Isomalt

1 Nonproprietary Names than 1,1-GPM. By shifting the ratio of the two components, the
solubility and crystal water content can be adjusted, see Section
BP: Isomalt
10. GalenIQ 720 has a GPM : GPS ratio of 1 : 1; GalenIQ 721
PhEur: Isomaltum
has a GPM : GPS ratio of 1 : 3.

2 Synonyms 6 Functional Category

GalenIQ; hydrogenated isomaltulose; hydrogenated palati- Base for medicated confectionery; coating agent; granulating
nose; E953; Isomaltidex 16500; Palatinit. agent; sweetening agent; tablet and capsule diluent.

3 Chemical Name and CAS Registry Number 7 Applications in Pharmaceutical Formulation

or Technology
Isomalt [64519-82-0]
Isomalt is a mixture of two stereoisomers: Isomalt is a noncariogenic excipient used in a variety of
6-O-a-D-glucopyranosyl-D-sorbitol (1,6-GPS) [534-73-6] pharmaceutical preparations including tablets or capsules,
1-O-a-D-glucopyranosyl-D-mannitol dihydrate (1,1-GPM) coatings, sachets, and suspensions, and in effervescent tablets.
[20942-99-8] It can also be used in direct compression and wet granulation.(1)
In buccal applications such as chewable tablets it is
4 Empirical Formula and Molecular Weight commonly used because of its negligible negative heat of
solution, mild sweetness, and ‘mouth feel’.(2,3) It is also used
C12H24O11 344.32 (for anhydrous) widely in lozenges, sugar-free chewing gum, and hard-boiled
C12H24O112H2O 380.32 (for dihydrate) candies, and as a sweetening agent in confectionery for diabetics.
See also Section 18.
5 Structural Formula
8 Description
Isomalt is a sugar alcohol (polyol) that occurs as a white or
almost white powder or granular or crystalline substance. It has
a pleasant sugarlike taste with a mild sweetness approximately
50–60% of that of sucrose.(2–4)

9 Pharmacopeial Specifications
See Table I. See also Section 18.

10 Typical Properties
Angle of repose: see Table II.
Compressibility: compression characteristics may vary, depend-
ing on the grade of isomalt used; see Figure 1.
Density (bulk): see Table II.
Density (tapped): see Table II.
Density (true):
1.52 g/cm3 for 1,6-GPS;
1.47 g/cm3 for 1,1-GPM.
Flowability: powder is cohesive; granules are free flowing.(2)
Glass transition temperature:
638C for a 1 : 3 mixture of 1,1-GPM and 1,6-GPS;
688C for 1,1-GPM;
598C for 1,6-GPS.(2)
Heat of combustion: 0.017 kJ/kg(5)
Heat of solution: þ14.6 kJ/mol for an equimolar mixture of
1,1-GPM and 1,6-GPS.(2)
Hygroscopicity: not hygroscopic until 85% RH, at 258C.(2) See
also Figure 2.
Melting point:
141–1618C for a 1 : 3 mixture of 1,1-GPM and 1,6-GPS;
166–1688C for 1,6-GPS;
168–1718C for 1,1-GPM.(2)
Generally, isomalt comprises a mixture of 1,6-GPS and 1,1- Minimum ignition temperature: >4608C
GPM. 1,6-GPS crystallizes without water and is more soluble Moisture content: see Figure 2.
 Isomalt 3 67

Table I: Pharmacopoeial specifications for isomalt. Table II: Typical physical properties of selected commercially
available isomalt grades, GalenIQ (Palatinit GmbH).
Test PhEur 2005
Grade Angle of Density Density
Identification þ repose (8) (bulk) (tapped)
Characters þ (g/cm3) (g/cm3)
Related products þ
Conductivity 420 mS cm–1 GalenIQ 720 38 0.43 0.48
Reducing sugars 40.3% GalenIQ 721 37 0.42 0.45
Lead 40.5 ppm GalenIQ 800 — 0.50 0.65
Nickel 41 ppm GalenIQ 810 — 0.59 0.70
Water 47.0% GalenIQ 960 33 0.82 —
Assay 98.0–102.0% GalenIQ 980 — 0.82 —
GalenIQ 981 — 0.78 —
GalenIQ 990 — 0.85 —
Particle size distribution:
approximately 90% >100 mm for GalenIQ 720;
approximately 58% >20 mm for GalenIQ 800;
approximately 99% >200 mm for GalenIQ 960. SEM: 3
pH: 3–10(3) Excipient: GalenIQ 810
Solubility: see Figure 3. Manufacturer: Palatinit GmbH
Magnification: 65
SEM: 1 Voltage:10 kV
Excipient: GalenIQ 720
Manufacturer: Palatinit GmbH
Magnification: 400
Voltage: 5 kV

