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1. Introduction

Chitosan is a linear aminopolysaccharide composed of β-(1→4)-linked 2-amino-2-deoxy-D-glucose units together with a variable fraction of N-acetyl-D-glucosamine residues, obtained by deacetylation of chitin under alkaline conditions ^[1]. Its practical appeal rests on a combination rarely found together: a polycationic backbone, film- and fibre-forming ability, biodegradability and low toxicity, which together support applications in biomedicine, food packaging, water treatment and functional coatings ^[2]. Unlike cellulose, whose dissolution requires the disruption of a dense hydrogen-bond network by rather aggressive media, chitosan dissolves readily in dilute aqueous acids; unlike most synthetic polyelectrolytes, it is obtained from an abundant waste stream of the seafood industry and retains a semicrystalline morphology inherited from the chitin precursor ^[3].

This apparently simple solubility behaviour conceals a set of coupled variables. The degree of deacetylation, the molar mass, the distribution of acetyl groups along the chain, the crystalline form and the thermal history of the solid all influence how a given sample responds to a given solvent ^[4][5]. A sample with a degree of deacetylation above roughly 70% normally dissolves in dilute acetic acid within hours, whereas a sample of the same origin with a substantially lower degree of deacetylation may only swell ^[6].^[6]Reported "solubility" therefore depends on how the test was made — contact time, temperature, solids content, stirring and the criterion used to declare dissolution — and comparisons between studies are often difficult because these conditions differ ^[7].

The purpose of this entry is to organise the solvent families that have been demonstrated to dissolve or plasticise chitosan, to relate them to the molecular interactions responsible for dissolution, and to indicate how the choice of solvent propagates into processing and material properties. Sections 2 to 4 treat the structural determinants of solubility and the two aqueous families — acidic and alkaline — that dominate laboratory and industrial practice. Sections 5 to 7 cover non-aqueous systems, ionic liquids and deep eutectic solvents. Section 8 discusses solvent selection criteria, Section 9 the regeneration and shaping routes that convert a chitosan solution into a material, and Section 10 the open issues that limit wider use of the newer solvent families.

2. Structural Determinants of Chitosan Solubility

2.1. Composition: Degree of Deacetylation and Molar Mass

The degree of deacetylation, usually expressed as the percentage of glucosamine units, is the first parameter that determines whether a sample is soluble at all. Commercial chitosans commonly fall between 70% and 95%, and the value obtained depends on the analytical method — infrared spectroscopy, potentiometric titration, elemental analysis and nuclear magnetic resonance give systematically different results for the same material ^[8][9]. Because the method is rarely stated together with the value, literature comparisons of "soluble" and "insoluble" samples carry an intrinsic uncertainty of several percentage points. Within a given series, solubility improves as the degree of deacetylation rises: the larger population of free amino groups provides more protonation sites, and the lower population of acetyl groups weakens the hydrophobic association that drives aggregation in water ^[10].

Molar mass acts in the opposite direction. Depolymerisation lowers the viscosity of the resulting solution and removes the longest chains, which are the ones most likely to remain associated; enzymatic and oxidative degradation are therefore routinely used deliberately, to produce low-molar-mass chitosans that dissolve in water or in very weakly acidic media even at near-neutral pH ^[10]. The trade-off is a loss of mechanical performance in the final material, so processability and end-use properties must be balanced rather than optimised independently ^[11].

2.2. Protonation and the Acid–Base Boundary

The defining chemical feature of chitosan is the primary amino group, with an apparent pK_a of the conjugate acid of about 6.3 for the fully deacetylated chain. Below this pH the amino groups are protonated, the chain becomes a cationic polyelectrolyte, and electrostatic repulsion plus counter-ion osmotic pressure overcome the attraction between chains. Above it, the net charge falls, the chain collapses, and the polymer precipitates or forms a physical gel ^[12]. This boundary is not sharp: protonation depends on the local electrostatic environment, so the effective pK_a shifts with the degree of ionisation, the ionic strength and the degree of deacetylation, and dissolution is observed over a transition region rather than at a single pH value ^[13].

