Using Lipid Formulations To Enhance Bioavailability In Early Development

When a molecule enters Phase I, there are several options available for making a formulation. The commonly used approach is to use an API in a bottle or capsule formulation. These are especially suitable for compounds that have a sufficiently high bioavailability and low variability in pharmacokinetics (PK), as it is easier to bridge the Phase I formulation with the actual market formulation used in later phases. If a compound has medium variability and reasonable bioavailability, it is possible to use an already formulated approach that has an API blend in the capsule or tablet and softgel. This depends, though, on the specifics of the API and the options available. For highly potent APIs or low-dosed APIs, softgels may be a good solution, but an API blend in capsules or tablets is commonly used in early stages.

An estimated 70 percent of current research pipelines include increasingly complex molecules that are difficult to formulate due to high variability and/or poor bioavailability. These characteristics are often a major cause of product failures. To overcome this, lipidic systems have historically been used to take advantage of intrinsic digestion processes within the GI tract to facilitate the absorption of APIs and improve bioavailability. Yet, because there is no single “magic” formulation available that overcomes all challenges in relation to bioavailability, companies must screen various formulation options to explore which one offers the best bioavailability enhancement.

To prevent delays and costly issues during the development of these molecules, it is important to understand what potential mechanisms of increased absorption with lipid formulations and appropriate screening tools are available, as well as what subsequent steps should be followed for scale-up and industrialization.