By Dave A. Miller
There is a widening gap between the discovery of potential new drugs and their successful product development. Drugs are increasingly complex and diverge from Lipinski’s rule of 5, the industry standard for predicting a drug’s bioavailability and solubility. Contemporary literature reports that greater than 70% of new chemical entities (NCEs) currently in development are not easily dissolved in water and thus not practical for oral absorption. Most of these compounds require formulation intervention to enable sufficient bioavailability and achieve therapeutic efficacy. Amorphous solid dispersions (ASDs) are becoming invaluable in literally “solving” this drug solubility problem (see Figure).
The widespread adoption of ASD technology is apparent by the rapidly increasing number of commercial products and ASDs in late-stage clinical development. Spray-drying and melt-extrusion are the principal manufacturing technologies for amorphous dispersions, but even these venerable technologies are starting to fail to meet product development needs. Largely, this is because of the molecule’s high melting point, its poor solubility in organic solvents, or high molecular complexity and thermal instability. Hence, there is an immediate and growing necessity for advanced manufacturing and formulation technologies to meet the challenges presented by the complex molecules in contemporary development pipelines.
From the public’s perspective, this equates to potentially hundreds of medicines for many of today’s incurable diseases already discovered that are either inaccessible or at least many years away from becoming viable drugs available to help patients. Additionally, many drugs that do succeed in clinical trials and become approved medicines are not nearly bioavailable enough to work well. With new technologies in ASD, it may be possible to bring many more, higher efficacy drugs to patients.
KinetiSol is a pharmaceutical manufacturing technology that was adapted from the plastics recycling industry to overcome formulation and processing challenges specifically for amorphous solid dispersions. KinetiSol is a nonsolvent, mechanical process that rapidly mixes active pharmaceutical ingredients with pharmaceutical polymers at the molecular level with minimal thermal stress. KinetiSol has also been shown to overcome processing challenges with certain pharmaceutical polymers to enable their use in ASD applications for improved formulations.
At the November AAPS symposium entitled, “Enhanced Amorphous Solid Dispersions with KinetiSol®: Industry Case Studies,” I will present real world case studies by industry scientists that illustrate the applications of KinetiSol for the enablement of the ASD approach with challenging NCEs, expanded formulation options resulting in enhanced drug products, and improved manufacturing efficiency through non-solvent, short-duration thermal processing. Colleagues will also present advanced solid-state analytical techniques and biopharmaceutical performance evaluation methodologies utilized in their comparative evaluation of KinetiSol products versus those made by melt extrusion and spray drying. Additionally, keep an eye out for a special theme issue in AAPS PharmSciTech on advanced amorphous solid dispersions as well as a webinar answering the question, “What does one do when spray-drying and melt-extrusion fail?”