3D printed pills with desired drug release
(Nanowerk News) Do not be surprised to see pills of an unusual shape in the future. They may look cute at first glance, but they can release drugs in the body in a controlled manner. Using a combination of advanced computational methods and 3D printing, objects are generated that dissolve in liquids in a predetermined manner.
A group of computer scientists from the Max Planck Institute for Informatics in Saarbrücken, Germany, and the University of California at Davis, have discovered a process that depends solely on the shape of objects for time-controlled discharges. This will have important implications for the pharmaceutical industry, which has recently begun to focus heavily on 3D printing.
Funny looking pills are not a design gimmick, they can release the drug in any desired time regime!
Controlling pharmaceutical drug levels in patients is an important part of treatment. In the case of intravenous infusion, the concentration in the blood is determined by the drip rate multiplied by the proportion of drug in the IV solution. A constant drug level can be achieved by initially giving a large dose and maintaining it from then on on smaller doses.
With oral administration, this regime is much more difficult to ascertain. One idea is to use a multi-component, multi-ingredient structure with different drug concentrations at different locations, which is difficult to fabricate. On the other hand, the major advances in 3D printing and its insurmountable ability to create complex shapes, make free-form drugs with constant biochemical distribution in the carrier materials currently a viable option. For such drugs, release depends only on geometric shapes, which are easier to ascertain and control.
The project led by Dr. Vahid Babaei (MPI for Informatics) and Prof. Julian Panetta (UC Davis), produces 3D objects that dissolve in the desired function of time, thereby releasing their content in a controlled manner. By cleverly combining mathematical modeling, experimental setup, and 3D printing, the team was able to 3D print a shape that produced the drug in a given amount of time as it dissolved. It can be used to regulate predetermined drug concentrations via oral delivery.
Since no external influences are possible after ingestion in the gastrointestinal tract, the desired time-dependent drug release must be produced by the (soluble surface active) form of the specimen. With a little effort, the time dependent dissolution can be calculated from a given geometric shape. For a ball, for example, it is highly proportional to the decreasing surface of the ball.
The research team proposed forward simulations, based on the geometric intuition that objects are dissolved one layer at a time. However, most practitioners are interested in first determining the desired release and then finding a soluble form that fits that release profile. Even with this efficient forward simulation, reverse engineering to find the right three-dimensional shape for the desired drug regime has significant difficulties.
This is where topology optimization (TO) finds application: the forward simulation is reversed to find shapes that exhibit certain properties. Originally developed for mechanical components, TO has gained a wide range of applications. The team was the first to propose a reverse design strategy to find the shape of the release behavior based on topology optimization. The dissolution was validated experimentally: the measured release curve was very close to the desired value.
In an experimental setting, objects are printed using a filament-based 3D printer. This dissolution is then evaluated by the camera system, i.e. it is measured actually, not just calculated by a mathematical model. For this purpose, the optical transmission of the solvent is optically recorded.
Unlike the measurement methods commonly used so far, which directly determine the concentration of the active substance (eg by titration), this method is much faster and simpler to perform. By the way, optical methods for measuring the density of active ingredients have been used for some time: when grapes are pureed to make wine, the sugar content (Öchsle) of grape juice is determined by refractometry.
Reverse design methods can also incorporate the different fabricability constraints of different manufacturing systems. For example, it can be modified to produce extruded shapes and thus not hinder mass production. Beyond the applications discussed in pharmaceuticals, further possibilities include the production of catalytic bodies or even coarse granular fertilizers.
