Table II: Pharmacopeial specifications for sodium lauryl sulfate.

 

Test JP 2001 PhEur 2005 USPNF 23    

Identification + + +    

Alkalinity + + +    

Heavy metals — — 40.002%    

Sodium chloride 48.0% + +    

Sodium sulfate + + +    

Unsulfated alcohols 44.0% — 44.0%    

Nonesterified alcohols — 44.0% —    

Total alcohols 559.0% — 559.0%    

Organic volatile impurities — — +    

Water 45.0% — —    

Assay (as C12H25NaO4S) — 585.0% —  

�Stability and Storage Conditions

Sodium lauryl sulfate is stable under normal storage conditions. However, in solution, under extreme conditions, i.e., pH 2.5 or below, it undergoes hydrolysis to lauryl alcohol and sodium bisulfate.

The bulk material should be stored in a well-closed container away from strong oxidizing agents in a cool, dry place.

Inc ompatibilities

Sodium lauryl sulfate reacts with cationic surfactants, causing loss of activity even in concentrations too low to cause precipitation. Unlike soaps, it is compatible with dilute acids and calcium and magnesium ions.

Solutions of sodium lauryl sulfate (pH 9.5–10.0) are mildly corrosive to mild steel, copper, brass, bronze, and aluminum. Sodium lauryl sulfate is also incompatible with some alkaloidal salts and precipitates with lead and potassium salts.

Method of Manufacture

Sodium lauryl sulfate is prepared by sulfation of lauryl alcohol, followed by neutralization with sodium carbonate.

Safety

Sodium lauryl sulfate is widely used in cosmetics and oral and topical pharmaceutical formulations. It is a moderately toxic material with acute toxic effects including irritation to the skin, eyes, mucous membranes, upper respiratory tract, and sto- mach. Repeated, prolonged exposure to dilute solutions may cause drying and cracking of the skin; contact dermatitis may develop.(3) Prolonged inhalation of sodium lauryl sulfate will damage the lungs. Pulmonary sensitization is possible, resulting in hyperactive airway dysfunction and pulmonary allergy. Animal studies have shown intravenous administration to cause marked toxic effects to the lung, kidney, and liver. Mutagenic testing in bacterial systems has proved negative.(4)

Adverse reactions to sodium lauryl sulfate in cosmetics and pharmaceutical formulations mainly concern reports of irrita- tion to the skin(3,5–7) or eyes(8) following topical application.

Sodium lauryl sulfate should not be used in intravenous preparations for humans. The probable human lethal oral dose is 0.5–5.0 g/kg.

LD50 (mouse, IP): 0.25 g/kg(9) LD50 (mouse, IV): 0.12 g/kg LD50 (rat, oral): 1.29 g/kg LD50 (rat, IP): 0.21 g/kg

LD50 (rat, IV): 0.12 g/kg

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Inhalation and contact with the skin and eyes should be avoided; eye protection, gloves, and other protective clothing, depending on the circumstances, are recommended. Adequate ventilation should be provided or a dust respirator should be worn. Prolonged or repeated exposure should be avoided. Sodium lauryl sulfate emits toxic fumes on combustion.

Sodium Lauryl Sulfate 689

Regulatory Status

GRAS listed. Included in the FDA Inactive Ingredients Guide (dental preparations; oral capsules, suspensions, and tablets; topical and vaginal preparations). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.

Related Substances

Cetostearyl alcohol; cetyl alcohol; magnesium lauryl sulfate; wax, anionic emulsifying.

Magnesium lauryl sulfate

Empirical formula: C12H26O4S·HMg

CAS number: [3097-08-3]

Comments: a soluble tablet lubricant.(10) The EINECS number for magnesium lauryl sulfate is 221-450-6.

Comments

A specification for sodium lauryl sulfate is contained in the Food Chemicals Codex (FCC). The EINECS number for sodium lauryl sulfate is 205-788-1.

