For pharmaceutical purposes, micron-sized drugs are required for several dosage forms-such as for oral or pulmonary use. The common way for micronization is the milling of previously formed larger crystals. However, this technique is ineffective and shows disadvantages such as electrostatic effects, broad particle size distributions, and the creation of thermodynamically unstable areas due to the high-energy input. Disruptions in the crystal lattice can cause physical or chemical instability. In this study, microcrystals were not produced using comminution techniques but by controlled association in order to obtain naturally grown particles. The drug was dissolved in a solvent. Precipitation was carried out in the presence of hydroxypropylmethylcellulose (HPMC) as a stabilizing agent by pouring a nonsolvent into the solution rapidly. After drying the obtained fine disperse suspension by spray-drying, the drug is obtained as dry powder in micron-sized particle size. In this study, several drugs were exemplarily in situ micronized: in the case of the poorly water-soluble drugs for oral use, ibuprofen and ECU-R1, the technique is used in order to increase the dissolution rate. In the case of drugs for pulmonary use [ECU-R2 as an example of a poorly water-soluble drug and disodiumcromoglycate (DSCG) as an example of a water-soluble drug], the technique was employed in order to obtain a drug powder with an improved aerodynamic behaviour which results in an increased fine particle fraction. The properties of the in situ micronized drug powders were compared to the jet-milled drug. The dissolution rate is significantly enhanced (ECU-01:common drug, 4% after 20 min; in situ micronized: 93% after 20 min) due to the large surface, which is hydrophilized due to the adsorbed stabilizer as shown by a decreased contact angle. Furthermore, the powder flow is increased. As the in situ micronized drug powder is less cohesive compared to the jet-milled drug, the aerodynamic behaviour is improved, which results in an increased fine particle fraction (FPF < 5 mum). The FPF (measured without excipients and without an inhalation device) of jet-milled drugs is 7% (DSCG) or 13% (ECU-R2) while fine particle fractions of 75% (DSCG) or 78% (ECU-R2), respectively, are obtained with the in situ micronized powders. (C) 2004 Elsevier B.V. All rights reserved.