What is galenic pharmacy?

In many medications, the proportion of a certain active pharmaceutical substance is a mere one percent. What else is contained in a capsule?
This depends entirely on the active ingredient. In the case of substances that are not highly effective, such as antibiotics, this proportion is much higher – up to 50 percent. We are always talking about milligrams, amounts that patients are not able to weigh out themselves. For this reason, the medication is packaged and accurately dosed inside a pill which, in addition to the active ingredient, contains a number of excipients.

What is the purpose of excipients?
During the manufacture of pills, all substances are loaded into a press which shakes vigorously and forms the pill. The consistency must be just right. I compare it to building a sandcastle: if the sand is dry, the castle will collapse. This is why the material must retain some residual moisture which can be achieved through the prior production of a granulate. Other excipients include releasing agents and lubricants, as well as an enteric coating, which prevents the premature release of the active ingredient and assists in its delivery to the desired site of action.

And why are some pills small while others are quite large?
This has indeed something to do with the active ingredient. If it is voluminous, we still have to include excipients. This will easily result in a pill that weighs one and a half grams – and which is quite large as a result. Contraceptive pills, on the other hand, contain only a few micrograms of active substance, and these pills remain tiny even after the addition of excipients.

As an expert in drug delivery, you are responsible for the right mix of medications. How do you approach this task?
When working with novel substances, we first establish their solubility. Up to 90 percent of new substances perform very well during screening, but they must also be able to reach their target destination in the body. For highly soluble substances, it is sufficient to drink 200 milliliters of water with the medication. The substance will solubilize well inside the stomach, and it is subsequently absorbed in the small intestine. In these cases, formulation development is relatively simple as we are able to proceed in a standardized fashion. Substances of limited solubility present more of a challenge, and we must consider different approaches. At the same time, we must take into account the degree of permeation, meaning, how effective is this active ingredient inside the body, after it has permeated the cell membranes of the digestive tract and reached the blood? In the case of active ingredients with limited solubility, we have to employ one or the other formulation trick.

Tell us about it!
If I know that a substance is sensitive to acids, I can apply a certain coating to the pill to make sure that sensitive molecules will only be released inside the intestine. Improving the solubility of insoluble active ingredients may be achieved by spray-drying, and embedding them, together with excipients. There is also the hot melt extrusion method: solid solutions are manufactured in amorphous states which allows easy release of the active substance.

Pill, cream or injection: which dosage method is the best?
In most cases, the goal is for the patient to be able to take the medication orally. Every one of us prefers taking a pill to self-injection or even receiving a drug via an intravenous infusion. Those who ever had to give themselves thrombosis injections will know what I mean. Nobody enjoys this. This is why we in formulation attempt to make active substances available in pill form. However, this is not always possible. For example, large molecules such as insulin preparations would be digested in the stomach, and they would not be able to be transported across the intestinal lining into the bloodstream – or to such a small extent that we would create unacceptable side effects. There are also many substances which are not stable at room temperature, including insulin.

In this case, what do you do?
We are quite familiar with the properties of most pharmaceutical ingredients, which means that we know whether it makes sense to explore different dosage forms. If it is not worth it, we follow a different route of drug administration early on: injection or the transdermal patch which releases the active substance into the skin. The advantage of the patch is that the pharmaceutical can be kept at a consistently high level.

How is the active ingredient transported to its destination?
This is exactly what is being tested during pharmacokinetic studies. This area of research is about determining how the substance behaves inside the body; how it is distributed and metabolized, and how quickly it is excreted. Thanks to its countless tiny folds and villi, the small intestine has a huge surface area through which substances reach the blood and subsequently circulate through the body. Medications, however, are intended to work only in a specific area inside the body, which is achieved thus: in the case of localized pain, for example, enzymes are released, and the anti-inflammatory medication inside a pill attaches itself to this very enzyme. The medication is recognized in the exact location where it is needed – the classic lock-and-key principle.

And this works every time?
Like with any key, sometimes you manage to get it into the lock, even though it’s not a perfect fit. You will not be able to open the door, the key is stuck. An active pharmaceutical substance will sometimes end up in places where it does not fit one hundred percent. This is how side-effects are triggered.

Is this one of the major goals of modern drug delivery science: minimizing side effects?
Absolutely. We want to manufacture medications in such a way that ideally their effect will only play out in the target cell. Much progress is being made at the moment, especially in the field of oncology; instead of relying on the shotgun approach, targeted therapies are now more frequently employed. At the same time, I believe that there will never be therapies that are entirely free of side-effects. But of course, we want to improve therapies overall – with evermore effective medications.

This takes a lot of stamina and patience. Only very few drugs will make it to the pharmacy.
It’s true, we must be quite resilient. High frustration tolerance helps in times of setbacks. I mainly work on RNA formulations; I was quite emotional when I received my first mRNA vaccine – our own academic research for the past 20 years has contributed to bringing RNA therapeutics closer to application. In the pharmaceutical industry, it is more likely to be involved in novel product development on a regular basis.

Artificial intelligence could increase the success rate. How far has drug delivery research advanced?
The development of active pharmaceutical substances – before drug delivery is considered – has already come a long way. With respect to drug delivery, the application of AI is still in its infancy – even though in many cases, AI is better equipped than humans to recognize connections: if pharmaceutical ingredients must be combined with multiple excipients, we experiment until all the respective proportions within the formulation are optimized. This involves much trial and error. We could probably do without some of these experiments, although this is also the part that is especially exciting.

What can we expect from future medications?
Better sex-specific efficacy – meaning, gender medicine. But also improved ability to treat children in a more targeted fashion; after all, they are not mere “little adults”. And from a research perspective, we would like to support personalized therapy: developing medications that are a perfect fit. Finding a way to make individual treatments that don’t overwhelm our health system possible – this is what we are working on.