Process analytical technology (PAT) is defined by the FDA as a mechanism to design, analyze, and control pharmaceutical manufacturing processes through the measurement of critical process parameters that affect critical quality attributes of an active pharmaceutical ingredient (API).
Continuous manufacturing is a method of producing pharmaceutical products from start to finish on a single, uninterrupted production line. This process is in contrast to batch manufacturing, which requires transporting, testing, and re-feeding materials from one process to the next.
Optical coherence tomography (OCT) is a technique for obtaining sub-surface images of translucent or opaque materials at a resolution equivalent to a low-power microscope. It is effectively ‘optical ultrasound’, imaging reflections from within tissue to provide cross-sectional images.
Tablet coating is a process by which an essentially dry, outer layer of coating material is applied to the surface of a dosage form in order to confer specific benefits over uncoated variety. Coatings may be applied to various oral dosage forms such as particles, powders, granules, crystals, pellets and tablets.
The objectives of tablet coating include:
– Masking the bitter taste and unpleasant odor of some drugs.
– Improving product appearance for aesthetic or commercial purposes (aiding in brand identification).
– Improving product appearance for aesthetic or commercial purposes (aiding in brand identification).
– Preventing drug-induced irritation at a specific site within the gastrointestinal tract, e.g. the stomach for non-steroidal anti-inflammatory drugs (NSAIDs).
– Protecting the drug from the external environment (particularly air, moisture, and light) in order to improve stability.
– Enhancing ease of swallowing large dosage forms.
– Facilitating handling, particularly in high-speed packaging/filling lines, and automated counters in pharmacies, where the coating minimizes cross-contamination due to dust elimination.
– Reducing the risk of interaction between incompatible materials.
– Retarding loss of volatile ingredients.
– Modifying and/or controlling the rate of drug release as in repeat-action, delayed-release (enteric-coated) and sustained-release products.
– Controlling the site of action of drugs e.g., colon delivery.
– Avoiding inactivation of drug in the stomach e.g., enteric coating
The thickness of a film coating on a product can vary depending on the specific requirements of the drug product. The thickness of the coating can be measured using various techniques, including lever micrometer, OCT, magnetic dry film thickness gauge, eddy current dry film thickness gauge, and destructive testing
In the pharmaceutical industry, coating process is a technique used to apply a coating to the surface of a dosage form in order to confer specific benefits over uncoated variety 1. Coatings may be applied to various oral dosage forms such as particles, powders, granules, crystals, pellets and tablets 1.
An enteric coating, also known as gastro-resistant coating is a barrier applied to oral medication that controls the location in the digestive tract where it is absorbed
Functional coatings are a class of coatings that provide additional functions beyond the traditional protection and decoration properties.
Dissolution test is done to verify the release of drug in the solution for a pharmaceutical products.
Is the force applied in a tablets press in order to obtain a tablet
It is a device to apply a coating to a product
Involve assessing manufacturing facilities, processes, and quality control to ensure compliance with regulatory standards.
Pharmaceutical are substances used for medical treatment including, including drugs and medication.
Uncoated tablets are solid dosage forms of pharmaceutical that do not have a coating or outher layer.
Coated tablets are pharmaceutical whit a layer of coating applied to the outer surface of the tablet
The compression index in pharmaceuticals refers to the ratio of the final tablet volume to the initial volume of the powder blend before compression.
Small, free-flowing particles formed by agglomeratingor combining powdered ingredients
Are small spherical or spheroidal multiparticulate units
It is a fluid bed tecnique use to coat particles with a nozzle place in the top of the machine
Food and Drung Administration, is a regulatory agency responsible for protecting and promoting public health by controlling and supervising the safety
Any instrument, apparatus, contrivance, or machine designed for a particular purpose
A pharmaceutical processing equipment used in the film coating of solid dosage forms like tablets, pellets, or granules.
Measure of mass per unit volume and is typically expressed in units such as grams per cubic centimeter (g/cm³) or kilograms per liter (kg/L).
The unevenness or irregularity of a surface.
The state of being uniform, consistent, or similar throughout.
Machine used for coating tablets or other solid dosage forms
In the pharmaceutical industry, “in-line” can be used to describe a production process in which analyses are performed during production itself, rather than on samples taken after production 3. This approach can help to identify and correct any issues during production, reducing the risk of batch failures and product recalls 3.
In the pharmaceutical industry, real-time batch release is a process that allows for the release of a batch of a drug product based on real-time data collected during the manufacturing process. This approach is intended to provide a more efficient and streamlined process for batch release while maintaining the required quality standards.
In the pharmaceutical industry, batch release is a process that ensures that each batch of a drug product has been manufactured, tested, and released in compliance with regulatory requirements 1. The batch release process is typically performed by a Qualified Person (QP) who is responsible for certifying that the batch meets the required quality standards
Interferometry is a technique that uses the interference of superimposed waves to extract information. It is used in various fields of science and industry, such as astronomy, optics, metrology, and spectroscopy. In optical coherence tomography (OCT), interferometry is used to capture images of the internal structure of a sample at different depths. This is achieved by measuring the time delay and intensity of light reflected from different layers of the sample
A spectrometer is a scientific instrument used to separate and measure spectral components of a physical phenomenon 1. Spectrometers are used in many applications, including industrial automation, automotive systems, medical devices, and consumer electronics
In the field of optical coherence tomography (OCT), depth scan measurement refers to the ability of an OCT system to capture images of the internal structure of a sample at different depths. This is achieved by measuring the time delay and intensity of light reflected from different layers of the sample
Direct thickness measurement is a term used in the field of measurement technology to describe the ability to measure the thickness of an object without contact 1. There are several techniques available for direct thickness measurement, including optical coherence tomography (OCT), ultrasound imaging, and laser scanning
The term “sensor” can refer to a wide range of devices that detect and respond to physical stimuli such as light, sound, temperature, pressure, and motion. Sensors are used in many applications, including industrial automation, automotive systems, medical devices, and consumer electronics.
Axial resolution is an important parameter in optical coherence tomography (OCT) imaging. It refers to the ability of an OCT system to distinguish two points that are longitudinally adjacent to each other in the image 12. The axial resolution of an OCT system is determined by the spectral bandwidth of the light source and is inversely proportional to it
The term “acquisition speed” can have different meanings depending on the context. For example, in the field of spectrometry, acquisition speed refers to the rate at which a spectrometer can acquire data points 1. In the context of data acquisition systems, acquisition speed refers to the rate at which data can be sampled and converted from analog to digital format 2
Coating thickness in pharmaceutical application can be measured with different methods directly, using calipers, OCT or indirectly, using weigh gain, NIR, Raman
They are pharmaceutical forms obtained extruding one material containing the active ingredient inside another material that allows a programmed release of the active ingredient
They are pharmaceutical forms in form of patches layered with an active ingredient. Applied to the skin the active ingredient is slowly released.
It is a fluid bed equipment use to coat particles with a nozzle place in the bottom. It allows very homogineous coating
It is a type of coating that applied to a tablet prevent the light to pass it creating scattering to light beams
OCT device produced by Phyllon
It is the sensor that connected to the OCT unit transmit the light beam and receive the reflected light
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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:
|  |
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) |
|  |
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 |
|  |
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
