Analytical technique peeks inside oral dosage forms

A technique known as X-ray computed tomography (CT) can provide valuable insights when testing for substandard or counterfeit medicines, say Japanese researchers.

The team tested six brands of the cholesterol-lowering drug atorvastatin calcium bought over the Internet from Japanese language websites - including the originator brand Lipitor and various generics - and tested them for their drug content and how quickly they dissolved a release their active ingredient.

The products were bought from the top three websites appearing after a web search for Lipitor - the brand name for atorvastatin in Japan where it is co-promoted by Astellas and Pfizer - and tested them using a battery of techniques including Raman spectroscopy and powder X-ray diffraction (PXRD).

Of the six brands tested, the researchers found that all of the products had active ingredient levels within 2-4 per cent of the labelled amount (10mg) and almost identical dissolution profiles. One showed a significantly lower drug release than the others, however, which could suggest the tablet had a lower bioavailability.

To investigate further, the scientists used X-ray CT to image the interior of the tablets and found that while Lipitor and the other drugs had fairly uniform fine particles, the drug with the errant result consisted of "heterogeneous coarse particles and multiple massive aggregates" which could affect its performance.

While all the samples met Japanese specifications for atorvastatin tablets and looked similar using Raman, the use of X-ray CT provides valuable additional information about the make-up of the tablets.

"This is the first report applying X-ray CT to tablets obtained on the Internet and indicates that unqualified prescription drugs are easily distributed on the Internet without any quality assurance," write the authors.

"We expect that it could be used more widely to clarify the internal structure of the numerous other drugs available via the Internet."

The research is published in the Journal of Drug Delivery Science and Technology (February 2016).