mother liquor
Mechanisms
│
├── Surface Straining
│ - Larger particles deposit on surface
│ - Pass quickly through medium if smaller than pores
│
├── Depth Straining
│ - Particles travel along pore until reaching narrowing point
│ - Trapped due to size or shape
│
├── Depth Filtration
│ - Particles entrapped in depth of medium
│ - Attached to pore wall or another particle via surface forces
│
└── Cake Filtration
- Begins with layer of particles on filter surface
- Larger pores bridged by smaller particles
- Accumulation of particle cake acts as filter medium
- Important for solid recovery in pharmaceutical processes

Factors
│
├── Pressure Increase
│ - Proportionate flow increase unless cake is highly compressible
│ - Highly compressible cake may decrease or terminate flow
│
├── Area Increase
│ - Increases flow and life proportionally to square of area
│ - Reduces cake thickness and resistance
│
├── Cake Thickness
│ - Cake resistance inversely proportional to thickness
│ - Average flow rate inversely proportional to cake deposited
│
├── Viscosity
│ - Filtrate flow rate inversely proportional to viscosity
│ - Filtration efficiency affected by temperature changes
│
└── Permeability Coefficient
- Examined in terms of porosity and surface area
- Porosity influenced by deposition rate
- Surface area inversely proportional to particle diameter
- Coarse precipitate easier to filter than fine precipitate
- Most clarification problems resolved empirically by varying factors
FILTER MEDIA Characteristics
│
├── Retention Capability
│ - Retains solids without plugging
│ - Removes particles above desired size in clarification
│
├── Resistance
│ - Offers minimum resistance
│ - Resistance remains stable during filtration
│
├── Cake Discharge
│ - Allows easy discharge of cake
│
├── Chemical and Physical Inertness
│ - Chemically and physically inert
│ - Does not swell when in contact with filtrate or washing liquid
│
└── Mechanical Strength
- Sufficient mechanical strength to withstand pressure drop and stress

Types
│
├── Depth Filters
│ - Mainly polymeric fibrous materials
│
├── Filter Fabrics
│ - Woven from natural fibers (cotton) and synthetic fibers (nylon, glass)
│ - Includes stainless steel wire cloth for durability and resistance to plugging
│ - Used with filter aids for cake filtration
│ - Suitable for support elements and rapid cleaning
│
├── Non-Woven Filter Media
│ - Includes felts, bonded fabrics, and kraft papers
│ - Felts offer controlled particle retention with high flow rates and low pressure drop
│ - Recommended for gelatinous solutions or fine particulate matter
│
└── Membrane Filters
- Basic tools for microfiltration, ultrafiltration, nanofiltration, and reverse osmosis
- Made of various materials like cellulose esters, nylon, Teflon, polyvinyl chloride, etc.
- Surface or screen filters, often requiring prefiltration to avoid clogging
- Selection based on particle size for effective removal

│
├── Porous Stainless Steel Filters
│ - Used for clarification of liquids like milk, syrup, sulfuric acid, and caustic soda
│ - Easily cleaned and sterilized for reuse
│
├── Ceramic Cartridges
│ - Cleanable for reuse by back-flushing
│
└── Asbestos and Porcelain Filter Candles
- Acceptable for some sterile filtrations along with membrane filters
Filter Aids
│
├── Description
│ - Resistance to flow increases as layer of solids builds up
│ - Poorly flocculated solids offer higher resistance
│ - Rate of cake filtration varies with volume of liquid
│ - Filter medium becomes plugged with accumulation of solids
│
├── Function
│ - Reduce resistance to flow
│ - Form fine surface deposit to screen out solids
│ - Form highly porous and non-compressible cake
│
├── Influence of Quantity
│ - Quantity greatly influences filtration rate
│ - Too little aid increases resistance
│ - Too much aid adds thickness without increasing porosity
│
└── Typical Plot
- Flow rate and permeability are directly proportional
- Flow rate peaks as aid concentration increases, then decreases
- Ideal aid functions physically or mechanically without absorption or chemical action

