Scientists develop 3D printed pills for controlled release within the body

In the future, 3D printed pharmaceuticals will take on unconventional shapes. These pills are far more than just an artistic innovation. They are intended to deliver controlled drug releases within the body. This breakthrough is the result from combining high-level computation techniques with the rapidly evolving field of 3D print to fabricate objects which dissolve in fluids according to a predetermined pace.

A joint team of Computer Scientists from the Max Planck Institute for Informatics in Saarbrücken, Germany, and the University of California at Davis have pioneered this technique, predicated solely on the form of the object for timed release. This development has significant implications for pharmaceutical companies, who are currently prioritizing 3D-printing research.

Regulating the levels of pharmaceutical drugs within patients’ bodies is a critical aspect of medication administration. In intravenous infusions, the concentration of the drug in the bloodstream can be calculated by multiplying the infusion rate by the proportion of the drug in the solution. Typically, a steady drug level can be achieved by first administering a high dose and then smaller maintenance doses. Oral administration makes it more difficult to adhere to this regimen.

A multi-component structure with different drug concentrations in different places is one solution, but this can be difficult to manufacture. The 3D-printing technology, with its unmatched ability to produce elaborate shapes, offers an alternative solution for freeform drugs that maintain a constant biochemical distribution. In this situation, the release of the drug is dependent solely on its geometric shape. This simplifies the control and assurance of drug delivery.

The project is led by Dr. Vahid BABAEI (Max Planck Institute for Informatics), and Prof. Julian Panetta from the University of California at Davis. The 3D printed pills are programmed to dissolve within a certain timeframe. This allows for controlled drug releases. The team uses a combination of mathematical modelling, experimental arrangement and 3D printing to create 3D forms which release timed amounts of drug as they dissolve. This technique can be used for oral administration to deliver predetermined concentrations of drugs.

The shape of the specimen (the active surface that dissolves), must achieve the desired time-dependent release. A given geometric form can be predicted to have a time dependent dissolution with some computational input. In the case of a ball, the dissolution corresponds to the decreasing spherical surfaces. The team of researchers proposes a simulation that is based on the geometric intuition, which states that objects will dissolve in layers. However, the challenge lies in reverse engineering – defining a desired release pattern first and subsequently identifying a shape that dissolves to match that release profile.

Topology Optimization (TO) is a solution that identifies shapes with certain properties by inverting simulations. TO was originally designed for mechanical components but has now been applied in a wide range of applications. The team has developed a topology optimization-based inverse design technique to determine shape from release behavior. Experiments confirm the dissolution, and the released curves are in line with the predicted values.

In the experiment, objects are created using a 3D printer that uses filament. A camera system is used to evaluate the dissolution, providing real measurements instead of theoretical calculations based on a mathematical formula. This is achieved by optically recording the solvent’s optical transmittance. Comparatively to other measurement methods that directly measure the concentration of active ingredients (e.g. This method is quicker and easier to implement than traditional measurement methods, which directly quantify the active ingredient concentration (e.g. The use of optical methods to measure active ingredient density has been established for some time, as in the case of determining grape juice sugar content (Öchsle) by refractometry during wine production.

Inverse design can be used to accommodate the different constraints of fabricability inherent in different manufacturing systems. The inverse design method can be used to produce extruded forms, which does not interfere with mass production. Other potential applications include catalytic bodies and coarse granular fertilisers.