When the pharmaceutical industry discusses sustainable development, the selection criteria for excipients are undergoing a transformation: functionality was once the sole guiding principle, and now environmental responsibility is placed on an equally important footing. The several iterations of capsule materials in oral solid dosage forms clearly reflect this trend.
I. HPMC: A Solution for Gelatin Substitution, Yet Not the Final Answer
Hydroxypropyl methylcellulose (HPMC) capsules, as a plant-based alternative to gelatin capsules, have been widely adopted over the past decade and more. Their advantages are well-defined: stable raw material sources, elimination of zoonotic disease and religious risks, better compatibility with moisture or heat-sensitive active pharmaceutical ingredients (APIs), and official inclusion in the pharmacopoeias of various countries.
However, when measured against the standards of green pharmaceutical manufacturing, HPMC has evident limitations. As a semi-synthetic polymer material, its production involves the chemical modification of natural cellulose, including high-temperature dispersion and hydration processes that consume considerable energy. Additional gelling agents are also often required in its formulation. It can be said that HPMC has addressed the issue of eliminating animal-derived sources, but it still falls short of true environmental sustainability.
II. Pullulan: A Closer Option to the Natural Circular Economy
Pullulan is a naturally water-soluble extracellular polysaccharide produced by the fermentation of Aureobasidium pullulans, boasting excellent film-forming properties. For capsule applications, it offers several distinct advantages over HPMC.
1. Outstanding Oxygen Barrier Performance
The oxygen barrier capacity of pullulan capsules represents a hard technical edge. Academic reviews have confirmed that pullulan possesses superior film-forming and barrier properties, and it has been designated as Generally Recognized as Safe (GRAS) by the US Food and Drug Administration (FDA) (Carolina Krebs de Souza et al., 2023). Patent literature also explicitly notes pullulan's excellent film-forming, oxygen-barrier and gas-barrier properties (Qingdao University of Science and Technology, 2015). Pullulan capsules are thus a more suitable choice for oxygen-sensitive ingredients such as probiotics and Omega-3 fatty acids.
2. Rapid Disintegration and Simplified Formulation
In terms of disintegration performance, a study measured the disintegration of fast-dissolving pullulan films and found that the film disintegrated in less than 3 minutes and fully dispersed within 30 seconds (Bárbara Felin Osmari et al., 2025). The disintegration time limit of pullulan capsules can also be regulated through formulation design without the need for additional fast disintegrants (Qingdao University of Science and Technology, 2015). Formulation simplification reduces the risk of excipient interactions and clarifies the pathways of human absorption and metabolism of the active ingredients.
3. Fermentative Production and Complete Biodegradability
Pullulan is produced via microbial fermentation using renewable biomass such as starch or sucrose as raw materials, avoiding the chemical modification steps required for HPMC and aligning more closely with the concept of low-carbon biomanufacturing. Academic reviews clearly state that pullulan is biodegradable and exhibits non-toxic and non-immunogenic properties (Carolina Krebs de Souza et al., 2023). It can be completely degraded in the human gastrointestinal tract and, when discarded into the natural environment, can be broken down by microorganisms into water and carbon dioxide without leaving hazardous residues.
III. A Full-Chain Perspective: Practical Considerations for the Supply Chain
Judging whether a material is environmentally sustainable requires a whole life cycle analysis, spanning raw material acquisition to waste disposal.
On the raw material side, pullulan is produced by fermentation from renewable biomass, while HPMC relies on chemical modification of natural cellulose—giving pullulan an inherent environmental advantage.
In application, pullulan's low oxygen permeability reduces the need for high-barrier packaging, thereby lowering the carbon footprint of the packaging process. After disposal, its complete biodegradability aligns with the direction of the circular economy.
On the supply chain front, pullulan was once constrained primarily by cost. However, advances in fermentation technology and the advancement of large-scale production are driving a gradual reduction in costs. According to statistics and forecasts from QYResearch, the global market sales of pullulan plant-based capsules reached 587 million US dollars in 2024 and are projected to rise to 1.17 billion US dollars by 2031, with a Compound Annual Growth Rate (CAGR) of 10.5% from 2025 to 2031 (QYResearch, 2025). Economies of scale will help enhance the stability of the pullulan supply chain.
IV. Conclusion: Not a Simple Substitution, but a Demand-Based Selection
The shift from gelatin to HPMC and then to pullulan is not a mere material replacement, but a gradual deepening of the industry's understanding of "sustainability". HPMC solved the problem of animal-derived raw materials, and pullulan has taken a further step on this basis: it delivers excellent performance in the critical aspects of oxygen barrier and disintegration, while demonstrating lower potential environmental costs across three key links—raw material sourcing, production methods and end-of-life degradation.
For B2B customers such as pharmaceutical manufacturers, health supplement brands and Contract Development and Manufacturing Organizations (CDMOs), choosing pullulan capsules is more than just selecting an excipient; it is also a strategic layout for future supply chains. As compliance requirements for Environmental, Social and Governance (ESG) become increasingly stringent, supply chain sustainability will sooner or later become a mandatory access standard. Future competition in the pharmaceutical industry will hinge not only on who can produce more stable pharmaceuticals, but also on who can deliver these pharmaceuticals to patients with a smaller environmental cost.
References
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Carolina Krebs de Souza, Tabli Ghosh, Nishtha Lukhmana, Sahil Tahiliani, Ruchir Priyadarshi, Tuany Gabriela Hoffmann, Shiv Dutt Purohit, Sung Soo Han. Pullulan as a sustainable biopolymer for versatile applications: A review. Materials Today Communications, 2023, 35: 106477. DOI: 10.1016/j.mtcomm.2023.106477.
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Bárbara Felin Osmari, et al. Fast-Dissolving Pullulan Film as a Solid Dosage Form for Sublingual Administration of Nifedipine-Loaded Nanocapsules. AAPS PharmSciTech, 2025, 26(7): 200. DOI: 10.1208/s12249-025-03197-2.
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Qingdao University of Science and Technology. A hollow capsule with controllable disintegration time limit and its preparation method. Chinese Invention Patent CN104739798A, 2015.
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QYResearch. Global and China Pullulan Plant-based Capsule Market Status and Future Development Trends 2025-2031. March 2025. Report Code: 5178436.
Post time:2026-04-09