Typical Properties

Data shown below are for the racemate. See Section 17 for other data for the D- and L- forms.

Acidity/alkalinity: pH = 2.35 (1% w/v aqueous solution at 258C)

Boiling point: 1508C (with decomposition)

Density (bulk): 0.81 g/cm3 Density (tapped): 0.92 g/cm3 Dissociation constant:

pKa1 = 3.40 at 258C; pKa2 = 5.05 at 258C.

Melting point: 131–1328C

Solubility: freely soluble in ethanol (95%) and water but practically insoluble in benzene. A saturated aqueous solution contains about 56% malic acid at 208C. See Table II.

Table II: Solubility of malic acid.

Solvent Solubility at 208C

Acetone 1 in 5.6

Diethyl ether 1 in 119

Ethanol (95%) 1 in 2.6

Methanol 1 in 1.2

Propylene glycol 1 in 1.9

Water 1 in 1.5–2.0

Specific gravity:

1.601 at 208C;

1.250 (saturated aqueous solution at 258C).

Malic Acid 437

Viscosity (dynamic): 6.5 mPa s (6.5 cP) for a 50% w/v aqueous solution at 258C.

Stability and Storage Conditions



CAS number: [636-61-3]

Synonyms: (R)-(+)-hydroxybutanedioic acid; D-(+)-malic acid.

Melting point: 99–1018C

Specific rotation [a]20: +5.28 (in acetone at 188C).

Malic acid is stable at temperatures up to 1508C. At temperatures above 1508C it begins to lose water very slowly to yield fumaric acid; complete decomposition occurs at about 1808C to give fumaric acid and maleic anhydride.

Malic acid is readily degraded by many aerobic and anaerobic microorganisms. Conditions of high humidity and elevated temperatures should be avoided to prevent caking.

The effects of grinding and humidity on malic acid have also been investigated.(2)

The bulk material should be stored in a well-closed container, in a cool, dry place.

Incompatibilities

Malic acid can react with oxidizing materials. Aqueous solutions are mildly corrosive to carbon steels.

Method of Manufacture

Malic acid is manufactured by hydrating maleic and fumaric acids in the presence of suitable catalysts. The malic acid formed is then separated from the equilibrium product mixture.

Safety

Malic acid is used in oral, topical, and parenteral pharmaceu- tical formulations in addition to food products, and is generally regarded as a relatively nontoxic and nonirritant material. However, concentrated solutions may be irritant.

LD50 (rat, oral): 1.6 g/kg(3) LD50 (rat, IP): 0.1 g/kg

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Malic acid, and concentrated malic acid solutions may be irritant to the skin, eyes, and mucous membranes. Gloves and eye protection are recom- mended.

Regulatory Status

GRAS listed. Both the racemic mixture and the levorotatory isomer are accepted as food additives in Europe. The DL- and L- forms are included in the FDA Inactive Ingredients Guide (oral preparations). Included in nonparenteral and parenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.

Related Substances

Citric acid; fumaric acid; D-Malic acid; -Malic acid; tartaric acid.

D-Malic acid

Empirical formula: C4H6O5

Molecular weight: 134.09

L-Malic acid

Empirical formula: C4H6O5

Molecular weight: 134.09

CAS number: [97-67-6]

Synonyms: apple acid; (S)-(–)-hydroxybutanedioic acid; L-(–)- malic acid.

Boiling point: ≈1408C (with decomposition)

Melting point: 99–1008C

Solubility: practically insoluble in benzene. See also Table III.

Table III: Solubility of L-malic acid

Solvent Solubility at 208C

Acetone 1 in 1.6

Diethyl ether 1 in 37

Dioxane 1 in 1.3

Ethanol (95%) 1 in 1.2

Methanol 1 in 0.51

Water 1 in 2.8

Specific gravity: 1.595 at 208C

Specific rotation [a]20: —5.78 (in acetone at 188C)

Comments

A specification for malic acid is contained in the Food Chemical Codex (FCC). The EINECS number for malic acid is 202-601- 5.

Specific References

Sweetman SC, ed. Martindale: The Complete Drug Reference,

34th edn. London: Pharmaceutical Press, 2005: 1709.

Piyarom S, Yonemochi E, Oguchi T, Yamamoto K. Effects of grinding and humidification on the transformation of conglomer- ate to racemic compound in optically active drugs. J Pharm Pharmacol 1997; 49: 384–389.

Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th edn. New York: Wiley, 2004: 2273.

General References

Allen LV. Featured excipient: flavor enhancing agents. Int J Pharm Compound 2003: 7(1): 48–50.

