Sorbitol

1 Nonproprietary Names Table I: Uses of sorbitol.

BP: Sorbitol
Use Concentration (%)
JP: D-Sorbitol
PhEur: Sorbitol Humectant 3–15
IM injections 10–25
USP-NF: Sorbitol Moisture control agent in tablets 3–10
Oral solutions 20–35
Oral suspensions 70
2 Synonyms Plasticizer for gelatin and cellulose 5–20
Prevention of ‘cap locking’ in syrups and elixirs 15–30
C*PharmSorbidex; E420; 1,2,3,4,5,6-hexanehexol; Liponic 70-
Substitute for glycerin and propylene glycol 25–90
NC; Liponic 76-NC; Meritol; Neosorb; Sorbitab; sorbite; D- Tablet binder and filler 25–90
sorbitol; Sorbitol Instant; sorbitolum; Sorbogem. Toothpastes 20–60
Topical emulsions 2–18

3 Chemical Name and CAS Registry Number

D-Glucitol [50-70-4]
8 Description
Sorbitol is D-glucitol. It is a hexahydric alcohol related to mannose
4 Empirical Formula and Molecular Weight and is isomeric with mannitol.
C6H14O6 182.17 Sorbitol occurs as an odorless, white or almost colorless,
crystalline, hygroscopic powder. Four crystalline polymorphs and
one amorphous form of sorbitol have been identified that have
5 Structural Formula slightly different physical properties, e.g. melting point.(3) Sorbitol is
available in a wide range of grades and polymorphic forms, such as
granules, flakes, or pellets that tend to cake less than the powdered
form and have more desirable compression characteristics. Sorbitol
has a pleasant, cooling, sweet taste and has approximately 50–60%
of the sweetness of sucrose.
See also Section 18.

9 Pharmacopeial Specifications
See Table II. See also Section 18.
6 Functional Category
Humectant; plasticizer; stabilizing agent; sweetening agent; tablet
and capsule diluent. 10 Typical Properties
Acidity/alkalinity pH = 4.5–7.0 for a 10% w/v aqueous solution.
Compressibility Compression characteristics and the degree of S
7 Applications in Pharmaceutical Formulation or lubrication required vary, depending upon the particle size and
Technology grade of sorbitol used. The spray-dried forms of sorbitol afford
Sorbitol is widely used as an excipient in pharmaceutical formula-
tions. It is also used extensively in cosmetics and food products; see SEM 1: Excipient: sorbitol; manufacturer: SPI Pharma; lot no.: 5224F8;
Table I. magnification: 100.
Sorbitol is used as a diluent in tablet formulations prepared by
either wet granulation or direct compression.(1–5) It is particularly
useful in chewable tablets owing to its pleasant, sweet taste and
cooling sensation. In capsule formulations it is used as a plasticizer
for gelatin. Sorbitol has been used as a plasticizer in film
formulations.(6,7)
In liquid preparations(8) sorbitol is used as a vehicle in sugar-free
formulations and as a stabilizer for drug,(9) vitamin,(10,11) and
antacid suspensions. Furthermore, sorbitol is used as an excipient in
liquid parenteral biologic formulations to provide effective protein
stabilization in the liquid state.(12) It has also been shown to be a
suitable carrier to enhance the in vitro dissolution rate of
indometacin.(13) In syrups it is effective in preventing crystallization
around the cap of bottles. Sorbitol is additionally used in
injectable(14) and topical preparations, and therapeutically as an
osmotic laxative.
Sorbitol may also be used analytically as a marker for assessing
liver blood flow.(15)

67 9
 6 80 Sorbitol

Table II: Pharmacopeial specifications for sorbitol. Table III: Mean particle sizes for various grades of sorbitol.

