Drying Flashcards
Drying process - main points
It is (generally) the last and more critical operation in manufacturing pharmaceutical ingredients: Drying before packaging ensures quality performances in terms of material processing (intermediate materials, e.g. flowability) and product stability (final product)
During manufacturing drying is essential to guarantee process performances e.g. granulation, compaction
Moisture content in air
Moisture content is defined as the amount of water contained in a material
%Moisture by volume (MV) is defined as the molecules of water per unit volume by the total number of molecules per unit volume
In case of air, it can be defined as kg of contained water per kg of dry air (water free)
Moisture content differs from the relative humidity
Humidity
Humidity is referred as the amount of water vapour present in the air
Relative Humidity (RH), indicates the amount of moisture in the air as a percentage of the maximum amount of moisture that the air can hold (at a specified temperature)
The maximum water content in air depends on temperature, having higher content with increased temperature
Relative Humidity is temperature dependent
relationship between temperature and moisture content in air
What does this mean in practice?
The higher the temperature, the higher is the amount of water vapour that can be hold
In practice
In practice:
water evaporation from a solid to the air (with increase in MV) is promoted by increasing the temperature
BUT if vapour is not removed, the drying efficiency will fall
Dew point
The dew point is:
related to the quantity of moisture in the air
the temperature to which moisture condense and evaporate at the same rate (equivalent to 100%RH or saturated with water vapour)
When the dew point is reached, and the temperature further cooled, the water vapour will condense (RH cannot exceed 100%!)
impact of dew point on manufacture
During the drying process of temperature sensitive material it might be necessary to cool down the supplied air
It is important to avoid to design a drying process with conditions close to the dew point
what 2 things change during drying?
During drying, moisture content AND temperature can change:
Evaporation of water from the material to the drying air
It is possible to saturate the drying air, if air exchange is not applied (or the rate is not properly designed)
Cooling of drying air to reduce heat-exchange with the material
Reduction of water solubility in air and condensation of water should be considered
Moisture content in materials
Moisture content analysis
Quality control
Hygroscopic substances
Moisture content is the quantity of water contained in a material
Moisture content analysis is important in defining the material quality (quality control applied in most production sites and laboratories)
Hygroscopic substances attract and hold water molecules from the surrounding environment (as function of temperature and relative humidity)
Moisture content in paper
Paper is hygroscopic, hence absorbs and loses moisture accordingly to the ambient relative conditions
If less moisture in air- paper releases moisture
If more moisture in air - paper absorbs moisture
Wet solids: total mixture
Total moisture is the total amount of water (or liquid phase) associated with a wet solid
TOTAL = FREE + EQUILIBRIUM
Free moisture content
Free moisture content is the amount of water that can be easily removed e.g. evaporation
Also known as unbound water
Equilibrium moisture content
Equilibrium moisture content is the portion of water that is more difficult to be removed
Also known as bound water
Equilibrium moisture
Once unbound water is removed, the remaining moisture is in equilibrium with the moisture in the air
Only variation of the external conditions could influence the equilibrium moisture content
Example: reduction of %RH using silica gels or phosphorous pentoxide to remove water from the conditioned air.
Describe solute migration
Movement of solution in a wet system during drying
The solute is transported towards the surface, being left where the solvent evaporates
Inter-granular migration
Inter-granular migration: the solute moves between granules towards the surface
Differences in solute composition between granules
Intra-granular migration
Intra-granular migration: granules are separated during the process
Even distribution of solute within a granule
Inhomogeneity between granules impact what?
Quality aspects
Dose
Manufacturing
Appearance
So try to reduce solute migration
How to reduce solute migration phenomena
Initial moisture content
Slow convective drying
Drying by microwave radiation
Dynamic drying methods (“granules in motion”)
Factors to consider when choosing drying methods
Heat sensitivity of materials used
- Heat source AND transfer
- Heat transfer surface
Materials physical characteristics
Solvent/liquid to be removed e.g. boiling point
Efficient mass transfer of evaporated liquid
Efficient vapour removal from drying air
Amount of material to be processed e.g. scale-up considerations
Sterility
How are drying methods for wet solids categorised?
Drying methods for wet solids are categorised as function of the heat transfer methods:
Convection - flames
Conduction - metal rod on a flame
Radiation - the sun
For wet solids, how are the following mechanisms used in machines? i.e. what machines are used:
1) Convection
2) Conduction
3) Radiation
1) Fluidized-bed
2) Vacuum-oven
3) Microwave
Fluidized bed drier - how it works
Capacity
Drying time
Optimised contact between warm drying air and wet powders/particles Typical capacities (0.4-1.2 kg) with drying times of 20-40 min
Fluidized bed drier - what will an increase in air velocity cause?