Anonymous. Malic and fumaric acids. Manuf Chem Aerosol News

1964; 35(12): 56–59.

Berger SE. In: Kirk-Othmer Encyclopedia of Chemical Technology, vol.

13, 3rd edn. New York: Wiley-Interscience, 1981: 103.

Authors

SC Owen.

Date of Revision

12 August 2005.

Maltitol

Nonproprietary Names

BP: Maltitol PhEur: Maltitolum

Synonyms

Amalty; C*PharmMaltidex;  E965;  hydrogenated  maltose;

Malbit; Maltisorb; Maltit; D-maltitol.

Chemical Name and CAS Registry Number

4-O-a-D-Glucopyranosyl-D-glucitol [585-88-6]

Empirical Formula and Molecular Weight

C12H24O11 344.32

Structural Formula

 

Functional Category

Coating agent; diluent; granulating agent; sweetening agent.

Applications in Pharmaceutical Formulation or Technology

Maltitol is widely used in the pharmaceutical industry in the formulation of oral dosage forms. It is a noncariogenic bulk sweetener, approximately as sweet as sucrose, well adapted as a diluent for different oral dosage forms, wet granulation, and hard coating.

SEM: 1

Excipient: Maltisorb P200 Manufacturer: Roquette Fre`res

 

Pharmacopeial Specifications

See Table I.

Table I: Pharmacopeial specifications for maltitol.

 

Test PhEur 2005    

Identification +    

Characters +    

Appearance of solution +    

Conductivity 420 mS·cm—1    

Reducing sugars 40.2%    

Related substances +    

Lead 40.5 ppm    

Nickel 41 ppm    

Water 41.0%  

Microbial contamination

Aerobic bacteria 4102/g

Fungi 4102/g

Bacterial endotoxins +

Assay (dried basis) 98.0–102.0%

Typical Properties

Description

Compressibility: 9.5%

Density (bulk): 0.79 g/cm



3 (1)

Maltitol occurs as a white, odorless, sweet, crystalline powder. It is a disaccharide consisting of one glucose unit linked with one sorbitol unit via an a-(1→4) bond.

Density (tapped): 0.95 g/cm3 (1)

Flowability: 5 seconds(1)

Melting point: 148–1518C

Maltitol 439

Particle size distribution: 95% 4 500 mm, 40% 5 100 mm in

size for Maltisorb P200 (Roquette); 95% 4 200 mm, 50%

100 mm in size for Maltisorb P90 (Roquette). Solubility: freely soluble in water. See also Table II. Viscosity (dynamic): see Table III.

Table II: Solubility of maltitol (Maltisorb).(1)

Solvent Solubility at 208C unless otherwise stated

Water 1 in 0.67

1 in 0.48 at 408C

1 in 0.33 at 608C

1 in 0.22 at 808C

1 in 0.18 at 908C

Table III: Viscosity (dynamic) of aqueous maltitol (Maltisorb) solutions at 208C.(1)

Concentration of aqueous maltitol solution (% w/v) Viscosity (mPa s)

 

10 8    

20 10    

30 11    

40 15    

50 24    

60 70    

11

Stability and Storage Conditions  

Maltitol has good thermal and chemical stability. When it is heated at temperatures above 2008C, decomposition begins (depending on time, temperature, and other prevailing condi- tions). Maltitol does not undergo browning reactions with amino acids, and absorbs atmospheric moisture only at relative humidities of 89% and above, at 208C.

Incompatibilities

—

Method of Manufacture

Maltitol is obtained from hydrogenated maltose syrup. Starch is hydrolyzed to yield a high-concentration maltose syrup, which is hydrogenated with a catalyst. After purification and concentration, the syrup is crystallized.

Safety

Maltitol is used in oral pharmaceutical formulations, con- fectionery, and food products and is considered to be noncariogenic. It is generally regarded as a nontoxic, nonaller- genic, and nonirritant material.

Digestion of maltitol follows two different metabolic path- ways: absorption in the small intestine and fermentation in the large intestine (colon). These two metabolic pathways must thus be considered when evaluating the energy value.

The hydrolysis of maltitol in the small intestine releases sorbitol and glucose. Glucose is actively transported and rapidly absorbed, whereas sorbitol absorption is passive. The nonabsorbed sorbitol and nonhydrolyzed maltitol are fermen- ted by the microflora in the colon. The relative importance of



the two absorption pathways depends on numerous individual factors and is related to the quantity of maltitol ingested. Excessive oral consumption (>50 g daily) may cause flatulence and diarrhea.

