A Review of Circular Pharmaceutics: Plant Mucilage as Tunable Bio-Based Polymers for Advanced Drug Delivery

Abstract

Plant mucilage is considered here as a tunable polysaccharide platform for drug delivery within a circular approach to materials and manufacturing. Its biphasic architecture of neutral arabinoxylan domains interwoven with an uronate-rich pectic matrix governs hydration, gelation, viscoelastic behavior, and mucoadhesion at relevant solids. These properties can support roles as a disintegrant, film former, rheology modifier, and sustained-release matrix without heavy synthetic crosslinkers. Composition matters measurably. Uronate-to-neutral sugar ratios, branching and acetylation, residual cations, and moisture history map onto junction density and transport, shifting release from barrier control toward coupled diffusion and polymer relaxation. Greener extraction routes receive focused attention. Deep eutectic and natural eutectic solvents, microwave assistance, and ultrasound can raise yield and preserve functionality when solvent recovery, selectivity, and energy use are verified at pilot scale. To make results comparable across cultivars and processes, the review highlights compositionally explicit analytics and small-amplitude oscillatory rheology with uncertainty reporting to define grade-to-function fingerprints. The systems view is practical. Low-value residues supply feedstock. Closed-loop solvent management and pharmacopoeial microbiology underpin quality. Reverse logistics, take-back options, and returnable packaging keep end-of-life in scope alongside release, stability, and safety. Viewed together, these elements show how mucilage can deliver advanced performance with lower waste and credible scale-up for pharmaceutical applications.

1. Introduction

Biological macromolecules have moved to the forefront of pharmaceutical innovation, not as peripheral excipients but as central determinants of drug delivery performance and material sustainability. Among these, plant mucilage represents a distinctive class of polysaccharide-based macromolecules whose physicochemical behavior is directly related to its molecular composition and architecture. In this review, plant mucilage refers to the polysaccharide-rich material isolated from mucilage-bearing plant tissues, rather than to a source from which a separate class of macromolecules is subsequently extracted. Its principal macromolecular components are neutral and acidic heteropolysaccharides, particularly arabinoxylans and pectic polysaccharides such as homogalacturonan and rhamnogalacturonan-I, together with other uronic-acid-rich domains. Their branched structures support hydration, swelling, and intermolecular association under physiological conditions, resulting in natural mucoadhesion and controlled drug diffusion without the need for synthetic crosslinkers [1,2,3]. Evidence that Opuntia ficus-indica (cactus) cladodes are rich in high-molecular-weight polysaccharides that underpin hydration and barrier behavior further supports this mucoadhesive rationale [4].

This combination of structure and functionality allows mucilage to perform roles traditionally filled by multiple synthetic excipients. Depending on its molecular-weight and charge distributions, it can act as a disintegrant, a film-forming matrix, a rheology modifier, or a sustained-release agent; importantly, these capabilities can be tuned through mild extraction/fractionation that selectively enriches neutral vs. anionic fractions and adjusts gelation and viscosity profiles [1,5]. Recent advances in greener extraction, particularly deep eutectic solvents (DESs) and natural deep eutectic solvents (NADESs), offer higher yields and solvent-recovery potential for polysaccharides while preserving functionality [6,7]. In parallel, targeted reviews on linseed/flaxseed mucilage document how extraction conditions shape composition, rheology, and downstream performance, reinforcing the structure–function link central to biological macromolecules [5]. At the same time, plant mucilage can be sourced from renewable biomass streams such as husks, press cakes, seed coats, and cladodes, supporting valorization of agricultural residues [1,5].

Yet the relevance of plant mucilage extends beyond its biodegradability or agricultural origin. The field now faces a deeper challenge: moving from linear material use toward systems where polymers are designed to circulate through regenerative pathways with minimal waste. In this context, the pharmaceutical performance of mucilage polysaccharides cannot be separated from how the mucilage-bearing biomass is sourced, how its polysaccharide-rich fraction is extracted and processed, and how the resulting material is incorporated into pharmaceutical products or returned to productive use. A polymer that excels in vitro but requires solvent-intensive extraction or generates persistent residues fails the test of sustainable practice. Current policy and methodology work—e.g., the GREENER framework for pharmaceuticals—explicitly calls for integrating environmental criteria (solvent burden, persistence, emissions) alongside efficacy in materials selection and formulation [8]. This systems view is increasingly reflected in sustainability roadmaps for pharmacy and medicines practice [9,10].

