Chitosan

• BPChitosan Hydrochloride
• Ph. Eur.Chitosan Hydrochloride

chitosani hydrochloridum; deacetylated chitin; poliglusam; poly-D-glucosamine; Protasan

Poly-β-(1→4)-2-amino-2-deoxy-D-glucose, partially N-acetylated (partially deacetylated chitin) · [9012-76-4]

(C6H11NO4)n (glucosamine repeat unit) · ≈ 10 000–1 000 000 (grade-dependent)

Release-modifying polymer, Gelling agent, viscosity modifier

Typical concentrations: — · Dosage forms: Solid

Chitosan is used as a mucoadhesive polymer, permeation enhancer (particularly for nasal and oral delivery), film former, gel former and matrix for modified-release tablets, beads and microspheres; it also forms nanoparticles and polyelectrolyte complexes with anionic polymers and nucleic acids. Solutions of about 0.5–2% w/v in dilute acid are commonly used to prepare gels, films and coatings. It is also used in wound dressings and haemostatic products and as a dietary supplement.

An odourless, white or creamy-white to pale yellow powder or flakes. Commercial grades differ widely in molecular weight, degree of deacetylation and viscosity.

Degree of deacetylation

commonly about 70–95% for pharmaceutical grades

pKa

about 6.5 (amino groups)

Solubility

the free base is insoluble in water at neutral and alkaline pH and in organic solvents, but dissolves in dilute acids (for example 1% acetic acid) below about pH 6; the hydrochloride is soluble in water

Viscosity

strongly dependent on molecular weight and degree of deacetylation; grades range from low to very high viscosity in 1% acid solution

Charge

cationic polyelectrolyte in acidic solution

The powder is stable at room temperature but hygroscopic; it is best stored tightly closed in a cool, dry place, and refrigeration is often recommended. Solutions in acid gradually lose viscosity through depolymerisation, which is faster at higher temperature, and are susceptible to microbial and enzymatic degradation.

Incompatible with strong oxidising agents. As a polycation it interacts with anionic substances, including anionic surfactants, alginates, carbomers, xanthan gum and anionic drugs, forming complexes or precipitates; it precipitates from solution when the pH is raised above about 6.5.

Made from chitin, obtained from the shells of crustaceans such as shrimp and crab, which are demineralised with dilute acid and deproteinised with dilute alkali; the chitin is then deacetylated with hot concentrated sodium hydroxide. Chitosan from fungal sources is also available.

Of low oral toxicity and generally regarded as biocompatible and biodegradable. Large oral doses can cause gastrointestinal discomfort and may reduce absorption of fat-soluble vitamins and minerals. Material of crustacean origin is a theoretical concern for people with shellfish allergy, although purified chitosan contains very little protein.

Observe normal precautions for the quantity handled. Avoid inhaling the dust; gloves, eye protection and a dust mask are recommended.

Chitosan hydrochloride is described in the Ph. Eur. Chitosan is widely used in medical devices such as wound dressings and haemostats and in dietary supplements, but its use in licensed medicines is still limited.

Chitin; chitosan hydrochloride; chitosan glutamate; trimethyl chitosan; carboxymethyl chitosan.

Because molecular weight, degree of deacetylation and residual protein and metals vary greatly between sources and suppliers, these should be specified and controlled for each application. Its mucoadhesion and permeation-enhancing effects arise from the positive charge, so they are greatest at slightly acidic pH and are lost at neutral pH unless quaternised derivatives such as trimethyl chitosan are used.