1. Drying

2. DRYING is an important operation in pharmaceutical practice, since it is commonly the last stage of the process before packaging and has a considerable effect on the properties of the product.
Correct drying can prevent deterioration or can ensure that a product is readily soluble or is free­flowing.
Drying is defined as the final removal of liquid from solids by thermal vaporization, leaving a `dry' solid.

3. Dryers for Dilute Solutions and Suspensions
The objective of these dryers is to spread the liquid to a large surface area for heat and mass transfer and to provide an effective means of collecting the dry solid.
Two main types are used, the first spreading the liquid to a thin film and the second dispersing the liquid to a spray of small droplets.

4. Drum Dryer (Film Dryer)
The drum dryer consists of a drum heated internally, usually by steam, and rotated on its longitudinal axis.
The liquid is applied to the surface and spread to a film; this may be done in various ways, but the simplest method is that shown in the diagram, where the drum dips into a feed pan.
Drying rate is controlled by using a suitable speed of rotation and drum temperature. The product is scraped from the surface of the drum by means of a doctor knife.

5. Advantages
(a) The method gives rapid drying, the thin film spread over a large area resulting in rapid heat and mass transfer.
(b) The equipment is compact, occupying much less space.
(c) Heating time is short, being only a few seconds.
(d) The drum can be enclosed in a vacuum jacket, enabling the temperature of drying to be reduced.
(e) The product is obtained in flake form, which is convenient for many purposes.

6. The only disadvantage is that operating conditions are critical and it is necessary to impose careful control on feed rate, film thickness, speed of rotation and temperature difference.
The drum dryer can handle a variety of materials, either as solutions or suspensions; substances that are dried by this method include milk products, starch products, ferrous salts, and suspensions of kaolin or zinc oxide.

7. Spray Dryer
The spray dryer provides a large surface area for heat and mass transfer by atomizing the liquid to small droplets. These are sprayed into a stream of hot air, so that each droplet dries to a solid particle.
There are many forms of spray dryer and Fig. is a typical design, in which the drying chamber resembles the cyclone ensuring good circulation of air, to facilitate heat and mass transfer, and that dried particles are separated by the centrifugal action.

8. The character of the particles is controlled by the droplet form; hence the type of atomizer is important.
Jet atomizers are easily blocked and the droplet size is likely to vary, but this is not so with rotary types.
Liquid is fed on to the disc, which is rotated at high speed ; a film is formed and spreads from the small disc to a larger, inverted, hemi-spherical bowl, becoming thinner, and eventually being dispersed from the edge in a fine, uniform spray.
In addition, the rotary atomizer has the advantage of being equally effective with suspensions of solids and it can operate efficiently at various feed rates.

9. Spray Dryer 2 3 8 12 1 7 9 11 6 10 4 5 Feed Tank Centrifugal Atomizer
Drying Chamber
Inlet Air Filter
Air Supply Fan
Air Heater
Triple Inlet Duct
Adjustable Air Disperser
Cooling Air Fan
Chamber Product Collector
Cyclone Product Collector
Exhaust Fan
Hot Air
Liquid Feed
Dry Powder + Hot Air 2 3 8 12 1 7 9 11 6 10 4 5

11. Advantages of the Spray Drying Process
(a) The droplets are small, giving a large surface area for heat and mass transfer, so that evaporation is very rapid.
(b) Because evaporation is very rapid, the droplets do not attain a high temperature, most of the heat being used as latent heat of vaporization.
(c) The characteristic particle form gives the product a high bulk density and, in turn, ready solubility.

12. (d) Provided that a suitable atomizer is used, the powder will have a uniform and controllable particle size.
(e) The product is free-flowing, with almost spherical particles, and is especially convenient for tablet manufacture.
(f) Labour costs are low, the process yielding a dry, free-flowing powder from a dilute solution, in a single operation with no handling.

13. Disadvantages
(a) The equipment is very bulky and with the auxillary equipment (fans, heaters, separators, etc.) is expensive.
(b) The thermal efficiency is rather low, since the air must still be hot enough when it leaves the dryer to avoid condensation of moisture.

14. The spray dryer can be used for drying almost any substance, in solution or in suspension. It is most useful for thermolabile materials.
Examples of substances that are spray dried include borax, citric acid, hexamine, sodium phosphate, gelatin, acacia and extracts, while starch, barium sulphate and calcium phosphate are typical of insoluble materials.
In addition, the method is widely used for products of indirect pharmaceutical interest, such as milk, soap, and detergents.

16. Dryers for Solid Materials
GENERAL PRINCIPLES
Equilibrium Moisture Content
Exposure to air at a definite temperature and humidity will cause a material to lose or gain moisture until an equilibrium moisture content is attained.
The values will vary, depending on the temperature and humidity of the air and on the properties of the material, being low with non­porous solids, but higher and variable with fibrous or colloidal organic substances.