However, most current research still evaluates plant mucilage as an isolated substitute for conventional excipients rather than as part of a pharmaceutical materials cycle. The available evidence is also fragmented. Many studies report individual properties, such as extraction yield, swelling, viscosity, mucoadhesion, film formation, or drug-release behavior, using different extraction procedures, purification levels, analytical methods, and formulation conditions. These differences limit direct comparison among mucilage sources and make it difficult to establish clear relationships between composition, processing, and pharmaceutical performance. In addition, sustainability claims often rely mainly on natural origin or biodegradability, with limited consideration of feedstock availability, water and energy consumption, solvent recovery, batch-to-batch variability, scale-up, regulatory requirements, and end-of-life management. This limitation is increasingly important as sustainability roadmaps for pharmacy and medicines practice call for environmental performance to be considered alongside product quality and therapeutic function [9,10].

These limitations provide the basis for applying circular pharmaceutics to plant mucilage. In this context, circular pharmaceutics refers to the integration of material performance with responsible sourcing, efficient extraction and purification, solvent and water recovery, productive use of residual biomass, formulation design, and appropriate management of the final product after use. Plant mucilage is particularly relevant because its polysaccharide-rich fractions can be recovered from renewable plant tissues and, in some cases, agricultural or food-processing by-products. Once adequately characterized, these fractions can serve as binders, disintegrants, film-forming agents, rheology modifiers, mucoadhesive materials, and controlled-release matrices in tablets, oral and buccal films, hydrogels, transdermal systems, and other drug-delivery platforms. Nevertheless, renewable origin alone does not make mucilage circular; its overall value depends on whether pharmaceutical performance can be achieved with consistent quality and a lower material and processing burden.

Accordingly, this review examines plant mucilage through an integrated structure–processing–performance framework. It focuses on neutral and acidic polysaccharide fractions, including arabinoxylan-rich and pectin-rich materials obtained from seeds, seed coats, husks, press cakes, fruits, and cladodes. Particular attention is given to how chemical composition, molecular-weight distribution, charge, extraction, fractionation, and formulation influence hydration, rheology, mucoadhesion, film formation, and controlled drug release. These relationships are considered alongside biomass valorization, solvent and energy use, process recovery, quality control, scale-up, regulatory expectations, and end-of-life management. The purpose is not simply to present plant mucilage as a natural alternative to synthetic excipients, but to assess critically the conditions under which it can provide reproducible drug-delivery performance within a lower-waste pharmaceutical system.

2. Circular Pharmaceutics: A New Paradigm for Bio-Based Drug Delivery Polymers

2.1. Introducing the Idea of Circular Pharmaceutics

Circular pharmaceutics reframes drug-delivery materials as assets that circulate through value loops—from renewable feedstocks and low-impact extraction to long-use performance, recovery, and benign end-of-life—rather than as linear consumables (Figure 1). In practice, it braids three strands: (i) circular-economy design of supply chains and logistics for medicines, (ii) greener chemistry and materials selection during discovery and manufacturing, and (iii) life-cycle thinking for dosage-form polymers, including reuse, recycling, or safe biodegradation. Recent roadmaps for circularity in pharma logistics (e.g., returnable transport items, digital track-and-trace) show measurable waste and carbon reductions at the system level, but also expose organizational frictions and data gaps that drug-product developers must anticipate from day one [11,12]. Parallel agendas in green pharmacy argue for minimizing environmental load of APIs and excipients across design-to-disposal, complementing circularity with actionable heuristics for procurement, dispensing, and take-back [13,14]. In discovery and preformulation, the GREENER framework—“G” for Good Practice, “R” for Reduced Off-target Exposure, through “R” for Reduced Emissions—bridges medicinal chemistry and environmental risk, urging polymers/excipients and APIs that meet efficacy while lowering persistence and ecotoxicity [8]. Where polymer choices are material, recent reviews of biodegradable and bio-based systems (blends, biocomposites) underscore trade-offs—mechanical integrity vs. degradability, processing energy vs. end-of-life—that a circular brief must resolve early via life-cycle assessment (LCA)-informed targets [15,16,17]. All things considered, the paradigm is not a slogan but an engineering obligation: specify renewable inputs, choose benign solvents/energy-lean processing, build durability and reparability (where relevant) into devices/delivery platforms, and define end-of-life fates that are either closed-loop or safely biodegradable with quantified impacts via LCA [16,17,18].

