Protection of Hygroscopic Pharmaceutical and Nutraceutical Active Ingredients via Film Coating Technologies: A Review

Abstract

Hygroscopicity poses a significant challenge in the formulation of pharmaceutical and nutraceutical products, as moisture absorption often leads to chemical degradation, physical instability, and compromised therapeutic efficacy. This narrative literature review, evaluated the comparative effectiveness of various polymeric systems and coating technologies as moisture barriers across diverse dosage forms, including tablets, powders, granules, and particulates. We analyzed a spectrum of barrier materials, including cellulose derivatives, polyvinylpyrrolidone, polyvinyl alcohol (PVA), methacrylates, and shellac, contrasting conventional solvent based techniques (fluid bed, spray drying, freeze drying coating) with advanced methodologies (hot melt coating, electrostatic dry coating, and Atomic Layer Deposition/ALD). Conventional coating systems utilizing HPMC and PVA were found to maintain moisture uptake below 1.5% during long-term storage (40°C/75% RH). However, more advanced strategies demonstrated superior protective capabilities, for instance, hotmelt coating employing lipid-based excipients (Precirol ATO 5) reduced moisture absorption by up to 85% at 75% RH. Furthermore, electrostatic dry coating showed a significant reduction in weight gain, decreasing from 6.5% to 3.3% compared to uncoated cores over a 48-hour period. Notably, ALD provided the most robust protection, preserving the amorphous stability of sensitive particles for up to two years under extreme conditions. This review highlights that film coatings not only mitigate moisture induced degradation but also enhance shelf life and improve the mechanical properties of dosage forms. These results underscore the versatility of coating technologies, enabling formulators to tailor strategies for highly moisture sensitive compounds.

Introduction

Hygroscopicity refers to the ability of a substance to absorb or retain moisture from its surrounding environment.1,2 Hygroscopicity is classified into four categories based on the percentage of weight gain at 25°C and 80% Relative Humidity (RH) over 24 hours: non hygroscopic (0–0.12% w/w), slightly hygroscopic (0.2–2% w/w), hygroscopic (2–15% w/w), and very hygroscopic (>15% w/w).3 In pharmaceutical and nutraceutical formulations, the presence of hygroscopic active ingredients poses a significant challenge due to their high sensitivity to humidity.4,5 Exposure to moisture can initiate undesirable chemical reactions, such as hydrolysis, which may compromise the therapeutic efficacy of the active compound and potentially lead to the formation of degradation products that pose risks to human health.6,7 Highly hygroscopic substances typically possess polar functional groups in their structure, such as hydroxyl (-OH) or carbonyl (-C=O), allowing them to form hydrogen bonds with water molecules. These interactions contribute to the hydrophilic nature of the substance, promoting water absorption from the humid atmosphere and causing the material to become damp or partially dissolve. Many pharmaceutical active ingredients with polar functional groups tend to absorb moisture.8,9 Various organic compounds and salts, such as carboxylic acids,10 amino acids,11 sugars,11 magnesium salts, such as carboxylic acids,12 exhibit varying levels of hygroscopicity, influenced by functional group structure, molecular weight, and water solubility.13

Increased hygroscopicity can affect active substances physicochemical properties, stability, and bioavailability.14,15 Physically, moisture absorption can induce clumping and deliquescence, leading to material degradation, discoloration, and transitions in crystalline structure.16–19 Chemically, absorbed moisture acts as a catalyst for hydrolytic reactions, thereby compromising the chemical integrity of the active compound, reducing its molar mass, and disrupting both the overall crystallinity and thermal stability of the formulation.20 To mitigate the adverse effects associated with high hygroscopicity, robust strategies are required to shield active ingredients from environmental moisture. Consequently, film coating technology has emerged as the most effective and widely adopted intervention for addressing these stability challenges within pharmaceutical formulations.21 Techniques for reducing moisture-induced instability include molecular changes like salt production and crystal engineering as well as external interventions like customized packaging. However, molecular changes run the danger of changing the active ingredient’s physicochemical characteristics, and if the patient breaks the main seal, package protection is jeopardized. As a result, film coating is a better option as it provides an inherent physical barrier that shields the dosage form for the duration of its life without changing the chemical structure of the active component.21,22

