Matthias Wolfgang, Ioannis Koutsamanis, Martin Spoerk
• Optical coherence tomography enables real-time monitoring of co-extrusion processes.
• Tomographic reconstruction reveals defects and other morphological features.
• New insights into co-extrusion processes possible within fractions of a second.
• Excellent correlation between OCT and the reference (optical microscopy).
• Membranes up to 400 µm thickness reconstructed at a few microns resolution.
Co-extruded core-membrane formulations have been extensively explored as long-acting subcutaneous implants or vaginal inserts, guaranteeing zero-order release. Although the membrane thickness and homogeneity determine the final drug release, these parameters are still evaluated offline via destructive testing. The present study aims at tackling this shortcoming by introducing an in-line, non-invasive, fast and reproducible methodology based on optical coherence tomography (OCT) to evaluate the membrane characteristics of ethylene vinyl acetate (EVA) based co-extrudates. The novel setup enables a membrane representation and thickness analysis in real time during the manufacturing process, while the characterized membrane thicknesses are in good agreement with those obtained by optical microscopy. In addition, OCT offers novel insights into essential membrane characteristics that have not been visualized before. A case in point is the visualization of potential membrane defects, e.g. delaminated membranes, rough surfaces or viscosity mismatches in the core-membrane interface. Due to the obtained wealth of information combined with the instantaneous and destruction-free measurement, OCT has the potential to become the process analytical technology of choice for co-extruded dosage forms.
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A simple and User Friendly OSeeT software, monitors the growth of the coating thickness and other characteristics throughout the whole process or at-line measurement. Each black spot on the chart corresponds to one thickness evaluation. Individual evaluations can be reviewed clicking on the black spots.
Screenshot of the Results tab in our OSeeT Pharma 1D software at the end of a coating process
| Direct measurements with standard OseeT software | Indirect measurements with new development software | |
|---|---|---|
| Typical use case | monitoring of transparent or semi-transparent coatings without scattering pigments | monitoring of scattering coatings (containing e.g. TiO₂, Fe₂O₃ etc.), uncoated products investigation, correlation of compression force to dissolution |
| Coating layers | visible in OseeT images | not visible in OseeT images |
| Calibration and correlation | not necessary – initial results are available right after the first measurements | A model needs to be created to correlate light penetration depth with the desired parameters (coating thickness, compression force, dissolution time) |
| Evaluation | based on visible interfaces between coating and core | based on penetration depth of light into the sample |
| Example OCT images |  |
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| Images from | Wolfgang et al., Ascertain a minimum coating thickness for acid protection of enteric coatings by means of optical coherence tomography (2022) | Elisabeth Fink, Elen Gartshein, Johannes G. Khinast. Extending the Use of Optical Coherence Tomography to Scattering Coatings Containing Pigments |
Comment regarding direct measurement imgs: Imgs are from following time points: 65, 130, 240 min. Include the time points on the images on the HP as on the images of the indirect measurements
Samples measured at 3 different time points of a coating process.
Evaluated area shown in color.
Depending on the intended application, there are different systems or combinations of OseeT systems and probe heads available.
Base Unit | Use Case | Specification | Image |
HW 1.5 | Mainly tablets |
|  |
HW 2.0 | Samples with layer thicknesses between 12 µm and 150 µm (in certain cases up to 400 µm or more possible) Suitable dosage forms: tablets, pellets, polymer films, co-extrudates, transdermal patches |
Compared to HW 1.5:
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UHR OCT | Pellets with very thin coating layers starting from about 4.5 µm (UHR OCT is not recommended for tablets and coatings thicker than about 50 µm) |
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Sampling Device | Use Case | Characteristics | Image |
SDP | At-line measurements mainly with pellets or tablets |
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SDT | At-line measurement of tablets in a little perforated drum, mimicking an in-line coating process movement of the samples |
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Probe | Use Case | In-line installation | Image |
Pan Probe | Monitoring of drum coating processes, co-extrudates, films, patches |
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Fluid Bed Monitoring Probe | In-line monitoring for coating processes of pellets and other multi-particulates |
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OSeeT was originally developed for direct measurement of transparent and semi-transparent materials. High concentrations of pigments in the coating formulation (i.e., titanium dioxide or iron oxide) are scattering the light beam and therefore limiting the direct insight into the material. By establishing advanced image analysis metrics, a second stream of OSeeT software has been developed to evaluate coatings with highly scattering pigments as well as uncoated dosage forms (beta version).
Application range of OSeeT (in the pharmaceutical field)
Transparent or semi-transparent coated products
OSeDirect measurement of coating thickness, roughness, homogeneity for:
• Tablets and capsules at-line and in-line
• Pellets at-line and in-line
• Co-extruded dosage forms
• Thin drug layer of transdermal patches and oral films
Uncoated products
Indirect measurement of uncoated samples and correlation with critical quality attributes (e.g. dissolution or tablet hardness) – beta version of the software
Non-transparent coated products
Indirect measurement of the thickness of scattering coatings (beta version) and correlation with critical quality attributes (e.g. dissolution) – beta version of the software
