By Annabel Igonin, Senior Manager Pharmaceutical Formulation Development, Product Development, Lonza Ploermel, France and Jenifer Mains, Senior Manager Pharmaceutical Formulation Development, Product Development, Lonza Edinburgh, UK
A large majority (80% or more) of drug candidates currently under development are poorly water-soluble and experience bioavailability challenges, leading to difficulties in drug product formulation. Drug developers today also face accelerated development timelines, often due to specialized medicines and regulatory pathways such as orphan drugs, break-through and fast-track designations and NDA 505(b)2 programs. Both of these challenges are especially pressing for small or emerging pharma and biotech companies, which tend to lack resources in-house for bioavailability enhancement or rapid drug development.
Several technologies, including particle size reduction and nano-milling, salt formation, amorphous solid dispersions and lipid-based drug delivery systems, have extensive track records in enhancing oral bioavailability. These technologies can also be used in the context of accelerated drug development. But not all technologies are appropriate for all molecules, and developers can benefit from avoiding spending time and API testing different technologies.
The choice between enabling technologies depends on physichochemical and biologic parameters, as well as the target product profile of the candidate drug. One effective approach to technology selection relies on using in silico and in vitro formulation and testing methodologies that are highly correlated to in vivo performance. Such R&D-derived capabilities may help drug developers quickly and accurately select the most effective bioavailability-enhancing technologies for candidate molecules, avoiding a lengthier trial-and-error approach. For certain molecules, the most appropriate technology for bioavailability enhancement and accelerated development will be lipid-based formulations (LBF), supported by in silico development tools.