Many active pharmaceutical ingredients dissolve only poorly in water. If a drug is taken orally in the form of a tablet, it is possible that the active ingredient dissolves only insuffi­ciently in the gastro­intestinal tract and thus cannot be completely absorbed by the human body. Increasing solubility and the associated increase in bio­availability is therefore one of the key challenges in current pharma­ceutical research. Over the past few years, a team lead by Cornelia Keck from the Philipps-Universität Marburg has developed a solution to this problem – “smartFilms” or paper tablets.

In this approach, the respective active ingredient is first dissolved in a suitable solvent. Subse­quently, commercial paper is loaded with the active ingredient solution. The solvent eva­porates and the active ingredient molecules remain distributed in the cellulose matrix of the paper. However, they do not crystal­lize but remain in an amorphous state up to a certain paper-to-active ingredient ratio. The advantage: the amorphous form of an active ingredient exhibits signi­ficantly increased solubility in aqueous media, thus enabling the application of poorly soluble drugs. “Our method represents a particularly simple and cost-effective way of stabi­lizing amorphous active ingre­dients”, explains Cornelia M. Keck, head of the working group at the Institute of Pharma­ceutical Technology & Biopharmacy.

Nevertheless, veri­fication of the crystal­linity state of the active ingredient is necessary. A team from the Semi­conductor Photonics group of the department of physics at Philipps University Marburg uses terahertz radiation for this purpose. “Since terahertz radiation interacts with crystal vibrations, it can be used to study crystalline solids, among many other things. Terahertz spectro­scopy is therefore well suited for determining the crystallinity of active pharma­ceutical ingredients,” says Martin Koch. In their study, the researchers inves­tigated indo­methacin, an analgesic that is mostly used in the course of rheumatic diseases, as well as for swelling or inflam­mation. They found that indo­methacin is amorphous up to a loading of 15 % in the paper.

At higher loadings, the active ingredient subse­quently crystallizes into a different crystal form, the alpha form. This dissolves better in aqueous media than the original crystal form of indomethacin and is therefore also an improve­ment on the commercially available (gamma) form. “One advantage of our studies using terahertz spectro­scopy is that we can measure the paper tablets non-destructively without having to first transfer them into smaller samples. This represents a significant advantage over the more established X-ray diffrac­tometry. Our results also illustrate that terahertz spectro­scopy can be a promising method in the quality assurance of pharma­ceutical products,” explains Enrique Castro-Camus, visiting professor in the department of physics at Philipps University Marburg. (Source: U. Marburg)

Reference: J. Ornik et al.: Non‑destructive crystallinity assessment of indomethacin in tablets made from smartFilms® using terahertz time‑domain spectroscopy, Sci. Rep. 12, 6099 (2022); DOI: 10.1038/s41598-022-10041-1

Link: Semiconductor Photonics, Dept. of Physics and Material Sciences Center, Philipps-Universität Marburg, Marburg, Germany