Characteristics:
│
├── Structure
│ - Permits formation of pervious cake
│
├── Particle Size Distribution
│ - Suitable for retention of solids
│
├── Suspension
│ - Able to remain suspended in liquid
│
├── Purity
│ - Free of impurities
│ - Inert to the liquid being filtered
│ - Free from moisture (in certain cases)
│
├── Performance Comparison
│ - Equivalence determined by flow rate and clarity of filtered solution
│ Types of Filter Aids
│
├── Types ├── Diatomite (Diatomaceous Earth)
│ - Processed from fossilized diatoms
│ - Diatomite (Diatomaceous Earth) │ - Irregularly shaped porous particles
│ - Forms a rigid, incompressible cake
│ - Cellulose │ - Primarily silica, relatively inert and insoluble
│
│ - Asbestos ├── Cellulose
│ - Highly compressible
│ │ - Costs two to four times more than diatomite or perlite
│ - Reserved for applications incompatible with silica compounds
├── Application Techniques │ - Used as a coarse pre-coat
│
│ - Precoating └── Asbestos
- Good retention on coarse screens

│ - Body-mix - Limited application due to high cost and toxic leaching of fibers into filtrate
- May be used in pharmaceutical industry followed by membrane filtration

│
├── Selection Process
│ - Trial and error in laboratory or plant
│ - Quality vs. flow rate consideration
│
└── Pharmaceutical Considerations
- Inertness is crucial
- Absorption properties may affect product quality

- Filter aids are primarily used to reduce resistance in filtration by forming a porous cake.
- Diatomite (diatomaceous earth) is the most common filter aid, processed from fossilized diatoms.
- Cellulose is another filter aid option, albeit more compressible and expensive than diatomite.
- Asbestos is also used but has limited application due to cost and potential toxicity concerns.
- Filter aids can be applied using either pre-coating or body-mix techniques.
- Selection of filter aids involves a balance between flow rate and quality, with inertness being crucial.
- Pharmaceutical applications prioritize fine grades of filter aids to ensure product quality.
Filtration Equipment
│
├── Classification
│ ├── By End Product Desired
│ │ - Filtrate
│ │ - Cake Solids
││
│ ├── By Method of Operation
│ │ - Batch
│ │ - Continuous
││
│ ├── By Type of Operation
│ │ - Non-Sterile Filtration
│ │ - Sterile Filtration
│ │ - Centrifugation Filtration
│ │ - Centrifugation Sedimentation
││
│ └── By Type of Driving Force
│ - Gravity
│ - Vacuum
│ - Pressure
│ - Centrifugation
│
└── Various Equipment Types
├── Gravity Filtration
│ - Uses gravity as driving force
│
├── Vacuum Filtration
│ - Uses vacuum pressure to draw liquid through filter
│
├── Pressure Filtration
│ - Applies pressure to force liquid through filter medium
│
└── Centrifugation Filtration
- Uses centrifugal force to separate solids from liquid
Gravity Filters
│
├── Operating Principle
│ - Relies on gravity-generated low operating pressure
│ - Typically < 1.03 × 104 N/m^2
│ - Low filtration rates unless large surface areas are used
│
├── Applications
│ - Common in laboratory filtration for small volumes
│ - Used in water treatment for clarification prior to deionization or distillation
│ - Porous ceramics used for small-scale water purification
│
└── Types of Gravity Filters
├── Thick Granular Bed Filters
│ - Common in water treatment
│
├── Hollow "Candle" Filters
│ - Porous ceramics allow fluid to pass through
│
└── New Gravity Filter Systems
- Cylindrical, rectangular, hydro-clear gravity filters
- Utilize granular particles in a basin
- Fluid streams pass through basin, capturing particles physically and/or chemically

