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Particle size distribution: average particle size ≈150 mm (Improved Kelmar)

Solubility: potassium alginate is soluble in water, dissolving to form a viscous hydrophilic colloidal solution. It is insoluble in ethanol (95%) and in hydroalcoholic solutions in which the alcohol content is greater than 30% by weight; also insoluble in chloroform, ether, and acids having a pH lower than about 3. When preparing solutions of potassium alginate it is important to ensure proper dispersion of the particles, as poor dispersion will lead to the formation of large lumps of unhydrated powder and significantly extended hydration times.

Viscosity (dynamic): 400 mPa s (for a 1% dispersion of Improved Kelmar). Vicosities of 4.32 × 103 mPa s (2.5% dispersion) and 31.1 × 103 mPa s (4% dispersion) have been reported.(1)

Potassium alginate hydrates readily in hot or cold water; in solution, the acid groups of the alginate become ionized and a viscous solution is obtained. The viscosity is proportional to the concentration and molecular weight of the material used. As the temperature rises, a reversible decrease in viscosity occurs. The addition of calcium ions to potassium alginate solutions results in crosslinking and in the formation of gels; where the crosslinks formed are strong and numerous, the gel becomes thermally irreversible.

Stability and Storage Conditions

In the solid state, potassium alginate is a stable material that is not prone to microbial spoilage. Over time, a slow reduction in the degree of polymerization can occur, which may be reflected in a reduction in the viscosity of solutions. As both temperature and moisture can impair the performance of potassium alginate, storage below 258C is recommended.

Potassium alginate solutions are stable at pH 4–10; long- term storage outside this range can result in depolymerization of the polymer through hydrolysis. Gelation or precipitation of the alginate can occur at pH values less than 4. Liquid or semisolid alginate formulations should be preserved: suitable preservatives are sodium benzoate, potassium sorbate, or parabens.

Potassium alginate should be stored under cool, dry conditions in a well-closed container.

Incompatibilities

Incompatible with strong oxidizers.

Method of Manufacture

Alginate obtained from brown seaweed is subjected to demineralization, extraction, and precipitation of alginic acid. Following neutralization, the potassium alginate obtained is dried and milled.

Potassium Alginate 595

Safety

Potassium alginate is widely used in food products. It is currently used as an excipient only in experimental pharma- ceutical formulations.

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. When heated to decomposi- tion, potassium alginate emits acrid smoke and irritating fumes.

Regulatory Status

GRAS listed. Accepted for use in foods in the USA and Europe.

Related Substances

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

Comments

Although not included in any pharmacopeias, a specification for potassium alginate is contained in the Food Chemicals Codex (FCC); see Table I.

Table I: Food Chemicals Codex specifications for potassium alginate.(3)

Test FCC 1996

Arsenic 43 mg/kg

Heavy metals 40.002% (as lead)

Lead 45 mg/kg

Loss on drying 15.00%

Assay 89.2–105.5%

Specific References

Vennat B, Lardy F, Arvouey-Grand A, Pourrat A. Comparative texturometric analysis of hydrogels based on cellulose derivatives, carraghenates and alginates. Evaluation of adhesiveness. Drug Dev Ind Pharm 1998; 24(1): 27–35.

Vennat B, Quan ZQ, Pouget MP, Pourrat A. Procyanidin hydrogels. Influence of calcium on the gelling of alginate solutions. Drug Dev Ind Pharm 2003; 20(17): 2707–2714.

Food Chemicals Codex, 4th edn. Washington, DC: National Academy Press, 1996: 312

USPNF: Potassium benzoate

Synonyms

Benzoate of potash; benzoic acid potassium salt; E212; kalium benzoat; potassium salt trihydrate; ProBenz PG.

Chemical Name and CAS Registry Number

Potassium benzoate [582-25-2]

Empirical Formula and Molecular Weight

C7H5KO2 160.21

Structural Formula

Functional Category

Antimicrobial preservative; tablet and capsule lubricant.

