GSK and AstraZeneca fund NMR studies in a bid to improve manufacturing QC

The studies, published in the Journal of Pharmaceutical Sciences and CrystEngComm, strive to wipe out variation in the active pharmaceutical ingredient (API) production or storage process produces a range of different polymorphs - or versions - of a desired compound by characterising all possible variations.

“By characterising all the polymorphs you understand all the manufacturing process, you understand the bioavailability, and you understand what variables on the production line could affect the compound,”​ Brown said.

“This is very important for manufacturers because the interactions between organic molecules are quite week. They can easily switch from one form to another, and this could provide different and adverse affect on patient.”​

The researchers say their work shows the broad spectrum of uses for NMR magnets – normally used to identify liquid structures – which now includes characterising solid dose form molecules thanks to the 'magic angle spinning' platform.

Lead researcher Steven Brown told in-PharmaTechnologist.com that: “NMR tech is not commonly used to test how solid particles dissolve because it only works on moving molecules. Well over 95 per cent of experiments are for applications in liquid solutions.​

“In our studies we used magic angle spinning which rapidly spins the solid state molecule so that the particles are not fixed. They still aren’t as free as liquid, but it’s good enough to use NMR on them.”​

The authors claim the tech is a leap forward for the industry, which is still commonly using the “largely ineffective”​ X-Ray diffraction method to characterise solid state molecules.

“The problem with X-ray diffraction is that a number of polymorphs do not readily form crystals of sufficient size and quality for their structure to be solved,”​ he said. "In other words, they do crystallise, but the crystals are very small."​

He added the new research could also speed up the patent process. “Manufacturers are now obliged to characterise the different polymorphs in order to gain patent approval,”​ he said.

When contacted to ask about the study, neither GSK nor AstraZeneca were available for comment, but Brown told us that both firms are now looking to bring the tech in-house.

No margin for error​

Speaking about the type of effect the wrong polymorph can have on a drug, Brown cited a case in the 1990s, in which Abbott’s HIV AIDS medication Norvir was rendered inactive my a slight variation in temperature.

Production was halted and Abbott withdrew the capsule.

Brown said: “This is avoidable when you know all the polymorphs.”​