Specific References

Smith BJ. SDS polyacrylamide gel electrophoresis of proteins.

Methods Mol Biol 1994; 32: 23–34.

Riekkola ML, Wiedmar SK, Valko IE, Siren H. Selectivity in capillary electrophoresis in the presence of micelles, chiral selectors and non-aqueous media. J Chromatogr 1997; 792A: 13–35.

Wigger-Alberti W, Krebs A, Elsner P. Experimental irritant contact dermatitis due to cumulative epicutaneous exposure to sodium lauryl sulphate and toluene: single and concurrent application. Br J Dermatol 2000; 143: 551–556.

Mortelmans K, Haworth S, Lawlor T, et al. Salmonella mutageni- city tests II: results from the testing of 270 chemicals. Environ Mutagen 1986; 8 (Suppl. 7): 1–119.

�

Blondeel A, Oleffe J, Achten G. Contact allergy in 330 dermatological patients. Contact Dermatitis 1978; 4(5): 270–276.

Bruynzeel DP, van Ketel WG, Scheper RJ, von Blomberg-van der Flier BME. Delayed time course of irritation by sodium lauryl sulfate: observations on threshold reactions. Contact Dermatitis 1982; 8(4): 236–239.

Eubanks SW, Patterson JW. Dermatitis from sodium lauryl sulfate in hydrocortisone cream. Contact Dermatitis 1984; 11(4): 250–

251.

Grant WM. Toxicology of the Eye, 2nd edn. Springfield, IL: Charles C Thomas, 1974: 964.

Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th edn. New York: Wiley, 2004: 3258–3259.

Caldwell HC, Westlake WJ. Magnesium lauryl sulfate–soluble lubricant [letter]. J Pharm Sci 1972; 61: 984–985.

General References

Hadgraft J, Ashton P. The effect of sodium lauryl sulfate on topical drug bioavailability. J Pharm Pharmacol 1985; 37 (Suppl.): 85P.

Nakagaki M, Yokoyama S. Acid-catalyzed hydrolysis of sodium dodecyl sulfate. J Pharm Sci 1985; 74: 1047–1052.

Vold RD, Mittal KL. Determination of sodium dodecyl sulfate in the presence of lauryl alcohol. Anal Chem 1972; 44(4): 849–850.

Wan LSC, Poon PKC. The interfacial activity of sodium lauryl sulfate in the presence of alcohols. Can J Pharm Sci 1970; 5: 104–107.

Wang L-H, Chowhan ZT. Drug–excipient interactions resulting from powder mixing V: role of sodium lauryl sulfate. Int J Pharm 1990; 60: 61–78.

Authors

S Behn.

Date of Revision

15 August 2005.

Sodium Metabisulfite

Nonproprietary Names

BP: Sodium metabisulphite JP: Sodium metabisulfite PhEur: Natrii metabisulfis USPNF: Sodium metabisulfite

Synonyms

Disodium disulfite; disodium pyrosulfite; disulfurous acid, disodium salt; E223; natrii disulfis; sodium acid sulfite; sodium pyrosulfite.

Chemical Name and CAS Registry Number

Sodium pyrosulfite [7681-57-4]

Empirical Formula and Molecular Weight

Na2S2O5 190.1

Structural Formula

Na2S2O5

Functional Category

Antioxidant.

Applications in Pharmaceutical Formulation or Technology

Sodium metabisulfite is used as an antioxidant in oral, parenteral, and topical pharmaceutical formulations, at con- centrations of 0.01–1.0% w/v. Primarily, sodium metabisulfite is used in acidic preparations; for alkaline preparations, sodium sulfite is usually preferred; see Section 18. Sodium metabisulfite also has some antimicrobial activity, which is greatest at acid pH, and may be used as a preservative in oral preparations such as syrups.

In the food industry and in wine production, sodium metabisulfite is similarly used as an antioxidant, antimicrobial preservative, and antibrowning agent. However, at concentra- tions above about 550 ppm it imparts a noticeable flavor to preparations.

