Pharmaceuticals companies are constantly battling the problem of polymorphism in which an active drug can actually exist in more than one form or crystal structure which can cause the drug to act in very different ways. Now researchers at the University of Warwick and Astra Zeneca have devised a new method of using solid-state NMR (nuclear magnetic resonance) equipment to spot unwanted polymorphs that should be adopted as a routine tool by pharmaceutical companies.
NMR equipment is already used to detect polymorphism in pharmaceuticals. However the standard technique looks at the carbon 13C nuclei in the drugs by a method called cross-polarisation magic-angle spinning (CP MAS). This is a very insensitive technique as only 1 in 100 carbon nuclei are the 13C isotope. This means that 99 out of 100 carbon nuclei are a NMR-invisible form of carbon. Only one-dimensional spectra are routinely possible from such an experiment.
Researchers have long wished to be able to couple this carbon based solid–state NMR technique with one that looks at hydrogen nuclei. It has been possible to look at hydrogen when the sample is a solution (solution-state NMR) but this is not as easy in solid-state NMR as the extensive network of coupled together 1H nuclei leads to broad lines in the spectrum that are hard to tell apart. This makes it almost useless when you are examining a tablet. Tablets are also particularly difficult to examine as the active drug within the tablet is combined with a mixture of other filler compounds (excipients).
This breakthrough by the Warwick team opens up hydrogen nuclei to useful study by solid-state NMR which will bring immense benefits to the study of polymorphism in drugs and organic molecules in general. This is because hydrogen atoms are central to hydrogen bonding (as opposed to carbon atoms which "observe" from afar). Hydrogen bonding is often the driving force in determining how organic molecules do differ in their methods of "3D packing" forming polymorphs or pseudo-polymorphs (pseudo-polymorphism referring to crystal structures that differ through the inclusion or non inclusion of small molecules, eg with or without water). This new NMR technique can identify which pseudo polymorph of an active pharmaceutical is present in a complete tablet.
The research team led by Dr Steven Brown from the University of Warwick’s Department of Physics have exploited recent developments in NMR hardware and pulse sequence design allowing them to gain high-resolution 1H solid-state NMR spectra by a method called CRAMPS (combined rotation and multiple-pulse spectroscopy). By using this high-resolution two-dimensional 1H CRAMPS solid-state NMR they obtained a spectrum for a tablet formulation in less than 2 hours, which is equivalent to the time required for a good 13C CP MAS one dimensional spectrum.
Dr Steven Brown said: "This Hydrogen 1H solid-state NMR method gives powerful new insight that complements established Carbon 13C based techniques - this new approach should be adopted as a routine tool in pharmaceutical characterisation"
Peter Dunn | alfa
Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)
North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich
Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.
The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
23.03.2018 | Event News
19.03.2018 | Event News
16.03.2018 | Event News
23.03.2018 | Materials Sciences
23.03.2018 | Agricultural and Forestry Science
23.03.2018 | Physics and Astronomy