Crystalline active ingredient microparticles, method for producing the same and use thereof in drugs

Crystalline microparticles of a hydrophobic active substance prepared by a process comprising the steps of:

• preparing a suspension from primary particles of the hydrophobic active substance, the suspension comprising a solution of the hydrophobic active substance in a solvent having a solubility greater than 10 g/L, a non-solvent having a solubility less than 0.5 g/L for the hydrophobic active substance, and inert formed pieces having a particle size between 0.1-2 mm that do not dissolve in the solvent for the solution of the hydrophobic active substance or the non-solvent for the hydrophobic active substance, wherein a proportion of the inert formed pieces relative to the total volume of the suspension is about 20-80 vol. %, and wherein the primary particles of the active substance are crystalline and in the most stable crystal modification of the active substance;
• mixing the prepared suspension to cause crystallization of the hydrophobic active substance out of the suspension;
• separating the hydrophobic active substance in the form of particles;
• and
• drying the product particles, wherein the primary particles and the product particles are crystalline, are in the most stable crystal modification of the hydrophobic active substance, have a crystal surface area of 3-10 m2/g and the size distribution of the primary and product particles is each d50=1-2 μm, d99<6 μm and d100<12 μm.

Solid form particles comprising crystalline microparticles of a hydrophobic active substance and a hydrophilic, pharmaceutically acceptable excipient, the solid form particles formed by a method comprising:

• preparing a suspension from primary particles of the hydrophobic active substance, the suspension comprising a solution of the hydrophobic active substance in a solvent having a solubility greater than 10 g/L, a non-solvent having a solubility less than 0.5 g/L for the hydrophobic active substance, and inert formed pieces having a particle size between 0.1-2 mm that do not dissolve in the solvent for the solution of the hydrophobic active substance or the non-solvent for the hydrophobic active substance, wherein a proportion of the inert formed pieces relative to the total volume of the suspension is about 20-80 vol. %, and wherein the primary particles of the active substance are crystalline and in the most stable crystal modification of the active substance;
• mixing the prepared suspension to cause crystallization of the hydrophobic active substance out of the suspension,
• separating the hydrophobic active substance in the form of product particles,
• adding the hydrophilic, pharmaceutically acceptable excipient in a solution to the product particles, and
• drying the product particles and the hydrophilic, pharmaceutically acceptable excipient to produce the solid form of particles of the hydrophobic active substance, wherein the primary particles and the product particles are crystalline, are in the most stable crystal modification of the hydrophobic active substance, have a crystal surface area of 3-10 m2/g and the size distribution of the primary and product particles is each d50=1-2 μm, d99<6 μm and d100<12 μm.