Scientists develop shape-controlled drug delivery system

In the future, it won’t be surprising to come across pills with unconventional shapes. While they may appear amusing at first glance, these pills serve a purpose by releasing pharmaceuticals in a controlled manner inside the body. Thanks to a combination of advanced computational methods and 3D printing, it is now possible to create objects that dissolve in liquids according to a predetermined schedule.

A team of Computer Scientists from the Max Planck Institute for Informatics in Saarbrücken, Germany, and the University of California at Davis has pioneered a process that relies solely on the shape of an object to achieve time-controlled drug release. This development holds significant implications for the pharmaceutical industry, which has increasingly embraced 3D printing technology.

These peculiar-looking pills are not merely a design gimmick; they have the ability to release medication at desired intervals. Maintaining controlled drug levels in patients is a crucial aspect of medical treatment. In the case of intravenous infusion, the concentration of a drug in the bloodstream is determined by the infusion rate and the proportion of the drug in the IV solution. Achieving a constant drug level through oral administration is much more challenging.

One approach is to use multi-component, multi-material structures with varying drug concentrations at different locations, but this poses manufacturing difficulties. Conversely, the progress made in 3D printing allows for the creation of complex, free-form drugs with a consistent distribution of the active compound within the carrier material. For such drugs, the release mechanism depends solely on the geometric shape, which is easier to control and ensure.

Led by Dr. Vahid Babaei from the Max Planck Institute for Informatics and Prof. Julian Panetta from UC Davis, the research project involves printing 3D objects that dissolve over time, effectively releasing their contents in a controlled manner. Through a combination of mathematical modeling, experimental setups, and 3D printing techniques, the team is able to manufacture 3D shapes that deliver drugs in a timed manner when they dissolve. This method can be utilized to achieve predetermined drug concentrations through oral delivery.

Given that no external influence is possible once a drug is ingested into the digestive tract, the desired time-dependent drug release must be generated solely by the shape of the pill and its active dissolving surface. With considerable effort, the time-dependent dissolution can be calculated based on a given geometric shape. For instance, the dissolution rate of a sphere is strictly proportional to the diminishing surface area of the sphere.

The research team proposes a forward simulation approach, which assumes that objects dissolve one layer at a time. However, practitioners are primarily interested in defining a desired release profile and subsequently finding a shape that dissolves according to that profile. Even with an efficient forward simulation, reverse engineering to determine the appropriate three-dimensional shape for a desired drug regime presents significant challenges.

This is where topology optimization (TO) comes into play. Originally developed for mechanical components, TO has now found diverse applications. The team is the first to propose an inverse design strategy that utilizes topology optimization to find a shape based on desired drug release characteristics. The dissolution behavior is validated through experiments, with measured release curves closely aligning with the desired values.

In the experimental setup, objects are printed using a filament-based 3D printer. The dissolution process is then evaluated using a camera system, allowing for actual measurements rather than relying solely on mathematical models. This optical transmittance method of measuring dissolution is faster and simpler to set up compared to conventional techniques that directly determine the concentration of active ingredients through titration. Optical methods for measuring the density of active ingredients have been used for some time now—for instance, determining the sugar content (Öchsle) of grape juice in winemaking through refractometry.

The inverse design method can also incorporate various constraints related to the manufacturability of different systems.

Source: Max Planck Society

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