Deformulation is analytical process of separating, identifying, and quantifying mixed components.
Deformulation may be used for product development including competitive product comparisons, determination of alternatives to prohibited or abolished components, and confirmation of product identity with existing patents and manufacturing technology.
For pharmaceuticals, analysis of the layer state (film thickness, uniformity) of coated particles and confirmation of component distribution in tablets are performed in particle design and formulation development to control disintegration properties and elution behavior.
To achieve reasonable formulation development, confirmation of polymorphisms of crystals to eliminate risk of patent infringement and grade analysis of polymers related to physical properties such as viscosity and melting point can be performed.
Also, it can be used to investigate root causes of defects/deviations such as cracks in tablets during manufacturing.
Eurofins Analytical Science Laboratories, Inc. uses the following analytical technologies in deformulation.
| Chromatograph | Spectrometer | Microscope |
|
- HPLC - LC/MS - GC/MS |
- FT-IR microscope - Laser Raman microscope - ICP-MS - NMR - Time-of-flight secondary ion mass spectrometer (TOF-SIMS) - X-ray diffractometer |
- Digital microscope - Energy dispersive micro fluorescent X-ray analyzer (Micro-XRF) - SEM-EDX - X-ray photoelectron spectroscopy analyzer (XPS) - Confocal microscope - 3D X-Ray Micro-CT Scanner |
The main features and application examples of analytical instruments used in non-destructive and imaging analysis are shown below.
The difference in material density enables non-destructive analysis without cutting the material. The resolution is 0.3 μm.
It is possible to observe the internal structure such as cracks inside the formulation and the filling degree of capsules, and also to measure the film thickness of the formulation and particles.
Application example
Capsule filling degree
Measurement of film thickness of particles
An image with three dimensional information can be composed. It can be measured under atmospheric pressure without pretreatment, and the surface morphology can be imaged in color. The altitude difference in surface shape, surface roughness, surface area, and volume also can be measured.
Application example
Measurement of surface shape.
SEM-EDX enables elemental analysis with high magnification. The measurement can be performed in low vacuum without deposition, in high vacuum with high resolution, or in low/high vacuum. A measurement depth is ~1 μm.
It is possible to confirm the dispersion of ingredients in a formulation (elemental mapping) by targeting elements specific to the formulation ingredients.
Application examples
Elemental Distribution
[Elemental Mapping (right)] Red: main ingredients, yellow: excipients, blue: talc, green: titanium dioxide
A Laser Raman Microscope enables to obtain information on the molecular and crystal structure of a sample. Unknown substances can be identified by Raman spectra.
The automatic height adjustment function enables mapping of uneven samples that are less affected by water and glass. The measurement depth is ~0.8 μm.
Using spectral patterns that are specific to the formulation ingredients, it is possible to check the dispersion of tablets, granules and coatings (component distribution mapping). It also allows confirmation of crystal polymorphism.
Application examples
Component Distribution
Red: main ingredient, purple: lactose, blue: corn starch, green: talc
TOF-SIMS allows mass analysis of organic materials such as metals and inorganic materials. It also enables surface analysis (a few nm) at a high detection sensitivity and mapping by molecular weight.
By mapping targeting m / z specific to each component, the component dispersion can be observed.
Application examples
Mass distribution
[Coating film (Left figure)] Green: Mg, Red: 69 m/z, Ble: 45 m/z
[Inner core tablet (Right figure)] Green: Main ingredients, Red and Blue: Additives
Eurofins Analytical Science Laboratories, Inc. has a solid background supporting pharmaceutical formulation development for 13 years as a subsidiary of Astellas Pharma.
Even if you are not sure of the goals you target, we carefully listen to you requests and needs, and propose the best analysis methods.
Even if you have the specific goals, the analysis methods used may not be optimal. We can also propose analysis methods that meet your requirements.
Commercially available FT-IR libraries are used for the identification of drug components. In some cases, several candidate substances are listed and it is difficult to identify which is the targeted substance.
Therefore, we use a library of more than 2,000 substances filed over the years, and combine with other instrumental analyses to identify pharmaceutical components.
The number of imaging data acquired in deformulation such as CT-X-ray analysis can be several thousand or more varieties. Typically, we select and provide most suitable data.
However, some customers may want to analyze details such as component distribution and surface roughness at this location.
To meet that need, we implemented the "WebLab System".
The WebLab system allows you and us to share screens over the Internet to provide real-time analysis instructions, share results, and explain analysis.
This allows us to have more accurate and speedy communication with customer, and we can accelerate formulation development.
Eurofins Analytical Science Laboratories, Inc. proposes optimal methods based on our knowledges to support your formulation development.
We support your formulation development by using our deformulation techniques. Please feel free to contact us if you have any questions and requests.