Vacuum Filters
│
├── Scale of Usage
│ - Employed on a large scale
│ - Rarely used for crystalline precipitates or sterile filtration
│
├── Characteristics
│ - Simple and reliable machines
│ - Widely accepted in chemical, food, and pharmaceutical industries
│
└── Types
├── Continuous Vacuum Filters
│ - Most widely used for large-scale operations
│
└── Other Types (not specified)
Rotary Drum Filter
│
├── Structure
│ - Divided into sections
│ - Each section connected to a discharge head
│ - Rectangular shape with a curved profile
│ - Perforated metal surface covered with filter cloth
│
├── Operation
│ - Slurry fed to a tank with an agitator
│ - Drum rotates, passing through slurry
│ - Vacuum draws filtrate through filter medium (pick-up zone)
│ - Suspended solids deposit on drum surface as cake
│ - Cake held at drum surface by vacuum
│ - Washing and drainage in drying zone
│ - Cake removal zone: scraped or supported until breaking free
│
├── Cake Discharge
│ - Scraper, belt, roll, or string mechanisms
│ - Scraper for readily scraped cakes, roller for thixotropic cakes
│
└── Precoat Filters
- Precoat of filter aids (diatomaceous earth, perlite, cellulose) deposited on drum
- Used for high clarity and low solids content or sticky solids prone to clogging

Rotary Disc Filter

│
├── Structure
│ - Consists of several discs (up to 15 in larger machines)
│ - Each disc made up of sectors clamped together
│ - Sectors connected to vacuum system, compressed air, and receivers
│ - Special rotating valve for sequence control
│
├── Operation
│ - Similar to drum filter in operation sequence
│ - Vacuum, compressed air, and receivers used in correct sequence
│
└── Features
- Requires less floor space
- Lowest cost of filtration compared to other vacuum filters
Pressure Filters
│
├── Operation
│ - Mostly batch operated
│ - Continuous filters also available
│ - Mechanically complex and expensive
│ - Mainly used where added value to the product is high
│
├── Factors Influencing Filtration Rate
│ - Increased pressure
│ - Coarser particles
│ - Particle distribution with high uniformity
│ - Non-slimy or non-gelatinous solids
│ - Non-compressible cakes
│ - Lower liquid viscosity
│ - Higher temperatures

Plate and Frame Filter Press

│
├── Description
│ - Simplest of all pressure filters
│ - Most widely used
│
├── Function
│ - High degree of fluid clarification
│ - Harvesting of cake
│ - Used in batch mode for clarity
│
├── Structure
│ - Assembly of hollow frames and solid plates
│ - Frames and plates support filter media
│ - Feed flows through one side of the plate
│ - Filtrate collected on the other side
│ - Solids collect in frames
│
├── Versatility
│ - Number and type of filter sheets can be varied
│ - Suitable for coarse to fine filtrations
│ - Can be used for multistage filtration with special conduit arrangements
│
├── Economical
│ - Most economical filter per unit of filtering surface
│ - Material of construction can be chosen to suit process conditions

Disc Filters
│
├── Description
│ - Assemblies of felt or paper discs sealed into a pressure case
│
├── Assembly
│ - Discs may be preassembled into a self-supporting unit
│ - Each disc may rest on an individual screen or plate
│ - Single plate or multiples of single plates may be applied
│
├── Flow Direction
│ - Flow may be from inside outwards or outside inwards
│
├── Advantages
│ - Compactness
│ - Portability
│ - Cleanliness
│ - Overcomes deficiencies of filter press
│ - Suitable for pharmaceutical batch operations
Centrifugation Filtration
│
├── Description
│ - Centrifugal force used for liquid passage through filter medium
│ - Advantages for filtering very fine particles
│ - Effective alternative for solids recovery
│
├── Advantages
│ - Effective washing and drying
│ - Residual moisture much less than in pressure or vacuum filtration cakes
│ - Moisture content reduced to as low as 3% for coarse crystals
│
└── Applications
- Widely used for separating granular products from liquors
- Less effective for concentrated slurries with smaller particles

Perforated Basket
│
├── Description
│ - Perforated metal basket mounted on a vertical axis
│ - Rotated at a speed of 20 to 25 revolutions per second
│
├── Components
│ - Perforated metal basket
│ - Metal screen supporting cloth for solids retention
│ - Outer casing to collect liquid thrown out by centrifugal force
│
└── Operation
- Cake emptied by shoveling if no top suspension
- Top suspension allows cake withdrawal through traps in basket base

Laboratory Filtration Equipment

│
├── Gravity Filtration
│ - Conventional glass percolators
│ - Filtering funnel with filter paper or fibrous material
│
├── Suction Filtration
│ - Conical funnel and Buchner funnel
│ - Immersion and suction-leaf filters
│ - Immersion filter tubes (filter sticks)
│
└── Filter Paper Types
- Circular form for most common use
- Available in various textures, purities, and sizes
- Special types: activated carbon impregnated, diatomaceous earth impregnated