The counter-ion matters as much as the pH. Protonation with acetic, formic, lactic, citric or hydrochloric acid produces chitosan acetate, formate, lactate, citrate or hydrochloride, and these salts differ in water uptake, hygroscopicity and thermal stability ^[14]. Chitosan salts prepared with pharmaceutically acceptable acids are water soluble without any added acid, which is why chitosan hydrochloride and chitosan glutamate are supplied as directly soluble grades for formulations that cannot tolerate a low pH ^[11].

2.3. Solid-State Order and Its Consequences

Chitosan inherits from chitin a semicrystalline morphology, and dissolution must destroy it. The hydrated polymorph is more accessible to acid than the anhydrous form; annealing or prolonged drying of a sample shifts the balance towards the anhydrous form and measurably slows dissolution.^[5] Spectroscopic methods — infrared, solid-state nuclear magnetic resonance and X-ray diffraction — are the standard means of tracking these forms, and they show that the crystallinity index of the starting material is among the strongest predictors of dissolution kinetics in a given acid ^[8].

Once dissolved, the chain adopts a semi-flexible conformation whose stiffness depends on the fraction of acetyl groups and on the ionic strength of the medium. Increasing ionic strength screens the electrostatic contribution to stiffness, the chain contracts, and the intrinsic viscosity falls; this is one reason why the same chitosan in the same acid gives different viscosity readings when the acid concentration or the salt content is changed ^[15][16]. Acetyl-rich regions associate hydrophobically even in good solvents, so concentrated solutions frequently show aggregation that is absent at infinite dilution ^[17][18].

3. Aqueous Acidic Solvents

3.1. Dilute Organic and Mineral Acids

Dilute aqueous acids are the standard laboratory solvent and remain the workhorse of industrial processing. Acetic acid at about 0.1–1 mol L⁻¹ (roughly 0.5–5% v/v) is the most frequently used medium; formic, lactic, citric, glycolic, adipic and hydrochloric acids are used where a particular counter-ion, a lower odour, or a higher dissolving power is required ^[1][2]. Dissolution is normally carried out at room temperature over a few hours, with solids contents between 0.5% and 3% for rheological work and up to about 5–8% for film casting and fibre spinning, the upper limit being set by viscosity rather than by solubility.

The acid concentration is not a neutral parameter. Raising the acetic acid concentration increases the ionic strength, screens the electrostatic repulsion between protonated segments and promotes chain association, so both the measured viscosity and the chain dimensions change markedly as acid concentration is increased at fixed polymer concentration ^[15][16]. In practice this means that a solution prepared in 0.1 mol L⁻¹ acetic acid and one prepared in 1 mol L⁻¹ acetic acid are not interchangeable, even when both are optically clear.

3.2. Protonation Equilibria and Solution Rheology

Quantitative treatments relate the degree of ionisation to pH through an apparent pK_a that depends on the degree of ionisation itself, and show that solubility requires a threshold degree of protonation rather than full protonation ^[13]. This explains two observations that are otherwise puzzling: chitosan remains in solution at pH values somewhat above the nominal pK_a when the degree of deacetylation is high, and it precipitates below the nominal pK_a when the acetyl content is high enough for hydrophobic association to dominate. The same framework describes the thermosensitive chitosan/glycerol-phosphate systems, where raising the temperature transfers protons and drives a sol–gel transition without any change in composition ^[13].

Rheologically, chitosan solutions in dilute acid are shear-thinning and viscoelastic, with a zero-shear viscosity that scales steeply with concentration and molar mass. Semi-dilute solutions show the entangled behaviour expected of a stiff polyelectrolyte, with a pronounced dependence of the relaxation spectrum on ionic strength ^[16][17]. At higher concentrations, molecular association produces an additional slow relaxation process and can lead to a weak gel that interferes with filtration, spinning and casting; the effect is strongest for samples with a high acetyl content and for solutions aged at low shear ^[18].

3.3. Concentrated Acid and Salt-Forming Routes

Working far above the usual concentration range changes both the solvent quality and the chain conformation. In concentrated chitosan hydrochloride solutions the polymer remains dissolved at levels inaccessible in dilute acid, and the chain dimensions contract relative to those measured in dilute and semi-dilute regimes, indicating that the concentrated medium acts as a poorer solvent despite the high charge density ^[19]. Such concentrated systems are useful where high solids content is required, for instance in dope preparation, but they demand careful control of water activity, because small changes in water content shift the phase behaviour.