This technique aims to restrict water penetration into the core of the dosage form, thereby protecting the active ingredient from moisture-induced degradation. The solution diffusion model, which governs moisture permeability based on the solubility and diffusivity of water vapor inside the polymer matrix, explains why this protection goes beyond simple physical blockage. Film coatings offer several advantages, including superior mechanical properties, relatively fast processing, space efficiency, and adaptability to specific formulation requirements.23–25 Furthermore, the film layer acts as a barrier against moisture, light, and oxygen, providing comprehensive protection for moisture-sensitive actives. This barrier function not only prolongs product shelf life and enhances stability but also slows down degradation pathways such as hydrolysis and oxidation.26,27 However, the physicochemical characteristics of the chosen polymers as well as the particular coating technique used have a significant impact on how effective this protection is. Several film coating techniques have been developed, including fluid bed coating, pan coating, spray coating, freeze-dry coating, and advanced coating.28–31

One of the most implemented techniques in film coating technology is the solvent-based approach, widely applied in the pharmaceutical industry due to its efficiency and diagnostic capabilities in forming protective layers against moisture.32 The solvent-based film coating method involves depositing a thin polymer layer onto the surface of a tablet core through a spraying technique.24 The coating solution or suspension, which contains polymers and other ingredients such as pigments and plasticizers, is sprayed onto the rotating tablet cores within a container. The drying process is facilitated by the passage of hot air through the base of the tablets, enabling the evaporation of the solvent and leaving a thin film on the surface of each tablet core. The film’s formation depends on the polymer’s physicochemical properties. Plasticizers are added to lower the glass transition temperature and enhance the flexibility of the film, thus preventing the polymer film’s cracking or peeling. This is a crucial trade off in formulation, whereas plasticizers are necessary for mechanical integrity, their presence raises the free volume of the polymer, which may unintentionally promote greater rates of moisture transfer.26,33

Although solvent-based solutions are common, the industry is looking more and more into solvent-free options to improve formulation stability and process efficiency. Numerous coating techniques have been developed for solvent-based and solvent-free processes to enhance the efficiency of the coating process. However, each method has advantages and disadvantages, which must be considered when selecting the appropriate coating technology. Additionally, the coating layers uniformity and the formulations stability under varying storage conditions are critical factors in the coating process. Selecting appropriate polymer materials and applying suitable coating technologies are essential for producing stable, high-quality pharmaceutical products. Furthermore, in order to guarantee that the chosen moisture barrier retains its integrity for the duration of the product’s anticipated shelf life, these decisions must closely adhere to industrial regulatory frameworks, including ICH Q1A stability testing criteria. Previous literature reviews have discussed pharmaceutical film coating;25,34,35 however, a critical gap remains in the evaluation of specific moisture protection performance, particularly regarding the interplay between polymer hydrophilicity and coating methodologies. This review specifically evaluates the application of coating technologies across various pharmaceutical and nutraceutical solid oral dosage forms, including tablets, powders, granules, and microparticles. The goal of this methodical approach is to give formulators a useful, data-driven framework for choosing the best protection measures for extremely sensitive materials. The categorization of coating polymers, their methods for protecting against moisture, and a comparative analysis of the efficacy of modern coatings are covered in depth in the sections that follow. Figure 1 illustrates the use of polymers for film coating on hygroscopic substances (Created in BioRender https://BioRender.com/undefined, adapted from Chaerunisaa, A. Y. (2026)).

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Following excipients are mentioned in the study besides other: Precirol ATO 5, HPMC, PVA, povidone

Pitriani P, Mulyani AT, Wardhana YW, Chaerunisaa AY. Protection of Hygroscopic Pharmaceutical and Nutraceutical Active Ingredients via Film Coating Technologies: A Review. Drug Des Devel Ther. 2026;20:562981, https://doi.org/10.2147/DDDT.S562981