10. Drying in Pharmacy: Principles, Methods, Factors, and Equipment

DRYING

Drying is the process in which water or other solvents are removed from a substance by the application of heat. Removal of liquid from solids may be carried out either by mechanical methods, such as filtration or centrifugation, or by thermal methods in which the liquid is vaporised. In pharmaceutical manufacturing, drying is an essential unit operation because many products and intermediates must be converted into a stable, free-flowing, and easy-to-handle dry form.

Drying improves product stability, reduces the chances of microbial growth, decreases bulk and weight, and helps in further processing such as granulation, compression, and size reduction. It is widely used in the preparation of bulk drugs, granules, powders, biological products, and heat-sensitive materials. The selection of a drying method depends on the nature of the material, the heat sensitivity of the product, moisture content, and the final quality required.

OBJECTIVES OF DRYING

• To reduce decomposition caused by the presence of moisture.
• To prevent microbial growth and increase the shelf life of products.
• To reduce transportation and storage costs by decreasing bulk and weight.
• To improve the quality and market value of the product.
• To aid in granule formation during pharmaceutical processing.
• To facilitate processing of materials such as spray-dried lactose and dried aluminium hydroxide.
• To enable size reduction and improve handling characteristics.
• To prevent bacterial and mould growth, thereby increasing product stability.
• To improve the stability of substances such as aspirin, penicillin, and ascorbic acid in dry form.

MECHANISM OF DRYING

Drying is essentially a diffusion process in which moisture moves from the interior of the solid to the surface, from where it evaporates into the surrounding environment. As surface moisture is removed, internal moisture migrates outward due to concentration differences. An external drying medium, usually hot air or gas, supplies the necessary heat for evaporation and carries away the released vapour.

The overall drying process generally includes heat transfer to the wet material and mass transfer of moisture from the product to the drying medium. Initially, drying may occur rapidly if free moisture is present on the surface, but later the rate decreases as moisture must travel from the inner parts of the material. Thus, the internal structure of the material and the external drying conditions both influence the drying rate.

APPLICATIONS OF DRYING

1. Preparation of Bulk Drugs

• Dried aluminium hydroxide.
• Spray-dried lactose.
• Powdered extracts.

Drying is frequently used in the production of bulk pharmaceutical substances to obtain dry powders that are easy to store, weigh, and process further. It is especially valuable where moisture-sensitive materials must be converted to a stable form after crystallisation, precipitation, or granulation.

2. Preservation of Drug Products

Drugs	Type of Decomposition Prevented
Crude drugs of animal and vegetable origin	Chemical decomposition
Blood products, skin, and tissues	Microbial growth
Synthetic and semi-synthetic drugs	Chemical decomposition
Effervescent tablets, aspirin, penicillin	Chemical decomposition

Many pharmaceutical materials are unstable in the presence of moisture. Drying helps preserve such products by reducing hydrolysis, oxidation, microbial attack, and other forms of deterioration. This is particularly important for biological products and moisture-sensitive formulations.

3. Improved Characteristics

Drying of granules improves their flow properties and compression behaviour, which is important during tablet and capsule manufacture. Drying also improves the handling of sticky and viscous materials such as malt extract, oleoresins, and certain herbal extracts by converting them into more manageable forms.

4. Improved Handling

When moisture is removed, the product becomes lighter in weight and reduced in bulk. This decreases packaging, transportation, and storage costs and makes handling easier during manufacturing and distribution.

5. Purification of Crystalline Products

Drying helps purify crystalline products by removing the solvent that remains adhered to crystal surfaces after separation. This improves purity, stability, and suitability for further processing.

6. Prevention of Corrosion

Drying prevents corrosion caused by the presence of moisture in certain materials or gases. For example, dry chlorine gas is far less corrosive than moist chlorine gas, showing the practical importance of moisture removal in industrial handling.

FACTORS AFFECTING DRYING

• Particulate Diameter: Drying rate depends on particle diameter because surface area exposed to the drying medium changes with size.
• Size Uniformity: Non-uniform particle size affects diffusion path length and capillary movement of moisture.
• Physical Properties of Wet and Dry Solids: Particle size, surface area, pore size, and rheological properties influence drying behaviour.
• Product Mass Flow Rate: A constantly changing bed surface at an optimum speed increases drying efficiency.
• Hot Air Mass Flow Rate: Continuous movement of hot air prevents saturation with moisture and improves drying rate.
• Diameter of Dryer Section: Changes in dryer dimensions affect air flow characteristics and drying performance.
• Critical Moisture Content: This is the moisture level at which the constant-rate period ends and the falling-rate period begins.

