Unit 4: Filtration & Centrifugation

February 27, 2026

Semester 3
BP304T

Introduction to Filtration & Centrifugation

Filtration and centrifugation are separation operations essential in pharmaceutical manufacturing. Filtration clarifies solutions, sterilizes heat-labile products, and separates crystalline drugs. Centrifugation harvests cells, separates immiscible liquids, and isolates drug crystals.

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Syllabus & Topics

  • 1Filtration: Definition – separation of insoluble solid particles from a liquid or gas using a filter medium. Objectives: clarification, sterile filtration, crystal harvesting, solvent recovery.
  • 2Theories of Filtration: Surface/cake filtration (particles build up on filter medium surface), Depth filtration (particles trapped within filter medium), Cross-flow filtration (feed flows parallel to membrane – prevents cake build-up).
  • 3Darcy’s Law: V/A = k(ΔP/µL). Rate of filtration ∝ pressure × area / viscosity × cake resistance. Factors: Applied pressure, filter area, viscosity of filtrate, cake thickness, filter medium resistance.
  • 4Factors Influencing Filtration: Particle size (finer = slower), viscosity of liquid (higher = slower), applied pressure (higher = faster), filter medium (pore size, porosity), temperature (higher = lower viscosity = faster).
  • 5Filter Aids: Inert materials added to improve filtration rate. Types: Diatomaceous earth (Kieselguhr) – most common; Perlite; Cellulose. Added as pre-coat (on filter medium) or body feed (into liquid). Prevent filter medium blinding.
  • 6Filter Media: Woven (cotton, nylon, glass fiber), Non-woven (paper, fibers), Membranes (PVDF, nylon, cellulose acetate).
  • 7Filtration Equipment:
  • 8Plate and Frame Filter Press: Alternating plates and frames; filter medium between; batch; for pharmaceutical syrups, juice; high capacity; labor-intensive to clean.
  • 9Filter Leaf: Single frame with filter cloth; used in pilot scale, simple.
  • 10Rotary Drum Filter: Continuous; drum rotates with vacuum inside; pre-coat with filter aid; suitable for large volumes. Automatic cake discharge. Used for bulk API filtration.
  • 11Meta Filter (Meta-sintered candle filter): Corrugated stainless steel discs (Meta discs); robust; suitable for hot/corrosive liquids; easy to clean by backwashing.
  • 12Cartridge Filter: Disposable (polypropylene, PVDF); easy to install and replace; used at various pore sizes (10 µm pre-filter, 0.22 µm sterilizing). Widely used in pharmaceutical plants.
  • 13Membrane Filters: 0.22 µm (sterilizing grade); 0.45 µm (bioburden monitoring); complete size exclusion; used for sterile filtration of heat-labile solutions.
  • 14Seidtz/Seitz Filter (Depth filter sheets): Compressed asbestos-free filter sheet; for clarification and prefiltration.
  • 15Centrifugation: Definition – use of centrifugal force to separate particles/phases based on density differences.
  • 16Principle: In a rotating system, centrifugal force Fc = mω²r. Relative Centrifugal Force (RCF in g) = 1.12 × r × (N/1000)². Higher density particles sediment further from center at lower RPM.
  • 17Applications: Clarification of liquids, harvesting of cell cultures, separation of cream from milk, isolation of crystalline APIs.
  • 18Centrifugation Equipment:
  • 19Perforated Basket Centrifuge: Cylindrical basket with perforations and filter cloth; liquid passes through; wet cake retained; for separation of crystalline solids (harvesting sugar crystals, salt crystals). High speed batch.
  • 20Non-perforated Basket Centrifuge (Clarifying Centrifuge): Solid basket; solids collect on basket wall; liquid overflows; for cream separation, clarification of juices. Batch, manual cleaning.
  • 21Semi-continuous Centrifuge: Discharge of wet solid while machine is running (intermittent); higher throughput.
  • 22Super Centrifuge (Tubular Bowl Centrifuge): Very high speed (15,000-50,000 rpm); narrow tubular bowl; used for clarification of vaccines, blood fractionation, clarification of very fine particles/cell debris. Also called Cream-separator type.

Learning Objectives

Darcy’s Law: Write Darcy’s law for filtration and state two ways to increase filtration rate.
Filter Aids: Explain the purpose of filter aids and give two examples.
When to use Membrane Filter: State when a 0.22 µm membrane filter is used vs a rotary drum filter.
RCF vs RPM: Explain the difference between RPM and RCF in centrifugation.
Select Centrifuge: Which centrifuge would you use to harvest crystalline drug from a slurry?

Frequently Asked Questions (FAQs)

Q1. What is Darcy’s Law for Filtration?

Rate of filtration: dV/dt = A × ΔP / (µ × (Rm + α×c×V/A)), where V = volume of filtrate, A = area, ΔP = pressure, µ = viscosity, Rm = filter medium resistance, α = specific cake resistance, and c = mass of solids per unit volume. Simplified: Filtration rate increases when pressure and area increase, and when viscosity or cake resistance decreases.

Q2. What are Filter Aids and Why are They Used?

Filter aids are inert, incompressible materials added to prevent blinding of the filter medium and to reduce compressible cake resistance by forming an open, porous cake structure. They can be added by (1) Pre-coat method, where a layer is applied to the filter medium before filtration, or (2) Body feed method, where the aid is added directly to the liquid during filtration. Examples include Diatomaceous earth (Celite), Perlite, and asbestos-free cellulose.

Q3. What is Relative Centrifugal Force (RCF) and How is it Calculated?

RCF (g-force) = 1.12 × r × (N/1000)², where r is the radius in mm and N is the speed in RPM. RCF indicates how many times greater the centrifugal force is compared to gravity. Typical values: ~300 g for cell pellets (5 min), ~10,000 g for mitochondria, and 100,000–300,000 g for viruses and ribosomes (ultracentrifuge). RCF should always be specified instead of RPM because it accounts for rotor radius.

Q4. What is the Difference Between Perforated and Non-Perforated Basket Centrifuge?

Perforated basket centrifuge has holes lined with filter cloth; liquid passes through the basket while solids are retained on the cloth. It is used for crystalline solids such as sugar and API crystals and allows continuous separation. Non-perforated basket centrifuge (clarifier) has a solid wall without holes; solids settle against the basket wall by sedimentation, and clarified liquid exits from the top. It is used for cream or fat separation and biological liquid clarification, and requires manual solids removal (boring or ploughing).

Q5. Why are Cartridge Filters Preferred in Modern Pharmaceutical Plants?

Cartridge filters are preferred because they are disposable (no cleaning validation required), provide consistent and validated pore sizes (e.g., 0.22 µm), allow easy installation and replacement, are available in compatible materials such as PVDF, nylon, and PES, can be gamma sterilized, and reduce cross-contamination risk due to single-use design. They are widely used for pre-filtration (10 µm) and sterilizing filtration (0.22 µm) of parenteral products.