Applications in Pharmaceutical Formulation or Technology

Potassium benzoate is predominantly used as an antimicrobial preservative in a wide range of beverages, foods and some pharmaceutical formulations. Preservative efficacy increases with decreasing pH; it is most effective at pH 4.5 or below. However, at low pH undissociated benzoic acid may produce a slight though discernible taste in food products.

Increasingly, potassium benzoate is used as an alternative to sodium benzoate in applications where a low sodium content is desirable.

Therapeutically, potassium benzoate has also been used in the management of hypokalemia. See also Table I.

Table I: Uses of potassium benzoate.

Use Concentration (%)

Carbonated beverages 0.03–0.08

Food products 40.1

Description

Potassium benzoate occurs as a slightly hygroscopic, white, odorless or nearly odorless crystalline powder or granules.

Aqueous solutions are slightly alkaline and have a sweetish astringent taste.

Pharmacopeial Specifications

See Table II.

Table II: Pharmacopeial specifications for potassium benzoate.

Organic volatile impurities +

Assay (anhydrous basis) 99.0–100.5%

Typical Properties

Acidity/alkalinity: aqueous solutions are slightly alkaline.

Melting point: >3008C

Solubility: see Table III.

Table III: Solubility of potassium benzoate.

Solvent Solubility at 208C unless otherwise stated

Ethanol (95%) 1 in 75

Ethanol (90%) 1 in 50

Ether Practically insoluble

Methanol Very slightly soluble

Water 1 in 2.46 at 138C

Specific gravity: 1.5

Stability and Storage Conditions

Potassium benzoate is stable at room temperature under normal storage conditions. Since it is slightly hygroscopic, potassium benzoate should be stored in sealed containers. Exposure to conditions of high humidity and elevated temperatures should be avoided.

Incompatibilities

Potassium benzoate is incompatible with strong acids and strong oxidizing agents.

Potassium Benzoate 597

Method of Manufacture

Potassium benzoate is prepared from the acid–base reaction between benzoic acid and potassium hydroxide.

Safety

Potassium benzoate is widely used in food products and is generally regarded as a nontoxic and nonirritant material. However, people with a history of allergies may show allergic reactions when exposed to potassium benzoate. Ingestion is inadvisable for asthmatics. Higher concentrations of potassium benzoate have been reported to cause irritation to mucous membranes.

The WHO acceptable daily intake of total benzoates including potassium benzoate, calculated as benzoic acid, has been estimated at up to 5 mg/kg of body-weight.(1,2)

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Potassium benzoate may be irritant to the eyes and skin. Eye protection and gloves are recommended. When exposed to heat, and when heated to decomposition, potassium benzoate emits acrid smoke and irritating fumes.

Regulatory Status

GRAS listed. Accepted as a food additive in Europe. Included in the Canadian List of Acceptable Non-medicinal Ingredients.

Related Substances

Benzoic acid; sodium benzoate.

Comments

The EINECS number for potassium benzoate is 209-481-3.

Specific References

FAO/WHO. Toxicological evaluation of certain food additives with a review of general principles and of specifications. Seventeenth report of the joint FAO/WHO expert committee on food additives. World Health Organ Tech Rep Ser 1974; No. 539.

FAO/WHO. Evaluation of certain food additives and contami- nants. Twenty-seventh report of the joint FAO/WHO expert committee on food additives. World Health Organ Tech Rep Ser 1983; No. 696.

Potassium Bicarbonate

Nonproprietary Names

BP: Potassium bicarbonate PhEur: Kalii hydrogenocarbonas USP: Potassium bicarbonate

Synonyms

Carbonic acid monopotassium salt; E501; monopotassium carbonate; potassium acid carbonate; potassium hydrogen carbonate.

Chemical Name and CAS Registry Number

Potassium bicarbonate [298-14-6]

Empirical Formula and Molecular Weight

Alkalizing agent; therapeutic agent.

