Drug nanocrystals of poorly soluble drugs produced by high pressure homogenisation

For many new chemical entities (NCE) of very low solubility oral bioavailability enhancement by micronisation is not sufficient, the next step taken was nanonisation. The production of drug nanocrystals by bottom up techniques (precipitation) is briefly described, main focus is given on particle diminution by high pressure homogenisation. Homogenisation can be performed in water (DissoCubes) or alternatively in non-aqueous media or water-reduced media (Nanopure). There is also a combination process of precipitation followed by a second high energy step, e.g. homogenisation (NANOEDGE). The result is a suspension of drug nanocrystals in a liquid, the so-called nanosuspension. Presented are the physical background of the diminution process, effects of production parameters (power density, number of homogenisation cycles) on crystal size, clinical batch production and scaling up of the production. As an important point the transfer of the liquid nanosuspensions to patient convenient oral dosage forms such as tablets and capsules is described.