Abstract: Methods for screening and preparing solid forms are described herein. Such methods comprise sonicating a solid paste to provide a sonicated paste. The sonicated paste may be analyzed for the presence of solid forms.

Abstract: Proteins may be made by genetically engineered microorganisms, the protein being stored in the form of inclusion bodies (IB). The proteins in the inclusion bodies are in an insoluble and inactive form. They may be dissolved using a solubilisation reagent (18), and the resulting solution diluted so that the proteins refold into the active form. This refolding of the protein is enhanced by subjecting a solution or suspension of the protein to low intensity sound waves (25), at a low enough intensity that the protein is not denatured. The intensity may be between 10 and 100 mW/cm2.

Abstract: A crystalline material sufficiently pure for use in pharmaceuticals may be made by forming a saturated solution of the material, changing the temperature of the solution so it becomes supersaturated, and subjecting the solution to irradiation by high intensity ultrasound, the frequency of the ultrasound being scanned over a range of frequencies. For example the ultrasound may be varied between 19.5 and 20.5 kHz, and this variation may be sinusoidal. Preferably the ultrasound is provided only briefly, say for less than 5 s, before allowing the solution to cool gradually without further irradiation. The ultrasound may be applied using a vessel with an array of ultrasonic transducers attached to a wall, so each transducer radiates no more than 3 W/cm2 yet the power dissipation within the vessel is between 25 and 150 W/litre. This method can reduce the metastable zone width to less than 10 K. It is applicable in particular to aspartame.

Abstract: A crystalline material sufficiently pure for use in pharmaceuticals may be made by forming a saturated solution of the material changing the temperature of the solution so it becomes supersaturated, and briefly subjecting the solution to irradiation by high intensity ultrasound, before allowing the solution to cool gradually without further irradiation. The ultrasound may be applied using a vessel with an array of ultrasonic transducers attached to a wall, so each transducer radiates no more than 3 W/cm2 yet the power dissipation within the vessel is between 25 and 150 W/litre. This method can reduce the metastable zone width to less than 10 K. There is no erosion of the wall and consequently no formation of small particles of metal. It is applicable for example to aspartame, and to amino acids.

Abstract: Small crystals are made by mixing a solution of a desired substance with an anti-solvent in a fluidic vortex mixer in which the residence time is less than 1s, for example 10 ms. The liquid within the fluidic vortex mixer (12) is subjected to high intensity ultrasound from a transducer (20, 22). The solution very rapidly becomes supersaturated, and the ultrasound can induce a very large number of nuclei for crystal growth. Small crystals, for example less than 5 ?m, are formed. The resulting suspension is treated so as to add or remove ingredients, and then spray dried using an atomiser tuned to create small droplets in such a way that each droplet should contain not more than one crystal. Crystal agglomeration is hence prevented.