Polyvinyl alcohol–based hard capsules with enhanced mechanical strength and gas barrier properties by montmorillonite incorporation

Abstract

This study evaluated polyvinyl alcohol (PVA) as a novel shell material for hard capsules. PVA offers high-water solubility, low toxicity, and excellent oxygen- and water vapor barrier properties. However, under humid conditions, PVA exhibits a pronounced loss of mechanical strength. To address this limitation, montmorillonite (MMT), a high aspect ratio filler, was incorporated into PVA, and the mechanical and barrier properties of films and hard capsule shells were evaluated. In unfilled PVA films, increasing relative humidity from 50% to 65% increased water uptake and reduced Young’s modulus to approximately one-quarter of its original value. By contrast, PVA–MMT composite films containing 9–17 wt% MMT showed substantial improvement in mechanical performance under high humidity, with a 180% increase in Young’s modulus at 9 wt% MMT, consistent with the Halpin–Tsai model. Oxygen- and water vapor permeability were reduced by 5–20-fold, indicating significant enhancement of gas barrier properties. Hard capsules prepared from PVA–MMT composites showed immediate-release dissolution comparable to commercial hypromellose capsules using acetaminophen. Overall, our findings demonstrate that MMT incorporation mitigates the humidity sensitivity of PVA, providing hard capsule shells with balanced mechanical strength and gas barrier properties suitable for pharmaceutical applications.

Introduction

Hard capsules are one of the oldest dosage forms in pharmaceutical history, developed by Mothes ∼100 years ago. In 1846, a cap–body, two-piece capsule was industrially developed [1], [2]. For decades, hard capsule shells were predominantly prepared using gelatin because of its unique physicochemical properties, particularly its ability to gel upon cooling, which enables efficient capsule production through dip-coating [3], [4]. Despite these advantages, gelatin-based capsules present several limitations. Gelatin is derived from animal sources, raising concerns of bovine spongiform encephalopathy and religious or ethical restrictions. The relatively high moisture content of gelatin capsules promotes the crystallization or degradation of moisture-sensitive drugs. Therefore, extensive efforts have been made to develop hard capsule materials, leading to the commercialization of hypromellose (HPMC) capsules since 1998 [5], [6], [7], [8] and pullulan-based capsules since the early 2000s [9], [10]. Hard capsules are widely used because they allow facile encapsulation of a broad range of pharmaceutical formulations. The market for hard capsules continues to expand, driven by increasing demand in the food and cosmetic industries, particularly for dietary supplements in aging populations.

Polyvinyl alcohol (PVA) is a synthetic polymer obtained by hydrolyzing polyvinyl acetate. The physicochemical properties of PVA are regulated by degree of hydrolysis and degree of polymerization. PVA—a water-soluble, semi-crystalline polymer rich in hydroxyl groups—has been extensively applied in various fields owing to its excellent water retention capacity, mechanical strength, and low toxicity. In the pharmaceutical field, PVA has been used as an excipient and coating material [11], [12], [13]. The range of biomedical applications of PVA has recently expanded, particularly in regenerative medicine [14], [15].

In recent years, PVA has attracted attention as a candidate material for hard capsule shells following gelatin and HPMC [16], [17], [18]. PVA-based capsules offer several advantages, including superior oxygen- and water vapor barrier properties, which can protect encapsulated drugs from oxidative- and moisture-induced degradation, while their high-water solubility does not hinder drug dissolution. PVA hard capsules are compatible with liquid formulations based on nonaqueous solvents, such as polyethylene glycol (e.g., PEG 400), which is liquid at temperature above 20℃. This enables poorly water-soluble drugs to be dissolved or dispersed in liquid media and encapsulated in hard capsules, potentially improving bioavailability [19], [20].

However, the pronounced sensitivity of PVA capsules to environmental humidity is a critical challenge and represents a major barrier to their practical application as hard capsule shell materials. Unlike HPMC capsules, which maintain compressive strength under humid conditions, PVA capsules exhibit gradual softening at high relative humidity (RH) and may crack under low-humidity conditions, resulting in significant variability in mechanical properties. Previous studies have explored blending PVA with other polymers such as HPMC, which has been reported to improve processability, structural characteristics, and dissolution behavior of PVA-based capsule systems [21], [22]. However, such polymer blending approaches primarily rely on modification of the bulk matrix properties and may not provide sufficient control over moisture-induced plasticization and structural stability under varying humidity conditions.

In this study, we aimed to overcome the humidity-induced deterioration of PVA-based hard capsule shells by incorporating inorganic reinforcing fillers.Previous studies on PVA composite films [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33] have reported that incorporating nano-cellulose, graphene oxide, tungsten disulfide nanotubes, kaolin, fumed silica, and MMT as rigid fillers into PVA significantly improves tensile strength and Young’s modulus. In particular, MMT, a representative layered silicate, possesses a high aspect ratio and large specific surface area, enabling strong interfacial interactions with PVA chains through hydrogen bonding and intercalation/exfoliation mechanisms. These interactions contribute to improved mechanical properties of PVA-based nanocomposites, as widely reported in the literature [27], [28], [29], [30], [31], [32], [33]. However, these reports were insufficient in terms of the effects of PVA type, ambient humidity, and moisture content. In addition, several studies [32], [33] have focused on films or hydrogels, and their application to hard capsule shell materials, particularly under controlled humidity conditions, has not been sufficiently investigated.

In this study, talc, kaolin, fumed silica, and MMT were selected as inorganic fillers because they have established histories of use in pharmaceutical applications and are considered suitable for oral administration [34].

To systematically screen capsule-base compositions, PVA–filler composite cast films were prepared. Their mechanical properties, moisture uptake behavior, and gas barrier performance were evaluated under controlled humidity conditions. Based on the results of the film-based screening, an optimized composite formulation was selected for hard capsule fabrication. The resulting PVA–MMT composite hard capsules were prepared as proof of concept and filled with acetaminophen. The in vitro dissolution behavior of PVA–MMT composite hard capsules and commercially available HPMC capsules was compared.

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Materials

PVA was supplied by Mitsubishi Chemical Corporation (Tokyo, Japan) under the commercial name Gohsenol EG. Three grades were used: EG-05P, EG-18P, and EG-40P, with degrees of polymerization of ∼500, 1600, and 2500, respectively. All PVA grades had a degree of hydrolysisof 86–89 mol%. The following inorganic fillers were incorporated into PVA: talc (Crown Talc, Matsumura Sangyo, Tokyo, Japan), kaolin (JP-100, Takehara Kogyo, Tokyo, Japan), and fumed silica (Aerosil 200, Aerosil Japan, Tokyo).

Chizuko Ishihara-Furo, Ayaka Kobayashi-Koike, Kohei Tahara, Polyvinyl alcohol–based hard capsules with enhanced mechanical strength and gas barrier properties by montmorillonite incorporation, European Journal of Pharmaceutics and Biopharmaceutics, 2026, 115115, ISSN 0939-6411, https://doi.org/10.1016/j.ejpb.2026.115115.