Unit Processes : Drying

What is drying?

Process of removing a liquid, usually water, from a wet material by transferring it into a gas phase, usually air

What is drying used for in pharmaceutical manufacturing?

• Remove residual moisture

• Improve powder stability

• Produce dry granules

• Prevent microbial growth

• Improve handling and storage

What is moisture content?

Moisture content describes the amount of moisture present in a material

It can be expressed as the amount of water relative to either:

• The wet mass of the material

• The dry mass of the material

Why is moisture content important?

The amount and state of moisture within a material can significantly affect its:

• Stability

• Flow properties

• Compressibility

• Drying behaviour

• Chemical properties

• Physical properties

• Microbial stability

Total moisture content = bound + unbound moisture content

Drying considerations

• Types of drying processes

• Heat-induced evaporation of the solvent - temperature, time

Which drying method is the best?

• Heat sensitivity

• Physical characteristics

• Nature of moisture content

• Scale of drying process

• Necessity for sterility

• Heat sources

What does an efficient drying process involve?

• Sufficient surface area

• Adequate eat transfer

• Efficient mass transfer

• Effective vapour removal

What are the different drying methods?

1. Convection

2. Conduction

3. Radiation

4. Spray drying

5. Freeze-drying

What is convection drying?

Convection involves a moving gas, usually heated air, passing over or through the material

Heat is transferred:

Hot air → material

At the same time, the moving air carries away evaporated moisture

Convection drying - fluididsed-bed dryer

• Fluidisation produces conditions of great turbulence

• If hot air is used, the turbulent conditions lead to high heat and mass transfer rates

• Fluidisation increases the efficiency of heat transfer and vapour removal

• Rapid drying process: economic advantage, minimum risk to thermolabile materials

• Drying at constant rate

• Temperature can be controlled precisely

• Attrition caused by the turbulence create spherical free-flowing products

• Reduced risk of soluble material migration

• Useful in granulation

• Fluidisation can produce dust

• Segregation can occur due to dust formation, and poor flow properties as a result of static charges

• Suspended organic materials can explode if ignited by sparking caused by static charges

What is conduction drying?

Conduction transfers heat through direct contact between the material and a heated surface

Heat moves:

Heated surface → material → moisture

Conduction drying - tray drying oven/vacuum oven

• A jacketed vessel with shelves provide a large area for heat transfer by conduction

• The oven is connected to a vacuum pump through a condenser and liquid receiver

• Drying at lower temperatures, water can be removed at 25-35 °C

• Reduction in pressure reduces temperature required

• Suitable for oxygen-sensitive materials

• Not used as extensively as it was formerly

• Low efficiency & expensive

• Risk of solute migration

What are advantages of conduction drying?

• Efficient heat transfer through direct contact

• Can be useful for materials that cannot tolerate large amounts of hot air

• Vacuum conditions can be combined with conduction to lower the boiling point of water

What is radiation drying?

Radiation drying transfers energy to the material using electromagnetic radiation

The material absorbs the radiation and converts it into thermal energy e.g. infrared drying

Radiation drying - microwave oven

• No transfer medium required

• Heat energy in the form of radiation appears as heat in the absorbed (drying) material

• Rapid drying at low temperatures

• High thermal efficiency

• The bed is stationary, no issues with dust and attrition

• Reduced solute migration

• Equipment is highly efficient and refined

• Suitable for small batches

• Can cause serious health issues

What is spray drying?

• Useful for drying solutions and suspensions

• Converts a liquid into a dry powder

• Provides a large surface area for heat and mass transfer

Follows fundamental steps:

1. Atomisation: converts fluid into a fine spray using pressure, centrifugal, electrostatic and ultrasound techniques

2. Droplet drying and particle formation: droplets are sprayed into a stream of circulating hot air

3. Particle collection

Importance of spray drying

• Ensures high surface area for heat and mass transfer

• Rapid evaporation & quick process (a droplet takes a fraction of second)

• Useful for thermolabile compounds

• Used for dry powder inhalers

• Control particles properties: improved flow

• Labour costs are low however, the equipment is very expensive

• Low thermal efficiency

What is freeze-drying?

• Freeze-drying stabilizes and extends the shelf life of molecules

• Freeze-drying is suitable for drying heat-sensitive materials such as proteins, vaccines, etc

• Freeze-drying involves freezing samples & removing water by sublimation at low pressure

Sublimation means the iced-water will turn into vapour directly, without an intermediary liquid phase

• Sublimation occurs at the Triple Point whare a material exist in 3 phases (solid, liquid & gas)

• Freeze-drying is used to prepare powders for injection

Importance of freeze-drying

• Suitable for heat sensitive materials

• Suitable for oxidation sensitive materials

• Produces dry, light and porous solids

• The products have rapid dissolution rate

• Products are hygroscopic

• Slow and expensive process

Drying issues

• Solute migration during drying

• Solute will be placed at the surface of the dried material

• Common issue when drying wet granules, binders and adhesives can be dissolved in granulation fluid

• Very common issue with Convection and Conduction drying

• Solute migration during drying leads to un-even distribution of the solute

• Solute migration include: intergranular migration (between granules) and intragranular migration (within individual granules)

• Intergranular migration i.e. when using tray drying (vacuum oven)

• Intragranular migration: happens when migration occurs within individual drying materials

• Solute migration during drying affects uniformity of content

Drying issues - intergranular migration

• The solute moves from granule to granule

• Result in maldistribution of the active drug

• Occurs with static bed of granules (tray drying)

• Solvent move from granule to granule towards the top surface of the bed

• Affect the uniformity of content of the produced tablets

Drying issues - intragranular migration

• The solute moves within an individual granule

• The solute moves towards the surface of the granule

• Fluidisation drying avoids intergranular migration as granules are separated however, solvent can still move to the periphery of each granule

Solute migrating consequences - loss of API

• Dissolved drug moves to the surface of granules

• Techniques such as fluidised bed dryer can cause abrasion

• Loss of drug/uniformity of content

Solute migrating consequences - mottling in coloured tablets

• Soluble colouring agent used in wet granulation

• Intragranular migration: coloured surface of granules with colourless interior

• Ball growth mechanisms i.e. breakage, abrasion make granules look different in terms of colours

• Mottled tablets

Solute migrating consequences - migration of soluble binder (can be beneficial)

• Soluble adhesives

• Intragranular migration: soluble adhesives at the surface of granules

• Hard granules, resistant to abrasion

• It can aid the compaction step in tabletting as result of binder–binder contact (rather than drug–drug or drug–excipient)

Preventing soluble migration

• Reduce the amount of granulation fluid

• Avoid tray drying

• Use a mix of “not uniform” granules in tableting

• Careful choose of granulation fluid (solubility and viscosity)

• Avoid excessive drying

• Use smaller granules to avoid intragranular migration