7. Size Separation in Pharmacy: Principles, Methods, and Applications

SIZE SEPARATION

Size separation is a unit operation used to separate or classify particles on the basis of differences in physical properties such as size, density, shape, and surface characteristics. It is also known as screening, sifting, or classifying. In pharmaceutical processing, this operation is important after size reduction because the material must often be divided into the desired particle size range before being used in a formulation. Particle size distribution refers to the number of particles present in each size range in a given sample of powder of specified weight. This distribution has a major effect on flow properties, blending behavior, dissolution, stability, and the overall quality of the final product.

The process of size separation is not limited to laboratory use; it is widely applied in industrial production and quality control as well. A uniform particle size helps improve dose accuracy, product appearance, and performance. In solid dosage forms, the correct particle size can influence how quickly a drug is released and absorbed, while in suspensions and powders it can affect settling, consistency, and texture. For this reason, size separation is considered an essential operation in pharmacy and pharmaceutical manufacturing.

OBJECTIVES OF SIZE SEPARATION

• To determine the average particle size and particle size distribution, which is the first step in the manufacturing of tablets and capsules.
• To obtain drugs with particle size around 10 µm so that they can be absorbed from the gastrointestinal tract rapidly and effectively, for example griseofulvin and aspirin.
• To evaluate the efficiency of different equipment used for size reduction.
• To remove unwanted oversized or undersized particles from the final product.
• To improve flow properties and packing characteristics of powders and granules.
• To obtain uniformity in formulations where consistent particle size is necessary for performance and stability.
• To support accurate quality control in pharmaceutical manufacturing.
• To improve the processability of powders during blending, granulation, and compression.

APPLICATIONS OF SIZE SEPARATION

• Release and Dissolution: The particle size of a drug can affect its release from dosage forms administered orally, parenterally, rectally, and topically. Finely powdered drugs have a larger surface area and therefore dissolve more easily in biological fluids, improving solubility and dissolution rate.
• Absorption and Drug Action: Drug absorption and pharmacological response are influenced by particle size. As dissolution rate increases, absorption usually becomes faster, which can lead to quicker and greater drug action.
• Physical Stability: Smaller particle size may improve physical stability in dispersions because Brownian movement helps reduce settling. However, the exact effect depends on the nature of the formulation and the system involved.
• Dose Uniformity: Tablets and capsules require good flow properties and uniform distribution of particles. Proper size separation helps maintain consistent weight, content uniformity, and reliable dosage delivery.
• Manufacturing Efficiency: In many processes, controlled particle size improves compression, blending, granulation, and final product handling.
• Quality Control: Size separation is also used to check whether the powder meets pharmacopoeial standards and whether milling equipment is performing properly.
• Industrial Processing: It is used in many industries for separating powders, grains, and particulate materials according to size.

MECHANISM OF SIZE SEPARATION

Size separation occurs through different mechanical methods depending on the nature of the material and the equipment used. The most common methods are agitation, brushing, and centrifugation. These methods help particles move in a way that allows smaller particles to pass through openings while larger particles are retained. The method selected depends on powder flow, stickiness, particle size, and the desired degree of separation.

In practical terms, the mechanism works by creating relative movement between the powder particles and the sieve surface. This movement may be produced by shaking, vibration, rotation, or the action of a brush. In centrifugal systems, the force acting on the particles is increased so that separation occurs more quickly. The efficiency of size separation depends on the mesh size, vibration intensity, moisture content of the powder, and the feeding rate of the material.

1. Agitation

Agitation is one of the most widely used mechanisms in sieving. In this method, the sieve is moved or shaken so that the particles are constantly in motion and can separate according to size. Repeated movement allows smaller particles to pass through the mesh openings while larger particles remain on the sieve surface. Agitation improves efficiency because the powder does not remain in one position for long, which reduces clogging and helps improve throughput.

