Reduction of Particle Size

As mentioned above, if R is significantly reduced (to values below 0.1 pm) the Brownian diffusion can overcome the gravity force and no sedimentation occurs. 

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In a biphasic solid-liquid medium irradiated by power ultrasound, major mechanical effects are the reduction of particles size leading to an increased surface area and the formation of liquid jets at solid surfaces by the asymmetrical inrush of the fluid into the collapsing voids. These liquid jets not only provide surface cleaning but also induce pitting and surface activation effects and increase the rate of phase mixing, mass transfer and catalyst activation. 

Reduction of particle size was found to increase the activity as long as the crystallinity was maintained or restored by calcination, etc. Surface features such as steps that act as active sites were also found to increase activity [54,57,84]. 

Reduction of particle size increases the total specific surface area exposed to the solvent, allowing a greater number of particles to dissolve more rapidly. Furthermore, smaller particles have a small diffusion boundary layer, allowing faster transport of dissolved material from the particle surface [58]. These effects become extremely important when dealing with poorly water-soluble drugs, where dissolution is the rate-limiting step in absorption. There are numerous examples where reduction of particle size in such drugs leads to a faster dissolution rate [59-61], In some cases, these in vitro results have been shown to correlate with improved absorption in vivo [62-64]. 

When considering reduction of particle size, one should be aware of potential instability enhancement. It is well known that grinding can reduce crystallinity [65] the resulting noncrystalline material may be more hygroscopic... 

There are two major problems associated with the x-ray method. The first problem is encountered during sample preparation. At this step, preferred orientation of the particles must be minimized [1], Reduction of particle size is one of the most effective ways of minimizing preferred orientation, and this is usually achieved by grinding the sample. Grinding, however, can also disorder the crystal lattice. Moreover, decreased particle size can cause a broadening of x-ray lines, which in mm affects the values of /c and /a. The relationship between the crystallite size, t, and its x-ray line breadth, /3, (assuming no lattice strain) is given by the Scherrer equation [2] ... 

The reduction of particle size by grinding can also result in significant alterations in structural properties, and DTA has been successfully used to follow... 

For a given solid material, a progressive reduction of particle size corresponds to increases in the surface/volume ratio and the escaping tendency of the molecules until the nature of the surface dominates the properties of the material. Two related thermodynamic consequences of this effect are an increase of solubility in any solvent and an increase of vapor pressure as the size of the particle is reduced. For a spherical particle of radius r, thermodynamic arguments lead to the Thomson-Freundlich equation [19] ... 

At a first glance, a very promising procedure for speeding up LC/MS analysis without compromising peak capacity of the separation would involve (1) reduction of particle size, (2) reduction of... 

REDUCTION OF PARTICLE SIZE OF DRUG SUBSTANCE FOR LOW-DOSE DRUG PRODUCTS... 

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