Safety

Ingestion of strong solutions of ammonia is very harmful and causes severe pain in the mouth, throat, and gastrointestinal tract as well as severe local edema with cough, vomiting, and shock. Burns to the esophagus and stomach may result in perforation. Inhalation of the vapor causes sneezing, coughing, and, in high concentration, pulmonary edema. Asphyxia has been reported. The vapor is irritant to the eyes. Strong solutions are harmful when applied to the conjunctiva and mucous membranes. Topical application of even dilute ammonia solutions, used to treat insect bites, has caused burns, particularly when used with a subsequent dressing.(2–4)

Ammonia Solution 45 

When used as an excipient, ammonia solution is generally present in a formulation in a highly diluted form.

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Care should be used in handling strong or concentrated ammonia solutions because of the caustic nature of the solution and the irritating properties of its vapor. Before containers are opened, they should be well cooled. The closure should be covered with a cloth or similar material while opening. Ammonia solution should not be tasted and inhalation of the vapor should be avoided. Ammonia solution should be handled in a fume cupboard. Eye protection, gloves, and a respirator are recommended.

Regulatory Status

Included in the FDA Inactive Ingredients Guide (oral suspen- sions, topical preparations). Included in nonparenteral medi- cines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.

Related Substances

Dilute ammonia solution.

Dilute ammonia solution Synonyms: ammonia water. Specific gravity: 0.95–0.96

Comments: several pharmacopeias include monographs for dilute ammonia solution. The JP 2001, for example, states



that ammonia water contains not less than 9.5% and not more than 10.5% w/v of ammonia (NH3).

Comments

Where ‘ammonia solution’ is prescribed therapeutically, dilute ammonia solution should be dispensed or supplied.

The EINECS number for ammonia solution is 231-635-3.

Specific References

Frohman IG. Treatment of physalia stings. J Am Med Assoc 1996;

197: 733.

Beare JD, Wilson RS, Marsh RJ. Ammonia burns of the eye: an old weapon in new hands. Br Med J 1988; 296: 590.

Payne MP, Delic JI. Ammonia. In: Toxicity Review 24. London: HMSO, 1991: 1–12.

Leduc D, Gris P, Lheureux P, et al. Acute and long term respiratory damage following inhalation of ammonia. Thorax 1992; 47: 755–

757.

General References

—

Authors

PJ Sheskey.

Date of Revision

12 August 2005.

Ammonium Alginate

Nonproprietary Names

None adopted.

Synonyms

Alginic acid, ammonium salt; ammonium polymannuronate; E404; Keltose.

Chemical Name and CAS Registry Number

Ammonium alginate [9005-34-9]

Empirical Formula and Molecular Weight

(C6H11NO6)n 193.16 (calculated)

217 (actual, average)

Ammonium alginate is the ammonium salt of alginic acid.

Structural Formula

 

The number and sequence of the mannuronate and glucuronate residues shown above vary in the naturally occurring alginate. The associated water molecules are not shown.

Functional Category

Diluent; emulsifier; film-former; humectant; stabilizer; thick- ener; thickening agent.

Applications in Pharmaceutical Formulation or Technology

Ammonium alginate is widely used in foods as a stabilizer, thickener and emulsifier. It is also used in pharmaceutical preparations as a color-diluent, emulsifier, film-former, and humectant.

Description

Ammonium alginate occurs as white to yellowish brown filamentous, grainy, granular, or powdered forms.

Pharmacopeial Specifications

See Section 18.

Typical Properties

Solubility: dissolves slowly in water to form a viscous solution; insoluble in ethanol and in ether.

Moisture content: not more than 15% at 1058C for 4 hours.

Stability and Storage Conditions

Ammonium alginate is a hygroscopic material, although it is stable if stored at low relative humidities and cool tempera- tures.

Incompatibilities

Incompatible with oxidizing agents and strong acids and alkalis.

Method of Manufacture

—

Safety

Ammonium alginate is widely used in cosmetics and food products, and also in pharmaceutical formulations such as tablets. It is generally regarded as a nontoxic and nonirritant material, although excessive oral consumption may be harmful.

