International Numbering System (INS) for Food Additives 504
Food additives Europe numbers: E504
Functional Category
Adsorbent; antacid; tablet and capsule diluent.
Applications in Pharmaceutical Formulation
As an excipient, magnesium carbonate is mainly used as a directly compressible tablet diluent in concentrations up to 45% w/w. Heavy magnesium carbonate produces tablets with high crushing strength, low friability, and good disintegration properties.(1–4) However, magnesium carbonate can have varying effects on dissolution and stability.(5,6) See also Section 12. Magnesium carbonate has been incorporated in microsphere formulations for the purpose of stabilizing encapsulated proteins.(7) It has also been coencapsulated in poly(lactide-co-glycolide) microsphere formulations to neutralize acidity and enhance the immunogenicity of a contraceptive peptide vaccine.(8) Magnesium carbonate is also used to absorb liquids, such as flavors, in tableting processes. Magnesium carbonate is additionally used as a food additive and therapeutically as an antacid.
Description
Magnesium carbonate occurs as light, white-colored friable masses or as a bulky, white-colored powder. It has a slightly earthy taste and is odorless but, since it has a high absorptive ability, magnesium carbonate can absorb odors. The USP 32 describes magnesium carbonate as either a basic hydrated magnesium carbonate or a normal hydrated magnesium carbonate. However, the PhEur describes magnesium carbonate as being a hydrated basic magnesium carbonate in two separate monographs: heavy magnesium carbonate (PhEur 6.5) and light magnesium carbonate (PhEur 6.4). The molecular formulas for heavy magnesium carbonate and light magnesium carbonate vary, but heavy magnesium carbonate may generally be regarded as the tetrahydrate [(MgCO3)3Mg(OH)24H2O], while light magnesium carbonate may be regarded as the trihydrate [(MgCO3)3 Mg(OH)23H2O]. The molecular weights of the heavy and light forms of magnesium carbonate are 383.32 and 365.30, respectively.
Stability and Storage Conditions
Magnesium carbonate is stable in dry air and on exposure to light. The bulk material should be stored in a well-closed container in a cool, dry place.
Incompatibilities
Incompatible with phenobarbital sodium,(4,10) diazepam solution at a pH 5 5,(11) some binary powder mixtures,(12) lansoprazole,(5) and formaldehyde.(13) Acids will dissolve magnesium carbonate, with the liberation of carbon dioxide. Slight alkalinity is imparted to water. Magnesium carbonate was also found to increase the dissolution of acetazolamide formulations at a pH of 1.12; however, dissolution was retarded at a pH of 7.4.(6)
Safety
Magnesium carbonate is used as an excipient in oral solid-dosage pharmaceutical formulations and is generally regarded as an essentially nontoxic and nonirritant material. However, the use of magnesium salts, such as magnesium carbonate, is contraindicated in patients with renal impairment. In certain studies, magnesium carbonate has been shown to be an effective phosphate binder in short-term use for patients with chronic kidney disease, but the effects of long-term use require further study.(14) The probable oral lethal dose in humans has been estimated at 0.5–5.0 g/kg bodyweight.(13) On contact with gastric acid, magnesium carbonate reacts in the stomach to form soluble magnesium chloride and carbon dioxide. Magnesium carbonate should therefore not be used as an antacid by those individuals whose stomachs cannot tolerate the evolution of carbon dioxide. Some magnesium is absorbed but is usually excreted in the urine. As with other magnesium salts, magnesium carbonate has a laxative effect and may cause diarrhea. Therapeutically, the usual dose of magnesium carbonate as an antacid is 250–500 mg, and 2.0–5.0 g as a laxative.