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Home , Disodium phosphate

, Monobasic

1 Nonproprietary Names Table I: Pharmacopeial specifications for sodium phosphate, BP: Anhydrous Sodium Dihydrogen Phosphate monobasic. Sodium Dihydrogen Phosphate Monohydrate Test PhEur 6.0 USP 32 Sodium Dihydrogen Phosphate Dihydrate þþ PhEur: Sodium Dihydrogen Phosphate Dihydrate Identification Characters þ — USP: Monobasic Sodium Phosphate Appearance of solution þ — Note that the BP 2009 contains three separate monographs for the Aluminum, calcium and — þ anhydrous, the monohydrate, and the dihydrate; the PhEur 6.0 related elements 4 4 contains a single monograph for the dihydrate; and the USP 32 Arsenic 2 ppm 8 ppm Chloride 4200 ppm 40.014% contains one monograph for the anhydrous, the monohydrate and Insoluble substances — 40.2% the dihydrate. See also Section 8. Heavy metals 410 ppm 40.002% Iron 410 ppm — 2 Synonyms pH 4.2–4.5 4.1–4.5 Reducing substances þ — Acid sodium phosphate; E339; Kalipol 32; monosodium orthopho- Sulfate 4300 ppm 40.15% sphate; ; natrii dihydrogenophosphas Water þþ dihydricus; , monosodium ; primary sodium Anhydrous — 42.0% phosphate; sodium biphosphate; sodium dihydrogen orthopho- Monohydrate — 10.0–15.0% Dihydrate 21.5–24.0% 18.0–26.5% sphate; sodium dihydrogen phosphate. Assay (dried basis) 98.0–100.5% 98.0–103.0%

3 Chemical Name and CAS Registry Number Anhydrous monobasic sodium phosphate [7558-80-7] 10 Typical Properties Monobasic sodium phosphate monohydrate [10049-21-5] Acidity/alkalinity pH = 4.1–4.5 for a 5% w/v of Monobasic sodium phosphate dihydrate [13472-35-0] the monohydrate at 258C. Density 1.915 g/cm3 for the dihydrate. 4 Empirical Formula and Molecular Weight Dissociation constant pKa = 2.15 at 258C

NaH2PO4 119.98 NIR spectra see Figures 1 and 2. Soluble 1 in 1 of water; very slightly soluble in ethanol NaH2PO4H2O 137.99 (95%). NaH2PO42H2O 156.01

5 Structural Formula 11 Stability and Storage Conditions See Section 4. Monobasic sodium phosphate is chemically stable, although it is slightly deliquescent. On heating at 1008C, the dihydrate loses all of its water of crystallization. On further heating, it melts with 6 Functional Category decomposition at 2058C, forming sodium hydrogen pyropho- S Buffering agent; emulsifying agent; sequestering agent. sphate, Na2H2P2O7. At 2508C it leaves a final residue of sodium metaphosphate, NaPO3. 7 Applications in Pharmaceutical Formulation or Aqueous solutions are stable and may be sterilized by autoclav- Technology ing. Monobasic sodium phosphate should be stored in an airtight Monobasic sodium phosphate is used in a wide variety of container in a cool, dry place. pharmaceutical formulations as a buffering agent and as a sequestering agent. Therapeutically, monobasic sodium phosphate is used as a mild saline and in the treatment of hypopho- 12 Incompatibilities sphatemia.(1–3) Monobasic sodium phosphate is an and is therefore Monobasic sodium phosphate is also used in food products, for generally incompatible with alkaline materials and carbonates; example, in baking powders, and as a dry acidulant and aqueous solutions of monobasic sodium phosphate are acidic and sequestrant. will cause carbonates to effervesce. Monobasic sodium phosphate should not be administered concomitantly with aluminum, calcium, or magnesium salts since 8 Description they bind phosphate and could impair its absorption from the The USP 32 states that monobasic sodium phosphate contains one gastrointestinal tract. Interaction between calcium and phosphate, or two molecules of water of hydration or is anhydrous. leading to the formation of insoluble calcium phosphate precipi- The hydrated forms of monobasic sodium phosphate occur as tates, is possible in parenteral admixtures.(4–6) odorless, colorless or white, slightly deliquescent crystals. The anhydrous form occurs as a white crystalline powder or granules. 13 Method of Manufacture Monobasic sodium phosphate is prepared by adding phosphoric 9 Pharmacopeial Specifications acid to a hot, concentrated solution of disodium phosphate until the See Table I. liquid ceases to form a precipitate with barium chloride. This

659 660 Sodium Phosphate, Monobasic

1.0 0.8 pharmaceutical formulation is not usually associated with adverse effects.

