In-line laser triangulation-based 3D profiling for real-time tablet monitoring in a rotary tablet press

Abstract

Direct in-line measurement of tablet geometry provides product-related information that complements indirect, force-based control strategies in rotary tablet presses. Here, a laser line triangulation profiling sensor was integrated at the ejection position of a rotary press to acquire 3D surface profiles of tablets. A semi-automated Python workflow was developed for signal filtering, coordinate correction, height calibration, tablet detection, and extraction of tablet height and surface topography. Sensor mode, exposure time, and acquisition frequency were optimized to enable simultaneous detection of the rotor and tablet surfaces.

Verification against caliper measurements yielded a mean difference of 1 µm with 95 % limits of agreement from −34 to +36 µm and a mean absolute error of 15 µm. In a 30-run Latin hypercube study, in-line tablet heights closely agreed with offline values measured after 24 h, indicating that rapid elastic recovery was largely complete at the measurement position. Adding laser-derived height to machine data reduced the cross-validated mean absolute error of tablet mass prediction from 1.71 to 1.20 mg, whereas tensile strength prediction improved only marginally. Imprints on biconvex oblong tablets remained clearly resolved at turret speeds of up to 50 rpm. Laser triangulation therefore offers a robust, chemometric-model-free PAT approach for simultaneous dimensional monitoring and surface inspection, with potential for 100 % inspection at industrial production speeds.

Introduction

Tablet dosage forms remain among the most widely used pharmaceutical products1 owing to their manufacturing efficiency, dosing accuracy, long-term stability, and high patient acceptance. Over recent decades, pharmaceutical development and manufacturing have increasingly adopted the principles of Quality by Design (QbD). QbD promotes a systematic understanding of the relationships between critical material attributes, critical process parameters, and critical quality attributes (CQAs).2 Within this framework, process analytical technology (PAT) aims to enable real-time monitoring of critical process parameters and quality attributes, thereby supporting process understanding and science-based quality assurance.3

The value of PAT has been demonstrated across numerous pharmaceutical manufacturing operations, particularly in continuous and semi-continuous production, where rapid process feedback is essential.4 Its potential is further amplified by the increasing adoption of data science, statistical learning, and model-based process control, as these approaches rely on timely and information-rich process measurements for model development, state estimation, prediction, and automated process adjustment.5, 6, 7

A broad range of PAT applications has consequently been reported for tablet compression and its associated upstream and downstream unit operations.8,9 As the CQAs of a tablet result from complex interactions between (intermediate) material attributes and compression conditions, direct in-line measurements throughout the process chain provide valuable opportunities to enhance process understanding, detect process deviations, and support real-time process monitoring and control. Within the tablet compression step UV/Vis,10,11 NIR,12, 13, 14 Raman,15 and terahertz spectroscopy16,17 as well as microwave resonance technology18 have been applied to measure a range of different tablet CQAs. These techniques provide detailed chemical and structural information and have proven valuable for monitoring material properties and predicting product quality. However, their successful implementation generally relies on multivariate calibration models that require extensive reference datasets and continuous maintenance throughout the product lifecycle. Model performance may further be affected by raw material variability, formulation changes, or instrument drift, making recalibration necessary and increasing implementation effort. For these reasons, there is growing interest in complementary PAT approaches that provide direct physical measurements without relying on chemometric models. Calibration-independent techniques can simplify implementation, accelerate process development, and improve robustness, particularly during early formulation development, where process conditions frequently evolve.

Beyond the implementation of conventionally defined PAT tools, the instrumentation of tablet presses with force sensors may itself be regarded as a form of PAT. Modern rotary tablet presses are already able to accept or reject individual tablets based on the measured compression force,19,20 since at a constant edge thickness a higher force implies a heavier tablet. The compression force thereby acts as an indirect PAT signal for the uniformity of dosage units. This signal is, however, inherently indirect and material-dependent, and the stiffness of the press affects the relationship between die fill and the measured force, whereas a direct geometric measurement of the tablet yields an orthogonal, product-related signal. The force-weight relationship is furthermore likely to be influenced by changes in the properties of the powder blend, such as overlubrication, heating of the dies, or changes in the particle size distribution within the feed frame.

