As we know, the use of each technology has several disadvantages. For example, the formation of salt is a complex process, in which the increase of solubility is not always predictable. This method is not suitable for neutral compound 37. As another example, solubilization techniques usually exhibit poor stability and patient acceptability 3. For some drugs, the selection of appropriate technology should consider some specific aspects, such as physical and chemical properties, excipient properties, dosage form characteristics.

        Particle size reduction is usually a simple method to improve solubility. The solubility is often related to the particle size. When the particle size becomes smaller, the interaction between the particle and the solvent is enhanced, thus increasing the solubility of 4,5. According to the Noyes Whitney equation, when the particle size decreases, the total effective surface area of the particles increases, thus improving the dissolution.

        Where, DC / DT is the dissolution rate of particles, D is the diffusion coefficient in the gastrointestinal medium, a is the effective surface area of particles in contact with the gastrointestinal fluid, h is the thickness of the diffusion layer around each particle, CS is the saturated solubility in the solution, and C is the concentration in the gastrointestinal tract. Except for a and C, all parameters in the formula are considered as constants, and a can be improved by reducing the particle size.

        Urbanization came into being in the 1990s. The particle size is reduced to submicron range. In recent years, the development of milling technology has led to the repeated production of particles 42,43 with particle size between 100 – 500 nm. Technology has also become a promising method to improve the solubility of poor water solubility. An example of the application of this technology is danazol, a water-insoluble compound μ G / ml, belonging to class II 33,41 of BCS classification. In 1983, Robertson and his colleagues ground the median particle size to 169 nm. In their study, danazol suspension showed higher oral bioavailability than ordinary suspension.