Sodium metabisulfite usually contains small amounts of sodium sulfite and sodium sulfate.

Description

Sodium metabisulfite occurs as colorless, prismatic crystals or as a white to creamy-white crystalline powder that has the odor of sulfur dioxide and an acidic, saline taste. Sodium meta- bisulfite crystallizes from water as a hydrate containing seven water molecules.

Pharmacopeial Specifications

See Table I.

�Table I: Pharmacopeial specifications for sodium metabisulfite.

Test JP 2001 PhEur 2005 USPNF 23

Identification + + +

Characters — + —

Appearance of solution + + — pH (5% w/v solution) — 3.5–5.0 —

Chloride — — 40.05%

Thiosulfate + + 40.05%

Arsenic 44 ppm 45 ppm 43 ppm Heavy metals 420 ppm 420 ppm 40.002% Selenium — — <0.005%

Iron 420 ppm 420 ppm 40.002%

Assay (as Na2S2O5) — 95.0–100.5%  —

Assay (as SO2) — — 65.0–67.4%

Typical Properties

Acidity/alkalinity: pH = 3.5–5.0 for a 5% w/v aqueous solution at 208C.

Melting point: sodium metabisulfite melts with decomposition at less than 1508C.

Osmolarity: a 1.38% w/v aqueous solution is isoosmotic with serum.

Solubility: see Table II.

Table II: Solubility of sodium metabisulfite.

Solvent Solubility at 208C unless otherwise stated

Ethanol (95%) Slightly soluble

Glycerin Freely soluble

Water 1 in 1.9

1 in 1.2 at 1008C

Stability and Storage Conditions

On exposure to air and moisture, sodium metabisulfite is slowly oxidized to sodium sulfate with disintegration of the crystals.(1) Addition of strong acids to the solid liberates sulfur dioxide.

In water, sodium metabisulfite is immediately converted to sodium (Na+) and bisulfite (HSO—) ions. Aqueous sodium metabisulfite solutions also decompose in air, especially on heating. Solutions that are to be sterilized by autoclaving should be filled into containers in which the air has been replaced with an inert gas, such as nitrogen. The addition of dextrose to aqueous sodium metabisulfite solutions results in a decrease in the stability of the metabisulfite.(2)

The bulk material should be stored in a well-closed container, protected from light, in a cool, dry place.

Incompatibilities

Sodium metabisulfite reacts with sympathomimetics and other drugs that are ortho- or para-hydroxybenzyl alcohol deriva-

Sodium Metabisulfite 691

tives to form sulfonic acid derivatives possessing little or no pharmacological activity. The most important drugs subject to this inactivation are epinephrine (adrenaline) and its deriva- tives.(3) In addition, sodium metabisulfite is incompatible with chloramphenicol owing to a more complex reaction;(3) it also inactivates cisplatin in solution.(4,5)

It is incompatible with phenylmercuric acetate when autoclaved in eye drop preparations.(6)

Sodium metabisulfite may react with the rubber caps of multidose vials, which should therefore be pretreated with sodium metabisulfite solution.(7)

Method of Manufacture

Sodium metabisulfite is prepared by saturating a solution of sodium hydroxide with sulfur dioxide and allowing crystal- lization to occur; hydrogen is passed through the solution to exclude air. Sodium metabisulfite may also be prepared by saturating a solution of sodium carbonate with sulfur dioxide and allowing crystallization to occur, or by thermally dehy- drating sodium bisulfite.

Safety

Sodium metabisulfite is widely used as an antioxidant in oral, topical, and parenteral pharmaceutical formulations; it is also widely used in food products.

Although it is extensively used in a variety of preparations, sodium metabisulfite and other sulfites have been associated with a number of severe to fatal adverse reactions.(8–19) These are usually hypersensitivity-type reactions and include bronch- ospasm and anaphylaxis. Allergy to sulfite antioxidants is estimated to occur in 5–10% of asthmatics, although adverse reactions may also occur in nonasthmatics with no history of allergy.

