Preparation of norfloxacin spherical agglomerates using the ammonia diffusion system

J Pharm Sci. 1998 Apr;87(4):519-23. doi: 10.1021/js960463w.


Agglomerated crystals of norfloxacin were prepared by a spherical crystallization technique using the ammonia diffusion system (ADS). This technique makes it possible to agglomerate amphoteric drugs like norfloxacin, which cannot be agglomerated by conventional procedures. When an ammonia-water solution of norfloxacin is poured into an acetone dichloromethane mixture under agitation, a small amount of ammonia is liberated in the system. The ammonia-water solution plays a role both as a good solvent for norfloxacin and as a bridging liquid, allowing the crystals' collection to take place in one step. It has been proven that the agglomeration mechanism follows three steps: first acetone enters into the droplets of ammonia-water (this emulsion is formed because of the system characteristics); dissolved norfloxacin is consequently precipitated while the droplets collect the crystals; simultaneously, a part of the ammonia contained in the agglomerates diffuses to the outer organic solvent phase, thereby forming the norfloxacin spherical agglomerates. The correct selection of solvents has enabled us to obtain a suitable stable crystalline shape.

MeSH terms

  • Ammonia / chemistry*
  • Anti-Infective Agents / chemistry*
  • Calorimetry, Differential Scanning
  • Diffusion
  • Norfloxacin / chemistry*
  • Solvents


  • Anti-Infective Agents
  • Solvents
  • Ammonia
  • Norfloxacin