The system, arising from a collaboration between the drug company and the US Food and Drug Administration, has been made possible by advances in chemical imaging technology that make it possible to acquire and analyse high-resolution images rapidly.
At present, the main emphasis of quality control in pharmaceuticals is on the potency and purity of the ingredients in a blend. But this discounts other physical factors, such as the size and distribution of the ingredient particles - the active compound, lactose and magnesium stearate for example - that can also affect the performance of a tablet.
At present these parameters are not routinely looked at in pharmaceutical QC, although they are in troubleshooting scenarios, but this may be short sighted. Inadequate process control of the blending process can lead to final tablet quality problems, such as undesirable dissolution characteristics, poor hardness, inconsistent appearance etc.
Standard near-infrared (NIR) spectroscopy - tipped make up the lion's share of the process spectroscopy market in 2009 according to a recent report - can measure the constituents and average blending characteristics of a blend. However, a chemical imaging system provides additional information - including the identities and relative arrangement and sizes of component particles, providing a more complete assessment of the mixture.
The Pfizer/FDA chemical imaging project aims to use optical technologies to take a series of images at differing wavelengths of the components of a pharmaceutical mixture - as they are being processed in a scale-up or manufacturing class blender - and to use these to ensure that the mixture is sound.
The prototype, called the Blend Monitor, was designed by US chemical imaging company Spectral Dimensions. This firm has been active in the chemical imaging sector for years, but until now has focused on systems that operate at a much smaller scale. Neil Lewis, the company's chief executive, said that the Blend Monitor is the first and only system based on chemical imaging that operates at a process scale.
According to FDA documents, Pfizer embarked on the project under the terms of a Cooperative Research and Development Agreement (CRADA) with the agency under the auspices of the agency's Good Manufacturing Practice and process analytical technology (PAT) initiatives, both aimed at raising quality standards in pharmaceutical production.
PAT's primary goal is the development of analytical instruments that can be used in-process. The first prototype Blend Monitor does not quite fulfil this objective, as it still requires the blender to be halted before measurements can be taken, although it does have the advantage that samples do not have to be taken out of the blender and it is a non-destructive process.
"The main problem is that the blender cannot turn with the Blend Monitor in place at present," Lewis told In-PharmaTechnologist.com. The next engineering challenge will be to get the imager to rotate with the blender, allowing measurements to be taken without interrupting the process. This work will begin once enough data has been generated to prove the usefulness of the approach, he said, noting that the first of these results was presented at the IFPAC meeting earlier this month.
In time, Spectral Dimensions hopes to develop a commercial version of the system, and Lewis said that the company remains free to take the technology to other companies. However, it is not an inexpensive technology: the firm's lab-scale imagers cost in the region of $200,000, and he said it was likely that a process-scale version would cost around $300,000 at present, although additional engineering may cut that figure.