A second, often underestimated, lever in circular pharmaceutics is the extraction and processing stage for bio-polymers. Conventional hot-water or acid extractions can be energy- and water-intensive; greener solvent systems such as DES and their ultrasonic-assisted variants now deliver higher yields, new fractions, and cleaner impurity profiles for polysaccharides, while cutting process emissions and enabling solvent recycling [19,20,21,22]. The promise is tempered by scale-up realities—viscosity management, solvent recovery energy, potential residuals—and by the need to correlate extraction selectivity with downstream performance in dosage forms. Nevertheless, the direction is clear: solvent and energy choices at kilogram scale can shift the footprint more than swapping a polymer at gram scale [22].

The system around the dosage form matters. Circular-economy analyses of medicine supply chains and hospital-pharmacy waste streams show that materials policy (what tablets/films/gels are made from) must align with reverse logistics (what happens after use) and with prescriber/dispensing behaviors (how much waste is created upfront) [9,23,24]. Circular pharmaceutics therefore asks formulation scientists to put numbers (carbon, water, toxicity proxies) beside performance metrics (release, stability), and to treat bio-based polymers not as automatically green but as materials whose gains appear only when extraction-to-end-of-life is engineered coherently [23,24].

2.2. The Role of Plant Mucilage in Steering Drug-Delivery Systems Toward Sustainability

Plant mucilages—hydrophilic, high-molar-mass, anionic or neutral polysaccharides from seeds, husks, and cladodes—offer a rare blend of renewability, biocompatibility, and tunable rheology that maps naturally onto circular pharmaceutics. Comprehensive reviews catalog their chemistry, hydration, gelation, and processing, positioning mucilage as a credible alternative to fossil-based excipients for disintegration control, mucoadhesion, and film formation [2,25,26,27]. Psyllium/Plantago mucilage has been directly investigated as a pharmaceutical excipient, including as a superdisintegrant and as a component of mucoadhesive controlled-release systems [28,29,30]. However, the Plantago mucilage–alginate bead study [29] represents a composite system, and its mucoadhesion and sustained-release performance should not be attributed to mucilage alone because sodium alginate and calcium-mediated gelation also contribute to the formulation behavior. Viewed together, the literature points to the same lever: plant mucilage marries renewable supply with functions that cut complexity and waste. The leverage depends on process choices; without solvent recovery and tight standards, upstream costs can swallow downstream gains. Figure 2 sketches this throughline—from source to mechanism to dosage form to outcome—and primes the next sections.

Opuntia ficus-indica (cactus) mucilage provides a useful example of the distinction between direct pharmaceutical evidence and non-pharmaceutical material evidence. Its film-forming capacity, moisture management, and viscoelastic behavior have been investigated extensively in food and packaging applications [31,32,33]. These studies provide useful information on mucilage composition, rheology, film formation, and processing, but they do not by themselves demonstrate pharmaceutical performance. Pharmaceutical translation therefore remains a separate question and requires formulation-specific evidence using appropriate drug-delivery models.

Abelmoschus esculentus (okra) mucilage exemplifies the move from natural thickener to functional biomedical excipient. Its branched rhamnogalacturonan-like structures provide mucoadhesion and controlled hydration; recent reports demonstrate sustained-release encapsulation and antioxidant co-benefits that could reduce additive loadings in oral systems, with the caveat that batch-to-batch compositional variance still complicates quality by design (QbD) specifications [34,35,36]. A sustainable pipeline also depends on greener extraction: DES- or ultrasound-assisted protocols have been reported to modify extraction time, temperature, and yield, with potential for solvent recycling depending on the solvent system and process configuration. However, these process-level advantages should not be equated with lower environmental impact unless solvent recovery, water use, energy demand, and downstream processing are quantitatively assessed, and unless toxicology on residuals and robust cleaning validation are completed before cGMP adoption [22].