Applications in Pharmaceutical Formulation or Technology

As an excipient, potassium bicarbonate is generally used in formulations as a source of carbon dioxide in effervescent preparations, at concentrations of 25–50% w/w. It is of particular use in formulations where sodium bicarbonate is unsuitable, for example, when the presence of sodium ions in a formulation needs to be limited or is undesirable. Potassium bicarbonate is often formulated with citric acid or tartaric acid in effervescent tablets or granules; on contact with water, carbon dioxide is released through chemical reaction, and the product disintegrates. On occasion, the presence of potassium bicarbonate alone may be sufficient in tablet formulations, as reaction with gastric acid can be sufficient to cause efferves- cence and product disintegration.

Potassium bicarbonate has also been investigated as a gas- forming agent in alginate raft systems.(1,2)

Potassium bicarbonate is also used in food applications as an alkali and a leavening agent, and is a component of baking powder.

Therapeutically, potassium bicarbonate is used as an alternative to sodium bicarbonate in the treatment of certain types of metabolic acidosis. It is also used as an antacid to neutralize acid secretions in the gastrointestinal tract and as a potassium supplement.

Description

Potassium bicarbonate occurs as colorless, transparent crystals or as a white granular or crystalline powder. It is odorless, with a saline or weakly alkaline taste.

Pharmacopeial Specifications

See Table I.

Table I: Pharmacopeial specifications for potassium bicarbonate.

Test PhEur 2005 USP 28

Identification + +

Characters + —

Appearance + —

Normal carbonates — 42.5%

Heavy metals 410 ppm 40.001%

Iron 420 ppm —

Sodium 40.5% —

Loss on drying — 40.3%

Organic volatile impurities — +

Assay 99.0–101.0% 99.5–101.5%

Typical Properties

Acidity/alkalinity: pH = 8.2 (for a 0.1 M aqueous solution)

Solubility: soluble 1 in 4.5 of water at 08C, 1 in 2.8 of water at 208C, 1 in 2 of water at 508C; practically insoluble in ethanol (95%).

Specific gravity: 2.17

Stability and Storage Conditions

Potassium bicarbonate should be stored in a well-closed container in a cool, dry location. Potassium bicarbonate is stable in air at normal temperatures, but when heated to 100–2008C in the dry state, or in solution, it is gradually converted to potassium carbonate.

Incompatibilities

Potassium bicarbonate reacts with acids and acidic salts with the evolution of carbon dioxide.

Method of Manufacture

Potassium bicarbonate can be made by passing carbon dioxide into a concentrated solution of potassium carbonate, or by exposing moist potassium carbonate to carbon dioxide, preferably under moderate pressure.

Potassium bicarbonate also occurs naturally in the mineral calcinite.

Potassium Bicarbonate 599

Safety

Potassium bicarbonate is used in cosmetics, foods, and oral pharmaceutical formulations, where it is generally regarded as a relatively nontoxic and nonirritant material when used as an excipient. However, excessive consumption of potassium bicarbonate or other potassium salts may produce toxic manifestations of hyperkalemia.

Handling Precautions

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

Regulatory Status

GRAS listed. Accepted as a food additive in Europe (the E number E501 refers to potassium carbonates). Included in nonparenteral medicines licensed in the UK and USA (chewable tablets; effervescent granules; effervescent tablets; lozenges; oral granules; oral suspensions). Included in the Canadian List of Acceptable Non-medicinal Ingredients.

Related Substances

Sodium bicarbonate.

Comments

One gram of potassium bicarbonate represents approximately 10 mmol of potassium and of bicarbonate; 2.56 g of potassium bicarbonate is approximately equivalent to 1 g of potassium. A specification for potassium bicarbonate is contained in the Food Chemicals Codex (FCC).

The EINECS number for potassium bicarbonate is 206- 059-0.

Specific References

Johnson FA, Craig DQM, Mercer AD, Chauhan S. The effects of alginate molecular structure and formulation variables on the physical characteristics of alginate raft systems. Int J Pharm 1997; 159: 35–42.