2311 (10) 1850 LD50 (rat, IM): 0.25 g/kg LD50 (rat, oral): 8.29 g/kg

0.0 15 Handling Precautions Observe normal precautions appropriate to the circumstances and log(1/R) quantity of material handled. Monobasic sodium phosphate may be 1716 2326 irritant to the skin, eyes, and mucous membranes. Eye protection 1771 1799 and gloves are recommended.

− − 10000 × [2nd deriv. log(1/R)] 1.0 0.2 16 Regulatory Status 1100 1300 1500 1700 1900 2100 2300 2500 GRAS listed. Accepted for use as a food additive in Europe. Wavelength/nm Included in the FDA Inactive Ingredients Database (injections; infusions; ophthalmic, oral, topical, and vaginal preparations). Figure 1: Near-infrared spectrum of anhydrous monobasic sodium Included in nonparenteral and parenteral medicines licensed in the phosphate measured by reflectance. UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients. 1.0 1.3 1390 1404

1142 1446 17 Related Substances 1305 Dibasic sodium phosphate; monobasic potassium phosphate. 0.0 Monobasic potassium phosphate

1769 Empirical formula KH2PO4 1343 Molecular weight 136.09 1459 1916 CAS number [7778-77-0] 1163 log(1/R) Synonyms E340; monopotassium phosphate; potassium acid phosphate; potassium biphosphate; potassium dihydrogen orthophosphate.

1422 Appearance Colorless crystals or a white, odorless, granular or 1000 × [2nd deriv. log(1/R)] −2.0 −0.2 crystalline powder. 1100 1300 1500 1700 1900 2100 2300 2500 Acidity/alkalinity pH 4.5 for a 1% w/v aqueous solution at 8 Wavelength/nm 25 C. Solubility Freely soluble in water; practically insoluble in ethanol (95%). Figure 2: Near-infrared spectrum of monobasic sodium phosphate Comments 1 g of monobasic potassium phosphate represents dihydrate measured by reflectance. approximately 7.3 mmol of potassium and of phosphate. The EINECS number for monobasic potassium phosphate is solution is then concentrated and the monobasic sodium phosphate 231-913-4. is crystallized. S 18 Comments 14 Safety One gram of anhydrous monobasic sodium phosphate represents Monobasic sodium phosphate is widely used as an excipient in approximately 8.3 mmol of sodium and of phosphate. parenteral, oral, and topical pharmaceutical formulations. One gram of monobasic sodium phosphate monohydrate Phosphate occurs extensively in the body and is involved in represents approximately 7.2 mmol of sodium and of phosphate. many physiological processes since it is the principal anion of One gram of monobasic sodium phosphate dihydrate represents intracellular fluid. Most foods contain adequate amounts of approximately 6.4 mmol of sodium and of phosphate. phosphate, making hypophosphatemia(1) virtually unknown except A specification for sodium phosphate monobasic is contained in in certain disease states(2) or in patients receiving total parenteral the Food Chemicals Codex (FCC).(11) nutrition. Treatment is usually by the oral administration of up to The EINECS number for monobasic sodium phosphate is 231- 100 mmol of phosphate daily. 449-2. The PubChem Compound ID (CID) for monobasic sodium Approximately two-thirds of ingested phosphate is absorbed phosphate dihydrate is 23673460. from the gastrointestinal tract, virtually all of it being excreted in the urine, and the remainder is excreted in the feces. 19 Specific References Excessive administration of phosphate, particularly intrave- 1 Lloyd CW, Johnson CE. Management of hypophosphatemia. Clin nously, rectally, or in patients with renal failure, can cause Pharm 1988; 7: 123–128. hyperphosphatemia that may lead to hypocalcemia or other severe 2 Holland PC et al. Prenatal deficiency of phosphate, phosphate electrolyte imbalances.(7–9) Adverse effects occur less frequently supplementation, and rickets in very-low-birthweight infants. Lancet following oral consumption, although act as mild saline 1990; 335: 697–701. when administered orally or rectally (2–4 g of monobasic 3 Rosen GH et al. Intravenous phosphate repletion regimen for critically sodium phosphate in an aqueous solution is used as a laxative). ill patients with moderate hypophosphatemia. Crit Care Med 1995; 23: 1204–1210. Consequently, gastrointestinal disturbances including diarrhea, 4 Eggert LD et al. Calcium and phosphorus compatibility in parenteral nausea, and vomiting may occur following the use of monobasic nutrition solutions for neonates. Am J Hosp Pharm 1982; 39: 49–53. sodium phosphate as an excipient in oral formulations. However, 5 Niemiec PW, Vanderveen TW. Compatibility considerations in par- the level of monobasic sodium phosphate used as an excipient in a enteral nutrient solutions. Am J Hosp Pharm 1984; 41: 893–911. Sodium Propionate 661