• Oscillatory motion: The sieve is moved to and fro by a rotating shaft, producing motion in the plane of the sieve.
• Vibrating motion: The sieve is subjected to high-speed vibration using an electrical or mechanical device.
• Gyratory motion: An eccentric flywheel causes the sieve to move in a circular motion around a fixed axis.

2. Brushing

In brushing, a brush mounted on a handle is attached to the middle portion of a circular sieve and rotates along its surface. This action helps push material through the openings and prevents clogging of the mesh. Brushing is especially useful for greasy, sticky, or cohesive powders such as waxes and soaps, which do not pass easily through a sieve by simple vibration alone. The brush action also helps distribute the material more evenly across the sieve surface.

3. Centrifugation

Centrifugation uses a vertical cylindrical sieve fitted with a high-speed rotor at the centre. As the rotor rotates, particles are thrown outward by centrifugal force. Fine particles pass through the sieve openings, while larger particles are retained and moved away from the centre. Air currents are also created inside the apparatus, which help in the separation process. This method is suitable when rapid separation of fine particles is needed and when large-scale continuous processing is required.

CLASSIFICATION OF POWDERS ACCORDING TO IP

Grade of Powder	Sieve Through Which All Particles Must Pass (No.)	Nominal Aperture Size (µm)	Sieve Through Which 40% Particles Pass (No.)	Nominal Aperture Size (µm)
Coarse powder	10	1700	44	355
Moderately coarse powder	22	710	60	250
Moderately fine powder	44	355	85	180
Fine powder	85	180	120	125
Very fine powder	120	125	350	45

Detailed Description of Powder Grades

• Coarse powder (10/44): All particles pass through sieve no. 10 with a nominal mesh aperture of 1700 µm, but not more than 40% of the powder by weight passes through sieve no. 44 with a nominal aperture of 355 µm.
• Moderately coarse powder (22/60): All particles pass through sieve no. 22 with a nominal mesh aperture of 710 µm, but not more than 40% of the powder by weight passes through sieve no. 60 with a nominal aperture of 250 µm.
• Moderately fine powder (44/85): All particles pass through sieve no. 44 with a nominal mesh aperture of 355 µm, but not more than 40% of the powder by weight passes through sieve no. 85 with a nominal aperture of 180 µm.
• Fine powder (85/120): All particles pass through sieve no. 85 with a nominal mesh aperture of 180 µm, but not more than 40% of the powder by weight passes through sieve no. 120 with a nominal aperture of 125 µm.
• Very fine powder (120/350): All particles pass through sieve no. 120 with a nominal mesh aperture of 125 µm, but not more than 40% of the powder by weight passes through sieve no. 350 with a nominal aperture of 45 µm.
• Microfine powder (350): At least 90% by weight passes through sieve no. 350 with a nominal aperture of 45 µm.
• Superfine powder: At least 90% of the particles are smaller than 10 µm.

EQUIPMENT FOR SIZE SEPARATION

The equipment used for size separation varies depending on the material to be separated, the particle size range, and the required precision. Common equipment in pharmaceutical industries includes sieves, cyclone separators, air separators, sedimentation tanks, and elutriation devices. Among these, sieves and cyclone separators are among the most frequently used because they are simple, effective, and suitable for many routine operations.

Selection of equipment depends on several factors such as particle size, moisture content, density, and the nature of the powder. For example, dry free-flowing powders can be processed easily by sieving, while fine particles in a gas stream are better handled using a cyclone separator. In industrial practice, the equipment must also be easy to clean, maintain, and validate to meet pharmaceutical standards.

Sieves

A sieve is used to separate particles based on size by allowing smaller particles to pass through openings while retaining larger ones. It is also used to remove unwanted material and to classify powders into different size ranges. In pharmaceutical work, sieving is an important analytical and processing method. When liquids are separated from solids, a special type of sieve called a strainer is used. Sieves help in both quality control and production operations.

