Magnesium Carbonate
1 Nonproprietary Names 8 Description
BP: Heavy Magnesium Carbonate Magnesium carbonate occurs as light, white-colored friable masses
Light Magnesium Carbonate or as a bulky, white-colored powder. It has a slightly earthy taste
JP: Magnesium Carbonate and is odorless but, since it has a high absorptive ability, magnesium
PhEur: Magnesium Carbonate, Heavy carbonate can absorb odors.
Magnesium Carbonate, Light The USP 32 describes magnesium carbonate as either a basic
hydrated magnesium carbonate or a normal hydrated magnesium
USP: Magnesium Carbonate
carbonate. However, the PhEur describes magnesium carbonate as
being a hydrated basic magnesium carbonate in two separate
2 Synonyms
monographs: heavy magnesium carbonate (PhEur 6.5) and light
Carbonic acid, magnesium salt (1:1); carbonate magnesium; magnesium carbonate (PhEur 6.4). The molecular formulas for
Destab; E504; hydromagnesite; magnesii subcarbonas levis; mag- heavy magnesium carbonate and light magnesium carbonate vary,
nesii subcarbonas ponderosus. See Sections 4 and 17. but heavy magnesium carbonate may generally be regarded as the
tetrahydrate [(MgCO3)3Mg(OH)24H2O], while light magnesium
3 Chemical Name and CAS Registry Number carbonate may be regarded as the trihydrate [(MgCO3)3
Magnesium carbonate anhydrous [546-93-0] Mg(OH)23H2O].
See also Sections 4 and 17. The molecular weights of the heavy and light forms of
magnesium carbonate are 383.32 and 365.30, respectively.
4 Empirical Formula and Molecular Weight
Magnesium carbonate is not a homogeneous material but may 9 Pharmacopeial Specifications
consist of the normal hydrate, the basic hydrate, and the anhydrous
material MgCO3, which is rarely encountered. Basic magnesium See Table II.
carbonate is probably the most common form, and may vary in
formula between light magnesium carbonate, (MgCO3)3 10 Typical Properties
M
Mg(OH)23H2O, and magnesium carbonate hydroxide,
(MgCO3)4Mg(OH)25H2O. Normal magnesium carbonate is a Angle of repose
hydrous magnesium carbonate with a varying amount of water, 42–508 for granular heavy magnesium carbonate;
MgCO3xH2O. 56–608 for spray-dried heavy magnesium carbonate.(3)
See also Sections 8, 13, and 17. Density (bulk)
Heavy magnesium carbonate: 0.207–0.56 g/cm3;(9)
5 Structural Formula
Light magnesium carbonate: 0.12 g/cm3.
See Section 4. Density (tapped)
Heavy magnesium carbonate: 0.314–0.783 g/cm3;(9)
6 Functional Category
Light magnesium carbonate: 0.21 g/cm3.
Adsorbent; antacid; tablet and capsule diluent. Density (true) Heavy magnesium carbonate: 1.966–2.261 g/cm3 (9)
7 Applications in Pharmaceutical Formulation or SEM 1: Excipient: magnesium carbonate USP; manufacturer: Mallinckrodt
Technology Chemicals Co.; lot no.: KJGJ; magnification: 60; voltage: 20 kV.
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 formula-
tions 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.
See Table I.
Table I: Uses of magnesium carbonate.
Use Concentration (%)
Absorbent of liquid, in tableting 0.5–1.0
Tablet excipient (direct compression) 445
39 7
3 98 Magnesium Carbonate
SEM 2: Excipient: magnesium carbonate USP; manufacturer: Mallinckrodt 1.1 0.4
1000 × [2nd deriv. log(1/R)]
1389 1415
Chemicals Co.; lot no.: KJGJ; magnification: 600; voltage: 20 kV.
2304
1478
0.0
1og(1/R)
2206
1462 2321
1437
1402
−2.3 −0.2
1100 1300 1500 1700 1900 2100 2300 2500
Wavelength/nm
Figure 1: Near-infrared spectrum of heavy magnesium carbonate
measured by reflectance.
0.8 0.3
1000 × [2nd deriv. log(1/R)]
1389 1415
2305 2462
0.0
1og(1/R)
1462 2206 2321 2426
Table II: Pharmacopeial specifications for magnesium carbonate. 1437
Test JP XV PhEur 6.5 USP 32
(heavy form),
M PhEur 6.4 (light
form)(a)
Identification þ þ þ 1402
Characters — þ — −1.6 −0.2
1100 1300 1500 1700 1900 2100 2300 2500
Microbial limits — — þ
Color of solution — þ — Wavelength/nm
Soluble salts 410.0 mg 41.0% 41.0%
Acid-insoluble 42.5 mg 40.05% 40.05%
Figure 2: Near-infrared spectrum of light magnesium carbonate
substances
measured by reflectance.
Arsenic 45 ppm 42 ppm 44 ppm
Calcium 40.6% 40.75% 40.45%
Heavy metals 430 ppm 420 ppm 40.003% 14.64–14.78 m2/g for basic heavy magnesium carbonate.
Iron 4200 ppm 4400 ppm 40.02%
Sulfates
Heavy form — 40.6% — 11 Stability and Storage Conditions
Light form — 40.3% —
Magnesium carbonate is stable in dry air and on exposure to light.
Chloride — 4700 ppm —
Precipitation þ — — The bulk material should be stored in a well-closed container in a
Assay (as MgO) 40.044.0% 40.0–45.0% 40.0–43.5% cool, dry place.
(a) Note that except where indicated all of the PhEur test limits apply to both the heavy
and light forms of magnesium carbonate. 12 Incompatibilities
Incompatible with phenobarbital sodium,(4,10) diazepam solution at
a pH 5 5,(11) some binary powder mixtures,(12) lansoprazole,(5)
Moisture content At relative humidities between 15% and 65% and formaldehyde.(13) Acids will dissolve magnesium carbonate,
the equilibrium moisture content of heavy magnesium carbonate with the liberation of carbon dioxide. Slight alkalinity is imparted to
at 258C is about 1% w/w; at relative humidities above 75% the water. Magnesium carbonate was also found to increase the
equilibrium moisture content at 258C is about 5% w/w.(3) dissolution of acetazolamide formulations at a pH of 1.12; however,
NIR spectra see Figures 1 and 2. dissolution was retarded at a pH of 7.4.(6)
Particle size distribution
Heavy magnesium carbonate: 7–43 mm median particle size;(9) 13 Method of Manufacture
Light magnesium carbonate: 99.95% through a 44.5 mm (#350 Depending upon the manufacturing process used, the composition
mesh) sieve for light magnesium carbonate. of the magnesium carbonate obtained may vary from normal
Solubility Practically insoluble in water but soluble in water hydrated magnesium carbonate to basic hydrated magnesium
containing carbon dioxide. Insoluble in ethanol (95%) and other carbonate.
solvents. Magnesium carbonate dissolves and effervesces on Light magnesium carbonate may be manufactured by saturating
contact with dilute acids. an aqueous suspension of dolomite, CaMg(CO3)2, with carbon
Specific surface area dioxide under pressure. On increase of the temperature, calcium
7.8–18.2 m2/g for granular heavy magnesium carbonate; carbonate precipitates almost entirely. The filtered solution is then
4.4–15.5 m2/g for spray-dried heavy magnesium carbonate;(3) heated to boiling; the magnesium bicarbonate in the solution loses
Magnesium Carbonate 39 9
carbon dioxide and water, and light magnesium carbonate Synonyms Carbonic acid, magnesium salt (1 : 1), mixture with
precipitates. magnesium hydroxide and magnesium hydrate; dypingite; E504.
Heavy magnesium carbonate may be manufactured by mixing a Appearance Odorless, white-colored bulky powder or light,
hot concentrated solution of magnesium chloride or magnesium friable masses.
sulfate with a solution of sodium carbonate. The heavy magnesium Melting point On heating at 7008C it is converted into
carbonate may be either precipitated to produce a granular material magnesium oxide.
or spray-dried. Varying the temperature of the reaction solutions Specific gravity 1.45
produces heavy magnesium carbonate with differing physical Comments The EINECS number for magnesium carbonate
properties: e.g. material with a higher specific surface area is hydroxide is 235-192-7.
produced at a lower reaction temperature. Low processing Normal magnesium carbonate
temperature provided the largest surface area, which produced Empirical formula MgCO3xH2O
optimum granules or spray-dried powder.(3) If dilute magnesium CAS number [23389-33-5]
chloride or magnesium sulfate solutions are used for the reaction, a Synonyms Carbonic acid, magnesium salt (1 : 1), hydrate; mag-
less dense material is produced. nesium carbonate, normal hydrate; E504.
Magnesium carbonates in varying states of hydration are also Appearance Odorless, white-colored bulky powder or light,
found as minerals in nature. friable masses.