6 Pereira-da-Silva L et al. Compatibility of calcium and phosphate in four 20 General References parenteral nutrition solutions for preterm neonates. Am J Health Syst Sweetman SC, ed. Martindale: The Complete Drug Reference, 36th edn. Pharm 2003; 60: 1041–1044. 7 Haskell LP. Hypocalcaemic tetany induced by hypertonic-phosphate London: Pharmaceutical Press, 2009; 1682. enema [letter]. Lancet 1985; ii: 1433. 8 Larson JE et al. Laxative phosphate poisoning: pharmacokinetics of serum phosphorus. Hum Toxicol 1986; 5: 45–49. 21 Authors 9 Martin RR et al. Fatal poisoning from sodium phosphate enema: case report and experimental study. J Am Med Assoc 1987; 257: 2190– ME Quinn, PJ Sheskey. 2192. 10 Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th edn. New York: Wiley, 2004; 3274. 22 Date of Revision 11 Food Chemicals Codex, 6th edn. Bethesda, MD: United States Pharmacopeia, 2008; 901. 7 January 2009.

Sodium Propionate

1 Nonproprietary Names propionates, caprylates, or other antifungal agents, in the form of BP: Sodium Propionate ointments or solutions for the treatment of dermatophyte infections. Eye drops containing 5% w/v sodium propionate have also been PhEur: Sodium Propionate used. See Section 18. USP-NF: Sodium Propionate In food processes, particularly baking, sodium propionate is used as an antifungal agent; it may also be used as a flavoring agent 2 Synonyms in food products. In veterinary medicine, sodium propionate is used (1) E281; ethylformic acid, sodium salt, hydrate; methylacetic acid, therapeutically as a glucogenic substance in ruminants. sodium salt, hydrate; natrii propionas; sodium propanoate hydrate; sodium propionate hydrate. 8 Description Sodium propionate occurs as colorless transparent crystals or as a 3 Chemical Name and CAS Registry Number granular, free-flowing, crystalline powder. It is odorless, or with a Propionic acid, sodium salt, hydrate [6700-17-0] slight characteristic odor, and is deliquescent in moist air. Sodium Propionic acid, sodium salt, anhydrous [137-40-6] propionate has a characteristic, slightly cheeselike taste, although by itself it is unpalatable. 4 Empirical Formula and Molecular Weight 9 Pharmacopeial Specifications C3H5NaO2xH2O 114.06 (for monohydrate) See Table I. C3H5NaO2 96.06 (for anhydrous) S

5 Structural Formula Table I: Pharmacopeial specifications for sodium propionate. Test PhEur 6.0 USP32–NF27 Identification þþ Characters þ — Appearance of solution þ — Alkalinity — þ pH 7.8–9.2 — Water — 41.0% Heavy metals 410 ppm 40.001% þ 6 Functional Category Related substances — Readily oxidizable substances þ — Antimicrobial preservative. Iron 410 ppm — Loss on drying 0.5% — 7 Applications in Pharmaceutical Formulation or Assay (dried basis) 99.0–101.0% 99.0–100.5% Technology As an excipient, sodium propionate is used in oral pharmaceutical formulations as an antimicrobial preservative. Like propionic acid, 10 Typical Properties sodium propionate and other propionic acid salts are fungistatic Antimicrobial activity Sodium propionate, propionic acid, and and bacteriostatic against a number of Gram-positive cocci. other propionates possess mainly antifungal activity and are Propionates are more active against molds than is sodium benzoate, used as preservatives primarily against molds; they exhibit but have essentially no activity against yeasts; see Section 10. essentially no activity against yeasts. Although, in general, Therapeutically, sodium propionate has been used topically in propionates exhibit little activity against bacteria, sodium concentrations up to 10% w/w alone or in combination with other propionate is effective against Bacillus mesenterium, the organ-