Johnson FA, Craig DQM, Mercer A, Chauhan S. The use of image analysis as a means of monitoring bubble formation in alginate rafts. Int J Pharm 1998; 170: 179–185.

BP: Potassium chloride JP: Potassium chloride PhEur: Kalii chloridum USP: Potassium chloride

Synonyms

Chloride of potash; chloropotassuril; dipotassium dichloride; E508; potassium monochloride.

Chemical Name and CAS Registry Number

9 Pharmacopeial Specifications

See Table I.

Table I: Pharmacopeial specifications for potassium chloride.

Test JP 2001 PhEur 2005 USP 28

Identification + + +

Acidity or alkalinity + + +

Appearance of solution + + —

Loss on drying 40.5% 41.0% 41.0% Iodide or bromide + + + Aluminum — 41 ppm 41 mg/g

Arsenic 42 ppm — —

Barium — + —

Potassium chloride [7447-40-7]

Empirical Formula and Molecular Weight

KCl 74.55

Calcium and magnesium

Therapeutic agent; tonicity agent.

Applications in Pharmaceutical Formulation or Technology

Potassium chloride is widely used in a variety of parenteral and nonparenteral pharmaceutical formulations. Its primary use, in parenteral and ophthalmic preparations, is to produce isotonic solutions.

Potassium chloride is also used therapeutically in the treatment of hypokalemia.

Many solid-dosage forms of potassium chloride exist including: tablets prepared by direct compression(1–4) and granulation;(5,6) effervescent tablets; coated, sustained-release tablets;(7–10) sustained-release wax matrix tablets;(11) micro- capsules;(12) pellets; and osmotic pump formulations.(13,14)

Experimentally, potassium chloride is frequently used as a model drug in the development of new solid-dosage forms, particularly for sustained-release or modified-release products.

Potassium chloride is also used widely in the food industry as a dietary supplement, pH control agent, stabilizer, thickener, and gelling agent. It can also be used in infant formulations.

Description

Potassium chloride occurs as odorless, colorless crystals or a white crystalline powder, with an unpleasant, saline taste. The crystal lattice is a face-centered cubic structure.

impurities

Assay (dried basis) 599.0% 99.0–100.5% 99.0–100.5%

Typical Properties

Acidity/alkalinity: pH ≈7 for a saturated aqueous solution at 158C.

Boiling point: sublimes at 15008C

Compressibility: see Figure 1.(3,4)

Density: 1.99 g/cm3; 1.17 g/cm3 for a saturated aqueous solution at 158C.

Melting point: 7908C

Osmolarity: a 1.19% w/v solution is iso-osmotic with serum.

Particle size distribution: typical distribution(5) is 10% less than 30 mm, 50% less than 94 mm, and 90% less than 149 mm in size. Mean particle diameter is 108 mm. Finer powders may be obtained by milling.

Solubility: see Table II.

Table II: Solubility of potassium chloride.

Solvent Solubility at 208C unless otherwise stated

Acetone Practically insoluble

Ethanol (95%) 1 in 250

Ether Practically insoluble

Glycerin 1 in 14

Water 1 in 2.8

1 in 1.8 at 1008C

Specific surface area: 0.084 m2/g (BET method)(5)

Potassium Chloride 601

Figure 1: Compression characteristics of potassium chloride.(3) Tablet diameter = 10 mm.

Stability and Storage Conditions

Potassium chloride tablets become increasingly hard on storage at low humidities. However, tablets stored at 76% relative humidity showed no increase or only a slight increase in hardness.(2) The addition of lubricants, such as 2% w/w magnesium stearate,(1) reduces tablet hardness and hardness on aging.(2) Aqueous potassium chloride solutions may be sterilized by autoclaving or by filtration.

Potassium chloride is stable and should be stored in a well- closed container in a cool, dry place.

