Scientists of the D. I. Mendeleev Russian State Technical University, a participant of the Tulatech REC, have developed intestinal-soluble capsules of prolonged action for the treatment of chronic intestinal diseases

13/09/2021
Crohn's disease and ulcerative colitis are severe chronic intestinal diseases, against which there are no effective medicines yet. The main approach in their therapy is taking medications that reduce inflammation and restore the intestinal mucosa. At the same time, there are still no funds on the market that can gradually release the active substance inside the body, which could significantly increase the effectiveness of therapy.

Scientists of the D. I. Mendeleev Russian State Technical University, a participating university of the Tulatech REC, have developed a technology of intestinal-soluble capsules that contain a biopolymer complex. Capsules secrete the active substance at a controlled rate, which provides a prolonged effect and high bioavailability of the drug. In the near future, it is planned to conduct a series of preclinical studies of the safety and effectiveness of the drug, which will allow us to switch to the production of the drug.

- Despite the fact that these diseases have been known for a long time, there are still no effective means for their prevention and therapy. This is largely due to the multi-etiological nature of the occurrence of such diseases, as well as the lack of detailed molecular mechanisms of pathogenesis/ At the same time, there are already active pharmaceutical substances that have proven their effectiveness in the treatment of Crohn's disease and chronic colitis. And our task was to make a ready-made dosage form based on these compounds, which would have a prolonged effect, that is, for a sufficiently long time it could release the active substance in the body , " comments Andrey Kuskov, head of the Department of Technology of Chemical, Pharmaceutical and Cosmetic Products of the Russian State Technical University

To create a dosage form, the researchers used a biopolymer material that slowly dissolves in the body's environment. Before that, the specialists of the "Center for Strategic Planning and Management of Biomedical Health Risks" of the FMBA of Russia analyzed possible candidates of active molecules for the treatment of chronic intestinal diseases and selected specific active pharmaceutical substances — short-chain fatty acid and its derivatives. And the scientists of the RCTU have selected the necessary conditions for obtaining a ready-made dosage form-a complex that consists of a biopolymer and a pharmaceutical substance.

"It is important to emphasize that in our work we used all the raw materials available on the market and already approved for applications in pharmaceuticals," notes Andrey Kuskov. "We purchased the biopolymer, pharmaceutical substance, soluble capsules, and other related substances in the open access, our know-how was precisely the development of the technology for obtaining the complex "biopolymer + active substance", followed by its packaging in intestinal-soluble capsules. This approach significantly reduces the path to the actual production of the drug, if all the tests are successfully passed."

Drug trials and future plans

The researchers tested the developed dosage form according to the standards of the State Pharmacopoeia of the Russian Federation according to the methods for intestinal-soluble capsules. Scientists placed the capsules for a long exposure, first in an acidic environment, simulating their presence in the stomach, and then in an alkaline environment — to simulate being in the intestines. After certain periods of time, they took samples and determined the content of the active substance in the medium using chromatography and spectroscopy methods.

It turned out that the main phase of the release of an active pharmaceutical substance occurs precisely in an alkaline environment that mimics the intestines. At the same time, the rate of release of the active substance can be controlled by changing the parameters during the synthesis of the "biopolymer + active substance" complex. The researchers note that the biopolymer used in the work should not contribute to intestinal irritation, which often happens when using other substances, but such an effect has yet to be studied in subsequent experiments.

As a result, the scientists showed that the finished dosage form, which is an intestinal-soluble capsule containing the active substance, obtained using the technology developed by them, has the effect of prolonged release of the active substance at a controlled rate. They also produced an experimental batch of such capsules in an amount sufficient for conducting a series of preclinical studies of their effectiveness and safety, planned by the FSBI "CSP" of the FMBA of Russia.

"We expect that the planned preclinical studies of the dosage form developed by us will be successful and will allow us to proceed to preclinical studies of this drug in the future,” says Andrey Kuskov. "If successful, it will be possible to obtain a fundamentally new drug for the treatment of chronic inflammatory bowel diseases of a non-infectious nature, which will have a long-term, prolonged effect on the pathogenic intestinal microflora and an anti-inflammatory effect on epithelial cells.