Particle size reduction of drug substances: When should it be considered

One of the first parameters to establish of a newly discovered solid drug substance or API is the aqueous solubility. Solubility equilibria and permeability are important solid state characteristics of any API as a drug substance and also in the drug product.

The Developability Classification System was established and categorises drug substances in terms of solubility and permeability. There are two approaches that can be applied to enhance the solubility and oral bioavailability of drug substances which are poorly soluble. One is chemical and the other physical.

If your new chemical entity has low aqueous solubility, a methodology to consider that might improve aqueous solubility is particle size reduction - a physical approach. Micronisation is often the technique that is employed producing material normally less than 10 microns in diameter, typically 1 to 2 microns.

With newly discovered APIs, material availability can be a premium and in small quantities. In order to conserve material, and as an alternative to jet milling, low shear wet milling can be employed to produce material to 1 to 2 microns in diameter on small amounts of drug substance to allow for further pharmacokinetic evaluation.

This data can further guide the development of your drug substance and MorphCryst Consulting can provide support in this area.