Particle Size Analysis

Pharmaceutical powder particles range from about 10 mm in diameter to 1 micron or less. Particle size analysis is helpful in the determination of size, shape, distribution of drug and other components used in pharmaceutical formulations. Powder particle size influences a various physical and physiological factors. They are as follows:

  1. Content uniformity or dose uniformity of drug substances in sold dosage forms.
  2. Size reduction increases specific surface area of the active medicament and hence enhances the rate of dissolution and bioavailability.
  3. In suspensions formulation, the particles suspendibility and uniform dispersion of solids in the liquid phase is increased.
  4. In aerosol formulation, the drug particle in micronized form penetrate deep into the affected area of the body. Examples are bronchodilators, anti-inflammatory and steroidal drugs.
  5. In semi-solid dosage forms such as ointments, creams and ophthalmic preparation, lack of grittiness of solid particles can be monitored.

Methods of particle size analysis

  1. Optical microscopy: Determination of particle size by this method involves the use of microscope fitted with scaled eyepiece micrometer. Particle size ranging from 0.2 to 100 µm can be determined by this method.
  2. Sieving method: A series of sieves are arranged in descending order of sieve number in a sieve shaker and the accurately weighed powder particles are passed through it. Then the proportion of powder passing through or being withheld on each sieve is determined. Particle size range of about 40–9500 µm can be determined accurately based on the sieve method.
  3. Sedimentation method: In this method, Andreasen apparatus is used and the terminal settling velocity of particles through a liquid medium in a gravitational or centrifugal environment is determined. Stoke’s law is used to calculate the rate of sedimentation. Particle size range of 0.8–300 µm can be determined by this method.
  4. Light scattering or light energy diffraction: The process of light scattering involves the use of He–Ne laser, ultrasonic probe and silicon photo diode detectors for particle size determination. Range of particle size determined by this method is 0.02–2000 µm.Light energy diffraction involves the determination of particle size by the reduction in light reaching the sensor as particles dispersed in a liquid or gas pass through the sensing zone. Range of particle size determined is 0.2–500 µm by this method.
  5. Laser holography: The method involves individually imaging and sizing of particles by three dimension photography with a holographic camera (in which a pulsed laser is fired through an aerosolized particle spray). The size range of particles determined by this method is 1.4–100 µm.
  6. Cascade impaction: The principle of this method depends upon that when a particle moves through an airstream, it will hit a surface that comes across its path and the particles are rebounded and separated into different size ranges by increasing the velocity of the airstream in which the particles moves.For an exact determination of the size and shape parameter of the powder particles, a combination of above methods discussed is preferred. Commercially used particle size analyzers are automated and linked with computers for data processing, distribution analysis and printout.

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