Food additives Europe numbers: E331
Functional Category
Alkalizing agent; buffering agent; emulsifying agent; sequestering agent.
Applications in Pharmaceutical Formulation
Sodium citrate, as either the dihydrate or anhydrous material, is widely used in pharmaceutical formulations; see Table I. It is used in food products, primarily to adjust the pH of solutions. It is also used as a sequestering agent. The anhydrous material is used in effervescent tablet formulations.(1) Sodium citrate is additionally used as a blood anticoagulant either alone or in combination with other citrates such as disodium hydrogen citrate. S 640 Sodium Citrate Dihydrate Therapeutically, sodium citrate is used to relieve the painful irritation caused by cystitis, and also to treat dehydration and acidosis due to diarrhea; see Section 14.
Description
Sodium citrate dihydrate consists of odorless, colorless, monoclinic crystals, or a white crystalline powder with a cooling, saline taste. It is slightly deliquescent in moist air, and in warm dry air it is efflorescent. Although most pharmacopeias specify that sodium citrate is the dihydrate, the USP 32 states that sodium citrate may be either the dihydrate or anhydrous material.
Stability and Storage Conditions
Sodium citrate dihydrate is a stable material. Aqueous solutions may be sterilized by autoclaving. On storage, aqueous solutions may cause the separation of small, solid particles from glass containers. The bulk material should be stored in an airtight container in a cool, dry place.
Incompatibilities
Aqueous solutions are slightly alkaline and will react with acidic substances. Alkaloidal salts may be precipitated from their aqueous or hydro-alcohol solutions. Calcium and strontium salts will cause precipitation of the corresponding citrates. Other incompatibilities include bases, reducing agents, and oxidizing agents.
Safety
After ingestion, sodium citrate is absorbed and metabolized to bicarbonate. Although it is generally regarded as a nontoxic and nonirritant excipient, excessive consumption may cause gastrointestinal discomfort or diarrhea. Therapeutically, in adults, up to 15 g daily of sodium citrate dihydrate may be administered orally, in divided doses, as an aqueous solution to relieve the painful irritation caused by cystitis. Citrates and citric acid 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 citrate- or citric acid-containing products.(2) See Section 17 for anhydrous sodium citrate animal toxicity data.