"Micron-Size Drug Particles: Common and Novel Micronization Techniques"
Prepared by:Lee Siang Hua (HT033441Y)
Prepared for: Assoc. Prof. Marc Garland
Date of submission: 16 March 2005
Dept. of Chemical & Biomolecular Engineering,
National University of Singapore,
10, Kent Ridge Crescent, Singapore 119260
In the pharmaceutical industry, the drug particle size is an important factor affecting the drug
characteristics and efficacy. This is particularly important for substances with low solubility and low
absorption rate at the application site. Drugs with poor water solubility are often used in micronized
particle size (<10
µm) (Müller and Rasenack: 2004). In additions, there is always a predetermined particle
size range suitable for pulmonary deposition of pharmaceutical aerosols, such as dry powder inhaler used
for asthmas treatment.
The advantages of micronized size particles are listed as follow:
1. Improvement in drug bioavailability of poorly soluble substances (solubility < 1 mg/mL) due to
increased in dissolution rate.
2. The diffusion layer around small particles is thinner, especially when the particle size is lower than
µm, which results in a faster distribution of the dissolved molecules.
3. The rate of absorption is not influenced by the hydrodynamic in the gastrointestinal tract, which
affect the thickness of the diffusion layer.
The two major micronization technologies are mechanically size reduction after crystallization and the
controlled particle size during productions. The challenges for mechanical size reductions are as follow:
1. Limited control of particle size, shape, morphology, surface properties, electrostatic charge,
oxidation, degradation, aggregation, cohesion and adhesion.
3. Broad particle size distribution.
5. Disruption of crystal lattice.
7. Further size reduction due to postmicronization stress relaxation.
8. Chemical degradation during milling.
Whereas, the major challenges faced for controlled particle size process are as follow:
1. Control of particle growth using stabilizing agent.
In the manufacturer points of view, technology with reasonable operating cost and capital cost while
producing desirable results is at utmost important. Each technology is selected based on the application
and particle properties required. Some pharmaceutical manufacturer in Singapore, such as Schering
Plough is using mechanical method, i.e. the fluid energy mill is used to produce their synthetic chemical
and steroid Active Pharmaceutical Ingredient (API), while freeze drying techniques is used in their