By Dr. David K. Lyon, Ph.D., Senior Fellow, Research
Bioavailability challenges are among the toughest problems faced by today’s formulators. Most of the prospective drugs in pharmaceutical pipelines today have low solubility, which means the active therapeutic ingredients can’t be absorbed when patients take them orally. In many cases, this low bioavailability can mean promising medicines are abandoned because no technology can be identified that delivers the required therapeutic dose conveniently.
To solve this critical problem—which industry experts estimate affects as many as 7 in 10 of the compounds in pharmaceutical pipelines today—numerous approaches have been developed. These include the use of salts, cocrystals, amorphous solid dispersions, and nano- or microcrystals manufactured with a variety of technologies—spray drying, particle-size reduction, hot-melt extrusion (HME), cyclodextrin complexation, and lipid-based technologies. These approaches may enable development of low-solubility compounds, bringing new medicines to market or reformulating existing products to improve performance, extending the product lifecycle.
However, the wide array of these enabling technologies spawns another dilemma for formulators: how to choose the optimum technology from among this sea of choices. What factors need to be considered and how can the selection process be streamlined so the development of promising compounds is not delayed?
At Lonza, we’ve studied technology selection in depth and developed a science-based process to guide development of low-solubility compounds to improve bioavailability. Our approach recognizes several important facts.