Nonproprietary Names
USP:Ammonium Chloride
PhEur:Ammonium Chloride
USP:Ammonium chloride
Synonyms
Ammonii chloridum; ammonium muriate; E510; sal ammoniac; salmiac.
Chemical Name and CAS Registry Number
Ammonium chloride [12125-02-9]
Empirical Formula and Molecular Weight
NH4Cl 53.49
Structural Formula
See Section 4.
Functional Category
Acidifying agent; therapeutic agent.
Applications in Pharmaceutical Formulation or Technology
Technology Ammonium chloride is used as an acidifying agent in oral formulations. It is also used as a food additive and antiseptic agent.(1) Ammonium chloride is used in the treatment of severe metabolic alkalosis to maintain the urine at an acid pH in the treatment of some urinary tract disorders or in forced acid diuresis.(2–4) It is also used as an expectorant in cough medicines.(5)
Description
Ammonium chloride occurs as colorless, odorless crystals or crystal masses. It is a white, granular powder with a cooling, saline taste. It is hygroscopic and has a tendency to cake.
Pharmacopeial Specifications
See Table I. Table I: Pharmacopeial specifications for ammonium chloride. Test PhEur 6.0 USP 32 Identification Characters Appearance of solution Acidity or alkalinity Loss on drying þ þ þ þ41.0% þ— — þ40.5% Residue on ignition — 40.1% Thiocyanate Bromides and iodides Sulfates — þ4150 ppm þ— — Sulfated ash 40.1% — Calcium 4200 ppm — Iron 420 ppm — Heavy metals 410 ppm 40.001% Assay (dried basis) 99.0–100.5% 99.5–100.5%
Typical Properties
Acidity/alkalinity pH = 4.5–5.5 (5.5% w/w aqueous solutions at 258C) Density (bulk) 0.6–0.9g/cm3 Hygroscopicity Hygroscopic with potential to cake. Melting point Decomposes at 3388C; sublimes without melting.(6) Solubility Soluble in water; hydrochloric acid and sodium chloride decrease its solubility in water. Also soluble in glycerin; sparingly soluble in methanol and ethanol. Almost insoluble in acetone, ether, and ethyl acetate. Specific gravity 1.527g/cm3 Vapor pressure 133.3Pa (1mmHg) at 1608C
Stability and Storage Conditions
Ammonium chloride is chemically stable. It decomposes completely at 3388C to form ammonia and hydrochloric acid. Store in airtight containers in a cool, dry place.
Incompatibilities
Ammonium chloride is incompatible with strong acids and strong bases. It reacts violently with ammonium nitrate and potassium chlorate, causing fire and explosion hazards. It also attacks copper and its compounds.
Method of Manufacture
Ammonium chloride is prepared commercially by reacting ammonia with hydrochloric acid.
Safety
Ammonium chloride is used in oral pharmaceutical formulations. The pure form of ammonium chloride is toxic by SC, IV, and IM routes, and moderately toxic by other routes. Potential symptoms of overexposure to fumes are irritation of eyes, skin, respiratory system: cough, dyspnea, and pulmonary sensitization.(7)Ammonium salts are an irritant to the gastric mucosa and may induce nausea and vomiting. LD50 (mouse, IP): 1.44g/kg(8) LD50 (mouse, oral): 1.3g/kg LD50 (rat, IM): 0.03g/kg(9) LD50 (rat, oral): 1.65g/kg(10) 42
Handling Precautions
Observe normal precautions appropriate to the circumstances and quantity of the material handled. All grades of ammonium chloride must be kept well away from nitrites and nitrates during transport and storage. They must be stored in a dry place, and effluent must not be discharged into the drains without prior treatment. Ammonium chloride decomposes on heating, producing toxic and irritating fumes (nitrogen oxides, ammonia, and hydrogen chloride).
Regulatory Status
GRAS listed. Included in the FDA Inactive Ingredients Database (oral syrup, tablets). Accepted for use as a food additive in Europe. Included in medicines licensed in the UK (eye drops; oral syrup). 17 Related Substances Ammonia solution.
Comments
Ammonium chloride has the ability to cross the red blood cell membrane, and a solution that is isotonic to blood will still cause hemolytic rupture because it acts as a hypotonic solution. A specification for ammonium chloride is contained in the Food Chemicals Codex (FCC).(11) The EINECS number for ammonium chloride is 235-186-4. The PubChem Compound ID (CID) for ammonium chloride is 25517. 19 Specific References 1 Gottardi W et al. N-Chlorotaurine and ammonium chloride: an antiseptic preparation with strong bactericidal activity. Int J Pharm 2007; 335: 32–40. 2 Mainzer F. Acid therapy with neutral salts. Klin Wochenschr 1927; 6: 1689–1691. 3 Portnoff JB et al. Control of urine pH and its effect on drug excretion in humans. J Pharm Sci 1961; 50: 890. 4 Davies HE. Rise in urine pH and in ammonium excretion during a water diuresis. J Physiol 1968; 194: 79–80P. 5 Coleman W. Expectorant action of ammonium chloride. Am J Med Sci 1916; 152: 569–574. 6 Zhu RS et al. Sublimation of ammonium salts: a mechanism revealed by a first-principles study of the NH4Cl system. J Phys Chem 2007; 111: 13831–13838. Ascorbic Acid 7 NIOSH Pocket Guide to Chemical Hazards (DHHS/NIOSH 97-140) 1997: 16. 8 Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th edn. New York: Wiley, 2004; 231. 9 Boyd EM, Seymour KGW. Ethylene diamine dihydrochloride. II. Untoward toxic reactions. Exp Med Surg 1946; 4: 223–227. 10 Smeets P. Ammonium chloride [and water treatment]. Tribune de l’Eau 1994; 47(570): 26–29. 11 Food Chemicals Codex, 6th edn. Bethesda, MD: United States Pharmacopeia, 2008; 46.
General References
Ingham JW. The apparent hydration of ions. III. The densities and viscosities of saturated solutions of ammonium chloride in hydrochloric acid. J Chem Soc 1929; 2059–2067. Kumaresan R et al. Simultaneous heat and mass transfer studies in drying of ammonium chloride in fluidized bed dryer. Process Plant Eng 2007; 25(3): 60–66.
Author
X He.
Date of Revision
27 February 2009.