A related and often overlooked route is the use of hydrated inorganic salts, which can act simultaneously as solvent and plasticiser. Certain hydrated salts disrupt the interchain hydrogen bonds of chitosan and give thermoplastic, processable compositions without any added acid, an approach that avoids the acid-catalysed chain scission discussed below and is attractive for melt-based processing ^[20].

3.4. Practical Limits: Chain Scission and Corrosion

Two limitations restrict the acidic route. First, chitosan undergoes acid-catalysed hydrolysis of the glycosidic bond, so prolonged standing of an acidic solution at elevated temperature reduces the molar mass and with it the mechanical properties of the material obtained from it; this degradation is the main reason why acidic dopes are usually prepared fresh and processed within hours to days ^[14]. Second, acidic media at the concentrations used for dissolution corrode standard stainless-steel equipment and require acid-resistant materials, neutralisation of the effluent and, in food and biomedical contexts, removal of residual acid from the product. These costs are modest at laboratory scale but become significant in large-scale film and fibre production ^[12].

4. Aqueous Alkaline and Urea-Based Solvents

4.1. Alkali–Urea Systems at Reduced Temperature

Solubility in acidic media is not the only option. Aqueous systems containing an alkali and urea dissolve chitosan when the solution is cooled, typically to between −20 °C and 0 °C, with the polymer added either directly or after a freeze–thaw cycle. A lithium hydroxide–urea–water composition was among the first to be reported specifically as a water-based system for chitosan processing, and it allows the polymer to be dissolved, cast and regenerated without any acid at all ^[21]. Urea is not a passive additive: it acts as a hydrogen-bond competitor that hinders the re-association of chains once the alkali has swollen the solid, and it is the combination — alkali to break the interchain hydrogen bonds, urea to keep them broken, low temperature to slow the reverse process — that makes the system work.

The practical consequences differ from those of the acidic route in ways that matter for processing. The solvent is alkaline, so no acid-resistant equipment is needed and no acid-catalysed depolymerisation occurs during standing; the price is the energy required for cooling and the fact that dissolution is often incomplete unless the sample has been properly pre-wetted ^[21][22].

4.2. Gelation and Homogeneous Derivatisation

The same alkali–urea media support two further operations that are difficult or impossible in acid. The first is controlled gelation. Chitosan solutions in aqueous alkali–urea gel on heating, and the transition is reversible and tunable through the alkali type, the urea content and the polymer concentration; the gel is physical, held together by hydrogen bonding and hydrophobic association rather than by covalent crosslinks ^[23]. A related composition produces gels with a distinctly different microstructure, showing that within a single solvent family the choice of alkali changes the morphology of the resulting network ^[24].

The second is homogeneous chemical modification. Because the polymer is molecularly dispersed in an alkaline medium, reactions that require a nucleophile — etherification with epoxides, and Michael addition to acrylamides — proceed uniformly along the chain instead of being limited to the accessible surface of a swollen particle ^[25][26]. Degrees of substitution achieved this way are difficult to reach heterogeneously, and the products retain the molar mass of the starting polymer better than those obtained under acidic conditions. Recent work with a weakly alkaline bicarbonate–urea system extends the same idea to a milder medium and characterises the rheology and gelation of the resulting solutions in detail ^[22].

4.3. Position Within the Solvent Landscape

Alkali–urea solvents occupy an intermediate position. They are water-based and cheap, like the acidic systems, but they avoid acid hydrolysis and enable homogeneous derivatisation, like the ionic liquids. Their limitations are the low operating temperature, the narrower range of soluble samples, and the fact that the polymer is uncharged in these media, so the solution rheology — and hence the processing window — differs from that of an acidic dope of the same concentration ^[21][22]. Figure 1 places the family in the wider solvent landscape.

Figure 1. Classification of chitosan solvent systems, arranged by medium and by the dominant interaction that brings the polymer into solution. Dissolution in aqueous media is confined to protonating (acidic) or strongly hydrogen-bond-disrupting (alkali–urea, hydrated salt) compositions; non-aqueous media rely on salt formation, dipolar aprotic carriers with lithium salts, ionic liquids or deep eutectic solvents.

