It’s well established that the oral administration is the preferred route of administration due to its non-invasive nature. The gastrointestinal tract is however a hostile environment designed to degrade ingested materials to facilitate uptake of nutrients, and simultaneously protect the intestinal epithelium. The drugs are exposed to various pHs, enzymes and mucus layers. The majority of new drug entities also suffers from poor solubility in the intestinal fluids, further complicating the process of reaching therapeutic drug concentration at the targeted site. As a consequence, many different formulation strategies have been evaluated based on the physicochemical properties of the drugs. Highly lipophilic compounds have successfully been formulated in solubilizing formulations e.g. lipid-based formulations. Drugs which poor solubility is attributed to the rigidity of their crystalline structure has been formulated in amorphous formulations e.g. amorphous solid dispersions.
The mechanism involved in the improved drug uptake is a complex interplay between the drug release, dissolution and digestion in the intestinal lumen, and the absorption over the intestinal epithelium. Yet, these parameters are commonly evaluated separately in vitro, disregarding the co-dependence of these parameters on each other. In 2019, we introduced an in vitro digestion-permeation model (the ENA) in which these parameters were studied simultaneously. The assay showed improved in vitro-in vivo correlation compared to the standardized models to evaluate lipid-based formulations in vitro. During the ERC PoC we aimed to further validate this assay and evaluate the performance of other drug formulations. However, meanwhile the ENA is highly valuable for mechanistic studies, the setup requires comparatively large amounts of drug. In addition, the sampling handling and analysis is time consuming. During the ERC PoC we aimed to develop a small scale, medium-throughput ENA (mENA) which will require smaller amounts of compound and formulation. The design would also allow for usage in automatic sampling equipment, further increasing the throughput. Within the ERC PoC we further aimed to identify a viable business proposition and strategy to bring the innovation. To ensure the solidity of the business we also aimed to develop a solid IPR strategy to guarantee commercial viability and novelty.
During the project, mENAs with different geometry has been designed and evaluated. The prototypes were 3D-printed and various membrane types were evaluated. Some key features have been identified, which impacts the drug flux over the absorptive membranes used in the system. Drug uptake from different formulation has been evaluated. The design facilitates the digestion of lipids – a necessity when evaluating uptake of drugs formulated in lipid-based formulations. In parallel, the full size ENA has been further validated for more drug formulations, results that are vital for the optimization of the mENA. To investigate potential business strategies, an executive market analysis was carried out within the project. Based on the outcome, a business strategy has been established. The insights gained during the market analysis have been incorporated into a business plan based on the ENA. A company, Enphasys, had been registered prior to the project start, and as the market analysis indicated that a service provider would be a viable option to bring the innovation to market work to attract customers were initiated resulting in attraction of our first paying costumer. Marketing material was also developed in parallel with the market analysis. Work concerning the IP rights were also evaluated within the project, and a patent was granted for the ENA (EP3678638 - IN VITRO INTESTINAL DRUG DISPOSITION DEVICE). During this process, the IP-rights of the ENA was transferred to the spin-off company Enphasys.
As the ENA is introduced to the market, more efficient formulation development can be achieved. The mENA developed in the project will allow for rapid screening of drug formulations, and unsuccessful formulations can be discarded at an early stage of drug development minimizing waste of time and resources. The top formulations can then be evaluated in the full sized ENA for a more mechanistic understanding of the processes involved, before moving into in vivo studies reducing the number of animals needed. This facilitates a more sustainably formulation development than currently being done. In the end, this will enable faster transition from drug discovery to patient use with reduced waste of time and resources.
