Optical coherence tomography as a viable tool for monitoring curing processes of functional pharmaceutical polymer coatings

Abstract

Functional pharmaceutical coatings are primarily applied to ensure a homogeneous coating with a desired and reproducible functionality. Some coating formulations require a curing step after the coating process to develop their full functionality. Consequently, a fundamental understanding of curing is particularly relevant for successful formulation development, the quality of the resulting film and an efficient process. This paper introduces optical coherence tomography (OCT) as a tool for unveiling the internal structural changes during curing. Temperature-dependent structural changes in commonly used methacrylic copolymers Eudragit L30 D-55 and RS 30D were studied. The recorded data revealed different behaviour of the two polymer grades. During temperature-induced curing, the scattering and film thickness of L30 D-55 decreased substantially compared to RS 30D. OCT measurements and changes in the refractive index and scattering intensities derived from grayscale histograms of the depth profiles corroborated these findings. Based on the presented data, it can be concluded that OCT can offer insights into curing processes that other currently available in-line monitoring technologies cannot provide.

Introduction

Functional coatings play an essential role in modern solid dosage forms since they protect and modify the drug release of the active pharmaceutical ingredient (API), enabling high effectiveness of the drug. For pellets or tablets, enteric coatings act as a protective film and a diffusion barrier against moisture and gastric juices. However, a profound scientific understanding and the ability to measure the curing process in situ are required for developing new coating materials and formulations for pharmaceutical products.

The coating process consists of three stages: spraying, film formation, drying and curing [1]. During the spraying phase, small droplets of the liquid coating hit the surface of the tablet. When enough droplets have accumulated on the surface, a film forms, and the drying phase starts in parallel. Both processes continue until no more coating material is added. Curing only starts above a certain temperature after the spraying phase. This temperature, commonly known as minimum film forming temperature (MFFT), is the minimum temperature needed for polymers to form a continuous, uniform film without cracks [2]. This temperature must not be confused with the white point temperature (WPT), which usually lies a few degrees below the MFFT. Below the WPT, the polymer forms an opaque mass, rather than a clear, transparent film [3]. It is important to note that there are two kinds of curing processes. The commonly used term “curing” means chemical curing, which includes polymerization of monomers to a final polymer (e.g., the classical superglue) or cross-linking between (different) polymers to form a final polymer (e.g., epoxy-resin). In the medical or pharmaceutical context, these chemical curing processes are used, e.g., for resin-based dental composites [4], [5], pressure-sensitive adhesive films for dermatological purposes [6] and controlled substance release applications [7], [8]. In this work, we focus on physical curing, which generally involves phase transitions or changes in the crystal structure of a material that do not affect the chemical bonding.

Commonly, chemical and physical curing of pharmaceutical polymer coatings is studied by measuring the release behaviour at different curing stages over time [9], [10]. However, the former is more commonly used in other fields than pharmaceutics. It is reasonable to assume that the curing process in the pharmaceutical context can also be studied using optical coherence tomography (OCT) since this technology has been successfully applied to monitor curing processes in other scientific contexts [11], [12], [13]. In the pharmaceutical field, OCT has been used for measuring coating thickness [14], [15], [16], [17], [18], [19]. However, to the best of our knowledge, it has not been applied for monitoring the curing behaviour of polymer coatings.

OCT is an optical tool that is based on low-coherence interferometry. It enables tomographic reconstruction of sub-surface structures from biological and non-biological samples with a spatial resolution in the single-µm domain and in real-time [20], [21]. Depending on the OCT light source and the optical properties of the studies samples, the penetration depth of OCT lies in the range of a few 100 µm. The tomographic information about the depth of the sample is created by superimposing the light that is backscattered from the sample over a reference light beam of known path length. Since the intensity of the backscattered photons corresponds to their penetration depth into the material, one-, two- or even three-dimensional depth profiles can be created. In some cases, factors such as increased coating thickness, a high density of strongly scattering particles in the coating, or inhomogeneities (e.g., fillers) can decrease the OCT penetration depth and impact signal fidelity. However, these challenges were not encountered in this work, because a highly reflective substrate was used. The abrupt change in reflectivity makes the determination of the coating thickness very reliable. This is also shown in the next section. Due to its simple yet robust setup and the high temporal resolution, OCT is suitable for in-line application and real-time data acquisition. It provides clear advantages over other non-destructive forms of coating characterization, such as Raman spectroscopy [22], [23], near-infrared (NIR) spectroscopy [24], [25], [26] and X-ray micro-diffraction [10], [27]. These techniques require either advanced calibration or, in the case of X-ray micro-diffraction, synchrotron radiation, which obviates in-line quality control.

Since OCT can visualize the structural changes during physical curing of pharmaceutical coatings based on the changes in the refractive index, reliable OCT measurements require an accurate determination of the change in the refractive index along with the OCT data (i.e., the OCT tomograms). One must keep in mind that surface features like curvature, roughness and porosity can influence the contrast and the output signal of OCT scans. This is particularly true when the difference in the refractive index between two layers is low, or when the porosity is so high that light scattering by air inclusions becomes dominant. Another aspect is that samples with strongly curved surfaces can move out of the focus during lateral scanning. However, this study only aims to demonstrate that OCT can be used to investigate curing processes in pharmaceutical coatings and enable real-time monitoring of curing processes for the first time. Therefore, factors that potentially decrease the data quality (i.e., roughness and curvature) were intentionally minimized. This novel OCT application may be particularly useful for the development of new types of coatings. An extensive understanding of the curing process can save time and resources in the long run, e.g., by reducing the number of experimental runs and saving valuable resources and working hours.

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Coating film preparation

To study the curing process, two commonly applied enteric polymers were selected: Eudragit® L30 D-55 and Eudragit® RS 30D. L30 D-55 is a classical, enteric coating polymer, consisting of an anionic copolymer based on methacrylic acid and ethyl acrylate. This polymer is known to show distinct curing effects, such as high brittleness [28]. While RS 30 D has a similar chemical structure, it differs in the arrangement of its monomers and does not show distinct curing behaviour.

Johannes Gruenwald, Matthias Wolfgang, Johannes G. Khinast, Stephan Sacher, Optical coherence tomography as a viable tool for monitoring curing processes of functional pharmaceutical polymer coatings, Journal of Industrial and Engineering Chemistry, 2026, ISSN 1226-086X, https://doi.org/10.1016/j.jiec.2026.02.032.

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