Dynamic vapor sorption for quality assessment of pharmaceutical coatings: a case study in enteric protection

Abstract

This study investigates the performance of different enteric coating systems by integrating dynamic vapor sorption (DVS), optical coherence tomography (OCT), and acid-stage dissolution testing to evaluate moisture sensitivity, structural integrity, and acid resistance of coated pharmaceutical tablets. Omeprazole-containing tablets were coated with three commercially available enteric systems and analyzed using DVS to assess sorption kinetics under controlled humidity and temperature conditions. OCT was employed to non-destructively evaluate coating thickness and uniformity. Functional performance was determined via acid-stage dissolution testing following FDA guidelines for delayed-release formulations. The DVS results revealed marked differences in moisture uptake behavior among the coatings, while OCT imaging identified variability in coating distribution, both of which were found to correlate with dissolution outcomes. Coatings with lower hygroscopicity and more consistent thickness profiles demonstrated acid resistance. These findings underscore the value of combining DVS and OCT as complementary analytical tools for the comprehensive evaluation of enteric coatings, enabling improved formulation design and quality control aligned with Quality by Design (QbD) principles.

Introduction

Pharmaceutical tablet coatings serve multiple critical purposes in the design and functionality of oral solid dosage forms. Beyond their traditional roles in improving tablet appearance, masking unpleasant tastes, and facilitating swallowing, coatings are essential in modulating drug release profiles and protecting active pharmaceutical ingredients (APIs) from environmental or physiological degradation.1,2 Enteric coatings represent advanced functional coating systems engineered to withstand gastric acidity and facilitate drug release in the more neutral to basic environment of the intestine. This is especially important for acid-labile APIs, such as omeprazole, where premature degradation in gastric fluid can drastically reduce bioavailability and therapeutic efficacy.1,3 In addition to protecting acid-labile APIs, enteric coatings are widely used for drugs that can induce gastric mucosal irritation.4 By enabling delayed release in the intestinal environment, these systems help mitigate local irritation, as observed for non-steroidal anti-inflammatory drugs such as diclofenac.4

A major challenge in developing robust enteric-coated tablets lies in controlling moisture uptake during manufacturing, storage, and transportation. Many enteric polymers, such as methacrylate-based or cellulose-derived systems, exhibit varying degrees of hygroscopicity, which can compromise film integrity and functional performance over time.5 Excess moisture can plasticize or weaken the polymer matrix, leading to cracking, swelling, or porosity, all of which may result in premature drug release in acidic conditions. Therefore, evaluating the moisture sorption behavior of coating systems is critical for predicting stability and ensuring consistent product quality.1,5

In this context, Dynamic Vapor Sorption (DVS) offers a highly sensitive and reproducible method for assessing how coating materials interact with humidity under controlled conditions. DVS measures changes in sample mass as a function of relative humidity (RH) and time, providing detailed sorption/desorption isotherms and kinetic data.6 This allows for precise characterization of the rate and extent of moisture uptake, hysteresis effects, and potential transitions in material state (e.g., glass transition, recrystallization). Compared to conventional gravimetric or loss-on-drying methods, DVS enables dynamic monitoring of moisture exchange at microgram sensitivity, making it especially suitable for studying small quantities of excipients and coatings.6,7

However, while DVS provides valuable information about the moisture behavior of coatings, it does not directly reveal information about their structural attributes, such as thickness, homogeneity, or uniformity, which are equally important determinants of functionality. To address this, Optical Coherence Tomography (OCT) has emerged as a powerful non-destructive imaging technique for the real-time evaluation of coated pharmaceutical products.8 OCT enables high-resolution, cross-sectional imaging of coatings in three dimensions, allowing for the visualization of layer structure, detection of defects, and quantitative measurement of coating thickness across tablet surfaces. Unlike traditional destructive methods such as cross-section microscopy, OCT preserves the integrity of the sample, supports in-process monitoring, and offers the potential for integration into process analytical technology (PAT) frameworks.9–11

The combination of DVS and OCT provides a complementary analytical approach to assessing enteric coatings. Together, these methods can offer predictive insights into a coating’s ability to provide effective acid resistance. To validate these physicochemical and structural findings, acid-stage dissolution testing is employed as a functional readout. According to USP 〈711〉 and FDA guidelines, enteric-coated tablets must withstand a defined duration in acidic media (typically 0.1 N HCl for two hours) without releasing a significant amount of the API.3,12,13 Variations in dissolution profiles can then be linked back to observed differences in coating integrity (via OCT) and moisture sorption behavior (via DVS).

