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As a continuation to the previous blog, we are discussing the individual methods in detail. Actually it was not planned but after getting such response & queries from reader it came like that,


• The bioavailability: intrinsically related to drug particle size.
• Increased surface area improves the dissolution properties.
• Achieved by micronisation & nanosuspension.
– Micronisation:
• Increases the dissolution rate of drugs through increased surface area; it does not increase equilibrium solubility.
• Done by milling techniques using jet mill, rotor stator colloid mills etc.
• Not suitable for drugs having a high dose number because it does not change the saturation solubility of the drug
– Nanosuspension:
• Nanosuspensions are sub-micron colloidal dispersion of pure particles of drug, which are stabilised by surfactants.
• Increased dissolution rate is due to larger surface area exposed, while absence of Ostwald ripening is due to the uniform and narrow particle size range obtained, which eliminates the concentration gradient factor.
• The nanosuspension approach has been employed for drugs including tarazepide, atovaquone, amphotericin B, paclitaxel and bupravaquone
• Techniques for the production of nanosuspensions
• Homogenization: The suspension is forced under pressure through a valve that has nano aperture. This causes bubbles of water to form which collapses as they come out of valves. This mechanism cracks the particles. Conventional homogenizers, sonicators, and high shear fluid processors.
• Wet milling: Active drug in the presence of surfactant is defragmented by milling. Other technique involves the spraying of a drug solution in a volatile organic solvent into a heated aqueous solution. Rapid solvent evaporation produces drug precipitation in the presence of surfactants.
• Other techniques for reduction of the particle size
– Sonocrystallisation: Recrystallization of poorly soluble materials using liquid solvents and antisolvents. By using ultrasound is Sonocrystallisation. Sonocrystallisation utilizes ultrasound power characterised by a frequency range of 20–100 kHz for inducing crystallisation. It’s not only enhances the nucleation rate but also an effective means of size reduction and controlling size distribution of the API. Most applications use ultrasound in the range 20 kHz-5 MHz. Supercritical fluid process
– Spray drying: Drying a liquid feed through a hot gas. The liquid feed varies depending on the material being dried and is not limited to food or pharmaceutical products and may be a solution, colloid or a suspension. This process of drying is a one step rapid process and eliminates additional processing. Spray drying of the acid dispersed in acacia solutions resulted in as much as a 50% improvement in the solubility of poorly water soluble salicylic acid.
– Supercritical Fluid Process: SCF process allows micronisation of drug particles within narrow range of particle size, often to sub-micron levels. Current SCF processes have demonstrated the ability to create nanoparticulate suspensions of particles 5 to 2,000 nm in diameter.


About the Author

majumdarshiv's picture
Author: majumdarshiv


zarrinfaria's picture

Dear Sir,
Good blog...is there any API available which can be converted from micro size to nano size by nano-milling technology??
Faria Zarrin

majumdarshiv's picture

Dear Faria Zarrin,

There are variety of examples, the oldest & well known is griseofluvin.


namanm's picture

What is main difference between micronisation & nanosuspension?
Great work, sir!

Naman Team Infinity



majumdarshiv's picture

Micronisation can be done without fluid, but nanosuspension is always carried out in presence of fluid as vehicle along with a surfactant.

vedikag's picture

what is the relation between bioavailability and size reduction ?

Vedika Gulati Team Infinity "∞" http://www.pharmainfo.net/blog/team-infinity

majumdarshiv's picture

In general particle size is inversely proportional to bioavilability.

juhis's picture

great to learn about the sonocrystallizaton technique of particle size reduction.

majumdarshiv's picture

Dear juhi,

You will get many such new things, so keep reading


Dear Sir,

Very much impressed by you blog and the information is really worth learning.Thank you sir

K.S.Kumar Upadhyayula

majumdarshiv's picture

Dear ks kumar upadhyayula,

Thanks for the comments, Keep reading & send your suggestion/comments to improvise.