Particle size reduction of an antimuscarinic compound

摘要

A stable crystalline micronized particulate of a glycopyrronium salt may be prepared by suspending the drug in a water-immiscible anti-solvent in which the drug has little or no solubility and micronizing the suspension. The resulting drug particles are physically stable with regard to agglomeration and/or aggregation on storage.

主权项

1. A process for preparing micronized particles of a pharmaceutically acceptable salt of glycopyrronium, said process comprising:
feeding an anti-solvent, which is a water-immiscible hydrocarbon or derivative thereof which is liquid at room temperature and pressure, and has a dielectric constant lower than 15 and a density of 1.3 to 2 g/cm3 to a micronization chamber of a wet milling apparatus, which optionally contains a grinding medium; suspending particles of the glycopyrronium salt in said anti-solvent, to obtain suspended particles; micronizing said suspended particles at a pressure equal to or lower than 200 kPa, to obtain micronized particle; and optionally, drying said micronized particles, whereby at least 90% of said micronized particles have a diameter of less than 10 microns.