Test JP XV PhEur 6.4 USP32–NF27 Grade Mean particle size (mm)

Identification þ þ þ Neosorb P100T 140
Characters — þ — Neosorb P20/60 650
Acidity or alkalinity þ — — Neosorb P30/60 480
pH — — 3.5–7.0 Neosorb P60 220
Appearance of solution þ þ þ Neosorb P60W 260
Arsenic 41.3 ppm — — Sorbitab SD 250 250
Chloride 40.005% — 40.005% Sorbitab SD 500 500
Sulfate 40.006% — 40.01%
Conductivity — 420 mS cm1 —
Glucose þ — —
Heavy metals 45 ppm — — Table IV: Solubility of sorbitol.
Lead — 40.5 ppm —
Microbial — þ — Solvent Solubility at 208C
contamination Chloroform Practically insoluble
Bacterial — 4102 cfu/g 4103 cfu/g Ethanol (95%) 1 in 25
Fungi — 4102 cfu/g 4102 cfu/g Ethanol (82%) 1 in 8.3
Bacterial endotoxins — þ þ(a) Ethanol (62%) 1 in 2.1
Nickel þ 41 ppm 41 mg/g Ethanol (41%) 1 in 1.4
Reducing sugars — 40.2% 40.3% Ethanol (20%) 1 in 1.2
Related products — 40.1% — Ethanol (11%) 1 in 1.14
Residue on ignition 40.02% — 40.1% Ether Practically insoluble
Total sugars þ — — Methanol Slightly soluble
Water 42.0% 41.5% 41.5% Water 1 in 0.5
Assay (anhydrous 597.0% 97.0–102.0% 91.0–100.5%
basis)

(a) 44 USP Endotoxin Units per g for parenteral dosage forms having a concentration
of less than 100 g of sorbitol per L and 42.5 USP Endotoxin Units per g for parenteral 11 Stability and Storage Conditions
dosage forms having a concentration of 100 g or more of sorbitol per L. Sorbitol is chemically relatively inert and is compatible with most
excipients. It is stable in air in the absence of catalysts and in cold,
dilute acids and alkalis. Sorbitol does not darken or decompose at
greater compression characteristics than standard grades of elevated temperatures or in the presence of amines. It is
sorbitol. nonflammable, noncorrosive, and nonvolatile.
Density 1.49 g/cm3 Although sorbitol is resistant to fermentation by many micro-
Density (bulk) organisms, a preservative should be added to sorbitol solutions.
0.448 g/cm3; Solutions may be stored in glass, plastic, aluminum, and stainless
0.6–0.7 g/cm3 for Sorbitab SD 250; steel containers. Solutions for injection may be sterilized by
autoclaving.
0.5–0.6 g/cm3 for Sorbitab SD 500.
The bulk material is hygroscopic and should be stored in an
Density (tapped)
airtight container in a cool, dry place.
0.400 g/cm3;
0.7 g/cm3 for Sorbitab SD 250; 12 Incompatibilities

S 0.6 g/cm3 for Sorbitab SD 500;