Incompatibilities

Potassium chloride reacts violently with bromine trifluoride and with a mixture of sulfuric acid and potassium permanga- nate. The presence of hydrochloric acid, sodium chloride, and magnesium chloride decreases the solubility of potassium chloride in water. Aqueous solutions of potassium chloride form precipitates with lead and silver salts.

Intravenous aqueous potassium chloride solutions are incompatible with protein hydrolysate.

Method of Manufacture

Potassium chloride occurs naturally as the mineral sylvite or sylvine; it also occurs in other minerals such as sylvinite, carnallite, and kainite. Commercially, potassium chloride is obtained by the solar evaporation of brine or by the mining of mineral deposits.

Safety

Potassium chloride is used in a large number of pharmaceutical formulations including oral, parenteral, and topical prepara- tions both as an excipient and as a therapeutic agent.

Potassium ions play an important role in cellular metabo- lism and imbalances can result in serious clinical effects. Orally

ingested potassium chloride is rapidly absorbed from the gastrointestinal tract and excreted by the kidneys. Potassium chloride is more irritant than sodium chloride when admins- tered orally, and ingestion of large quantities of potassium chloride can cause effects such as gastrointestinal irritation, nausea, vomiting, and diarrhea.

High localized concentrations of potassium chloride in the gastrointestinal tract can cause ulceration, hence the develop- ment of the many enteric-coated and wax matrix sustained- release preparations that are available.(15) Although it is claimed that some formulations cause less ulceration than others, it is often preferred to administer potassium chloride as an aqueous solution. However, solutions have also been associated with problems, mainly due to their unpleasant taste. Parenterally, rapid injection of strong potassium chloride solutions can cause cardiac arrest; in the adult, solutions should

be infused at a rate not greater than 750 mg/hour.

Therapeutically, in adults, up to 10 g orally, in divided doses has been administered daily, while intravenously up to 6 g daily has been used.

LD50 (guinea pig, oral): 2.5 g/kg(16) LD50 (mouse, IP): 1.18 g/kg

LD50 (mouse, IV): 0.12 g/kg LD50 (mouse, oral): 0.38 g/kg LD50 (rat, IP): 0.66 g/kg

LD50 (rat, IV): 0.14 g/kg LD50 (rat, oral): 2.6 g/kg

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled.

Regulatory Status

GRAS listed. Accepted as a food additive in Europe. Included in the FDA Inactive Ingredients Guide (injections, ophthalmic preparations, oral capsules, and tablets). Included in nonpar- enteral and parenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.

Related Substances

Sodium chloride.

Comments

Each gram of potassium chloride represents approximately

13.4 mmol of potassium; 1.91 g of potassium chloride is approximately equivalent to 1 g of potassium.

For diets where the intake of sodium chloride is restricted, salt substitutes for use in cooking or as table salt are available and contain mainly potassium chloride, e.g. LoSalt (Klinge Chemicals Ltd) is a blend of 2/3 potassium chloride and 1/3 sodium chloride with magnesium carbonate added as a flow- promoting agent. A specification for potassium chloride is contained in the Food Chemicals Codex (FCC).

The EINECS number for potassium chloride is 231-211-8.

Specific References

Hirai Y, Okada J. Calculated stress and strain conditions of lubricated potassium chloride powders during die-compression. Chem Pharm Bull 1982; 30: 2202–2207.

Lordi N, Shiromani P. Mechanism of hardness of aged compacts.

Drug Dev Ind Pharm 1984; 10: 729–752.

602 Potassium Chloride

Pintye-Hodi K, Sohajda-Szu¨ cs E. Study on the compressibility of potassium chloride part 1: direct pressing without auxiliary products [in German]. Pharm Ind 1984; 46: 767–769.

Pintye-Hodi K, Sohajda-Szu¨ cs E. Study on the compressibility of potassium chloride part 2: direct compressing with microgranu- lous celluloses [in German]. Pharm Ind 1984; 46: 1080–1083.