17. Ordinary atmospheric conditions are of the order of 20°C and 70 to 75 percent relative humidity.
So that, if exposed to the atmosphere, a substance such as kaolin will contain about 1 percent moisture; textile fibers, as in surgical dressings, will contain about 15 percent, while drugs, such as leaves, may have as much as 25 to 30 per cent.
Typical equilibrium moisture contents
at 20°C
(1) Drugs, such as leaves.
(2) Textile fibers.
(3) Inorganic substance, such as kaolin.

18. The effect of this variation of equilibrium moisture content is that:
When a material leaves a dryer it may or may not be bone dry, that is, completely free from moisture, depending on the temperature and humidity of the air at the dryer outlet
Even if a material is reduced to the bone-dry state, there will be a moisture regain if it is exposed to the atmosphere.
'Over-drying' should be avoided; that is, drying should be stopped when the moisture content has reached a level equivalent to the equilibrium moisture content under the conditions to which the material is to be exposed.

19. Moisture Content
The moisture present in a solid may exist in more than one physical condition:
BOUND MOISTURE
Bound moisture in a solid is liquid that exerts a vapour pressure less than that of the pure liquid at the same temperature. This reduction of vapour pressure may be because the liquid is in small capillaries, in solutions, in cells or is combined, for example, by adsorption to a surface.

20. EXPRESSION OF MOISTURE CONTENT
FREE MOISTURE
Free moisture at a particular temperature and humidity is the liquid in excess of the equilibrium moisture content.
EXPRESSION OF MOISTURE CONTENT
The moisture content is expressed as percentage moisture content, dry basis, that is, the number of parts by weight of moisture per hundred parts of bone dry solid.
Thus, 50 per cent moisture content, dry basis, represents 50 kg moisture per 100 kg dry solid. Alternatively, the statement may be made as parts per part and the previous quantity would be expressed as 0.5 kg/kg.

21. Rate of Drying
The rate at which drying occurs has been found to show certain phases, which are illustrated in Fig.,
From A to B the relationship is linear, which is known as the constant rate period.
From B to C the rate of loss of moisture decreases and is known as the falling rate period.
The end of the constant rate period, B, is referred to as the critical moisture content.
Fig. Drying curve
CMC = critical moisture content
EMC = equilibrium moisture content

22. CONSTANT RATE PERIOD
For given conditions of temperature and humidity, most substances dry at a similar rate in the constant rate period.
It is found that the evaporation rate is similar to that from a free liquid surface under the same conditions, indicating that the evaporation takes place from the wet surface of the solid and that the liquid is replaced from below as fast as it is vaporized.
Controlling factors in this period are the rate at which heat can be transferred and the removal of the vapour.

23. Heat Transfer
The general principles affecting heat transfer apply, so that in all cases a large area is necessary. If convection is the principal method of heat transfer, a suitable air flow is required with an appropriate temperature gradient, the former being of greater importance.
Rapid drying may lead to the formation of a surface `skin' that will hinder mass transfer and so reduce the drying rate.

24. Conduction dryers demand good contact between the heating surface and the solid. With radiant heat transfer, the efficiency is very high and, provided the emitters can `see' the surface of the solid, the heat transfer occurs at the surface where the drying is taking place.

25. Removal of Vapour
Drying in the constant rate period depends on mass transfer through the air boundary layers.
Turbulent flow conditions are required, which will lower the partial vapour pressure in the atmosphere and reduce the thickness of the air boundary layers.
The effect of both of these factors is to increase the partial pressure gradient, leading, in turn, to a higher mass transfer coefficient.

26. FIRST FALLING RATE PERIOD
As moisture is removed from the surface, a point will be reached when the rate of vaporization is insufficient to saturate the air in contact with the surface. Under these conditions, the rate of drying will be limited by the transfer of liquid to the surface and, since this becomes increasingly difficult, the rate decreases continuously.

27. During drying, moisture will be drawn from the lower pores, moving to smaller pores near the surface that have been emptied, or to the surface, according to the relative values of the suction potential.

28. SECOND FALLING RATE PERIOD
Any moisture that remains at the end of the first falling rate period is unable to move, so that drying cannot take place on the surface.
The plane of vaporization retreats from the surface into the body of the solid, and the drying rate depends on the movement of the vapour through the pores to the surface, in general, by molecular diffusion.

29. Types of Dryer
Dryers may be classifying according to the principal method of heat transfer: convection, conduction, or radiation.