SEM: 2 SEM: 4
Excipient: GalenIQ 721 Excipent: GalenIQ 981
Manufacturer: Palatinit GmbH Manufacturer: Palatinit GmbH
Magnification: 400 Magnification: 90
Voltage: 5 kV Voltage: 5 kV
36 8 Isomalt

SEM: 5
Excipent: GalenIQ 990
Manufacturer: Palatinit GmbH
Magnification: 130
Voltage: 10 kV

Figure 2: Sorption isotherms of isomalt DC types.(a,b)

&: Adsorption GalenIQ 720 (Palatinit GmbH)
&: Desorption GalenIQ 720 (Palatinit GmbH)
– – –: Crystal water GalenIQ 720 (Palatinit GmbH)
*: Adsorption GalenIQ 721 (Palatinit GmbH)
*: Desorption GalenIQ 721 (Palatinit GmbH)
– – –: Crystal water GalenIQ 721 (Palatinit GmbH)
(a)
Measured using Dynamic Vapor Sorption, Südzucker AG.
(b)
1,6-GPS occurs without crystal water and 1,1-GPM crystallizes with 2 mol crystal water (the
initial water content in commercial forms, see Section 18). The starting point of the curves
depends on the water content. The content of free water in the product is typically 0.5–1.0%.

11 Stability and Storage Conditions

Isomalt has very good thermal and chemical stability. When it is
melted, no changes in the molecular structure are observed. It
exhibits considerable resistance to acids and microbial influ-
ences.(1) Isomalt is non-hygroscopic, and at 258C does not
significantly absorb additional water up to a relative humidity
(RH) of 85%; paracetamol (acetaminophen) tablets based on
isomalt were stored for 6 months at 85% RH at 208C and
retained their physical aspect.(1)

Figure 3: Solubility of isomalt types in water.(2)

&: GalenIQ 720 (Palatinit GmbH)
*: GalenIQ 721 (Palatinit GmbH)

If stored under normal ambient conditions, isomalt is

chemically stable for many years. When it is stored in an
unopened container at 208C and 60% RH, a re-evaluation after
3 years is recommended.
Isomalt does not undergo browning reactions; it has no
reducing groups, therefore it does not react with other
Figure 1: Tablet crushing strength of isomalt (GalenIQ 720, Palatinit
ingredients in a formulation (e.g. with amines in Maillard
GmbH).
reactions).
Formulation: 99.5% isomalt, 0.5% magnesium stearate
Tablet weight: 240 mg
Diameter: 8 mm
12 Incompatibilities
Press: Fette P1200
Punch: concave —