Following oral ingestion, sodium metabisulfite is oxidized to sulfate and is excreted in urine. Ingestion may result in gastric irritation, owing to the liberation of sulfurous acid, while ingestion of large amounts of sodium metabisulfite can cause colic, diarrhea, circulatory disturbances, CNS depression, and death.

In Europe, the acceptable daily intake of sodium metabi- sulfite and other sulfites used in foodstuffs has been set at up to

3.5 mg/kg body-weight, calculated as sulfur dioxide (SO2). The WHO has similarly also set an acceptable daily intake of sodium metabisulfite, and other sulfites, at up to 7.0 mg/kg body-weight, calculated as sulfur dioxide (SO2).(20)

LD50 (rat, IV): 0.12 g/kg(21)

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Sodium metabisulfite may be irritant to the skin and eyes; eye protection and gloves are recommended. In the UK, the long-term (8-hour TWA) occupational exposure limit for sodium metabisulfite is 5 mg/m3.(22)

Regulatory Status

GRAS listed. Accepted for use as a food additive in Europe. Included in the FDA Inactive Ingredients Guide (epidural, inhalation; IM, and IV injections; ophthalmic solutions; oral preparations, rectal, topical, and vaginal preparations). Included in nonparenteral and parenteral medicines licensed

�

in the UK. Included in the Canadian List of Acceptable Non- medicinal Ingredients.

Related Substances

Potassium metabisulfite; sodium bisulfite; sodium sulfite.

Sodium bisulfite

Empirical formula: NaHSO3

Molecular weight: 104.07

CAS number: [7631-90-5]

Synonyms: E222; sodium hydrogen sulfite.

Appearance: white crystalline powder.

Density: 1.48 g/cm3

Solubility: soluble 1 in 3.5 parts of water at 208C; 1 in 2 parts of water at 1008C; and 1 in 70 parts of ethanol (95%).

Comments: most substances sold as sodium bisulfite contain significant, variable, amounts of sodium metabisulfite, as the latter is less hygroscopic and more stable during storage and shipment. See Section 18.

Comments

Sodium metabisulfite is used as an antioxidant at low pH, sodium bisulfite at intermediate pH, and sodium sulfite at higher pH values. A specification for sodium metabisulfite is contained in the Food Chemicals Codex (FCC).

The EINECS number for sodium metabisulfite is 231-673-0.

Specific References

Schroeter LC. Oxidation of sulfurous acid salts in pharmaceutical systems. J Pharm Sci 1963; 52: 888–892.

Schumacher GE, Hull RL. Some factors influencing the degrada- tion of sodium bisulfite in dextrose solutions. Am J Hosp Pharm 1966; 23: 245–249.

Higuchi T, Schroeter LC. Reactivity of bisulfite with a number of pharmaceuticals. J Am Pharm Assoc (Sci) 1959; 48: 535–540.

Hussain AA, Haddadin M, Iga K. Reaction of cis-platinum with sodium bisulfite. J Pharm Sci 1980; 69(3): 364–365.

Garren KW, Repta AJ. Incompatibility of cisplatin and Reglan injectable. Int J Pharm 1985; 24: 91–99.

Collins AJ, Lingham P, Burbridge TA, Bain R. Incompatibility of phenylmercuric acetate with sodium metabisulphite in eye drop formulations. J Pharm Pharmacol 1985; 37 (Suppl.): 123P.

Schroeter LC. Sulfurous acid salts as pharmaceutical antioxidants.

J Pharm Sci 1961; 50(11): 891–901.

Jamieson DM, Guill MF, Wray BB, May JR. Metabisulfite sensitivity: case report and literature review. Ann Allergy 1985; 54(4): 115–121.

Anonymous. Possible allergic-type reactions. FDA Drug Bull

1987; 17: 2.

