Many new drugs have solubility issues which can hinder their proper absorption by the body. Researchers at Harvard University in the US, in collaboration with École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland, have developed a new method to prevent the crystallization of active compounds, thereby increasing bioavailability.
Dr. Ester Amstad, and associate professor at EPFL, and the lead author on the publication said, “Each year, pharmaceutical companies refuse many drugs during early stages of their development because of their poor solubility in the body, which prevents their efficient uptake by the human body.” The results of the study were published in the journal, Science.
As many pharmaceutical compounds have a regular, organized molecular structure – or crystalline structure – it can be challenging to get these drugs to dissolve efficiently, after they are taken. The goal of Amstad’s research was to increase the solubility of these drugs, without changing the structure so much so that it would negatively impact drug loading, or complicate the formulation process.
“You have to imagine that the molecules will naturally group themselves in a crystalline form – if they are formulated using standard procedures – as molecules have enough time to arrange regularly,” said Amstad. “The method developed to suppress this process is very innovative. With this technique, we can increase the solubility of these drugs more than ten-fold.”
The researchers began by dissolving the drugs in an ethanol solution. Then, the solution was added to a microfluidic nebulizer that dropped nanoparticles of the liquid into a very fast moving stream of air. The air flows through a thin tube approximately the diameter of a human hair.
Due to the speed of the air in the tube, the alcohol evaporates from solution extremely quickly, and the dissolved drug molecules aren’t given enough to time to form crystal structures. The dried particles have a disorganized, amorphous structure which allows them to dissolve very quickly, and be more efficiently absorbed.
According to the researchers, this technique is still in the developmental stages, and is not ready to be scaled-up for industrial fabrication of ultra-soluble medications. It currently takes one hour to turn 5 milligrams of crystalline substance into amorphous nanoparticles.
This new technique has wide implications in pharmaceutical manufacturing, the food industry and surprisingly, in the protection of the environment. Due in part to the poor solubility of some currently-approved pharmaceuticals, the drug load in a single dose is higher. The unabsorbed fraction is expelled through the urine, and potentially ends up in lakes and groundwater.
“Increasing the solubility of these drugs could solve this issue. Although this was not the main goal of the project, this is a beneficial side-effect,” said Amstad.
- Preventing Crystallization to Improve Drug Efficiency – http://www.dddmag.com/news/2015/09/preventing-crystallization-improve-drug-efficiency
- Amstad, E., Gopinadhan, M., Holtze, C., Osuji, C., Brenner, M., Spaepen, F., and Weitz, D. (2015). Production of amorphous nanoparticles by supersonic spray-drying with a microfluidic nebulator. Science. 349 (6251), 956-960.