Drying

In pharmaceutical technology, drying is carried out for one or more of the following reasons:• To avoid or eliminate moisture which may lead to

degradation/corrosion and decrease the product or drug stability.

• To improve or keep the good properties of a material, e.g. flowability, compressibility.

• To reduce the cost of transportation of large volume materials ( liquids)

• To make the material easy or more suitable for handling.• The final step in: Evaporation- Filtration- Crystallization.

Difference between drying and evaporation:• In drying processes, the main operation usually carried out on

solid materials, e.g. powders, or products.• Drying in most of the cases means the removal of relatively

small amounts of water from solids .Evaporation include the removal of large amounts of water from solutions.

• In most cases, drying involves the removal of water at temperatures below its boiling point, whereas evaporation means the removal of water by boiling a solution.

• In drying , water is usually removed by circulating air over the material in order to carry away the water vapour , while in evaporation , water is removed from the material as pure water vapour mixed with other gases.

Terms used in Drying:• Total Moisture Content: This is the total amount of liquid

associated with a wet solid. The easily removable water is known as the free moisture content or unbound water.

• Free Moisture Content (unbound water content):This water exists as a liquid and exerts its fully vapour pressure, it can be removed readily by evaporation. During a drying process this water is easily lost but the resulting solid is not completely free from water molecules.

• Bound Water content: Part of the moisture present in a wet solid may be adsorbed on surfaces of the solid or be adsorbed within its structure to such an extent to prevent it from developing its full vapour pressure and from being easily removed by evaporation. Such moisture is described as “bound” and is more difficult to remove than unbound water.

• Equilibrium Moisture Content (EMC): The moisture content present in a solid under steady-state ambient conditions is termed the eq. moisture content. Its value changes with temperature, humidity and the nature of the solid.

• Absolute humidity: Amount/Mass of water/moisture present in unit mass of air at given temp and pressure.

• Relative humidity (RH): Amount of moisture present in 1kg of air to the amount of moisture required to saturate the same amount of air (at given temp and pressure).

• Air at a given temperature is capable of taking up water vapour until it is saturated (at 100% RH ).

• If the temperature is raised then the air will be able to take up more moisture and the relative humidity falls.

• The RH of air is dependent not only on the amount of moisture in the air , but also on its temperature, as the amount of water required to saturate air is itself dependent on temperature.

Measurement of RH:• Wet bulb thermometer: Thermometer with its bulb kept moist

with a cotton wick or muslin cloth immersed in water reservoir • Dry bulb thermometer

Wet bulb and Dry bulb thermometers

Choice of drying equipment:• Heat sensitivity of the product• Physical properties of the material to be dried – wet powder,

slurry/suspension, solution of drug• Source of heat• Residual moisture content required in the final product• Economy of the process of drying

Classification of Dryers• Based on mode of heat transfer –

Conductive/Convective/Radiation heat dryers• Based on physical nature of material being handled

Dryers for handling liquids (solutions and suspensions)• Drum Dryer• Spray Dryer• Freeze DryerThe main objective of these dryers is to provide large surface area for heat and mass transfer and efficient means for collection of dried solid. Two main designs are involved – Design in which the liquid is spread as thin film and second design in which the liquid is sprayed as fine droplets.

Drum Dryer:• Consists of a drum with 075-1.5 m dia and 2-4 m in length• Heated internally using steam as source• Liquid is applied on the surface of drum and is spread to a film• Liquid can be spread either by spraying on surface or by dipping the

drum in the liquid

• Drying rate is controlled by speed of rotation and temperature of heating source

• The product is scrapped from the surface by doctor’s knifeAdvantages:• Rapid drying due to thin film formation over large SA – so better heat

and mass transfer• Compact equipment• Heating time is short• Product obtained is in the form of flakes• Can be enclosed in vacuum jacket – so temperature for drying can be

reducedDisadvantage: Critical processing conditions – speed of rotation, temp., feed rate, film thicknessApplication: Can be used for solutions or dilute suspensions of thermostable drugs

Spray Dryer:• Provides large SA for heat and mass transfer• Liquid is sprayed into fine droplets into stream of hot air • Each droplet is heated by the incoming hot air and dried

completely into solid particle

• The drying chamber resembles a cyclone which provide better circulation of air, better heat and mass transfer and better separation of dried solid from moving air

• Spraying is done by atomizers/nebulizers• Atomizers provide small droplet size• Atomizers – Jet or Centrifugal (Rotatory Disc) can be used. Jet gets

clogged as the drying happens whereas RD is efficient (as it rotates at 20000 rpm thereby clogging is absent)

• Spray Dryers can have Co-current or Counter-current configuration for hot air flow

Spray Dryer:Advantages• Spray dried material are spherical and hollow • Good flow, bulk density, compressibility and good dissolution• Fine droplets provide large SA and therefore need less temp and

time for dryingDisadvantages• High cost• Not thermally efficient• Several critical parameters – inlet and outlet air temp, viscosity of

feed, feed temp., volatility of solvent, atomizer speed and rpm etc.Application: Useful for all solutions and suspensions particularly for thermo-labile drugs

Freeze Dryer:• For drying extremely heat sensitive materials – highly thermo-

labile drugs, proteins/ Enzymes or any biological products• Initially the liquid is frozen - pressure above the frozen state is

reduced and the solvent is removed by sublimation• There are two phase transitions – First liquid to solid and then

solid to vapour

Freeze Drying – Stages:• Freezing Stage – Liquid is frozen before application of vacuum to

avoid frothing - Shell freezing or Centrifugal freezing is used• Vacuum application stage – Pressure dropped below the triple

point of the solvent• Sublimation stage – heat of sublimation is provided and ice

sublimes slowly and porous solid is formed with o.5% moisture.• Primary drying and Secondary drying (to remove the remaining

0.5% moisture after primary dryingAdvantages• Drying at very low temp.• Product is light and porous• No contact with air – no oxidationDisadvantages• High hygroscopic material• Slow process and costly and complicated equipment

Dryers for handling wet solids (Slurries or pastes or damp solids)• Fixed bed dryers – convection• Dynamic bed dryers – convection• Vacuum oven – conduction• Infrared dryers – radiation• Microwave oven - radiation

• Fixed bed dryers – convection1. Tray dryer

2. Tunnel Dryers

• Dynamic bed dryers – convection1. Rotary Drum dryer

2. Fluid bed dryer

3. Vacuum oven4. Infrared dryer• IR rays are the source of heat in drying and evaporation in

Pharma industry• IR rays of 2.4 to 3.6 µm can be used for evaporation at 30 to 50

oC.• No medium is required• Falls on the body capable of absorbing it and appears as heat• For drying wet granules, but it absorbed very quickly but

surface materials and does not penetrate into the bed.

IR Dryers:• Surface material is dried more and exposed to temp increases on

further exposure to IR rays• Not used much due to this problem of over heating and less

penetration

Microwave Dryers:• Frequency of 300 MHz - 300 GHz with wavelength of 1m -

1mm.• Microwaves can be produced by devices like magnetron.• Absorbed by molecules that have dipole moment, like water and

other organic solvents• The QE in microwaves corresponds to bond energy is some

molecules (O-H bond)• When microwaves fall on molecules which have a dipole moment

and with bond energy corresponding to microwaves, the molecule rapidly aligns with the rapidly changing electric and magnetic field of waves and this causes generation of heat due to collisions and evaporation takes place.

• Only the solvent absorbs energy if the drug is not having a dipole.

• Drug is un-disturbed.