However, the s/o/w method requires a very low drug particle size in order to allow a complete encapsulation of the drug crystals. Due to the limited availability of micronized drug in the preclini- cal phases such material might need to prepared on a lab-scale. A number of drug properties including the hardness and elastic- ity of the drug crystals, the melting point, the hygroscopicity, and the sensitivity to thermal or other decomposition reactions will impact the selection of a successful method. For non-hygroscopic drugs a simple set-up with a smooth mortar and pestle might be appropriate to grind the drug and cooling the mortar on dry-ice will even increase the efficiency due to a higher brittleness of the drug at lower temperature. With this cryogenic grinding, drug particles less than 1–10 m can often be obtained. Hygroscopic drugs should be subjected to grinding in a controlled atmosphere, such as inside an air-tight grinding jar of a ball mill with liquid nitrogen cooling. However, a lower recovery is typical for such mills.