Many tablet CQAs are strongly governed by tablet volume and density. Mechanical strength, given as tensile strength, is closely related to solid fraction through the compactability of the formulation,21 whereas, assuming adequate blend uniformity, drug content is directly linked to tablet mass. Moreover, tablet porosity is known to substantially influence disintegration and dissolution and therefore serves as a suitable predictor of both performance attributes.22, 23, 24, 25 From a geometric perspective, tablets are largely constrained in two dimensions. While tablet length and width are primarily defined by the tooling and therefore show only limited variation,26 changes in tablet volume mainly arise from variations in tablet height.

Laser triangulation presents a calibration-free, material-independent measurement principle for the tablet height. By projecting a laser beam onto a surface and detecting the reflected light at a defined observation angle, the distance between the sensor and the object can be determined with high spatial and temporal resolution. Besides precise distance measurements, laser triangulation enables the acquisition of surface topography, three-dimensional geometries, and dimensional information in a completely non-contact and non-destructive manner. Consequently, the technique has become well established in industrial manufacturing for dimensional inspection, surface characterization, defect detection, robotic manufacturing, additive manufacturing, and automated quality control, where rapid and reliable geometric measurements are required.27, 28, 29, 30, 31, 32, 33 Although laser triangulation is a well-established measurement technique in non-pharma industrial metrology, its application in pharmaceutical manufacturing remains comparatively limited. Within pharmaceutical manufacturing, only a few applications have been reported to date. Laser triangulation has been used to monitor the powder filling level and bulk distribution within the feed frame of a rotary tablet press, providing valuable insight into die-filling dynamics and powder flow behavior.34 More recently, the technique has been successfully integrated as an off-line and in-line tool in roller compaction for the determination of ribbon thickness, enabling the subsequent estimation of ribbon porosity and solid fraction, and to measure the kinetics of elastic recovery of ribbons.35, 36, 37 Collectively, these studies demonstrate that laser triangulation can provide robust, calibration-independent geometric information. Owing to its high precision, potentially high sampling frequencies, and the relevance of tablet height for volume and density estimation, laser triangulation is of considerable interest for implementation in industrial rotary tablet presses. This is further supported by the increasing relevance of tablet surface monitoring for process understanding and quality control.

Beyond dimensional monitoring, the quality of the tablet surface is of increasing interest, as surface defects such as sticking and picking represent a well-recognized manufacturing problem.38 Camera-based two-dimensional inspection approaches combined with deep learning have accordingly been proposed for the automated recognition of such tablet defects.39, 40, 41 In contrast to these grey-scale or color image-based methods, laser triangulation provides quantitative height information, is largely independent of the illumination conditions, does not require the generation of a broad dataset for training, and operates directly in-process at high acquisition frequency rather than downstream of the press.

Line-based scanning systems are particularly attractive for this application. As objects pass through the projected laser line, high-resolution 3D surface profiles can be acquired. Triangulation-based 3D profiling therefore provides access to detailed information on tablet height and surface characteristics, making it a promising approach for in-line tablet monitoring.

The objective of the present study was to implement a laser triangulation profiling sensor directly into a rotary tablet press and to evaluate its suitability for real-time in-line monitoring of tablet height and surface properties considering industrially relevant operating conditions.

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Materials

70 % α-lactose monohydrate (Tablettose® 100, Meggle, Germany), 29 % microcrystalline cellulose (Vivapur® 101, JRS Pharma, Germany), and 1 % magnesium stearate (Parteck® Lub, Merck, Germany) were blended using a free-fall blender (LM20, L.B. Bohle, Germany) at 30 rpm. α-Lactose monohydrate and microcrystalline cellulose were initially blended for 5 min. Subsequently, magnesium stearate was added and the final blend was mixed for an additional 3 min. The material was blended 24 h before tableting and stored under controlled climatic conditions (21°C and 45 % rh) until use.

Jona Sandström, Mariano Patrizio Del Rio Reinoso, Leonie-Lara Dorothea Uth, Stefan Klinken-Uth, In-line laser triangulation-based 3D profiling for real-time tablet monitoring in a rotary tablet press, Journal of Pharmaceutical Sciences, 2026, 104529, ISSN 0022-3549, https://doi.org/10.1016/j.xphs.2026.104529.

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