Name: Sodium Alginate
CAS No: Sodium alginate [9005-38-3]
BP: Sodium Alginate PhEur: Sodium Alginate USP-NF: Sodium Alginate
Alginato sodico; algin; alginic acid, sodium salt; E401; Kelcosol; Keltone; natrii alginas; Protanal; sodium polymannuronate
Sodium alginate [9005-38-3]
Sodium alginate consists chiefly of the sodium salt of alginic acid, which is a mixture of polyuronic acids composed of residues of Dmannuronic acid and L-guluronic acid. The block structure and molecular weight of sodium alginate samples have been investigated.(1)
See Section 4.
Sodium alginate is used in a variety of oral and topical pharmaceutical formulations.(2) In tablet formulations, sodium alginate may be used as both a binder and disintegrant;(3) it has been used as a diluent in capsule formulations.(4) Sodium alginate has also been used in the preparation of sustained-release oral formulations since it can delay the dissolution of a drug from tablets,(5–7) capsules,(8) and aqueous suspensions.(9) The effects of particle size, viscosity and chemical composition of sodium alginate on drug release from matrix tablets have been described.(10) In topical formulations, sodium alginate is widely used as a thickening and suspending agent in a variety of pastes, creams, and gels, and as a stabilizing agent for oil-in-water emulsions. Recently, sodium alginate has been used for the aqueous microencapsulation of drugs,(11) in contrast with the more conventional microencapsulation techniques which use organicsolvent systems. It has also been used in the formation of nanoparticles.(12) The adhesiveness of hydrogels prepared from sodium alginate has been investigated,(13) and drug release from oral mucosal adhesive tablets,(14,15) buccal gels,(16,17) and vaginal tablets(18) based on sodium alginate have been reported. The esophageal bioadhesion of sodium alginate suspensions may provide a barrier against gastric reflux or site-specific delivery of therapeutic agents.(19,20) Other novel delivery systems containing sodium alginate include ophthalmic solutions that form a gel in situ when administered to the eye;(21,22) an in situ forming gel containing paracetamol for oral administration;(23) nasal delivery systems based on mucoadhesive microspheres;(24) and a freeze-dried device intended for the delivery of bone-growth factors.(25) Hydrogel systems containing alginates have also been investigated for delivery of proteins and peptides.(26) In addition, sodium alginate microspheres have been used in the preparation of a footmouth disease DNA vaccine,(27) and in an oral vaccine for Helicobacter pylori; (28) chitosan nanoparticles coated with sodium alginate may have applications in mucosal vaccine delivery systems.(29) Therapeutically, sodium alginate has been used in combination with an H2-receptor antagonist in the management of gastroesophageal reflux,(30) and as a hemostatic agent in surgical dressings.(31,32) Alginate dressings, used to treat exuding wounds, often contain significant amounts of sodium alginate as this improves the gelling properties.(33) Sponges composed of sodium alginate and chitosan produce a sustained drug release and may be useful as wound dressings or as tissue engineering matrices.(34) Lyophilized wound healing wafers composed of sodium alginate have been found to exhibit large reductions in viscosity following gamma irradiation.(35) Sodium alginate is also used in cosmetics and food products
Sodium alginate occurs as an odorless and tasteless, white to pale yellowish-brown colored powder
See Table II.