Niskanen T, Yliruusi J, Niskanen M, Kontro O. Granulation of potassium chloride in instrumental fluidized bed granulator part 1: effect of flow rate. Acta Pharm Fenn 1990; 99: 13–22.

Niskanen T, Yliruusi J, Niskanen M, Kontro O. Granulation of potassium chloride in instrumental fluidized bed granulator part 2: evaluation of the effects of two independent process variables using 32-factorial design. Acta Pharm Fenn 1990; 99: 23–30.

Fee JV, Grant DJW, Newton JM. The effect of surface coatings on the dissolution rate of a non-disintegrating solid (potassium chloride). J Pharm Pharmacol 1973; 25 (Suppl.): 149P–150P.

Thomas WH. Measurement of dissolution rates of potassium chloride from various slow release potassium chloride tablets using a specific ion electrode. J Pharm Pharmacol 1973; 25: 27–34.

Cartwright AC, Shah C. An in vitro dissolution test for slow release potassium chloride tablets. J Pharm Pharmacol 1977; 29: 367–369.

Beckett AH, Samaan SS. Sustained release potassium chloride products in vitro–in vivo correlations. J Pharm Pharmacol 1978; 30 (Suppl.): 69P.

Flanders P, Dyer GA, Jordan D. The control of drug release from conventional melt granulation matrices. Drug Dev Ind Pharm 1987; 13: 1001–1022.

Harris MS. Preparation and release characteristics of potassium chloride microcapsules. J Pharm Sci 1981; 70: 391–394.

Ramadan MA, Tawashi R. The effect of hydrodynamic conditions and delivery orifice size on the rate of drug release from the elementary osmotic pump system (EOP). Drug Dev Ind Pharm 1987; 13: 235–248.

Lindstedt B, Sjo¨ berg M, Hja¨ rtstam J. Osmotic pumping release from KCl tablets coated with porous and non-porous ethylcellu- lose. Int J Pharm 1991; 67: 21–27.

McMahon FG, Ryan JR, Akdamar K, Ertan A. Effect of potassium chloride supplements on upper gastrointestinal mucosa. Clin Pharmacol Ther 1984; 35: 852–855.

Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th edn. New York: Wiley, 2004: 3025–3026.

General References

Love DW, Foster TS, Bradley DL. Comparison of the taste and acceptance of three potassium chloride preparations. Am J Hosp Pharm 1978; 35(5): 586–588.

Staniforth JN, Rees JE. Segregation of vibrated powder mixes contain- ing different concentrations of fine potassium chloride and tablet excipients. J Pharm Pharmacol 1983; 35: 549–554.

BP: Potassium citrate PhEur: Kalii citras USP: Potassium citrate

Synonyms

Citrate of potash; citric acid potassium salt; E332; tripotassium citrate monohydrate.

Chemical Name and CAS Registry Number

2-Hydroxy-1,2,3-propanetricarboxylic acid tripotassium salt monohydrate [6100-05-6]

2-Hydroxy-1,2,3-propanetricarboxylic acid tripotassium salt anhydrous [866-84-2]

Empirical Formula and Molecular Weight

C6H5K3O7·H2O 324.41 (for monohydrate) C6H5K3O7 306.40 (for anhydrous)

Structural Formula

Functional Category

Alkalizing agent; buffering agent; sequestering agent.

Applications in Pharmaceutical Formulation or Technology

Potassium citrate is used in beverages, foods, and oral pharmaceutical formulations as a buffering and alkalizing agent. It is also used as a sequestering agent and as a therapeutic agent to alkalinize the urine and to relieve the painful irritation caused by cystitis.(1–5) See Table I.

Table I: Uses of potassium citrate.

Use Concentration (%)

Buffer for solutions 0.3–2.0

Sequestering agent 0.3–2.0

Description

Transparent prismatic crystals or a white, granular powder. Potassium citrate is hygroscopic and odorless, and has a cooling, saline taste.

Pharmacopeial Specifications

See Table II.

Table II: Pharmacopeial specifications for potassium citrate.

