Matthias Wolfgang a 1, Sandra Stranzinger a 1, Johannes G. Khinast a b
Matthias Wolfgang a 1, Sandra Stranzinger a 1, Johannes G. Khinast a b
Enteric coatings are designed to protect active pharmaceutical ingredients (APIs) against untimely release in the stomach. Acid protection of such coatings depends on the coating layer thickness and integrity, which must be determined in an accurate and reliable way to ensure the final product’s desired performance. Our work addresses the use of optical coherence tomography (OCT) for characterizing the coating thickness and variability of an enteric-coated drug product and linking them to resistance against gastric fluid. In this study, three batches of enteric-coated tablets drawn during the manufacturing process were investigated. An industrial OCT system was used to establish the coating thickness variability of single tablets (intra-tablet), all tablets in a batch (inter-tablet) and between the batches (inter-batch). Based on the large amount of OCT data, we calculated a critical coating thickness for the investigated film coating, which was found to be 27.4 µm. The corresponding distribution has a mean coating thickness of 44.3 µm ± 7.8 µm. The final coated product has a final mean coating thickness of 63.4 µm ± 8.7 µm, guaranteeing that all tablets meet the quality criterion (i.e., acid protection). Based on the measured thickness distributions, already known distribution functions were considered and an additional, new function was proposed for characterizing the coating thickness distributions in the early stages of industrial coating processes. The proposed approach can be transferred to in-line monitoring of the tablet coating processes, which could drastically improve the production efficiency by ultimately allowing real-time release testing (RTRT).
https://www.sciencedirect.com/science/article/abs/pii/S0378517322002356?via%3Dihub
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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 |
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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
