Micronization

Micronization is the process of reducing the average diameter of a solid material's particles. Usually, the term micronization is used when the particles that are produced are only a few micrometres in diameter. However, modern applications (usually in the pharmaceutical industry) require average particle diameters of the nanometer scale.

Traditional techniques

Traditional micronization techniques are based on friction to reduce particle size. Such methods include milling, bashing and grinding. A typical industrial mill is composed of a cylindrical metallic drum that usually contains steel spheres. As the drum rotates the spheres inside collide with the particles of the solid, thus crushing them towards smaller diameters. In the case of grinding, the solid particles are formed when the grinding units of the device rub against each other while particles of the solid are trapped in between.

Methods like crushing and cutting are also used for reducing particle diameter, but produce more rough particles compared to the two previous techniques (and are therefore the early stages of the micronization process). Crushing employs hammer-like tools to break the solid into smaller particles by means of impact. Cutting uses sharp blades to cut the rough solid pieces into smaller ones.

Modern techniques

Modern methods use supercritical fluids in the micronization process. The most widely applied techniques of this category include the RESS process (Rapid Expansion of Supercritical Solutions), the SAS method (Supercritical Anti-Solvent) and the PGSS method (Particles from Gas Saturated Solutions).

In the case of RESS, the supercritical fluid is used to dissolve the solid material under high pressure and temperature, thus forming a homogeneous supercritical phase. Thereafter, the solution is expanded through a nozzle and small particles are formed. At the rapid expansion point right at the opening of the nozzle there is a sudden pressure drop that forces the dissolved material (the solid) to precipitate out of the solution. The crystals that are instantly formed enclose a small amount of the solvent that, due to the expansion, changes from supercritical fluid to its normal state (usually gas), thus breaking the crystal from inside-out. At the same time, further reduction of size is achieved while the forming and breaking crystals collide with each other at the vicinity of the nozzle. The particles that are formed this way have a diameter of a few hundreds of nanometers.

In the SAS method, the solid material is dissolved in an organic solvent and a supercritical fluid is then also forced by means of pressure to dissolve in the system. In this way, the volume of the system is expanded, thus lowering the density, and therefore also the solubility of the material of interest is decreased. As a result, the material precipitates out of the solution as a solid with a very small particle diameter.

In the PGSS method the solid material is melted and the supercritical fluid is dissolved in it, like in the case of the SAS method. However, in this case the solution is forced to expand through a nozzle, and in this way nanoparticles are formed.

In all three methods described, the effect that causes the small diameter of the solid particles is the supersaturation that occurs at the time of the particle formation, like it was described in more detail in the case of the RESS process. The PGSS method has the advantage that because of the supercritical fluid, the melting point of the solid material is reduced. Therefore, the solid melts at a lower temperature than the normal melting temperature at ambient pressure. In addition, all these new techniques do not demand long processing times, like in the case of the traditional methods. As a result, they are thought to be more appropriate when thermo-labile materials need to be processed (like pharmaceuticals and foodstuff ingredients).

Examples

Progesterone can be micronized by making very tiny crystals of the progesterone.^[1] Micronized progesterone is manufactured in a laboratory from plants. It is available for use as HRT, infertility treatment, treat progesterone deficiency treatment, including dysfunctional uterine bleeding in premenopausal women. Compounding pharmacies can supply micronized progesterone in sublingual tablets, oil caps, or transdermal creams.^[2]

References

1. ^ wdxcyber.com >Progesterone - Its Uses and Effects Frederick R. Jelovsek MD. 2009
2. ^ project-aware > Managing Menopause > HRT > About Progesterone Page uploaded September 2002