Pharmaceutical powders | particle size reduction

Pharmaceutical powders | particle size reduction

In the pharmaceutical field “powder” can be intended as a set of solid particles, dry, having different shape and dimensions, and is the basis of different preparations like granulate, tablets, capsules, is part of the compounds of various pharmaceutical form like:

• Suspensions

• Suppositories

• Semisolid preparation for topical use, it may also represent a pharmaceutical form in itself; in this case we speak of powder for internal use or dispersions for external use.

Particle size reduction

Particle size reduction is useful or necessary for technical as well therapeutic purposes, i.e.:

• improve tolerability of ophthalmic preparations containing particles in suspension,


• obtain a most efficient delivery to the lungs in the inhalation therapy,

• improve the stability of the suspensions, increase the homogeneity of a formulation,

• increase the specific surface of the ingredient,

• increase the bioavailability of a poorly soluble drug

Suitable powder can be obtained through two different approaches:

• A physical and chemical approach (molecular aggregation)

• A mechanical approach (reduction of a coarse material in small particles)

The molecular aggregation

The molecular aggregation’s techniques involve the aggregation of ions or molecules in crystals or amorphous particles:

• Sublimation

• Crystallization (from temperature or solvent change)

• Precipitation

•Spray-drying (drying from spray)
In the precipitation and crystallization it is possible to affect the particle size varying the speed of some parameters, typically:

• Temperature change

• Addition of solvent

• Mixing of reagents Through the techniques of molecular aggregation it is possible to obtain very fine powder and regular particles the disadvantage may be represented by the loss of material

Particle size reduction

Generally speaking milling means mechanical reduction of a coarse material in small particles Depending on the size of the raw material and on the obtained final particle size distribution we speak of: 1. Crushing: a raw material is reduced in coarse pieces (some mm) 2. Milling: the final particle size range is from a few hundred to a few tens of μm 3. Micronization: final particle size less than 20μm

Material’s property which affect the milling process

Hardness: according to the scale
: adhesives materials are milled with difficulty; the milled particles tend to agglomerate, we can proceed suggest a co-milling with excipients.
Softening temperature
: heat released in milling can soften certain substances, i.e. fats, in such cases we can operate at low temperature.
Moisture content

: for substances with high humidity content it is recommended a pre-drying.
: substances with high degree of plasticity are difficult to be milled; it is suggested a cryo-milling or dissolving the powder in a solvent and then evaporating it.



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