5. Non-Aqueous and Salt-Forming Solvent Systems

5.1. Dipolar Aprotic Solvents With Lithium Salts

Combinations of a dipolar aprotic solvent with lithium chloride are widely used to dissolve and to characterise polyamides and polysaccharides, and they have been applied to the chitin family for both purposes. N,N-dimethylacetamide containing lithium chloride dissolves chitin fractions and permits their characterisation without degradation, which is why the system became a reference medium for molar-mass determination by size-exclusion chromatography ^[27]. For chitosan the same medium is used more often as an analytical solvent than as a processing solvent: it dissolves a wider range of samples than dilute acid, including those with a low degree of deacetylation, but it introduces lithium chloride that must be removed quantitatively from any material intended for biomedical or food use.

5.2. Salt Formation in Dimethyl Sulfoxide

A distinct mechanism operates in dimethyl sulfoxide. Chitosan is insoluble in the pure solvent, but the addition of an organic acid converts the polymer into its corresponding salt, which is soluble; dissolution therefore reports on salt formation rather than on solvent quality in the usual sense ^[28]. The approach is useful where an acidic aqueous medium is undesirable — for reactions that are water-sensitive, or for spectroscopic work in a non-protic environment — and it illustrates a general point: for a polymer bearing ionisable groups, adding a counter-ion can be as effective as changing the solvent.

5.3. Fluorinated and Strong-Acid Solvents for Electrospinning

Electrospinning imposes requirements that ordinary chitosan solutions do not meet: the solution must be volatile enough for the jet to dry before it reaches the collector, and conductive enough to be stretched by the field. Concentrated acetic acid satisfies both conditions and was among the first media used to spin chitosan fibres directly, without a carrier polymer ^[29][30]. Mixtures of a fluorinated alcohol with acetic acid give finer and more uniform fibres, because the fluorinated component lowers the surface tension and increases the volatility of the dope ^[31].

These solvents are effective but unattractive beyond the laboratory. Fluorinated alcohols are expensive, volatile and toxic, concentrated acetic acid is corrosive, and both leave residues that are unacceptable in implantable materials. Their continuing use reflects the fact that no water-based system yet matches them for fibre uniformity, and solvent substitution remains an active target ^[30][31].

6. Ionic Liquids

6.1. Imidazolium and Related Salts

Ionic liquids dissolve chitosan by a mechanism closer to that operating for cellulose than to protonation: the anion accepts hydrogen bonds from the hydroxyl and amino groups, the cation separates the chains, and the polymer dissolves without chemical modification. Imidazolium salts with chloride or acetate anions are the most studied; binary mixtures of imidazolium chlorides dissolve and allow blending of chitosan with other polysaccharides, giving composite dopes that cannot be prepared from acidic solutions because the components differ in their protonation behaviour ^[32]. Chitin and chitosan dissolved in ionic liquids were shown early on to be usable as reversible sorbents for carbon dioxide, which demonstrated that the dissolved polymer remains chemically accessible and that the solvent can be cycled ^[33].

6.2. Processing, Derivatisation and Material Outcomes

Because ionic liquids dissolve chitosan without protonating it, they enable reactions that acidic media preclude, and the resulting solutions can be coagulated into films, fibres, beads and monolithic gels. Reviews of the field document the range of chemical modifications carried out in these media and the biomedical materials obtained from them, together with the practical constraint that dissolution usually requires elevated temperature and prolonged stirring under dry conditions ^[34][35]. Water is the enemy of the process: it competes for the anion and precipitates the polymer, so both the solvent and the polymer must be dried, and the solvent must be recovered and dried again for reuse.

Recent work has begun to quantify the two obstacles that have kept ionic liquids out of industrial use. Systematic optimisation of dissolution in a chloride ionic liquid shows that acceptable dissolution requires temperatures and times that would be expensive to reproduce at scale, and ecotoxicity testing of the same system gives results that argue against releasing the solvent into ordinary waste streams ^[36]. Mixtures of an ionic liquid with water offer a partial way out: they dissolve cellulose, chitosan and chitin with far less solvent and at lower viscosity, at the cost of a narrower composition window in which the mixture remains a solvent ^[37].