Types of Sieves

• Woven wire sieves: Made from metal wire in plain or twilled weave. These are preferred for fine sieving and are commonly used in hand sieves and mills.
• Bolting cloth sieves: Made from silk, nylon, or cotton. They are used for fine powders and have micrometre-sized openings.
• Bar screens: Used for large and heavy materials. The bars are fixed parallel to each other and are suitable for rough separation.
• Punched plates: Sheet metal with round, oval, square, or rectangular perforations used mainly for coarse sizing.

Standards of Sieves

• Tyler standard sieve series in the USA.
• US standard sieve series in the USA.
• British standard sieve series in the UK.
• German DIN standard in Germany and Europe.
• IP standard sieve series in India.
• International test sieve series (ISO) worldwide.

Specifications for Pharmacopoeial Testing

• Sieve number: The number of meshes present per linear length of 25.4 mm.
• Nominal aperture size: The distance between adjacent wires, representing the side of a square opening.
• Nominal wire diameter: The specified diameter of wire used in the mesh, which ensures both strength and proper opening size.
• Approximate percentage sieving area: The mesh area as a percentage of total sieve area, usually maintained around 35 to 40 percent.
• Aperture tolerance average size: The permitted variation in aperture size, expressed as a percentage.

Cyclone Separator

Principle

A cyclone separator is a sedimentation device that works on the principle of centrifugal force rather than gravitational force. It is used to separate solid particles from a fluid stream, usually air, by forcing the stream into a rotating motion. The heavier particles move outward toward the walls of the cyclone, while the lighter fluid or fine particles continue toward the outlet. This makes the cyclone separator highly useful for separating coarse material from air or gas streams.

Construction

• Upper part: Contains a tangential inlet and a fluid outlet at the top center, extending inward into the separator.
• Lower part: A conical base fitted with an outlet for solid particles.

Working

The suspension or particle-laden stream is introduced into the cyclone through the tangential inlet at high speed. This creates a rotating motion inside the cylindrical body. Due to centrifugal force, the heavier particles move outward and strike the walls, after which they lose momentum and fall down into the conical base. The cleaned fluid or fine particles move upward through the central outlet. This continuous swirling motion allows efficient separation without the use of moving parts inside the chamber.

Applications

• Used for the separation of suspended solids from liquids, especially when the solid is dispersed in air.
• Used for separating heavy or coarse fractions from fine dust.
• Useful in industrial dust collection and air-pollution control systems.
• Applied where rapid continuous separation is required.

SUMMARY OF POWDER GRADES AS PER IP

Grade	Sieve Pass (All)	Sieve Pass (40%)	Particle Size
Coarse	#10 (1700µm)	#44 (355µm)	Coarse
Moderately Coarse	#22 (710µm)	#60 (250µm)	Medium-coarse
Moderately Fine	#44 (355µm)	#85 (180µm)	Medium-fine
Fine	#85 (180µm)	#120 (125µm)	Fine
Very Fine	#120 (125µm)	#350 (45µm)	Very fine
Microfine	#350 (45µm) – 90% pass		Microfine
Superfine	90% particles <10µm		Superfine

COMPARISON: TYPES OF SIEVES

Type	Material	Best Suited For	Common Equipment
Woven Wire Sieves	Metal wire	Fine sieving	Hand sieves, roller mill, ball mill
Bolting Cloth Sieves	Silk, nylon, cotton	Fine powders	Hummer screens
Bar Screens	Metal bars	Large, heavy pieces	Grizzlies
Punched Plates	Sheet metal	Coarse sizing	Hammer mills

In summary, size separation is a core pharmaceutical unit operation that supports product quality, consistency, and performance. It ensures that powders and granules are classified correctly for further processing and final dosage form preparation. Sieves, brushing systems, and cyclone separators are practical tools that make this possible in both laboratory and industrial settings. A good understanding of powder grades, sieve standards, and separation mechanisms is essential for students and professionals working in pharmaceutical technology.