Increase in air velocity will induce a pressure drop with powders/particles suspended in the air
Frictional drag equal to gravitational force (Stokes’ Law)
Further increase will cause particle free move
Such turbulence induce: Particle mixing with good contact with air Maximised surface area of the powder bed Efficient heat and mass transfer Reduced drying time Good vapour removal
Advantages of fluidized-bed dryer
Efficient heat transfer (minimising effects on thermosensitive materials)
Homogeneous process:
Movement of particles guarantees drying of all individual ones
Uniform temperature, as result of turbulence
Free movement of particles reduces:
-Migration process
-Separation/aggregation phenomena
Fluidized bed dryer disadvantages
Turbulence might damage granules
Reduction of size
Production of dust
Small particles might need specific attention to be removed from the fluidizing air
Particle movement in turbulence and warm environment might cause charges of static electricity
Adequate electrical grounding is essential
Vacuum open
Large area for heat conduction (direct contact between hot surface and material)
Airtight seal to control the drying air
Vacuum pump to bring operating pressure to 0.03-0.06 bar (low air content minimises risk of oxidation)
Temperature between 25-35°C are sufficient to boil water (convenient for thermo-sensitive materials)
Generally used for small-scale processes e.g. development laboratories
Microwive drying - how it works
Better results with what kind of molecules?
What is loss factor?
- Microwave penetration in wet material generate uniform heat
- Better results are obtained with ‘small’ polar molecules
- Loss factor is defined as ratio of absorbed microwave energy to the provided energy: higher values return better performances for heat generation
- Different solvents have different loss factor, which is the result of their electronic molecular structure
Microwave advantages
Rapid dry at controlled temperatures
Energy absorbed in the wet material, not in the air
Stationary conditions minimise small particles movement
Uniform heating reduces solute migration effect
Microwave disadvantages
Small batch size
Shielding from radiation is essential
Pharmaceutical driers for solutions and suspensions
- Spray dryer
- freeze drying
Spray dryer
How it works
Generates large surface area to promote:
-Heat exchange
-Mass transfer
Particle formation and drying occur in one process
Small droplets provide a larger surface area: beneficial for heat exchange and mass transfer
Circulating air to dry each individual particle
Spray dryer final particle size
Final particle size is determined by the initial droplet volume
Uniform and constant flow rate of the solution through the nozzle
Droplet formation faster than solvent evaporation
Sprayer dryer optimisers
Several atomizers have been developed to optimise:
droplet size (1-500 μm),
jet stream (uniformity),
solution feed rate (up to 100 L/hour),
Spray dryer atomizers
-Solid-stream jet atomizer
-solid-stream shaped orifice e.g. v-shaped orifice, flat jet
-Rotary atomizer (hollow cone jet)
-Two-fluid nozzle (gas flow promotes formation of smaller droplets)
-Ultrasonic nozzle: vibration used to reduce droplet size
Note: the higher the flow rate, the smaller the droplets
Two-fluid nozzle atomizer
Generally combines interaction of high velocity gas and fluid stream: the design of the nozzle determine where the mix between air and liquid occur
Spray dryer
impact of surface area
particle size of dry powder compared to generated droplets?
Large surface area: beneficial for heat exchange and mass transfer
Particle size of dry powder is smaller than generated droplets
Spray dryer: drying chamber
Tangent air flow to increase droplets residence time and allowing a more effective drying process
Different size from laboratory batch products to scale-up systems
Products are relatively uniform in size
Freeze drying
How it works
Obtained products have what characteristics?
High-vacuum conditions do what?
Low drying temperature making this process:
-Suitable for heat-sensitive materials
-Able to minimise chemical decomposition and enzymatic activity
Obtained products are porous, with faster solubility due to larger surface area
High-vacuum conditions minimise the contact with air, hence oxidation in reduced
Freeze-drying basic principle
The triple point: solid to vapour transition
- 01 degrees celcius
- 006 pressure (atmospheres)
Freeze-drying process steps
Presence of solutes does what?
Freezing: Freezing temperature are well below the normal freezing point of water
The presence of solute(s) shifts the phase diagram
Vacuum: Pressure is reduced below the triple point
Sublimation: Ice is tranformed to vapour at the frozen surface
Surface area and sublimation time should be evaluated to optimized the drying process
Primary drying: Porous dry product with about 0.5% moisture
(Secondary drying): happens at higher temperature (50-60°C)
Packaging: necessary step to protect the product from air moisture