6.3. Assessment

Ionic liquids are the most versatile chitosan solvents available and the least practical. They dissolve a wide range of samples, tolerate chemical modification, and give access to morphologies that acidic dopes cannot produce. Against this stand the viscosity of the resulting dopes, the cost of the solvent, the need for dry handling and recycling, incomplete toxicological data, and the difficulty of removing the last traces of solvent from a dense coagulated material ^[34][36]. Their use is therefore justified where the product value is high or where the chemistry cannot be done otherwise.

7. Deep Eutectic Solvents

7.1. Composition and Dissolving Power

Deep eutectic solvents are mixtures of a hydrogen-bond acceptor, most often choline chloride, with a hydrogen-bond donor such as urea, glycerol, a carboxylic acid or a polyol. They share with ionic liquids the ability to disrupt interchain hydrogen bonds but differ in being cheaper, easier to prepare from commodity components, and generally less toxic. Their application to polysaccharides has been reviewed comprehensively, and the picture that emerges is of a family that dissolves some polysaccharides readily and others only partially, with chitosan responding better than chitin in most reported systems ^[38].

The composition of the hydrogen-bond donor controls the outcome. Acidic donors protonate the amino groups and add an electrostatic contribution to the hydrogen-bond disruption, which is why choline chloride–carboxylic acid mixtures dissolve chitosan more effectively than choline chloride–urea at the same temperature; the same mixtures have been used to extract chitin from shrimp-shell waste, where the acidic component removes minerals and the eutectic solvent dissolves the protein and polysaccharide fractions in separate steps ^[39].

7.2. Reactive and Extractive Roles

Two newer developments extend the role of deep eutectic solvents beyond dissolution. In the first, the solvent participates in the reaction: a reactive deep eutectic solvent acts simultaneously as medium and as reagent, so etherification of chitosan gives a cationic derivative without a separate solvent, catalyst or work-up step ^[40]. In the second, the solvent is used to extract the polymer from the raw biomass in one operation; natural deep eutectic solvents have been used to obtain chitosan directly from shell waste, combining demineralisation, deproteinisation and deacetylation into a shorter route ^[41].

Both directions are attractive because they remove steps rather than replace a solvent. Both are also early-stage: the number of compositions studied is small relative to the space that could be explored, yields and degrees of deacetylation vary strongly with the source material, and the solvent is difficult to recover from the viscous, polymer-rich phase that results ^[38][41].

8. Solvent Selection: Criteria and Trade-offs

8.1. What Solubility Parameters Can and Cannot Tell

Cohesive-energy-density descriptors, whether expressed as Hansen solubility parameters or as Kamlet–Taft polarity and hydrogen-bond terms, are useful for a first screening of candidate media and are widely applied to polysaccharides. Their predictive power for chitosan is limited, however, because dissolution is rarely a simple matching of cohesive energies: in acidic water it is driven by protonation, in alkali–urea by low-temperature hydrogen-bond screening, in dimethyl sulfoxide by salt formation, and in ionic liquids by anion–hydrogen-bond acceptance. A solvent whose parameters lie close to those of the repeat unit may therefore fail completely, while one whose parameters lie far away may dissolve the polymer quantitatively ^[34][38]. Solubility parameters are best used to compare solvents within one mechanism, not across mechanisms.

8.2. Practical Criteria

In practice, a solvent is chosen against a small number of criteria that are rarely all satisfied at once. The polymer must retain its molar mass during dissolution and standing; the dope must reach a workable solids content at a viscosity compatible with the shaping operation; the solvent must be removable, recoverable and acceptable under the regulatory regime of the intended application; and the coagulation step must give the morphology required of the final material. Table 1 summarises how the main solvent families compare against these criteria.

Table 1. Representative solvent systems for chitosan and their practical trade-offs.

9. Regeneration, Shaping and Material Outcomes

9.1. Coagulation and the Regeneration Step

A chitosan solution becomes a material when the solvent quality is destroyed in a controlled way. In acidic systems this is done by raising the pH, usually in an alkaline coagulation bath that deprotonates the chain and precipitates it into a hydrogel; the temperature of that bath influences the kinetics of solvent–non-solvent exchange and therefore the cross-section, porosity and mechanical properties of the fibre or film produced ^[42]. In ionic liquids and deep eutectic solvents, water or alcohol plays the same role, and the rate of exchange is the main variable available for controlling morphology ^[34].

