NIR studies back up usefulness of technique for QC
used to check the active pharmaceutical ingredient content of
tablets - even if they are present in very low quantities -
supporting its use in process analytical technology (PAT), a system
of quality control favoured by the US Food and Drug Administration.
Researchers at Pfizer and the University of London in the UK have shown that NIR can be used effectively for process control testing of Lipitor (atorvastatin), the company's top-selling cholesterol-lowering drug. And their work provides further evidence of the suitability of NIR as a faster alternative to conventional methods such as high-performance liquid chromatography (HPLC) in this setting.
The FDA's PAT initiative was unveiled in its final form a few days ago. In its report, the agency notes that conventional pharmaceutical manufacturing is generally carried out using batch processing, with laboratory testing conducted on collected samples to evaluate quality. While this is effective, the downside is that quality problems are often detected too late to avoid the loss of the affected batch.
Using PAT, which relies on real-time, in process measurements, it is hoped that problems will be picked up early, allowing remedial action to be swiftly taken.
In the latest study, the UK researchers conducted an experiment to study the feasibility of using NIR as a single tablet assay for atorvastatin in Lipitor 10mg tablets, to compare the results with those achieved at another site (to test reproducibility) and to see if the technique was transferable to an on-line process instrument, in accordance with PAT.
"This represented a significant challenge, due to the low concentration of atorvastatin present," they told the recent British Pharmaceutical Conference in Manchester.
NIR has become an established method of testing for actives in pharmaceutical products, particularly now that the European Medicines Evaluation Agency has drafted a guideline on the technique. However, its use has tended to be limited to those products containing high levels of active ingredient (i.e. more than 50 per cent w/w).
Using this approach, a small area of the tablet (typically 30 microns across) is scanned to produce a single NIR spectrum from which an image map is created. Once again, this can be compared to a reference database.
Nine bathes of Lipitor were tested in the study using two Bruker Matrix-T FT spectrophotometers, a process instrument configured for on-line tablet analysis. They found that equivalent and accurate readings could be taken between the two off-line instruments and the on-line instrument, and demonstrated the potential for transferring the method to further manufacturing sites, as samples from three locations were included in the development procedure.
Identifying counterfeit drugs
Meanwhile, another presentation at the BPC, by the same research group, showed that NIR can be used to identify counterfeit medicines, offering a quicker alternative to HPLC, which is time consuming and requires skilled personnel.
The technique was able to distinguish between Viagra (sildenafil), Pfizer's much copied drug for erectile dysfunction, and generic versions of the drug sold in areas of the world with looser intellectual property protection.
The power of the technique in spotting fake drugs comes in its ability to compare the spatial distribution of components within a tablet and compare it with other counterfeit samples, which could help in tracing their source.