In this study, we evaluated three different enteric coating systems by integrating DVS, OCT, and acid-stage dissolution testing. Each system is assessed for its moisture sorption capacity, coating uniformity, and acid resistance, enabling a multidimensional characterization of coating performance. By combining the complementary insights obtained from each technique, this work aims to establish a more comprehensive and predictive framework for coating quality evaluation.

This study aims to establish a robust analytical methodology for evaluating enteric coatings by combining OCT and DVS under the framework of Quality by Design (QbD).14,15 This dual approach enhances method understanding and performance prediction by addressing structural (coating thickness and uniformity via OCT) and functional (moisture sorption behavior via DVS) attributes. This integrated methodology offers a predictive, science-based platform for formulation optimization and quality assurance throughout the product lifecycle.14,16,17

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Materials

2.1.1. Reagents and chemicals.

Acetonitrile (Reag. Ph. Eur., suitable for HPLC gradient elution), used both as a mobile phase component and diluent, was procured from M&B Stricker Laborfachhandel GbR (Bernried am Starnberger See, Germany). Buffer solution for the mobile phase was prepared using ammonium bicarbonate (BioUltra, ≥99.5% purity) and 25% ammonia solution, both from Sigma-Aldrich (St Louis, United States). Additional reagents included sodium hydroxide (Dri™, ≥97% purity), and hydrochloric acid (37%) from Sigma-Aldrich. All analytical and sample preparation procedures utilized purified water generated by Triton UV purification system (Neptec, Elbtal, Germany). Sample filtration was performed using nylon syringe filters (0.22 μm) supplied by YETI Merz Brothers GmbH (Haid, Austria).

2.1.2. Standards, samples, and excipients.

Omeprazole powder (100% purity) was procured from Shenzhen Nexconn Pharmatechs Ltd (Shenzhen, China). MicroceLac®, a co-processed excipient consisting of 75% alpha-lactose monohydrate and 25% microcrystalline cellulose, was obtained from MEGGLE GmbH & Co. (Wasserburg, Germany). Sodium starch glycolate (EXPLOTAB®, Type A) and sodium stearyl fumarate (PRUV®) were supplied by JRS Pharma (Polanco, Spain). Sub-coating of the tablet cores was carried out using Opadry® II, a clear polyvinyl alcohol-based film coating system from Colorcon (Harleysville, USA). The enteric top-coating systems used in this study included Aquarius™ control ENA from Ashland (Wilmington, USA), along with Acryl-EZE®, Nutrateric®, Surelease® (25% solids ethylcellulose dispersion), and NS Enteric®, all sourced from Colorcon (Harleysville, USA).

The formulation prototype and manufacturing process were previously established based on earlier studies.18,19 The tablet formulation is shown in Table 1, and the manufacturing process is described in SI (Tables S1 and S2). For this study, only tablets that were compliant with acid-stage dissolution requirements,20 as demonstrated in previous experiments,19 were included.

Table 1 Formulation of core omeprazole tablets

Jesús Alberto Afonso Urich, Michael Piller, Anna Sophie Neubauer, Anna Fedorko and Raymar Andreina Lara García, Dynamic vapor sorption for quality assessment of pharmaceutical coatings: a case study in enteric protection, RSC Pharmaceutics, DOI: 10.1039/d6pm00129g, https://pubs.rsc.org/en/content/articlehtml/2026/pm/d6pm00129g

Read also our introduction article on Quality by Design (QbD) here: