Name: Magnesium Carbonate
CAS No: Magnesium carbonate anhydrous [546-93-0]
BP: Heavy Magnesium Carbonate Light Magnesium Carbonate JP: Magnesium Carbonate PhEur: Magnesium Carbonate, Heavy Magnesium Carbonate, Light USP: Magnesium Carbonate
Carbonic acid, magnesium salt (1:1); carbonate magnesium; Destab; E504; hydromagnesite; magnesii subcarbonas levis; magnesii subcarbonas ponderosus
Magnesium carbonate anhydrous [546-93-0]
Magnesium carbonate is not a homogeneous material but may consist of the normal hydrate, the basic hydrate, and the anhydrous material MgCO3, which is rarely encountered. Basic magnesium carbonate is probably the most common form, and may vary in formula between light magnesium carbonate, (MgCO3)3 Mg(OH)23H2O, and magnesium carbonate hydroxide, (MgCO3)4Mg(OH)25H2O. Normal magnesium carbonate is a hydrous magnesium carbonate with a varying amount of water, MgCO3xH2O
See Section 4.
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
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
See Table II.
Angle of repose 42–508 for granular heavy magnesium carbonate; 56–608 for spray-dried heavy magnesium carbonate.(3) Density (bulk) Heavy magnesium carbonate: 0.207–0.56 g/cm3 ; (9) Light magnesium carbonate: 0.12 g/cm3 . Density (tapped) Heavy magnesium carbonate: 0.314–0.783 g/cm3 ; (9) Light magnesium carbonate: 0.21 g/cm3 . Density (true) Heavy magnesium carbonate: 1.966–2.261 g/cm3 (9) Moisture content At relative humidities between 15% and 65% the equilibrium moisture content of heavy magnesium carbonate at 258C is about 1% w/w; at relative humidities above 75% the equilibrium moisture content at 258C is about 5% w/w.(3) NIR spectra see Figures 1 and 2. Particle size distribution Heavy magnesium carbonate: 7–43 mm median particle size;(9) Light magnesium carbonate: 99.95% through a 44.5 mm (#350 mesh) sieve for light magnesium carbonate. Solubility Practically insoluble in water but soluble in water containing carbon dioxide. Insoluble in ethanol (95%) and other solvents. Magnesium carbonate dissolves and effervesces on contact with dilute acids. Specific surface area 7.8–18.2 m2 /g for granular heavy magnesium carbonate; 4.4–15.5 m2 /g for spray-dried heavy magnesium carbonate;(3)
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.
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)
Depending upon the manufacturing process used, the composition of the magnesium carbonate obtained may vary from normal hydrated magnesium carbonate to basic hydrated magnesium carbonate. Light magnesium carbonate may be manufactured by saturating an aqueous suspension of dolomite, CaMg(CO3)2, with carbon dioxide under pressure. On increase of the temperature, calcium carbonate precipitates almost entirely. The filtered solution is then heated to boiling; the magnesium bicarbonate in the solution loses carbon dioxide and water, and light magnesium carbonate precipitates. Heavy magnesium carbonate may be manufactured by mixing a hot concentrated solution of magnesium chloride or magnesium sulfate with a solution of sodium carbonate. The heavy magnesium carbonate may be either precipitated to produce a granular material or spray-dried. Varying the temperature of the reaction solutions produces heavy magnesium carbonate with differing physical properties: e.g. material with a higher specific surface area is produced at a lower reaction temperature. Low processing temperature provided the largest surface area, which produced optimum granules or spray-dried powder.(3) If dilute magnesium chloride or magnesium sulfate solutions are used for the reaction, a less dense material is produced. Magnesium carbonates in varying states of hydration are also found as minerals in nature.
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.
Observe normal precautions appropriate to the circumstances and quantity of material handled. Magnesium carbonate may be irritant to the eyes; eye protection is recommended. OSHA standards state that IPA 8-hour time weighted airborne average is 10 mg/m3 . (13)
GRAS listed. Accepted as a food additive in Europe. Included in the FDA Inactive Ingredients Database (oral capsules and tablets). Included in nonparenteral medicines licensed in the UK.
Magnesium carbonate anhydrous; magnesium carbonate hydroxide; normal magnesium carbonate. Magnesium carbonate anhydrous Empirical formula MgCO3 Molecular weight 84.31 CAS number [546-93-0] Synonyms Carbonic acid, magnesium salt anhydrous (1 : 1); E504; magnesite. Appearance Odorless, white-colored bulky powder or light, friable masses. Melting point Decomposes at 3508C. Magnesium carbonate hydroxide Empirical formula (MgCO3)4Mg(OH)25H2O Molecular weight 485.65 CAS number [39409-82-0] Synonyms Carbonic acid, magnesium salt (1 : 1), mixture with magnesium hydroxide and magnesium hydrate; dypingite; E504. Appearance Odorless, white-colored bulky powder or light, friable masses. Melting point On heating at 7008C it is converted into magnesium oxide. Specific gravity 1.45 Comments The EINECS number for magnesium carbonate hydroxide is 235-192-7. Normal magnesium carbonate Empirical formula MgCO3xH2O CAS number [23389-33-5] Synonyms Carbonic acid, magnesium salt (1 : 1), hydrate; magnesium carbonate, normal hydrate; E504. Appearance Odorless, white-colored bulky powder or light, friable masses
Magnesium carbonate has been 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) It has also been found to retard the dissolution of ciprofloxacin, sparfloxacin, and cephradine.(15–17) In addition, magnesium carbonate has been shown to alter the pharmacokinetics of halofantrine, increasing the time to reach maximum plasma concentration and reducing maximum plasma concentrations.(18) Because drug interactions can occur with a variety of antacids,(15–19) the potential for these effects should be considered when designing pharmaceutical formulations containing magnesium carbonate. A specification for magnesium carbonate is contained in the Food Chemicals Codex (FCC).(20) The EINECS number for magnesium carbonate is 208-915-9.