Investing in Techniques for Developing Amorphous Materials

The use of amorphous materials presents many opportunities for the pharmaceutical industry in terms of increased solubility and bioavailability, particularly as a growing number of insoluble active pharmaceutical ingredients (APIs) are developed.

However, materials with as much promise as amorphous solids are of course accompanied by significant challenges to overcome, in particular stabilising the structures while maintaining their advantageous properties.

Just 12 amorphous drugs are currently available on the market, although more are in development, and companies are investing in their capabilities in techniques such as spray drying and hot melt extrusion to further development in this area.

Developing amorphous materials

Hovione, one of the companies currently developing an amorphous drug, has been expanding its ability to produce amorphous materials in recent years, one of the key reasons for its strong performance in 2010.

Commenting upon the purchase of spray drying equipment from US firm Acusphere,Doug Hecker, a business development professional in the Particle Design Business, explained aseptic spray drying offers the "perfect, cost effective alternative" to lyophilisation in a number of cases.

He told in-PharmaTechnologist.com developers "historically went after the most stable form of the API" – the crystal form. This is in contrast to an amorphous material which has a less rigid crystal lattice, allowing for greater solubility and bioavailability.

As scientists sought to use the crystal form, spray drying was not a popular technology, however this is beginning to change.

"Scientists are now accepting spray drying as an enabling and commercially viable technology for all materials, including proteins and peptides [that] if done correctly, [generates] more consistent and homogeneous product," Hecker told the news provider.

Although he acknowledged while it is increasing in popularity, spray drying is not likely to become a common feature in manufacturing facilities.

Spray drying advancements

In September 2010, Bend Research announced it has been granted a patent for "making spray-dried solid amorphous dispersions of drugs using pressure nozzles."

The company claims the new patent helps address one of the key problems associated with traditional spray drying techniques, the production of fines – very small particles.

"As a result, solid amorphous dispersions produced using conventional processes often have poor flow characteristics and are difficult to collect efficiently and formulate into solid dosage forms," Bend Research explained.

By using a pressure nozzle as part of the spray drying process, dense particles are developed which are ideal for creating drugs in solid dosage forms.

The end produce has fewer fines and is simpler to handle downstream, but still holds the increased solubility and bioavailability of amorphous solids. 

Rod Ray, president and chief executive officer of the company, added: "Having patents that protect intellectual property offers them another key benefit by adding value to the formulations our scientists and engineers produce."

Hot melt extrusion

Another key technology in the development of more stable amorphous materials is hot melt extrusion (HME), which some argue offers benefits over many spray drying techniques.

"Operators can use HME to form solid dispersions in a continuous process but, unlike spray drying, solvent evaporation, and coprecipitation techniques, HME does not require organic or hazardous solvents," Erik Greb, writing for PharmaTech.com, said.

As the technique does not require either water or drying equipment, it allows manufacturers to conserve space within their premises, Greb explained. It is also a continuous process, meaning it is less time consuming than batch processing, and produces a more uniform disposal of small particles.

The process of extrusion, which has been used for some time within the plastics industry, involves forcing materials through a die under controlled conditions to create a uniform new material.

Again, the technology was said to not be widely used in the past due to unfamiliarity among those in the industry, but signs suggest this is now changing.

Bend Research last year invested in its third piece of equipment for HME, of an intermediate size, which it said would decrease the amount of a drug needed for development work.