Density (true) 1.507 g/cm3
Flowability Flow characteristics vary depending upon the particle
size and grade of sorbitol used. Fine powder grades tend to be
poorly flowing, while granular grades have good flow proper-
ties.
Heat of solution 110.9 J/g (–26.5 cal/g)
Melting point
Anhydrous form: 110–1128C;
Gamma polymorph: 97.78C;
Metastable form: 938C.
Moisture content Sorbitol is a very hygroscopic powder and
relative humidities greater than 60% at 258C should be avoided
when sorbitol is added to direct-compression tablet formulas.
See also Figure 1.
NIR spectra see Figure 2.
Osmolarity A 5.48% w/v aqueous solution of sorbitol hemihy-
drate is iso-osmotic with serum.
Particle size distribution Particle size distribution varies depend-
ing upon the grade of sorbitol; see Table III. For fine powder
grades, typically 87% <125 mm in size; for granular grades,
22% <125 mm, 45% between 125 and 250 mm, and 33%
between 250 and 590 mm. Individual suppliers’ literature should
be consulted for further information.
Solubility see Table IV. See also Section 17.
Sorbitol will form water-soluble chelates with many divalent and
trivalent metal ions in strongly acidic and alkaline conditions.
Addition of liquid polyethylene glycols to sorbitol solution, with
vigorous agitation, produces a waxy, water-soluble gel with a
melting point of 35–408C. Sorbitol solutions also react with iron
oxide to become discolored.
Sorbitol increases the degradation rate of penicillins in neutral
and aqueous solutions.(16)
13 Method of Manufacture
Sorbitol occurs naturally in the ripe berries of many trees and
plants. It was first isolated in 1872 from the berries of the Mountain
Ash (Sorbus americana).
Industrially, sorbitol is prepared by high-pressure hydrogenation
with a copper–chromium or nickel catalyst, or by electrolytic
reduction of glucose and corn syrup. If cane or beet sugars are used
as a source, the disaccharide is hydrolyzed to dextrose and fructose
prior to hydrogenation.
14 Safety
Sorbitol is widely used in a number of pharmaceutical products and
occurs naturally in many edible fruits and berries. It is absorbed
more slowly from the gastrointestinal tract than sucrose and is
metabolized in the liver to fructose and glucose. Its caloric value is
approximately 16.7 J/g (4 cal/g). Sorbitol is better tolerated by
 Sorbitol 68 1
50 16 Regulatory Status
GRAS listed. Accepted for use as a food additive in Europe.
Included in the FDA Inactive Ingredients Database (intra-articular
Equilibrium moisture at 25°C (%)
40 and IM injections; nasal; oral capsules, solutions, suspensions,
syrups and tablets; rectal, topical, and vaginal preparations).
Included in parenteral and nonparenteral medicines licensed in the
UK. Included in the Canadian List of Acceptable Non-medicinal
30 Ingredients.

17 Related Substances
20 Maltitol solution; mannitol; xylitol.

18 Comments
10 Sorbitol may be substituted for sucrose to prepare 70–90% w/v
syrups.
Several different grades of sorbitol, with different polymorphic
form, particle size, and other physical characteristics are commer-
0 cially available, e.g. Neosorb (Roquette Frères). Pyrogen-free grades
0 10 20 30 40 50 60 70 80 90 100
are also available from some suppliers.
Relative humidity (%) Sorbitol is also available in liquid form and occurs as a clear,
colorless, syrupy liquid, which is miscible with water (see Table V).
Figure 1: Equilibrium moisture content of sorbitol USP–NF. Liquid sorbitol is an aqueous solution of a hydrogenated, partly
0.5 0.6 hydrolyzed starch. Partially dehydrated sorbitol solutions are also
1000 × [2nd deriv. log(1/R)]

2046 2240 2273 2446 available, which are produced by partial dehydration of liquid
1417 1678 sorbitol. Sorbo sorbitol solution (Corn Products Specialty Ingre-
dients) is used as a bulking agent, sweetener and humectant.
0.0 Sorbitol Special (SPI Pharma) is a noncrystallizing polyol solution
log(1/R)

used for soft gelatin capsules. The USP 32 and JP XV list sorbitol
solution. The BP 2009 and PhEur also include partially dehydrated
1206 1691 1817 2113 2363
liquid sorbitol (PhEur 6.3), liquid sorbitol (crystallizing) (PhEur
6.0), and liquid sorbitol (non-crystallizing) (PhEur 6.0).
A study has shown that sorbitol may affect the bioavailability/
bioequivalence of drugs by increasing gastrointestinal fluid influx
2064 2286 2473
and motility, which reduces time for drug absorption. It may also be
−1.0 −0.2 employed as a cathartic in the management of poisoning.(22)
1100 1300 1500 1700 1900 2100 2300 2500 A specification for sorbitol is contained in the Food Chemicals
Wavelength/nm Codex (FCC).(23)
The EINECS number for sorbitol is 200-061-5. The PubChem
Compound ID (CID) for sorbitol includes 5780 and 82170.
Figure 2: Near-infrared spectrum of sorbitol measured by reflectance.