Maltitol exhibits a low glycemic index and can therefore, under medical supervision, have a place in the diet of diabetic patients. The intake of maltitol must be taken into account for the calculation of the daily glucidic allowance.

The WHO in considering the safety of maltitol did not set a value for the acceptable daily intake since the levels used in food to achieve a desired effect were not considered a hazard to health.(2,3)

Handling Precautions

Observe normal precautions appropriate to circumstances and quantity of material handled. Eye protection and gloves are recommended.

Regulatory Status

GRAS listed. Accepted for use as a food additive in Europe. Included in oral pharmaceutical formulations. Included in the Canadian List of Acceptable Non-medicinal Ingredients.

Related Substances

Sorbitol.

Comments

Maltitol is not fermented by oral bacteria and is neither acidogenic nor cariogenic. A specification for maltitol syrup is contained in the Food Chemicals Codex (FCC). The EINECS number for maltitol is 209-567-0.

Specific References

Roquette Fre`res. Technical literature: Maltisorb crystalline mal- titol, 1999.

FAO/WHO. Evaluation of certain food additives and contam- inants. Thirty-third report of the joint FAO/WHO expert committee on food additives. World Health Organ Tech Rep Ser 1989; No. 776.

FAO/WHO. Evaluation of certain food additives and contam- inants. Forty-sixth report of the joint FAO/WHO expert committee on food additives. World Health Organ Tech Rep Ser 1997; No. 868.

General References

Moskowitz AH. Maltitol and hydrogenated starch hydrolysate. In: Nabors LO, Gelardi RC, eds. Alternative Sweeteners, 2nd edn. New York: Marcel Dekker, 1991: 259–282.

Portman MO, Kilcast D. Psycho-physical characterization of new sweeteners of commercial importance for the EC food industry. Food Chem 1996; 56(3): 291–302.

Authors

X Duriez.

Date of Revision

26 August 2005.

Maltitol Solution

Nonproprietary Names

BP: Liquid maltitol

PhEur: Maltitolum liquidum USPNF: Maltitol solution

Synonyms

E965; hydrogenated glucose syrup; Finmalt L; Lycasin HBC; Lycasin 80/55; Maltisorb 75/75; Maltisweet 3145; maltitol syrup.

Chemical Name and CAS Registry Number

Maltitol solution [9053-46-7]

Empirical Formula and Molecular Weight

The PhEur 2005 describes liquid maltitol as an aqueous solution of a hydrogenated, partly hydrolyzed starch, with not less than 68% w/w of solid matter and not more than 85% w/w. This is composed of a mixture of mainly D-maltitol (550% w/w), D-sorbitol (48% w/w), and hydrogenated oligo- and polysaccharides, all quoted on an anhydrous basis.

The USPNF 23 describes maltitol solution as an aqueous solution of a hydrogenated, partially hydrolyzed starch. It contains, on the anhydrous basis, not less than 50% w/w of D-maltitol (C12H24O11) and not more than 8.0% w/w of D-sorbitol (C6H14O6). See also Section 18.

Structural Formula

See Section 4.

Functional Category

Suspending agent; sweetening agent.

Applications in Pharmaceutical Formulation or Technology

Maltitol solution is used in oral pharmaceutical formulations as a bulk sweetening agent, either alone or in combination with other excipients, such as sorbitol. Maltitol solution is also used as a suspending agent in oral suspensions as an alternative to sucrose syrup since it is viscous, noncariogenic, and has a low calorific value. It is also noncrystallizing and therefore prevents ‘cap-locking’ in syrups and elixirs.

Maltitol solution is additionally used in the preparation of pharmaceutical lozenges(1) and is also used in confectionery and food products.

Description

Maltitol solution is a colorless and odorless, clear viscous liquid. It is sweet-tasting (approximately 75% the sweetness of sucrose).

Pharmacopeial Specifications

See Table I.

Table I:  Pharmacopeial specifications for maltitol solution.

 

Test PhEur 2005 USPNF 23    

Identification + +    

Characters + —    

Appearance of solution + —    

Conductivity 410 mS·cm—1 —    

pH — 5.0–7.5    

Reducing sugars 40.2% 40.3%    

Lead 40.5 ppm —    

Nickel 41 ppm 41 ppm    

Water 15.0–32.0% 431.5%    

Residue on ignition — 40.1%    

Maltitol (dried basis) 550.0% 550.0%    

Sorbitol (dried basis) 48.0% 48.0%