Dr Niklas Sandler, chief technology officer at Nanoform, explains why the use of nanonisation and artificial intelligence (AI) can help pharmaceutical manufacturers unlock added value for bioavailable nanoparticles.
Soluble Tablet
Nanonisation, the process of manufacturing nanometer-scale particles, is a powerful technique for increasing the bioavailability of drug substances by enhancement of dissolution rates and solubility. It is estimated that half of all drug substances currently working their way through pharma pipelines exhibit poor solubility. This can all too easily result in failure during clinical development, as poorly soluble compounds are absorbed less efficiently into the body. Overcoming the problem of low solubility by simply increasing dose is often not an option, as it can either be practically unfeasible or result in increased side effects. Nanoparticles have a clear advantage over microparticles in terms of bioavailability, which can best be explained by the difference in relative surface area between particles on the nanometer versus the micrometer scale. A 100-fold decrease in the size of a cubic particle will increase its surface area to volume ratio by 100 times. This dramatically increases the particle’s exposure to solvent and leads to an observed increase in dissolution rates, directly correlating to increased solubility and better absorption into the body.
One drug on the market for which this increased relative surface area was crucial for successful commercialisation is aprepitant, used in the treatment of chemotherapy-induced nausea. Aprepitant is a largely non-polar compound that shows very poor solubility in water and is absorbed through a small section of the upper gastrointestinal tract. It was only through the manufacture of nanoparticles that the drug could be made sufficiently soluble to take advantage of this narrow absorption window. However, the manufacture of these nanoparticles required a complex milling process, which is unreproducible for many drug substances in development, and introduces numerous excipients into the final drug formulation. New technology must therefore be investigated as a means to better overcome the industry’s formulation challenges and help enable more promising drug candidates to reach the market.