9.2. Fibres, Films and Membranes

Wet spinning of an acidic dope into an alkaline bath gives continuous filaments whose properties depend on draw ratio, coagulation temperature and washing ^[42]. Electrospinning, which requires a volatile and conductive dope, produces sub-micrometre fibres directly from concentrated acetic acid or from fluorinated-alcohol mixtures, and crosslinking can be introduced in the same step so that the mat does not redissolve in contact with water ^[29][30][43]. The diameter, surface roughness and alignment of electrospun fibres are sensitive to the solvent composition and to the ambient humidity during spinning, which is why reported morphologies vary so widely between laboratories ^[44][45].

Cast films and membranes represent the largest volume of chitosan products. Solvent choice enters twice: through the viscosity of the dope, which sets the achievable thickness, and through the drying history, which sets the crystalline form and hence the barrier and mechanical properties. Composite membranes for the separation of water from organic liquids have been prepared from chitosan layers on porous supports, and their selectivity depends on the degree of swelling left by the casting solvent ^[46].

9.3. Gels, Aerogels and Porous Monoliths

When the solvent is removed by exchange with a miscible non-solvent and then by drying under conditions that preserve the wet structure, the result is an aerogel or a porous monolith with surface areas far above those of a dense film. Solvent-exchange routes applied to chitosan-containing hydrogels give lightweight monoliths whose pore structure is inherited from the phase separation that occurred in solution, so the solvent composition controls the final morphology as much as the drying method does ^[47]. Hydrogels formed from polysaccharide solutions, including those prepared in ionic liquids, extend the same principle to soft materials and remain one of the most active areas of application ^[48].

9.4. How the Application Selects the Solvent

The intended application closes the loop back to solvent choice. Tissue-engineering constructs are usually produced from acidic dopes because residual solvent can be washed out and the starting polymer is well characterised, but they face the molar-mass loss associated with acidic processing ^[49]. Packaging films and composites are produced at larger scale, where the cost of acid-resistant equipment and effluent treatment favours aqueous alkaline or plasticised routes where they can be made to work ^[50]. Antimicrobial formulations exploit the same cationic character that makes the polymer acid-soluble, and solvent residues that neutralise the amino groups would compromise the effect ^[51]. Where solubility itself is the obstacle, chemical modification — carboxymethylation, quaternisation, grafting — is used to produce derivatives that dissolve in plain water, at the cost of an additional synthetic step ^[52][53]. Figure 2 summarises the routes from solvent to material.

Figure 2. Dissolution–shaping–regeneration cycle for chitosan. The solvent determines the state of the chain in solution and, through the coagulation and drying steps, the morphology of the material obtained: films and membranes by casting, fibres by wet spinning or electrospinning, beads by dropwise coagulation, gels by physical or chemical crosslinking, and aerogels by solvent exchange followed by drying.

10. Perspectives and Outlook

Three developments are likely to shape the field. The first is the continued shift towards solvents that can be sourced from commodity chemicals and recovered cheaply, which favours deep eutectic solvents and aqueous systems over ionic liquids for high-volume products; the bottleneck is recovery from viscous, polymer-rich media rather than dissolution itself ^[38][41]. The second is the integration of dissolution with upstream processing, so that extraction, deacetylation and dissolution are combined into fewer steps, an approach already demonstrated for shell waste and for reactive eutectic media ^[12][40]. The third is standardisation: because reported solubilities depend on sample history, test conditions and the criterion used, comparable data across laboratories are scarce, and the absence of a shared protocol is arguably a bigger obstacle to solvent development than the chemistry of any particular system ^[9][14].

On the scientific side, the most useful next step is a quantitative link between the state of the chain in solution — dimensions, aggregation, charge — and the morphology obtained after a given coagulation path. Such a link would turn solvent selection from an empirical search into a design problem, and would make it possible to decide, in advance, whether a given solvent can produce a given morphology. Until it exists, the pragmatic rule remains the one that current practice follows: choose the mildest solvent that dissolves the sample at the solids content the shaping operation requires, and accept the extra cost of a stronger solvent only when the chemistry or the morphology cannot be obtained otherwise ^[34][36].