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of the material handled. Eye protection, gloves, and a dust respirator are recommended.

Regulatory Status

GRAS listed. Accepted in Europe for use as a food additive. Included in the FDA Inactive Ingredients Guide (oral, tablets).

Related Substances

Alginic acid; calcium alginate; potassium alginate; propylene glycol alginate; sodium alginate.

Comments

Alginates are commonly used in wound dressings.(1) Chitosan and alginates have been used together to produce sponges for use as wound dressings, or matrices for tissue engineering.(2) Alginate microspheres have been produced by internal gelation using emulsification methods.(3)

Although not included in any pharmacopeias, a specifica- tion for ammonium alginate is contained in the Food Chemicals Codex (FCC), see Table I.

Ammonium Alginate 47 

Table I: FCC specification for ammonium alginate.(4)

Test FCC 1996(4)

Identification +

Arsenic 43 mg/kg

Ash 44.0% after drying Heavy metals (as Pb) 40.002%

Lead 45 mg/kg

Loss on drying 415.0%

Assay 18.0–21.0% of CO2, corresponding to 88.7–103.6% ammonium alginate

Specific References

Morgan D. Wounds—what should a dressing formulary include?

Hosp Pharm 2002; 9(9): 261–266.



Lai HL, Abu’ Khalil A, Craig DQ. The preparation and characterization of drug-loaded alginate and chitosan sponges. Int J Pharm 2003; 251(1–2): 175–181.

Chan LW, Lee HY, Heng PW. Production of alginate microspheres by internal gelation using an emulsification method. Int J Pharm 2002; 242(1–2): 259–262.

Food Chemicals Codex, 4th edn. Washington, DC: National Academy Press, 1996: 24.

General References

—

Authors

D Thassu, S Shah.

Date of Revision

15 August 2005.

Ascorbic Acid

Nonproprietary Names

BP: Ascorbic acid JP: Ascorbic acid

PhEur: Acidum ascorbicum USP: Ascorbic acid

Synonyms

C-97; cevitamic acid; 2,3-didehydro-L-threo-hexono-1,4-lac- tone; E300; 3-oxo-L-gulofuranolactone, enol form; vitamin C.

Chemical Name and CAS Registry Number

L-(+)-Ascorbic acid [50-81-7]

Pharmacopeial Specifications

See Table I.

Table I: Pharmacopeial specifications for ascorbic acid.

Empirical Formula and Molecular Weight

C6H8O6 176.13

solution Organic volatile

impurities

— — +

Structural Formula

 

Functional Category

Antioxidant; therapeutic agent.

Applications in Pharmaceutical Formulation or Technology

Ascorbic acid is used as an antioxidant in aqueous pharma- ceutical formulations at a concentration of 0.01–0.1% w/v. Ascorbic acid has been used to adjust the pH of solutions for injection, and as an adjunct for oral liquids. It is also widely used in foods as an antioxidant. Ascorbic acid has also proven useful as a stabilizing agent in mixed micelles containing tetrazepam.(1)

Description

Ascorbic acid occurs as a white to light-yellow-colored, nonhygroscopic, odorless, crystalline powder or colorless crystals with a sharp, acidic taste. It gradually darkens in color upon exposure to light.

Assay 599.0% 99.0–100.5% 99.0–100.5%

Typical Properties

Acidity/alkalinity: pH = 2.1–2.6 (5% w/v aqueous solution)

Density (bulk):

0.7–0.9 g/cm3 for crystalline material; 0.5–0.7 g/cm3 for powder.

Density (particle): 1.65 g/cm3

Density (tapped):

1.0–1.2 g/cm3 for crystalline material; 0.9–1.1 g/cm3 for powder.

Density (true): 1.688 g/cm3

Dissociation constant:

pKa1 = 4.17;

pKa2 = 11.57.

Melting point: 1908C (with decomposition)

Moisture content: 0.1% w/w

Solubility: see Table II.