├── Filter Bags

│ - Made of fabric for gravity filtration
│ - Mounted for easy use
│
├── Glass Beads and Sand
│ - Limited use due to uncertainty of clarification
│
├── Minimum Laboratory Equipment
│ - Plate and frame press
│ - Membrane filter holder
│ - Single-element housing for disposable cartridges
│
└── Additional Equipment
- Various funnels and flasks for pharmaceutical filtration studies
- Filter papers impregnated with activated carbon or diatomaceous earth
Specialized Filtration: Sterile/Aseptic Operations
│
├── Purpose
│ - Clarify and sterilize heat-labile pharmaceutical solutions
│
├── Membrane Filters
│ - Basic tool for preparation of sterile solutions
│ - Porosity ratings: 0.2 μm or 0.45 μm
│ - Clogging issue addressed with prefiltration
│
├── FDA Guidelines
│ - 0.45 μm filters allowed for colloidal solutions
│ - 0.2 μm filters preferred where rapid clogging occurs
│
├── Applications
│ - Intravenous solutions, ophthalmics, and aqueous products
│ - Heat-labile oils and liquids with proteins require pretreatment
│
└── Gas Filtration
- Common applications: vent filtration, compressed air in sterilizers air/nitrogen in transfers and filling lines, fermentation
- Final filtration should be pressure-based to prevent contamination

Membrane Ultrafiltration
│
├── Definition
│ - Selective molecular separation process
│ - Removes dissolved molecules based on membrane size and configuration
│ - Solution passed under pressure through a very fine filter
│
├── Mechanism
│ - Retains most macromolecules while allowing smaller molecules and solvent to pass
│
├── Difference from Microfiltration
│ - Microfiltration: Removes particulates and bacteria
│ - Ultrafiltration: Separates molecules based on size
│
├── Applications
│ - Concentration of heat-labile products: vaccines, virus preparations, immunoglobulins
│ - Recovery of antibiotics, hormones, vitamins from fermentation broths
│ - Separation of cells from fermentation broth
│ - Clarification of solutions
│ - Removal of low-molecular-weight contaminants before conventional recovery
│ - Important for removing pyrogens
│
└── Molecular Weight Cut Off (MWCO)
- Characterizes selectivity and retentivity of membrane
Integrity Testing
│
├── Importance
│ - Essential for filtration systems, especially in sterilization filtration
│ - Predicts functional performance of a filter
│
├── Types of Tests
│ 1. Bubble Point Test
│ - Direct measure of largest pore in filter
│ - Failure to hold rated pressure indicates inefficient membrane or improper assembly
│
│ 2. Diffusion Test
│ - Recommended for high volume systems (e.g., multi-cartridge)
│ - Measures volume of air flowing through wet filter membrane from pressurized to atmospheric site
│
├── Purpose
│ - Detects damaged membrane
│ - Identifies system leaks
│ - Verifies sealing effectiveness
│
└── Characteristics
- Each filter has characteristic bubble point and diffusion rate of air through water
- Integrity test is nondestructive

Filter Selection
├── Purpose Determination
│ - Purpose dictates filter medium selection
│ - Example: 0.2 μm pore size for sterilizing filtration
│ - Plate and frame filter or woven-fiber filter for clarification
│
├── Pore Size Selection
│ - Typically smaller than smallest particle to be removed
│
├── Compatibility
│ - Filter medium must be compatible with liquid or gas to be filtered
│ - Consult chemical compatibility charts provided by vendors
│
├── Surface Area Calculation
│ - Based on filter media, pore size, required flow rate, and pressure differentials
│ - Adjust for liquid viscosity using clean water flow rate divided by liquid viscosity (centipoises)
│
├── Balancing Requirements
│ - Achieve balance between:
│ - Filter media and equipment capabilities
│ - Slurry characteristics
│ - Quality specifications for final product
│
└── Common Choice
- Batch pressure filter preferred
- Utilizes surface or depth filtration principles