14 Safety 18 Comments
Magnesium carbonate is used as an excipient in oral solid-dosage Magnesium carbonate has been found to increase the dissolution of
pharmaceutical formulations and is generally regarded as an acetazolamide formulations at a pH of 1.12; however, dissolution
essentially nontoxic and nonirritant material. However, the use of was retarded at a pH of 7.4.(6) It has also been found to retard the
magnesium salts, such as magnesium carbonate, is contraindicated dissolution of ciprofloxacin, sparfloxacin, and cephradine.(15–17) In
in patients with renal impairment. In certain studies, magnesium addition, magnesium carbonate has been shown to alter the
carbonate has been shown to be an effective phosphate binder in pharmacokinetics of halofantrine, increasing the time to reach
short-term use for patients with chronic kidney disease, but the maximum plasma concentration and reducing maximum plasma
effects of long-term use require further study.(14) The probable oral concentrations.(18) Because drug interactions can occur with a
lethal dose in humans has been estimated at 0.5–5.0 g/kg body- variety of antacids,(15–19) the potential for these effects should be
weight.(13) considered when designing pharmaceutical formulations containing
M
On contact with gastric acid, magnesium carbonate reacts in the magnesium carbonate.
stomach to form soluble magnesium chloride and carbon dioxide. A specification for magnesium carbonate is contained in the
Magnesium carbonate should therefore not be used as an antacid by Food Chemicals Codex (FCC).(20)
those individuals whose stomachs cannot tolerate the evolution of The EINECS number for magnesium carbonate is 208-915-9.
carbon dioxide. Some magnesium is absorbed but is usually
excreted in the urine. As with other magnesium salts, magnesium 19 Specific References
carbonate has a laxative effect and may cause diarrhea.
1 Haines-Nutt RF. The compression properties of magnesium and
Therapeutically, the usual dose of magnesium carbonate as an calcium carbonates. J Pharm Pharmacol 1976; 28: 468–470.
antacid is 250–500 mg, and 2.0–5.0 g as a laxative. 2 Armstrong NA, Cham T-M. Changes in the particle size and size
distribution during compaction of two pharmaceutical powders with
15 Handling Precautions dissimilar consolidation mechanisms. Drug Dev Ind Pharm 1986; 12:
2043–2059.
Observe normal precautions appropriate to the circumstances and
3 Cham T-M. The effect of the specific surface area of heavy magnesium
quantity of material handled. Magnesium carbonate may be irritant carbonate on its tableting properties. Drug Dev Ind Pharm 1987;
to the eyes; eye protection is recommended. OSHA standards state 13(9–11): 1989–2015.
that IPA 8-hour time weighted airborne average is 10 mg/m3.(13) 4 Peterson CL et al. Characterization of antacid compounds containing
both aluminum and magnesium. II: Codried powders. Pharm Res 1993;
16 Regulatory Acceptance 10(7): 1005–1007.
5 Tabata T et al. Manufacturing method of stable enteric granules of a
GRAS listed. Accepted as a food additive in Europe. Included in the new antiulcer drug (lansoprazole). Drug Dev Ind Pharm 1994; 20(9):
FDA Inactive Ingredients Database (oral capsules and tablets). 1661–1672.
Included in nonparenteral medicines licensed in the UK. 6 Hashim F, El-Din EZ. Effect of some excipients on the dissolution of
phenytoin and acetazolamide from capsule formulations. Acta Pharm
17 Related Substances Fenn 1989; 98: 197–204.
7 Sandor M et al. Effect of lecithin and MgCO3 as additives on the
Magnesium carbonate anhydrous; magnesium carbonate hydro- enzymatic activity of carbonic anhydrase encapsulated in poly(lactide-
xide; normal magnesium carbonate. co-glycolide) (PLGA) microspheres. Biochim Biophys Acta 2002;
1570(1): 63–74.
Magnesium carbonate anhydrous
8 Cui C et al. Injectable polymer microspheres enhance immunogenicity
Empirical formula MgCO3 of a contraceptive peptide vaccine. Vaccine 2007; 25(3): 500–509.
Molecular weight 84.31 9 Freitag F, Kleinebudde P. How do roll compaction/dry granulation
CAS number [546-93-0] affect the tabletting behaviour of inorganic materials? Comparison of
Synonyms Carbonic acid, magnesium salt anhydrous (1 : 1); four magnesium carbonates. Eur J Pharm Sci 2003; 19: 281–289.
E504; magnesite. 10 Nagavi BG et al. Solid phase interaction of phenobarbitone sodium
Appearance Odorless, white-colored bulky powder or light, with some adjuvants. Indian J Pharm Sci 1983; 45(Jul–Aug): 175–177.
friable masses. 11 Jain GK, Kakkar AP. Interaction study of diazepam with excipients in
Melting point Decomposes at 3508C. liquid and solid state. Indian Drugs 1992; 29(Jul): 545–546.
12 Jain GK, Kakkar AP. Interaction study of diazepam with excipients in
Magnesium carbonate hydroxide binary powder form. Indian Drugs 1992; 29(Jul): 453–454.
Empirical formula (MgCO3)4Mg(OH)25H2O 13 Hazardous Substances Data Bank (2008). Magnesium carbonate.
Molecular weight 485.65 [Link] (accessed 18 Feb-
CAS number [39409-82-0] ruary 2009).