Tsevat J, Gross GN, Dowling GP. Fatal asthma after ingestion of sulfite-containing wine [letter]. Ann Intern Med 1987; 107(2): 263.

Weiner M, Bernstein IL. Adverse Reactions to Drug Formulation Agents: a Handbook of Excipients. New York: Marcel Dekker, 1989: 314–320.

Fitzharris P. What advances if any, have been made in treating sulfite allergy? Br Med J 1992; 305: 1478.

Smolinske SC. Handbook of Food, Drug and Cosmetic Excipients. Boca Raton, FL: CRC Press Inc, 1992: 393–406.

Anonymous. Sulfites in drugs and food. Med Lett Drugs Ther

1986; 28: 74–75.

Baker GJ. Bronchospasm induced by bisulfite containing food and drugs. Med J Aust 1981; ii: 614–617.

Fwarog FJ, Leung DYM. Anaphylaxis to a component of isoethane. J Am Med Assoc 1982; 248: 2030–2031.

692 Sodium Metabisulfite

Koephe JW. Dose dependent bronchospasm from sulfites in isoethane. J Am Med Assoc 1984; 251: 2982–2983.

Mikolich DJ, McCloskey WW. Suspected gentamicin allergy could be sulfite sensitivity. Clin Pharm 1988; 7: 269.

Deziel-Evans LM, Hussey WJ. Possible sulfite sensitivity with gentamicin infusion. DICP Ann Pharmacother 1989; 23: 1032–

1033.

FAO/WHO. Evaluation of certain food additives and contami- nants. Thirtieth report of the joint FAO/WHO expert committee on food additives. World Health Organ Tech Rep Ser 1987: No. 751.

Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th edn. New York: Wiley, 2004: 3261.

Health and Safety Executive. EH40/2002: Occupational Exposure Limits 2002. Sudbury: Health and Safety Executive, 2002.

�General References

Halsby SF, Mattocks AM. Absorption of sodium bisulfite from peritoneal dialysis solutions. J Pharm Sci 1965; 54: 52–55.

Wilkins JW, Greene JA, Weller JM. Toxicity of intraperitoneal bisulfite.

Clin Pharmacol Ther 1968; 9: 328–332.

Authors

JT Stewart.

Date of Revision

17 August 2005.

Sodium Phosphate, Dibasic

Nonproprietary Names

BP: Anhydrous disodium hydrogen phosphate Disodium hydrogen phosphate

Disodium hydrogen phosphate dodecahydrate JP: Dibasic sodium phosphate

PhEur: Dinatrii phosphas anhydricus Dinatrii phosphas dihydricus Dinatrii phosphas dodecahydricus

USP: Dibasic sodium phosphate

Note that the BP 2004 and PhEur 2005 contain three separate monographs for the anhydrous, the dihydrate, and the dodecahydrate; the JP 2001 contains one monograph for the dodecahydrate; and the USP 28 contains one monograph for the anhydrous, the monohydrate, the dihydrate, the heptahy- drate, and the dodecahydrate. See also Section 8.

Synonyms

Disodium hydrogen phosphate; disodium phosphate; E339; phosphoric acid, disodium salt; secondary sodium phosphate; sodium orthophosphate.

Chemical Name and CAS Registry Number

Anhydrous dibasic sodium phosphate [7558-79-4] Dibasic sodium phosphate dihydrate [10028-24-7] Dibasic sodium phosphate dodecahydrate [10039-32-4] Dibasic sodium phosphate heptahydrate [7782-85-6] Dibasic sodium phosphate hydrate [10140-65-5] Dibasic sodium phosphate monohydrate [118830-14-1]

Empirical Formula and Molecular Weight

 

Na2HPO4 141.96    

Na2HPO4·H2O 159.94    

Na2HPO4·2H2O 177.98    

Na2HPO4·7H2O 268.03    

Na2HPO4·12H2O 358.08  

Structural Formula

Na2HPO4·xH2O where x = 0, 1, 2, 7, or 12.

