“They behave like stones in the body”
Her first steps on a long working day often lead Lena Mahlberg to the precision scales in Room 155, a lab in C Building on the PharmaCampus. Today, as on every other day, she is fully concentrated as she puts tiny white globules into small plastic tubes with a screw-top, determines the weight, adds fluids and weighs the tubes again. Lena Mahlberg is a pharmacist, and she is writing her doctoral thesis as a member of Prof. Denise Steiner’s working group at the Institute of Pharmaceutical Technology and Biopharmacy. Put in simple terms, she is looking in her research at the question of how poorly soluble drugs can be entered into the human body.
For pharmaceutical applications, this represents a challenge. On the one hand, such substances often have a great potential for the treatment of diseases. On the other hand, some trickery is necessary to get the organism to actually absorb them at all. “They behave like stones in the body,” is how Denise Steiner describes them. One strategy for making such a “stone” digestible in the intestine, she says, is to grind it down and turn it into fine “sand”. The trick is that the grains, which are just a few hundred nanometres in size, form a suspension with the surrounding fluid. One alternative is an emulsion. For this purpose, particles of the active ingredient are dissolved in oil and the oil droplets are distributed in water. “In this way, the bioavailability is increased – and the body can better absorb the active ingredient,” says Steiner.
Something else which represents a challenge is the question of how the active ingredient enters the body at all. In tablet form is obvious. But what about cases in which people cannot swallow any tablets – children for example, or older people who have difficulty swallowing? Some medicines which can be bought in pharmacies are administered by means of so-called orodispersible films which dissolve in the mouth and transfer the medicine straight into the blood via the mucous membrane in the mouth. Another strategy is based on the active ingredient being easily swallowed with saliva when the film has dissolved in the mouth. However, there are still some pitfalls in the case of poorly soluble active ingredients. Denise Steiner and her team are looking for ways to change this. A 2D pharma-printer adapted specially for the team’s research interests – and which is used in a similar form in the field of pharmaceuticals – makes it possible to manufacture orodispersible films containing active ingredients, and the researchers then examine the properties of these films. Today, Lena Mahlberg is preparing an “ink” containing an active ingredient.
The tiny white globules which she weighs aid the process. Later, acting as tiny “millstones”, their job will be to grind down in the centrifuge the active ingredient which Mahlberg will put into the test tube: griseofulvin, a naturally occurring compound which is used in research work as a model active ingredient. “We select the substances which we use not on the basis of their properties as active ingredients, but rather with a view to their chemical characteristics – representative of a series of substances with similar properties,” Mahlberg explains. She heads down the corridor towards Room 178, Here stands a dual centrifuge which propel the contents of the test tubes back and forth, as in a huge rattle, sometimes over the space of several hours. This makes it possible to keep the desired particle size of maximum 500 nanometres in diameter.
The next stop is Lab Room 179. Here, Mahlberg pours an orodispersible film made of cellulose-based gel onto a carrier plate. Using a so-called film-drawing device, she smooths it out and takes it back to the centrifuge room next door, where she puts it into a drying kiln standing next to the centrifuge. The drying process gives the film the correct consistency.
Now there is an interim stop in Room 175, where there is a special piece of equipment used for determining particle sizes – a so-called laser diffractor. On the basis of a laser beam which is deflected through the particles in the sample fluid, this device calculates the size distribution of the particles. This enables Mahlberg to check to see whether the active ingredient has been ground finely enough to be used for the further analyses to be undertaken. “This sample is a good one,” she says, clearly pleased. 90 percent of the particles are smaller than 500 nanometres.
It would be possible to produce an exact dose for each individual patient.
So, the “ink” is now ready. Lena Mahlberg takes it over to Room 155 – the lab with the precision scales. Here, too, the team’s centrepiece is to be found: the 2D pharma-printer. Mahlberg carefully places a cut-to-size piece of the orodispersible film on a holder and she applies the ink containing the active ingredient, using for this purpose a special syringe which she then fastens to the push button. She closes the front doors and programmes the printing programme on a control panel. The rest is performed by the printer alone: it presses unwanted air out of the fine tube through which the ink later flows; it calibrates the droplet size, then the print carriage starts up, applying the whitish ink to the film, dot by dot, until a grid consisting of 15 bite-sized rectangles is neatly covered in dots containing an active ingredient. The film is now complete.
However, Lena Mahlberg’s work is not yet finished. In subsequent steps in her work, she will check the finished product for its properties. How are the nanoparticles distributed on the film? How quickly will the film dissolve in the mouth? And how will the active ingredient be released? In order to find the answers to such questions, she takes as her guide the European Pharmacopeia, which contains rules governing tests on various forms of dosage. This enables her to lay down the basis for possible applications.
Behind all this there is the hope that maybe hospital pharmacies will be able in future to produce orodispersible films for their patients. “That would have a whole range of benefits,” says Denise Steiner. “It would be possible to produce an exact dose for each individual patient and thus reduce any side-effects.” It will also be possible, she adds, to print different active ingredients on one film. “There would no longer be any need for a cocktail of umpteen different tablets to be taken every day – as a lot of older people have to,” she says.
Author: Christina Hoppenbrock
This article is taken from the university newspaper wissen|leben No. 7, 6 November 2024
Background: Prof. Denise Steiner’s working group at the Institute of Pharmaceutical Technology and Biopharmacy
Prof. Denise Steiner is an engineer and has been heading the working group at the Institute of Pharmaceutical Technology and Biopharmacy at the University of Münster since 2023. One of the focuses of her research is the processing of poorly soluble active ingredients into firm, customisable dosage forms. Her group is working on the development of different nanoparticular systems which can optimise the way these substances are absorbed by the body and, as a result, improve their bioavailability. In this way, the same effects can be achieved with smaller dosages, and at the same time side-effects can be reduced.
Denise Steiner holds an endowed professorship in Pharmaceutical Technology which is being funded for ten years by the Rottendorf Foundation. After that, the University will be bearing the costs for the continuation of the professorship.