4 00 Magnesium Oxide
14 Spiegel DM. The role of magnesium binders in chronic kidney disease. and mercury porosimetry measurements of tablets. Eur J Pharm Sci
Semin Dial 2007; 20(Jul–Aug): 333–336. 2004; 22: 325–333.
15 Arayne MS et al. Interactions between ciprofloxacin and antacids – Freitag F et al. Coprocessing of powdered cellulose and magnesium
dissolution and adsorption studies. Drug Metabol Drug Interact 2005; carbonate: direct tableting versus tableting after roll compaction/dry
21(2): 117–129. granulation. Pharm Dev Technol 2005; 10(3): 353–362.
16 Hussain F et al. Interactions between sparfloxacin and antacids – Jaiyeoba KT, Spring MS. The granulation of ternary mixtures: the effect of
dissolution and adsorption studies. Pak J Pharm Sci 2006; 19(Jan): 16– solubility of the excipients. J Pharm Pharmacol 1980; 32: 1–5.
21. Khaled KA. Formulation and evaluation of hydrochlorothiazide liquisolid
17 Arayne MS et al. Cephradine antacids interaction studies. Pak J Pharm tablets. Saudi Pharm J 1998; 6(Jan): 39–46.
Sci 2007; 20(3): 179–184.
Law MFL, Deasy PB. Effect of common classes of excipients on extrusion-
18 Aideloje SO et al. Altered pharmacokinetics of halofantrine by an
spheronization. J Microencapsul 1997; 14(May): 647–657.
antacid, magnesium carbonate. Eur J Pharm Biopharm 1998; 463:
299–303.
19 Sadowski DC et al. Drug interactions with antacids: mechanisms and
clinical significance. Drug Safety 1994; 116: 395–407. 21 Author
20 Food Chemicals Codex, 6th edn. Bethesda, MD: United States
Pharmacopeia, 2008; 560. BF Truitt.
20 General References
Freitag F, Kleinebudde P. How do roll compaction/dry granulation affect the
22 Date of Revision
tableting behaviour of inorganic materials? Microhardness of ribbons 18 February 2009.
Magnesium Oxide
M
1 Nonproprietary Names auxiliary glidant.(2) It is also used as a food additive and as an
BP: Heavy Magnesium Oxide antacid, either alone or in conjunction with aluminum hydroxide.
Light Magnesium Oxide Magnesium oxide is additionally used as an osmotic laxative and a
JP: Magnesium Oxide magnesium supplement to treat deficiency states.
PhEur: Magnesium Oxide, Heavy
Magnesium Oxide, Light 8 Description
USP: Magnesium Oxide Two forms of magnesium oxide exist: a bulky form termed light
magnesium oxide and a dense form termed heavy magnesium oxide.
See Section 8.
The USP 32 and JP XV define both forms in a single monograph,
2 Synonyms while the BP 2009 and PhEur 6.4 have separate monographs for
each form. For the heavy variety, 15 g has an apparent volume
Calcined magnesia; calcinated magnesite; Descote; E530; Magcal; before settling of not more than 60 mL; for the light variety, 15 g has
Magchem 100; Maglite; magnesia; magnesia monoxide; magnesia an apparent volume before settling of not more than 100 mL as
usta; magnesii oxidum leve; magnesii oxidum ponderosum;
defined by the BP 2009 and PhEur 6.4.
Magnyox; Marmag; Oxymag; periclase.
Both forms of magnesium oxide occur as fine, white, odorless
powders. Magnesium oxide possesses a cubic crystal structure,
3 Chemical Name and CAS Registry Number
though the BP 2009 and PhEur 6.4 describe the appearance of light
Magnesium oxide [1309-48-4] magnesium oxide as an amorphous powder.
4 Empirical Formula and Molecular Weight 9 Pharmacopeial Specifications
MgO 40.30 See Table I.
5 Structural Formula
10 Typical Properties
See Section 4.
Acidity/alkalinity pH = 10.3 (saturated aqueous solution)
Boiling point 36008C
6 Functional Category
Melting point 28008C
Anticaking agent; emulsifying agent; glidant; tablet and capsule NIR spectra see Figure 1.
diluent. Particle size distribution 99.98% less than 45 mm in size (light
magnesium oxide).
7 Applications in Pharmaceutical Formulation or Refractive index 1.735
Technology Solubility Soluble in dilute acids and ammonium salt solutions;
Magnesium oxide is used as an alkaline diluent in solid-dosage very slightly soluble in pure water (0.0086 g/100 mL at 308C;
forms to modify the pH of tablets.(1) It can be added to solid-dosage solubility is increased by carbon dioxide); practically insoluble in
forms to bind excess water and keep the granulation dry. In ethanol (95%).
combination with silica, magnesium oxide can be used as an Specific gravity 3.58 g/cm3 at 258C (heavy magnesium oxide).