Functional Category

Buffering agent; sequestering agent.

Applications in Pharmaceutical Formulation or Technology

Dibasic sodium phosphate is used in a wide variety of pharmaceutical formulations as a buffering agent and as a sequestering agent. Therapeutically, dibasic sodium phosphate is used as a mild laxative and in the treatment of hypopho- sphatemia.(1,2)

Dibasic sodium phosphate is also used in food products; for example as an emulsifier in processed cheese.

�Description

The USP 28 states that dibasic sodium phosphate is dried or contains, 1, 2, 7, or 12 molecules of water of hydration.

Anhydrous dibasic sodium phosphate occurs as a white powder. The dihydrate occurs as white or almost white, odorless crystals. The heptahydrate occurs as colorless crystals or as a white granular or caked salt that effloresces in warm, dry air. The dodecahydrate occurs as strongly efflorescent, colorless or transparent crystals.

Pharmacopeial Specifications

See Table I.

Table I: Pharmacopeial specifications for sodium phosphate, dibasic(a).

 

Test JP 2001 PhEur 2005 USP 28    

Identification + + +    

Characters + + —    

Appearance of solution + + —    

pH 9.0–9.4 — —    

Reducing substances — + —    

Insoluble substances — — 40.4%    

Monosodium phosphate — 40.025 —    

Carbonate + — —    

Chloride 40.014% + 40.06%    

Anhydrous — 4200 ppm —    

Dihydrate — 4400 ppm —    

Dodecahydrate — 4200 ppm —    

Water — + —    

Anhydrous — — —    

Dihydrate — — —    

Dodecahydrate — 57.0–61.0% —    

Sulfates 40.038% + 40.2%    

Anhydrous — 4500 ppm —    

Dihydrate — 40.1% —    

Dodecahydrate — 4500 ppm —    

Arsenic 42 ppm + 416 ppm    

Anhydrous — 42 ppm —    

Dihydrate — 44 ppm —    

Dodecahydrate — 42 ppm —    

Heavy metals 410 ppm + 40.002%    

Anhydrous — 410 ppm —    

Dihydrate — 420 ppm —    

Dodecahydrate — 410 ppm —    

Iron — + —    

Anhydrous — 420 ppm —    

Dihydrate — 440 ppm —    

Dodecahydrate — 420 ppm —    

Loss on drying 57.0–61.0% + +    

Anhydrous — 41.0% 45.0%    

Monohydrate — — 10.3–12.0%    

Dihydrate — 19.5–21.0% 18.5–21.5%    

Heptahydrate — — 43.0–50.0%    

Dodecahydrate — — 55.0–64.0%  

Assay (dried basis) 598.0% 98.0–101.0% 98.0–100.5%

(a) PhEur 2005 (Suppl. 5.1) for the dodecahydrate.

694 Sodium Phosphate, Dibasic

Typical Properties

Acidity/alkalinity: pH = 9.1 for a 1% w/v aqueous solution of the anhydrous material at 258C. A saturated aqueous solution of the dodecahydrate has a pH of about 9.5.

Ionization constants:

pKa1 = 2.15 at 258C;(3) pKa2 = 7.20 at 258C; pKa3 = 12.38 at 258C.

Moisture content: the anhydrous form is hygroscopic and will absorb water on exposure to air, whereas the heptahydrate is stable in air.

Osmolarity: a 2.23% w/v aqueous solution of the dihydrate is isoosmotic with serum; a 4.45% w/v aqueous solution of the dodecahydrate is isoosmotic with serum.

Solubility: very soluble in water, more so in hot or boiling water; practically insoluble in ethanol (95%). The an- hydrous material is soluble 1 in 8 parts of water, the heptahydrate 1 in 4 parts of water, and the dodecahydrate 1 in 3 parts of water.