30. Heat Transfer Mechanisms
Convection
Conduction
Radiation

31. Mass Transfer Mechanisms
Diffusion
vapor
liquid
Capillary Flow
Shrinkage/Pressure Gradients
Gravity
Vaporization/Condensation

32. CONVECTION DRYERS Compartment (or Tray or Shelf) Dryers
The simplest form of dryer in this category is a cabinet with a heater, usually at the bottom to assist convection, but it is of limited value, giving virtually no control of heat transfer or humidity.

33. The situation can be improved by including a fan, so that forced convection takes place, with increased heat transfer and reduced local vapour concentrations, but control is still inadequate.
The best type in this category is the directed circulation form, in which air is heated and is directed across the material in a controlled flow.

34. Directed-circulation compartment dryer
The arrangement of the shelves causes air flows in the directions shown by the arrows.
Heaters are positioned as shown, so that the air is re-heated before passing over each shelf, which is an advantage since the air temperature is minimized.
As the air passes over each shelf, a certain amount of heat is given up to provide latent heat of vaporization.

35. The compartment dryer is very flexible and versatile, with good control of heat and humidity, if designed correctly.
The output, however, is limited due to size and to batch operation. Further, unless the material is moved (This difficulty can be overcome in a simple manner if the material is on trays; at intervals, the tray nearest to the air inlet is removed, all others moved one position nearer to the inlet, and a fresh tray of moist material inserted into the last position before the air outlet).

36. The effect is to obtain semi-continuous operation with greater efficiency by having counter­current movement of air and drying solid.
Uses include the drying of crude drugs, chemicals, powders, tablet granules, or items of equipment.

37. Tunnel Dryers
Such counter-current movement of air and drying solids is arranged much more conveniently in the tunnel dryer, where the drying method resembles the compartment dryer, but takes the form of a long tunnel, with heated air entering at one end and some means of moving the material to be dried at the opposite end.
Compared with the compartment dryer, the tunnel dryer has the advantage of being semi­continuous or continuous in operation; applications are similar, but more suitable for large-scale production.

39. Rotary Dryer
The rotary dryer is a modified form of the tunnel dryer in which the particles are passed through a rotating cylinder, counter-current to a stream of heated air.
Due to the rotation of the cylinder, the material is turned over and drying takes place from individual particles and not from a static bed.

40. The cylindrical shell is mounted with a slight slope, so that the material will move through the shell as it is slowly rotated.
To improve contact, the shell contains baffles or flights which lift the solids and spill the particles through the air stream.
The rotary dryer is used for continuous drying on a large-scale of any powdered or granular solid.

41. Classical Bed Dryer Adjustable Louvers Exhaust Outlet Fresh Air Inlet
Fan Screen
Heater

42. Fluidized Bed Dryer
Another method of obtaining good contact between hot air and particles is used in the fluidized bed dryer
Fluidization occurs when a flow of fluid upwards through a bed of particles reaches sufficient velocity to support the particles without carrying them away in the fluid stream.
The bed of particles then assumes the characteristics of a boiling liquid, hence the term fluidization.

43. The fluid responsible for fluidization may be a gas or a liquid, the choice of which will confer different properties on the fluidizing system. This will, in turn, affect the choice of processes that may be used.
At low fluid velocities the particles will simply remain in the loosely packed state in the bed.
At intermediate velocities, individual particles will become suspended in the fluid, flowing while the bed on the whole remains motionless relative to the column walls; the bed is now said to be fluidized

45. Vertical Fluid Bed Dryer8 1
Fresh Air Inlet Filter
Steam or Electric Heater
Air Circulating Fan
Air Volume Damper
Air Diffuser
Vessel Containing Material
Nylon Filter Bags
Air Exhaust 2 7 6 3 5 4

46. Conveying and air distributing surface
Conveyor Fluidized Bed Dryer
Exhaust Blower
Surge Hopper
Dust Collector
Exhaust Air Duct
Dry Material
Vibrating Conveyor
Conveying and air distributing surface

47. Pilot-scale pulsed fluid-bed dryer:
1- dryer, 2- rotating valve distributor, 3- forced draft fan, 4- induced draft fan, 5- feeder, 6- hopper, 7- bag filter, 8- electric heater and gas burner, 9- control panel.

48. Advantages
(a) Efficient heat and mass transfer give high drying rates.
(b) The fluidized state of the bed gives drying from individual particles and not from the entire bed. Hence, most of the drying will be at constant rate and the -falling rate period (when the danger of overheating is greatest) is very short.

49. (c) The temperature of a fluidized bed is uniform and can be controlled precisely.
(d) The fluidized state produces a free-flowing product.
(e) The free movement of individual particles eliminates the risk of soluble materials migrating.
(J) The containers can be mobile, making handling simple, and reducing labour costs.
(g) Short drying times mean that the unit has a high output from a small floor space.

