Dr. Mike Marcus, Lumetrics Senior Scientist works as part of the development team to design and manufacture precision non-contact thickness measurement and optical inspection systems. While at Kodak, he developed the field of low-coherence interferometry for use in product assessment and manufacturing process monitoring and control.
The technology was developed to provide new measurement capability, including accurately measuring uniformity of thickness of photographic emulsions on coating hopper slides and determining the thickness and group index of refraction of semi-transparent solids and liquids. The scientific protocols required for this work can also be applied to the development of standardized testing for veterinary and human pharmaceuticals, in addition to medical devices.
Below Dr. Marcus answers some of the frequently asked questions about these applications.
Q: So, how does this type of measurement help a 503B drug manufacturer get the concentration of something like an ophthalmic suspension correct?
A: In a fluid such as eye drops, you could measure the refractive index of the suspension in a bottle at a known temperature after the production process. The refractive index would change with concentration of the fluid and also varies in a known manner a function of temperature. In the standard instrument we use is one wavelength, but you can use multiple wavelengths to improve the resolution of the instrument if required.
Q: Is this process measuring purity or concentration in a batch of ophthalmic suspension?
A: We infer the concentration from previous data on the index of refraction at particular wavelengths versus known concentrations. To determine purity, we will need to perform Raman or IR spectroscopy, elemental analysis, and/or mass spectroscopy to perform a chemical analysis. These tests are part of the quality analysis of any drug.
Q: Do you have a specific example of the type of ophthalmic product this can help measure?
A: Yes, consider a well-known ophthalmic product such as Restasis. It comes in little tubes which are tiny, sealed structures with just 0.2 millimeters each, one drop for each eye. It’s an interesting manufacturing process with just 0.01% active ingredient that needs to be measured. As such, we need to know the refractive index of the entire batch of product before it is packaged. This is where non-contact optical measurement tools come into play.
Q: Can this process be used for solids as well such as tablets, capsules or even medical implantable devices?
A: This is tougher. For thick coatings on tablets or capsules it could measure the thick coating or outer layer, but it can’t verify the drug itself. We can also measure the thickness of implantable materials, products made of plastic are good candidates for this. Stents, dental plates, catheters, and interocular lenses are all good candidates too.
Q: How else is this technology being utilized by your team?
A: We have a new product and multi-wavelength contact lens differentiator that helps product engineers verify which material is correct using the whole index of the refraction curve. This allows us to match things better to the eye and individually tune it for people.
In addition, anyone who makes coated materials using a hopper (a slide that liquid flows down the slide before it goes onto material). Optical interferometry can measure the coating before it goes onto any material. Then multiple probes can be used to assess the thickness of multiple layers. This minimizes startup time by setting up the hoppers for constant monitoring. This process can be used for all photo emulsions and solvent coated materials.
Q: Any last thoughts, Dr. Marcus?
A: There’s no doubt that quality assessment for pharmaceuticals is tough. However, using refractive light measurement is a very exciting new frontier. When we work with our clients, Lumetrics partners with them to design a manufacturing process for liquids so we can set it up and get the right concentration to ensure that their product meets all applicable quality standards.