Stability and Storage Conditions

The anhydrous form of dibasic sodium phosphate is hygro- scopic. When heated to 408C, the dodecahydrate fuses; at 1008C it loses its water of crystallization; and at a dull-red heat (about 2408C) it is converted into the pyrophosphate, Na4P2O7. Aqueous solutions of dibasic sodium phosphate are stable and may be sterilized by autoclaving.

The bulk material should be stored in an airtight container, in a cool, dry place.

Incompatibilities

Dibasic sodium phosphate is incompatible with alkaloids, antipyrine, chloral hydrate, lead acetate, pyrogallol, resorcinol and calcium gluconate, and ciprofloxacin.(4) Interaction between calcium and phosphate, leading to the formation of insoluble calcium–phosphate precipitates, is possible in par- enteral admixtures.

Method of Manufacture

Either bone phosphate (bone ash), obtained by heating bones to whiteness, or the mineral phosphorite is used as a source of tribasic calcium phosphate, which is the starting material in the industrial production of dibasic sodium phosphate.

Tribasic calcium phosphate is finely ground and digested with sulfuric acid. This mixture is then leached with hot water and neutralized with sodium carbonate, and dibasic sodium phosphate is crystallized from the filtrate.

Safety

Dibasic sodium phosphate is widely used as an excipient in parenteral, oral, and topical pharmaceutical formulations.

Phosphate occurs extensively in the body and is involved in many physiological processes since it is the principal anion of intracellular fluid. Most foods contain adequate amounts of phosphate, making hypophosphatemia (phosphate defi- ciency)(1) virtually unknown except for certain disease states(2) or in patients receiving total parenteral nutrition. Treatment is usually by the oral administration of up to 100 mmol of phosphate daily.

�Approximately two-thirds of ingested phosphate is absorbed from the gastrointestinal tract, virtually all of it being excreted in the urine, and the remainder is excreted in the feces. Excessive administration of phosphate, particularly intra- venously, rectally, or in patients with renal failure, can cause hyperphosphatemia that may lead to hypocalcemia or other severe electrolyte imbalances.(5,6) Adverse effects occur less frequently following oral consumption, although phosphates act as mild saline laxatives when administered orally or rectally. Consequently, gastrointestinal disturbances including diarrhea, nausea, and vomiting may occur following the use of dibasic sodium phosphate as an excipient in oral formulations. However, the level of dibasic sodium phosphate used as an excipient in a pharmaceutical formulation is not usually

associated with adverse effects. LD50 (rat, oral): 17 g/kg(7)

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Dibasic sodium phosphate may be irritating to the skin, eyes, and mucous membranes. Eye protection and gloves are recommended.

Regulatory Status

GRAS listed. Accepted in Europe for use as a food additive. Included in the FDA Inactive Ingredients Guide (injections; infusions; nasal, ophthalmic, oral, otic, topical, and vaginal preparations). Included in nonparenteral and parenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.

Related Substances

Dibasic potassium phosphate; sodium phosphate, monobasic; tribasic sodium phosphate.

Dibasic potassium phosphate Empirical formula: K2HPO4 Molecular weight: 174.15

CAS number: [7758-11-4]

Synonyms: dipotassium hydrogen orthophosphate; dipotas- sium hydrogen phosphate; dipotassium phosphate; E340; potassium phosphate.

Appearance: colorless or white, granular, hygroscopic powder.

Acidity/alkalinity: pH = 8.5–9.6 for a 5% w/v aqueous solution at 258C.

Osmolarity: a 2.08% w/v aqueous solution of dibasic potassium phosphate is isoosmotic with serum.

Solubility: freely soluble in water; very slightly soluble in ethanol (95%).

Comments: one gram of dibasic potassium phosphate contains approximately 11.5 mmol of potassium and 5.7 mmol of phosphate.

Tribasic sodium phosphate

Empirical formula: Na3PO4·xH2O

Molecular weight: 163.94 for the anhydrous material

380.06 for the dodecahydrate (12H2O)

CAS number: [7601-54-9] for the anhydrous material.

Sodium Phosphate, Dibasic 695