Periodic Reporting for period 1 - SMARTA (A sustainable small scale model for formulation absorption screening)
Reporting period: 2022-06-01 to 2023-05-31
In this project Enphasys AB has explored a new business leg targeting sales of a miniaturized version of its current patented enabling absorption (ENA) device. The ENA is designed to mimic the upper small intestine which is the most important region it the gut for absorption of medicines and nutrients. Enphasys is currently providing services to partners in need of a better understanding of absorption of formulated drugs, both during the early development stage and the later clinical stages. The ENA provides mechanistic description of the absorption and importantly has shown to be the tool to use to identify which formulation that will support the highest absorption in higher species and in humans. It is currently suggested to be used instead of animal experiments, or at least, to reduce the number of animal experiments needed. During interviews we have identified that customers are interested in a smaller tool, to enable early screening of formulation performance. The target product profile here is a tool that can be used in an automated setting and that is in demand of less amount of formulation and with less detailed information coming out of the experiments as compared to the ENA being acceptable. In SMARTA, Enphasys therefore explored the financial value of a small scaled version of the ENA, worked to build stronger communication strategies around the company and its products and services, and carried out extensive experimental validation of the small scale version to understand how feasible it is to establish the new intended business area.
During the course of the project, the small scale version of ENA has been prototyped with 3D printing and as absorption membrane a lecithin-in-dodecane impregnated PVDF membrane which has been attached to the 3D printed donor chamber through heating has been used. A number of designs and assay conditions have been explored; for IP reasons the details cannot be fully revealed. We have studied absorption of a series of drugs of different physicochemical properties and their flux across the membrane when administered as solutions, suspensions and more advanced formulations such as lipid-based formulations. The down-scaling from the ENA to the miniEna is significant; the donor volume that we currently explore is only 0.6% of the standard volume used in the ENA. In spite of this we have been successful in maintaining a 'small intestinal lumen' in the donor chamber with enzymes being present to digest and activate some f the formulations, and pH being consistent during the assay. The design has now been locked in and we have explored potential manufacturers of the device. We have concluded on a partner to work with during up-scaling of the production and a number of sustainable plastics have been identified that will be used in the first exploration around production and suitability for the studies that we are to undertake.
The product has been designed to be compatible with the typical automated settings used in liquid handling stations that are state-of-the art in pharma and biotech industries. During early customer meetings that initiated the exploration of this business leg of Enphasys this was identified as critical aspects. Based on the communication strategy that we have been developed during SMARTA we continued discussions with key opinion leaders and big pharma; these discussions have (without any need for us to bring up the topic) fully confirmed the great interest in a small scale ENA-like product that customers can make us of themselves n their screening efforts of good formulations. When successful, the mini-ENA and the ENA can replace the vast majority of the animal experiments done during the formulation development and optimization; and area that currently make use of 60-80% of all animals during drug development. Hence, we foresee the mini-ENA and ENA to be important 3R tools to reduce and replace animal experiments, activities that are strongly pushed within the EU as well as by the FDA.