Test PhEur 2005 USP 28

Identification + +

Characters + —

Acidity or alkalinity + +

Loss on drying 4.0–7.0% 3.0–6.0%

Appearance of solution + —

Tartrate — +

Heavy metals 410 ppm 40.001%

Organic volatile impurities — +

Readily carbonizable substances + —

Assay (dried basis) 99.0–101.0% 99.0–100.5%

Typical Properties

Acidity/alkalinity: pH = 8.5 (saturated aqueous solution).

Density: 1.98 g/cm3

Melting point: 2308C (loses water of crystallization at 1808C).

Solubility: see Table III.

Table III: Solubility of potassium citrate.

Solvent Solubility at 208C

Ethanol (95%) Practically insoluble

Glycerin 1 in 2.5

Water 1 in 0.65

Stability and Storage Conditions

Potassium citrate is a stable, though hygroscopic material, and should be stored in an airtight container in a cool, dry place.

604 Potassium Citrate

Incompatibilities

Aqueous potassium citrate solutions are slightly alkaline and will react with acidic substances. Potassium citrate may also precipitate alkaloidal salts from their aqueous or alcoholic solutions. Calcium and strontium salts will cause precipitation of the corresponding citrates.

Method of Manufacture

Potassium citrate is prepared by adding either potassium bicarbonate or potassium carbonate to a solution of citric acid until effervescence ceases. The resulting solution is then filtered and evaporated to dryness to obtain potassium citrate.

Safety

Potassium citrate is used in oral pharmaceutical formulations and is generally regarded as a nontoxic and nonirritant material by this route of administration.

Most potassium citrate safety data relate to its use as a therapeutic agent, for which up to 10 g may be administered daily, in divided doses, as a treatment for cystitis. Although there are adverse effects associated with excessive ingestion of potassium salts, the quantities of potassium citrate used as a pharmaceutical excipient are insignificant in comparison to those used therapeutically.

Related Substances

—

Comments

Each gram of potassium citrate monohydrate represents approximately 9.25 mmol of potassium and 3.08 mmol of citrate. Each gram of potassium citrate anhydrous represents approximately 9.79 mmol of potassium and 3.26 mmol of citrate. A specification for potassium citrate is contained in the Food Chemicals Codex (FCC). The EINECS number for potassium citrate is 212-755-5.

Specific References

Elizabeth JE, Carter NJ. Potassium citrate mixture: soothing but not harmless? Br Med J 1987; 295: 993.

Gabriel R. Potassium sorbate mixture: soothing but not harmless? [letter] Br Med J 1987; 295: 1487.

Liak TL, Li Wan Po A, Irwin WJ. The effects of drug therapy on urinary pH: excipient effects and bioactivation of methenamine. Int J Pharm 1987; 36: 233–242.

Fjellstedt E, Denneberg T, Jeppsson JO, Tiselins HG. A comparison of the effects of potassium citrate and sodium bicarbonate in the alkalinization of urine in homozygous cystinuria. Urol Res 2001; 29(5): 295–302.

Domrongkitchaiporn S, Khositseth S, Stitchantrokul W, et al.

LD50

(IV, dog): 0.17 g/kg(6)

Dosage of potassium citrate in the correction of urinary abnormalities in pediatric distal renal tubular acidosis patients. Am J Kidney Dis 2002; 39(2): 383–391.

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Potassium citrate may be irritant to the skin and eyes and should be handled in a well- ventilated environment. Eye protection and gloves are recom- mended. When heated to decomposition, potassium citrate emits toxic fumes of potassium oxide.(6)

Regulatory Status

GRAS listed. Accepted as a food additive in Europe. Included in the FDA Inactive Ingredients Guide (oral solutions and suspensions; topical emulsions and aerosol foams). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.

Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th edn. New York: Wiley, 2004: 3026.

General References

Cole ET, Rees JE, Hersey JA. Relations between compaction data for some crystalline pharmaceutical materials. Pharm Acta Helv 1975; 50: 28–32.

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