13 Method of Manufacture
Isomalt is produced from food-grade sucrose in a two-stage
process. Beet sugar is converted by enzymatic transglucosida-
tion into the reducing disaccharide isomaltulose. This under-
goes catalytical hydrogenation to produce isomalt.
14 Safety
Isomalt is used in oral pharmaceutical formulations, confec-
tionery, and food products. It is generally regarded as a
nontoxic, nonallergenic, and nonirritant material.
Toxicological and metabolic studies on isomalt(5–10) have
been summarized in a WHO report prepared by the FAO/
WHO Expert Committee (JECFA), resulting in an acceptable
daily intake of ‘not specified’.(11)
The glycosidic linkage between the mannitol or sorbitol
moiety and the glucose moiety is very stable, limiting the
hydrolysis and absorption of isomalt in the small intestine.
There is no significant increase in the blood glucose level after
oral intake, and glycemic response is very low, making isomalt
suitable for diabetics. The majority of isomalt is fermented in
the large intestine. In general, isomalt is tolerated very well,
although excessive consumption may result in laxative
effects.(12–14)
Isomalt is not fermented by bacteria present in the mouth,
therefore no significant amount of organic acid is produced that
attacks tooth enamel.(15–17)
15 Handling Precautions
Observe normal precautions appropriate to the circumstances
and quantity of material handled. Eye protection, gloves, and a
dust mask or respirator are recommended.
16 Regulatory Status
GRAS listed. Accepted as a food additive in Europe.
17 Related Substances
—
18 Comments
Compression of isomalt without lubrication is difficult, and
problems such as die wall sticking, capping, and lamination
have been observed. The addition of a lubricant such as
magnesium stearate will reduce die wall adhesion. Co-extrusion
of isomalt with paracetamol (acetaminophen) significantly
improved the tableting properties of the mixtures, compared
to physical mixtures of drug and isomalt.(18) Direct molding is
also a potentially suitable technique for producing isomalt-
based tablets.(18)
It is anticipated that a specification for isomalt will soon be
included in the USPNF.(19)
A variety of different grades of isomalt are commercially
available that have different applications, e.g. GalenIQ 720
and 721 are used in direct compression, GalenIQ 810 is used in
wet granulation, GalenIQ 981 is used in coatings, and
GalenIQ 990 is used in boilings.
Isomalt 3 69
19 Specific References
1 Ndindayino F, Henrist D, Kiekens F, et al. Characterization and
evaluation of isomalt performance in direct compression. Int J
Pharm 1999; 189: 113–124.
2 Palatinit GmbH. Technical literature: Isomalt, GalenIQ, 2005.
3 Cerestar. Technical literature: IsoMaltidex, 2002.
4 Schiweck H. Palatinit—Production, technological characteristics
and analytical study of foods containing Palatinit. Alimenta 1980;
(19): 5–16.
5 Livesey G. The energy values of dietary fibre and sugar alcohols for
man. Nutr Res Rev 1992; (5): 61–84.
6 Waalkens-Berendsen DH, Koeter HB, van Marwijk MW. Embry-
otoxicity/teratogenicity of isomalt in rats and rabbits. Food Chem
Toxicol 1990; 28(1): 1–9.
7 Smits-Van Prooije AE, De Groot AP, Dreef-Van Der Meullen HC,
Sinkeldam EJ. Chronic toxicity and carcinogenicity study of
isomalt in rats and mice. Food Chem Toxicol 1990; 28(4): 243–
251.
8 Waalkens-Berendsen DH, Koeter HB, Sinkeldam EJ. Multigenera-
tion reproduction study of isomalt in rats. Food Chem Toxicol
1990; 28(1): 11–19.
9 Waalkens-Berendsen DH, Koeter HB, Schlüter G, Renhof M.
Developmental toxicity of isomalt in rats. Food Chem Toxicol
1989; 27(10): 631–637.
10 Pometta D, Trabichet D, Spengler M. Effects of a 12 week
administration of isomalt on metabolic control in type-II-diabetics.
Akt Ernährung 1985; 10: 174–177.
11 FAO/WHO. Toxicological evaluation of certain food additives and
contaminants. Twentieth report of the joint FAO/WHO expert
committee on food additives. World Health Organ Tech Rep Ser
1987; No. 539.
12 Livesey G. Tolerance of low-digestible carbohydrates: a general
view. Br J Nutr 2001; 85: S1, S7–S16.
13 Paige DM, Bayless TM, Davis LR. Palatinit digestibility in
children. Nutr Res 1992; 12: 27–37.
14 Storey DM, Lee A, Zumbe A. The comparative gastrointestinal
response of young children to the ingestion of 25 g sweets
containing sucrose or isomalt. Br J Nutr 2002; 87(4): 291–297.
15 Featherstone DB. Effect of isomalt sweetener on the caries process:
A review. J Clin Dent 1995; 5: 82–85.
16 Van de Hoeven JS. Influence of disaccharide alcohols on the oral
microflora. Caries Res 1979; 13: 301–306.
17 Gehring F, Karle EJ. The sugar substitute Palatinit with special
emphasis on microbial and caries-preventing aspects. Z Ernärung
1981; 20: 96–106.
18 Ndindayino F, Vervaet C, Van den Mooter G, Remon JP. Direct
compression and moulding properties of co-extruded isomalt/drug
mixtures. Int J Pharm 2002; 235: 159–168.
19 Isomalt. Pharmacopeial Forum 2005; 31(1): 89–92.
20 General References
Bauer KH, Lehmann K, Osterwald HP, Rothgang G. Coated
Pharmaceutical Dosage Forms: Fundamentals, Manufacturing
Techniques, Biopharmaceutical Aspects, Test Methods and Raw
Materials. Stuttgart: Medpharm Scientific Publications, 1998:
280.
Dörr T, Willibald-Ettle I. Evaluation of the kinetics of dissolution of
tablets and lozenges consisting of saccharides and sugar substitutes.
Pharm Ind 1996; 58: 947–952.
Fritzsching B, Schmidt T. A survey of isomalt as a sugarfree excipient
for nutraceuticals. Pharmaceutical Manufacturing and Packing
Sourcer 2000(Sept); 70–72.
Iida K, Leuenberger H, Fueg LM, et al. Effect of mixing of fine
carrier particles on dry powder inhalation property of salbutamol
sulfate (SS). Yakugaku-zasshi, J Pharm Soc Jpn 2000; 120(1): 113–
119.
O’Brien Nabors L, ed. Alternative Sweeteners: An Overview, 3rd edn.
New York: Marcel Dekker, 2001: 553.
37 0 Isomalt

Ndindayino F, Henrist D, Kiekens F, et al. Direct compression 21 Authors

properties of melt-extruded isomalt. Int J Pharm 2002; 235(1–2):
149–157. B Fritzsching, O Luhn, A Schoch.
Ndindayino F, Vervaet C, Van-den-Mooter G, Remon JP. Bioavail-
ability of hydrochlorothiazide from isomalt-based moulded tablets.
Int J Pharm 2002; 246: 199–202. 22 Date of Revision
Palatinit GmbH. http://www.palatinit.com/en/Homepage/ (accessed 1
September 2005). 15 September 2005.