These factors influence both heat transfer and moisture movement within the product. Proper control of these variables is necessary to achieve uniform drying, prevent overheating, and preserve product quality.

CLASSIFICATION OF DRYERS

• Direct Dryers: These use convective drying, where the material is heated by direct contact with hot air, gas, or combustion products.
• Indirect Dryers: These dry materials by contact with a heated surface or wall without direct contact with the heating medium.
• Common Dryers: Tray dryer, fluidised bed dryer, vacuum dryer, and freeze dryer.

Dryers can also be classified on the basis of the mode of heat transfer, pressure conditions, and the physical form of the material being dried. The selection depends on product sensitivity, required moisture level, and production scale.

FLUIDISED BED DRYER (FBD)

Principle

In a fluidised bed dryer, hot air or gas is passed upward through a perforated base containing wet granules or particles. When the air velocity is sufficient, the particles become suspended and behave like a boiling fluid. This fluidised condition provides uniform contact of hot air with the particles, leading to rapid and efficient drying.

Construction

• Made of stainless steel or suitable plastic material.
• Has a detachable bowl at the bottom for charging and discharging material.
• The bowl has a perforated base covered with a wire mesh.
• The upper section contains a fan for circulation of hot air.
• Air is introduced through a fresh air inlet, passed through a pre-filter, and heated by a heat exchanger.
• Filter bags are fitted above the drying bowl to retain fine particles.

Working

• Wet granules are placed in the detachable bowl.
• Fresh air passes through a pre-filter and then through a heat exchanger where it is heated.
• The hot air enters through the bottom perforated plate of the bowl.
• When the air velocity exceeds the settling velocity of particles, the granules become fluidised.
• Each granule gets surrounded by hot air, producing uniform and rapid drying.
• The air carrying moisture passes through filter bags and exits the system.
• The usual residence time is about 40 minutes.

Applications

• Drying granules for tablet compression.
• Mixing, granulation, and drying operations.
• Coating granules.
• Mixing pharmaceutical ingredients.

The fluidised bed dryer is widely used because of its rapid drying rate, uniform heat transfer, and suitability for granules and powders. It is especially popular in tablet manufacturing.

FREEZE DRYER (LYOPHILISATION)

Principle

Freeze drying, also called lyophilisation, is the removal of water from a frozen product by sublimation. In this process, ice changes directly into vapour without passing through the liquid state. This is achieved by maintaining the product below the triple point of water while applying vacuum, making freeze drying especially suitable for heat-sensitive materials.

Construction

• A drying chamber for loading trays or product containers.
• A source of heat such as radiation or heating coils.
• A vapour-condensing or adsorption system.
• A vacuum pump or steam ejector, or both.

Process of Freeze Drying

• Preparation and pre-treatment: The solution may be pre-concentrated to reduce the total amount of water to be removed.
• Pre-freezing: The product is frozen, often around -50°C, to solidify the water present.
• Primary drying: Under vacuum and below the triple point of water, ice sublimes directly into vapour, removing most of the moisture.
• Secondary drying: Residual moisture is removed by further heating under reduced pressure.
• Packing: After drying, the vacuum is replaced with inert gas and the containers are sealed.

Applications

• Manufacture of injections, solutions, and suspensions.
• Drying blood plasma and its fractionated products.
• Drying bacterial and viral cultures.
• Drying human tissues such as arteries and corneal tissue.
• Drying antibiotics and plant extracts.
• Drying steroids, vitamins, and enzymes.
• Drying foods such as prawns, mushrooms, meat, poultry, coffee, tea concentrates, and fruit juices.

Freeze drying gives highly stable products with minimal damage to heat-sensitive ingredients. It is widely used for biologicals, vaccines, enzymes, and injectable products where product activity and structure must be preserved.

FREEZE DRYING STAGES

Stage	Process	Parameters / Duration
Pre-treatment	Pre-concentration of solution	Reduces drying load
Pre-freezing	Freezing of product	About -50°C; cooling rate 1-3 K/min
Primary Drying	Sublimation of ice under vacuum	Below triple point; removes about 98-99% water
Secondary Drying	Removal of residual moisture	50-60°C under vacuum; may take 10-20 hours

COMPARISON OF COMMON DRYERS

Dryer	Principle	Best Suited For	Main Advantage
Tray Dryer	Hot air drying in trays	Small-scale batch drying	Simple construction and operation
Fluidised Bed Dryer	Suspension of particles in hot air stream	Granules and powders	Rapid and uniform drying
Vacuum Dryer	Drying under reduced pressure	Heat-sensitive materials	Lower drying temperature
Freeze Dryer	Sublimation of frozen water under vacuum	Biological and thermolabile products	Excellent stability and preservation