50. Disadvantages
(a) The turbulence of the fluidized state may cause attrition of some materials, with the production of fines.
(b) Fine particles may become entrained and must be collected by bag filters, with care to avoid segregation and loss of fines.
(c) The vigorous movement of particles in hot dry air can lead to the generation of charges of static electricity, and suitable precautions must be taken.
The fluidized bed dryer can be used for drying any powdered material; a special application is the drying of tablet granules, for which it is an excellent method.

51. CONDUCTION DRYERS Vacuum Oven
Vacuum dryers are substantially the same as tray dryers, except that they operate under a vacuum, and heat transfer is largely by conduction or by radiation. The trays are enclosed in a large cabinet, which is evacuated.

52. The water vapour produced is generally condensed, so that the vacuum pumps have only to deal with non-condensible gases. Another type consists of an evacuated chamber containing a roller dryer
A form of vacuum dryer commonly used in pharmaceutical practice is the vacuum oven.

53. Advantages
(a) The 'method is especially suitable for unstable materials; drying takes place at low temperature, minimizing damage to thermolabile materials, and vacuum operation reduces the risk of oxidation during drying.
(b) If used for manufacturing a dry extract, the product is porous and friable, so that it is especially useful for tabletting.
(c) The use of a condenser enables solvents to be recovered, which is useful with expensive or inflammable solvents.

54. Disadvantages (a) Heat transfer coefficients are low.
(b) The vacuum oven is of limited capacity.
(c) Labour and running costs are high.
(d) There is a danger of an excessive temperature gradient, especially as the coefficient of thermal conductivity of the material will decrease as it dries, leading to over-heating and to decomposition.

55. Vacuum drying is of specialized application and its uses include the drying of:
thermo-labile materials, such as penicillin.
products where the porous form is useful, such as dry extracts.
removal of liquids other than water, where the solvent recovery is advantageous, ethanol extractives, for example.

56. Freeze Drying
In a typical phase diagram, the boundary between gas and liquid runs from the triple point to the critical point. Freeze drying (blue arrow) brings the system around the triple point, avoiding the direct liquid-gas transition seen in ordinary drying (green arrow).

57. Freeze drying (also known as lyophilization) is a dehydration process typically used to preserve a perishable material or make the material more convenient for transport.
Freeze drying works by freezing the material and then reducing the surrounding pressure and adding enough heat to allow the frozen water in the material to sublime directly from the solid phase to gas.

58. A simplified freeze-drying machine

61. Pharmaceutical companies often use freeze drying to increase the shelf life of products, such as vaccines and other injectables.
By removing the water from the material and sealing the material in a vial, the material can be easily stored, shipped and later reconstituted to its original form for injection.

62. The freeze drying process
There are three stages in the complete freeze-drying process: freezing, primary drying, and secondary drying.
Freezing
The freezing process consists of freezing the material.

63. Primary drying
During the primary drying phase the pressure is lowered and enough heat is supplied to the material for the water to sublimate.
Secondary drying
The secondary drying phase aims to sublimate the water molecules that are adsorbed during the freezing process, since the mobile water molecules were sublimated in the primary drying phase.

64. Advantages
Drying takes place at very low temperatures, so that enzyme action is inhibited, and decomposition, particularly hydrolysis, is minimized.
The solution is frozen, so that the final dry product is a network of solid occupying the same volume as the original solution. Thus, there is no case-hardening and the product is light and porous.
The porous form of the product gives ready solubility.
There is no concentration of the solution prior to drying. Hence, salts do not concentrate and denature proteins as occurs with other drying methods.
Under high vacuum, there is no contact with the air, and oxidation is minimized.

65. Disadvantages There are two main disadvantages of freeze drying:
(a) The porosity, ready solubility, and complete dryness yield a very hygroscopic product. Unless dried in the final container and sealed in situ, packaging requires special conditions.
(b) The process is very slow and uses complicated plant, which is very expensive. It is not a general method of drying, therefore, but is limited to certain types of valuable products that cannot be dried by any other means.

66. Uses of Freeze Drying
The method is applied only to biological products; for example, antibiotics (other than penicillin), blood products, vaccines (such as BCG, yellow fever, smallpox), enzyme preparations (such as hyaluronidase) and microbiological cultures.

67. RADIANT HEAT DRYERS Sources of the radiant energy may be:
Lamps-so called infra-red lamps; usually the operating temperature is too high, giving a total emission of energy that is too great and that causes overheating.
Low temperature sources-electric rods or electric or gas-heated panels are used. They may operate at red heat or down to `black' heat (to about 500°C). Such sources give better heating control and are to be preferred.

68. Uses of Radiant Heat Drying
Dryers adapted for radiant heat transfer may be used for most materials, solid or liquid in thin layers.
The method is very effective for thin liquid films, as on drum dryers, and powders or granules may be dried quicker by radiant heat than by convection heating.
Care must be taken to avoid surface overheating.