Nanomaterial refers to a natural, incidental, or manufactured material comprising particles, either in an unbound state or as an aggregate wherein one or more external dimensions is in the size range of 1–100 nm for ≥50% of the particles, according to the number size distribution. In cases of environment, health, safety or competitiveness concern, the number size distribution threshold of 50% may be substituted by a threshold between 1 and 50%. Structures with one or more external dimensions below 1 nm, such as fullerenes, graphene flakes, and single wall carbon nanotubes, should be considered as nanomaterials. Materials with surface area by volume in excess of 60 m2/cm3 are also included. This defines a nanomaterial in terms of legislation and policy in the European Union. Based on this definition, the regulatory bodies have released their own guidance’s to support drug product development.
Size of the Nano Material
The most important feature to take into account is size, because it is applicable to a huge range of materials. The conventional range is from 1 to 100 nm. However, there is no bright line to set this limit. The maximum size that a material can have to be considered nanomaterial is an arbitrary value because the psychochemical and biological characteristics of the materials do not change abruptly at 100 nm.
The pharmaceutical manufacturing of nanomaterials involves two different approaches: top down and bottom down. The top down process involves the breakdown of a bulk material into a smaller one or smaller pieces by mechanical or chemical energy. Conversely, the bottom down process starts with atomic or molecular species allowing the precursor particles to increase in size through chemical reaction
Surface Area of Nano Material
The determination of the surface area by volume is a relational parameter, which is necessary when requested by additional legislation. The material is under the definition if the surface area by volume is larger than 60 m2/cm3, as pointed out. However, the PSD shall prevail, and for example, a material is classified as a nanomaterial based on the particle size distribution, even if the surface area by volume is lower than the specified 60 m2/cm3