Salvia hispanica (chia) and Linum usitatissimum (flax) mucilages have demonstrated film-forming and hydrogel-forming properties that are relevant to oral and buccal drug-delivery formats [37,38,39]. Related studies on tamarind kernel polysaccharide provide additional information on how plasticizers affect the mechanical and thermal behavior of plant-derived polysaccharide films [40]. However, this evidence should be regarded as a formulation analogue rather than direct evidence for mucilage-based pharmaceutical films. Chia mucilage has also been used to prepare films with tunable mechanical and barrier properties [39]. Because this work was conducted primarily in the context of biodegradable films and food-related applications, it provides supporting material evidence rather than direct evidence of pharmaceutical performance. In contrast, the chia mucilage-based hydrogel reported for pH-responsive drug delivery provides direct pharmaceutical evidence [38].

Cissampelos pareira yields a pectin-rich mucilage that already behaves like a functional excipient: it forms cohesive hydrogels and cast films, supports drug-layer architecture, and exhibits acceptable biocompatibility when processed under mild conditions. C. pareira provides a particularly useful example because the literature includes both mucilage-based pharmaceutical formulations and studies of isolated pectin. The leaf mucilage has been incorporated into pharmaceutical films together with carrageenan and Eudragit® NE30D, where formulation optimization was used to control tensile properties, moisture uptake, and erosion [41]. Because this is a composite system, the observed performance should be interpreted as the behavior of a mucilage-containing formulation rather than as evidence attributable to mucilage alone. Separately, isolated C. pareira pectin has been used to prepare a hydrogel patch containing Heliotropium indicum extract, providing direct pharmaceutical evidence for a pectin-based material derived from C. pareira [42]. Synthesizing these findings, these data place C. pareira mucilage in the function-per-mass sweet spot of circular pharmaceutics—mucoadhesion, filmability, and hydration-controlled swelling—that can reduce total excipient burden. Meanwhile, the remaining gaps are standardization (pectin domain composition) and method-of-manufacture LCA to prove that greener extraction actually lowers footprints relative to optimized hot-water baselines.

Phoenix dactylifera (date palm) is increasingly documented as a viable pharmaceutical excipient, with compositional analyses from fruit tissues detailing rheology and hydration kinetics that support binder/disintegrant roles and film formation [43]. A dedicated evaluation of modified P. dactylifera mucilage as an excipient reports acceptable flow, binding, and tablet performance, arguing it can substitute conventional gums in wet-granulated systems—an attractive route where agro-residues are abundant and reverse-logistics for packaging/tablets remains weak [44]. Use-case breadth is emerging: mucilage integrated into polymeric systems for transdermal delivery (e.g., nicotine plaster gels) illustrates solvent-lean gelation and mechanical tunability compatible with patient-friendly patches [45]. At the same time, nanoscale encapsulation studies point to sustained-release behavior and cytocompatibility considerations for bioactive cargos [46]. Viewed holistically, P. dactylifera provides a potential pharmaceutical-excipient pathway through mucilage isolation and formulation development, while scale-up will require control of residue quality, microbial limits, and process consistency [43,44].

Critically, mucilage’s contribution to sustainability is not automatic: energy/water footprints during extraction can erase end-of-life gains if processes are poorly chosen. Here, circular pharmaceutics pushes the field toward solvent-system innovation and standardized analytics that tie extraction selectivity (e.g., fractionating neutral vs. uronic-acid-rich domains) to performance in mucoadhesion, disintegration, or release—so that greener steps also yield better medicines. DES and hybrid ultrasound approaches in seeds and peels are instructive, but require comparative LCA vs. optimized hot-water baselines, and verified solvent recovery, before claims of superiority hold for pharmaceutical-grade material [20,22,47]. Meanwhile, dosage-form science offers clear use-phase advantages: mucoadhesive systems can lower dose and dosing frequency—cuts to upstream manufacturing and downstream waste—if clinical performance is maintained. Recent biopolymer mucoadhesion overviews and oromucosal design principles provide the mechanistic and translational bridge from bench materials to patient-level reductions in resource intensity [3,48,49].

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Suksaeree, J.; Maneewattanapinyo, P. A Review of Circular Pharmaceutics: Plant Mucilage as Tunable Bio-Based Polymers for Advanced Drug Delivery. Sci 2026, 8, 286. https://doi.org/10.3390/sci8100286

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