Dissolving market hurdles

25 May 2010

Development of a new formulation for poorly soluble drugs increases stability and dissolution, clearing the way to commercialization

A new formulation of the common pain reliever ibuprofen that makes it more soluble takes the headache out of commercialization.

A new formulation of the common pain reliever ibuprofen that makes it more soluble takes the headache out of commercialization.

© iStockphoto/REKINC1980

A means of processing poorly soluble drugs so that they can be stored as a solid, but rapidly dissolve and disperse once inside the body, has been developed by Shou-Cang Shen and co-workers at the Institute of Chemical and Engineering Sciences of A*STAR, Singapore.

The method, now under a Patent Cooperation Treaty international patent, uses a silica-based powder, SBA-15, to entrap drug molecules in pores of between 5 and 30 nanometers diameter. The pores in this material hold the molecules in an amorphous state and prevent them from forming lower-energy crystals that are poorly soluble and less active. The technology can be easily scaled-up for production and could open the way for previously discarded, biologically active compounds to be commercialized.

More than a third of the drugs listed in the US pharmacopoeia, and about half of active new compounds found or synthesized, are poorly water soluble; this limits their potential for commercialization. Much effort has been expended on investigating different ways of formulating such compounds to increase their capacity to dissolve. This essentially means limiting their reversion to a crystalline form. Until now, the techniques tried all had drawbacks.

SBA-15 is one of a newly discovered series of porous silica materials. The thick-walled pores of this powder are about the right size for storing typical drug molecules.

Using ibuprofen—a well-known, non-steroidal, anti-inflammatory drug and pain reliever—as a test compound, the researchers trialed several different methods of loading it into SBA-15. On the basis of two measures—how much ibuprofen could be carried, and what proportion of the drug ended up in crystalline form—they determined that the most effective method was ‘co-spray drying’, where equal amounts by weight of ibuprofen and SBA-15 are dissolved in ethanol. The resulting liquid was dried into a powder by spraying it as fine droplets into hot air.

The researchers stored the co-sprayed powder under the stressful conditions of 40 °C and 75% relative humidity for up to a year, and found it to be remarkably stable. Finally, they measured how quickly ibuprofen dissolves into water from the co-sprayed powder—95% was released within 15 minutes and it was completely dissolved within 50 minutes. No other method of delivery of ibuprofen, including pure crystals, was 100% dissolved within an hour.

“We are now doing optimization studies on the process,” says Shen. “Our objective is to overcome the scientific obstacle of bringing poorly soluble active ingredients to market.”

The A*STAR-affiliated researchers mentioned in this highlight are from the Institute of Chemical and Engineering Sciences.

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Shen, S.-C., Ng, W.K., Chia, L., Dong, Y.-C. & Tan, R.B.H. Stabilized amorphous state of ibuprofen by co-spray drying with mesoporous SBA-15 to enhance dissolution properties. Journal of Pharmaceutical Sciences 99, 1997–2007 (2010). | article

This article was made for A*STAR Research by Nature Research Custom Media, part of Springer Nature