In addition, SAS results in particles that have highly desirable properties for inhalation medicines. The particles generally are smaller than 10 µm and have a narrow size distribution. The process is tunable and can make 1–3-µm particles (e.g., for targeting the deep lung) or 3–5-µm particles (e.g., for targeting the upper respiratory airways). Particles made through SAS also are highly crystalline, free from amorphous domains, and, thus, highly stable. The particles' surfaces tend to be smooth and regular with low surface energy, and these characteristics reduce agglomeration and help improve downstream handling.

In the past 15 years, technology has advanced to the point where SAS can produce materials at manufacturing scale that comply with cGMP. New developments at CrystecPharma enable composite particles containing defined ratios of two or more drug substances (e.g., for combined drug therapy) to be manufactured. Clinical evidence indicates that SAS improves the performance of drug materials, compared with other manufacturing techniques. Products containing SAS-processed particles have improved drug bioavailability, led to simplified formulations, and reduced required doses, says York.

SAS also is superior to micronization in several ways. During micronization, particles are bombarded against the walls of a mill, and this intensive process can create high-energy sites on the surfaces of the materials being milled. These high-energy sites can cause potential chemical or physical changes in the material. One of the most problematic changes is the introduction of noncrystalline or amorphous domains in the product, which can reduce its stability. Micronized material also has highly charged surfaces and tends to be cohesive and difficult to disperse into an aerosol, says York.

If FDA approves Levadex, however, it would be the first product on the market manufactured through SAS. "That will take the risk out of these processes for a lot of potential clients," says York.