Acidity/alkalinity pH 7.2 (1% w/v aqueous solution) NIR spectra see Figure 1. Solubility Practically insoluble in ethanol (95%), ether, chloroform, and ethanol/water mixtures in which the ethanol content is greater than 30%. Also, practically insoluble in other organic solvents and aqueous acidic solutions in which the pH is less than 3. Slowly soluble in water, forming a viscous colloidal solution. Viscosity (dynamic) Various grades of sodium alginate are commercially available that yield aqueous solutions of varying viscosity. Typically, a 1% w/v aqueous solution, at 208C, will have a viscosity of 20–400 mPa s (20–400 cP). Viscosity may vary depending upon concentration, pH, temperature, or the presence of metal ions.(36–38) Above pH 10, viscosity decreases; see also Alginic Acid
Sodium alginate is a hygroscopic material, although it is stable if stored at low relative humidities and a cool temperature. Aqueous solutions of sodium alginate are most stable at pH 4–10. Below pH 3, alginic acid is precipitated. A 1% w/v aqueous solution of sodium alginate exposed to differing temperatures had a viscosity 60–80% of its original value after storage for 2 years.(39) Solutions should not be stored in metal containers. Sodium alginate solutions are susceptible on storage to microbial spoilage, which may affect solution viscosity. Solutions are ideally sterilized using ethylene oxide, although filtration using a 0.45 mm filter also has only a slight adverse effect on solution viscosity.(40) Heating sodium alginate solutions to temperatures above 708C causes depolymerization with a subsequent loss of viscosity. Autoclaving of solutions can cause a decrease in viscosity, which may vary depending upon the nature of any other substances present.(40,41) Gamma irradiation should not be used to sterilize sodium alginate solutions since this process severely reduces solution viscosity.(40,42) Preparations for external use may be preserved by the addition of 0.1% chlorocresol, 0.1% chloroxylenol, or parabens. If the medium is acidic, benzoic acid may also be used. The bulk material should be stored in an airtight container in a cool, dry place
Sodium alginate is incompatible with acridine derivatives, crystal violet, phenylmercuric acetate and nitrate, calcium salts, heavy metals, and ethanol in concentrations greater than 5%. Low concentrations of electrolytes cause an increase in viscosity but high electrolyte concentrations cause salting-out of sodium alginate; salting-out occurs if more than 4% of sodium chloride is present.
Alginic acid is extracted from brown seaweed and is neutralized with sodium bicarbonate to form sodium alginate.
Sodium alginate is widely used in cosmetics, food products, and pharmaceutical formulations, such as tablets and topical products, including wound dressings. It is generally regarded as a nontoxic and nonirritant material, although excessive oral consumption may be harmful. A study in five healthy male volunteers fed a daily intake of 175 mg/kg body-weight of sodium alginate for 7 days, followed by a daily intake of 200 mg/kg body-weight of sodium alginate for a further 16 days, showed no significant adverse effects.(43) The WHO has not specified an acceptable daily intake for alginic acid and alginate salts as the levels used in food do not represent a hazard to health.(44) Inhalation of alginate dust may be irritant and has been associated with industrial-related asthma in workers involved in alginate production. However, it appears that the cases of asthma were linked to exposure to seaweed dust rather than pure alginate dust.(45) LD50 (cat, IP): 0.25 g/kg(46) LD50 (mouse, IV): 0.2 g/kg LD50 (rabbit, IV): 0.1 g/kg LD50 (rat, IV): 1 g/kg LD50 (rat, oral): >5 g/kg
Observe normal precautions appropriate to the circumstances and quantity of material handled. Sodium alginate may be irritant to the eyes or respiratory system if inhaled as dust; see Section 14. Eye protection, gloves, and a dust respirator are recommended. Sodium alginate should be handled in a well-ventilated environment.
GRAS listed. Accepted in Europe for use as a food additive. Included in the FDA Inactive Ingredients Database (oral suspensions and tablets). Included as an excipient in nonparenteral medicines (oral capsules, modified release tablets, enteric-coated tablets and lozenges) licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.
Alginic acid; calcium alginate; potassium alginate; propylene glycol alginate.
A number of different grades of sodium alginate, which have different solution viscosities, are commercially available. Many different alginate salts and derivatives are also commercially available including ammonium alginate; calcium alginate; magnesium alginate, and potassium alginate. To assist in the preparation of dispersions of sodium alginate, the material may be mixed with a dispersing agent such as sucrose, ethanol, glycerol, or propylene glycol. A specification for sodium alginate is contained in the Food Chemicals Codex (FCC).(47) The PubChem Compound ID (CID) for sodium alginate is 6850754.