Name: Citric Acid Monohydrate
CAS No: 2-Hydroxy-1,2,3-propanetricarboxylic acid monohydrate [5949-29-1]
BP: Citric Acid Monohydrate JP: Citric Acid Hydrate PhEur: Citric Acid Monohydrate USP: Citric Acid Monohydrate
Acidum citricum monohydricum; E330; 2-hydroxypropane-1,2,3- tricarboxylic acid monohydrate
2-Hydroxy-1,2,3-propanetricarboxylic acid monohydrate [5949-29-1]
C6H8O7H2O 210.14
Citric acid (as either the monohydrate or anhydrous material) is widely used in pharmaceutical formulations and food products, primarily to adjust the pH of solutions. It has also been used experimentally to adjust the pH of tablet matrices in enteric-coated formulations for colon-specific drug delivery.(1) Citric acid monohydrate is used in the preparation of effervescent granules, while anhydrous citric acid is widely used in the preparation of effervescent tablets.(2–4) Citric acid has also been shown to improve the stability of spray-dried insulin powder in inhalation formulations.(5) In food products, citric acid is used as a flavor enhancer for its tart, acidic taste. Citric acid monohydrate is used as a sequestering agent and antioxidant synergist; see Table I. It is also a component of anticoagulant citrate solutions. Therapeutically, preparations containing citric acid have been used to dissolve renal calculi.
Citric acid monohydrate occurs as colorless or translucent crystals, or as a white crystalline, efflorescent powder. It is odorless and has a strong acidic taste. The crystal structure is orthorhombic
See Table II Note that the JP XV, PhEur 6.0 and USP 32 have separate monographs for the monohydrate and anhydrous material.
Acidity/alkalinity pH = 2.2 (1% w/v aqueous solution) Dissociation constant pKa1: 3.128 at 258C; pKa2: 4.761 at 258C; pKa3: 6.396 at 258C. Density 1.542 g/cm3 Heat of combustion 1972 kJ/mol (471.4 kcal/mol) Heat of solution 16.3 kJ/mol (3.9 kcal/mol) at 258C Hygroscopicity At relative humidities less than about 65%, citric acid monohydrate effloresces at 258C, the anhydrous acid being formed at relative humidities less than about 40%. At relative humidities between about 65% and 75%, citric acid monohydrate absorbs insignificant amounts of moisture, but under more humid conditions substantial amounts of water are absorbed. Melting point 1008C (softens at 758C) NIR spectra see Figure 1. Particle size distribution Various grades of citric acid monohydrate with different particle sizes are commercially available. Solubility Soluble 1 in 1.5 parts of ethanol (95%) and 1 in less than 1 part of water; sparingly soluble in ether. Viscosity (dynamic) 6.5 mPa s (6.5 cP) for a 50% w/v aqueous solution at 258C.
Citric acid monohydrate loses water of crystallization in dry air or when heated to about 408C. It is slightly deliquescent in moist air. Dilute aqueous solutions of citric acid may ferment on standing The bulk monohydrate or anhydrous material should be stored in airtight containers in a cool, dry place.
Citric acid is incompatible with potassium tartrate, alkali and alkaline earth carbonates and bicarbonates, acetates, and sulfides. Incompatibilities also include oxidizing agents, bases, reducing agents, and nitrates. It is potentially explosive in combination with metal nitrates. On storage, sucrose may crystallize from syrups in the presence of citric acid.
Citric acid occurs naturally in a number of plant species and may be extracted from lemon juice, which contains 5–8% citric acid, or pineapple waste. Anhydrous citric acid may also be produced industrially by mycological fermentation of crude sugar solutions such as molasses, using strains of Aspergillus niger . Citric acid is purified by recrystallization; the anhydrous form is obtained from a hot concentrated aqueous solution and the monohydrate from a cold concentrated aqueous solution.
Citric acid is found naturally in the body, mainly in the bones, and is commonly consumed as part of a normal diet. Orally ingested citric acid is absorbed and is generally regarded as a nontoxic material when used as an excipient. However, excessive or frequent consumption of citric acid has been associated with erosion of the teeth.(6) Citric acid and citrates also enhance intestinal aluminum absorption in renal patients, which may lead to increased, harmful serum aluminum levels. It has therefore been suggested that patients with renal failure taking aluminum compounds to control phosphate absorption should not be prescribed citric acid or citrate-containing products.(7)
Observe normal precautions appropriate to the circumstances and quantity of material handled. Eye protection and gloves are recommended. Direct contact with eyes can cause serious damage. Citric acid should be handled in a well-ventilated environment or a dust mask should be worn. It is combustible.
GRAS listed. The anhydrous form is accepted for use as a food additive in Europe. Included in the FDA Inactive Ingredients Database (inhalations; IM, IV, and other injections; ophthalmic preparations; oral capsules, solutions, suspensions and tablets; topical and vaginal preparations). Included in nonparenteral and parenteral medicines licensed in Japan and the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.
Anhydrous citric acid; fumaric acid; malic acid; sodium citrate dihydrate; tartaric acid. Anhydrous citric acid Empirical formula C6H8O7 Molecular weight 192.12 CAS number [77-92-9] Synonyms acidum citricum anhydricum; citric acid; E330; 2- hydroxy-b-1,2,3-propanetricarboxylic acid; 2-hydroxypropane 1,2,3-tricarboxylic acid. Appearance Odorless or almost odorless, colorless crystals or a white crystalline powder. Crystal structure is monoclinic holohedral. Dissociation constants pKa1: 3.128 at 258C; pKa2: 4.761 at 258C; pKa3: 6.396 at 258C. Density 1.665 g/cm3 Heat of combustion –1985 kJ/mol (–474.5 kcal/mol) Hygroscopicity At relative humidities between about 25–50%, anhydrous citric acid absorbs insignificant amounts of water at 258C. However, at relative humidities between 50% and 75%, it absorbs significant amounts, with the monohydrate being formed at relative humidities approaching 75%. At relative humidities greater than 75% substantial amounts of water are absorbed by the monohydrate. Melting point 1538C Solubility Soluble 1 in 1 part of ethanol (95%) and 1 in 1 of water; sparingly soluble in ether. Safety LD50 (mouse, IP): 0.9 g/kg(8) LD50 (mouse, IV): 0.04 g/kg LD50 (mouse, oral): 5.04 g/kg LD50 (mouse, SC): 2.7 g/kg LD50 (rabbit, IV): 0.33 g/kg LD50 (rat, IP): 0.88 g/kg LD50 (rat, oral): 3.0 g/kg LD50 (rat, SC): 5.5 g/kg Comments Anhydrous citric acid is listed in the PhEur 6.0 and USP 32. Anhydrous citric acid is one of the materials that have been selected for harmonization by the Pharmacopeial Discussion Group. For further information see the General Information Chapter <1196> in the USP32–NF27, the General Chapter 5.8 in PhEur 6.0, along with the ‘State of Work’ document on the PhEur EDQM website, and also the General Information Chapter 8 in the JP XV. The EINECS number for anhydrous citric acid is 201-069-1.
Citric acid monohydrate is one of the materials that have been selected for harmonization by the Pharmacopeial Discussion Group. For further information see the General Information Chapter <1196> in the USP32–NF27, the General Chapter 5.8 in PhEur 6.0, along with the ‘State of Work’ document on the PhEur EDQM website, and also the General Information Chapter 8 in the JP XV. A specification for citric acid monohydrate is contained in the Food Chemicals Codex (FCC).(9) The EINECS number for citric acid monohydrate is 201-069-1. The PubChem Compound ID (CID) for citric acid monohydrate is 22230.