diabetics than sucrose and is widely used in many sugar-free liquid

Table V: Physical properties of sorbitol in water solutions. S
vehicles. However, it is not considered to be unconditionally safe for Concentration (% Density Viscosity Refractive Freezing
diabetics. w/w) at 258C (g/cm3) at (mPa s) at index point (8C)
Reports of adverse reactions to sorbitol are largely due to its 258C 258C
action as an osmotic laxative when ingested orally,(17–19) which may 10 1.034 1.2 1.348 1.1
be exploited therapeutically. Ingestion of large quantities of sorbitol 20 1.073 1.7 1.365 3.8
(>20 g/day in adults) should therefore be avoided. 30 1.114 2.5 1.383 8.0
40 1.155 4.4 1.400 13.0
Sorbitol is not readily fermented by oral microorganisms and has
50 1.197 9.1 1.418 26.0
little effect on dental plaque pH; hence, it is generally considered to 60 1.240 26.0 1.437 —
be noncariogenic.(20) 70 1.293 110.0 1.458 —
Sorbitol is generally considered to be more irritating than 80 1.330 900.0 1.478 —
mannitol.
LD50 (mouse, IV): 9.48 g/kg(21)
LD50 (mouse, oral): 17.8 g/kg 19 Specific References
LD50 (rat, IV): 7.1 g/kg 1 Molokhia AM et al. Effect of storage conditions on the hardness,
disintegration and drug release from some tablet bases. Drug Dev Ind
LD50 (rat, SC): 29.6 g/kg
Pharm 1982; 8: 283–292.
2 Bolton S, Atluri R. Crystalline sorbitol tablets: effect of mixing time and
15 Handling Precautions lubricants on manufacturing. Drug Cosmet Ind 1984; 135(5): 44, 46,
47, 48, 50.
Sorbitol may be harmful if ingested in great quantities. It may be 3 DuRoss JW. Modification of the crystalline structure of sorbitol and its
irritant to the eyes. Observe normal precautions appropriate to the effects on tableting characteristics. Pharm Technol 1984; 8(9): 42–53.
circumstances and quantity of material handled. Eye protection, 4 Basedow AM, Möschl GA. Sorbitol instant – an excipient with unique
gloves, and a dust mask or respirator are recommended. tableting properties. Drug Dev Ind Pharm 1986; 12: 2061–2089.
 6 82 Soybean Oil
5 Schmidt PC, Vortisch W. [Influence of manufacturing method of fillers
and binders on their tableting properties: comparison of 8 commercially
available sorbitols.] Pharm Ind 1987; 49: 495–503[in German].
6 Krogars K et al. Development and characterization of aqueous amylose-
rich maize starch dispersion for film formation. Eur J Pharm Biopharm
2003; 56(2): 215–221.
7 Cervera MF et al. Solid state and mechanical properties of aqueous
chitosan-amylose starch films plasticized with polyols. AAPS Pharm Sci
Tech 2004; 5(1): E15.
8 Daoust RG, Lynch MJ. Sorbitol in pharmaceutical liquids. Drug
Cosmet Ind 1962; 90(6): 689–691773, 776, 777, 779, 781–785.
9 Sabatini GR, Gulesich JJ. Formulation of a stable and palatable oral
suspension of procaine penicillin G. J Am Pharm Assoc (Pract Pharm)
1956; 17: 806–808.
10 Bandelin FJ, Tuschhoff JV. The stability of ascorbic acid in various
liquid media. J Am Pharm Assoc (Sci) 1955; 44: 241–244.
11 Parikh BD, Lofgren FV. A further stability study of an oral multivitamin
liquid preparation. Drug Standards 1958; 26: 56–61.
12 Piedmonte DM et al. Sorbitol crystallization can lead to protein
aggregation in frozen protein formulations. Pharm Res 2007; 24(1):
136–146.
13 Valizdeh H et al. Physicochemical characterization of solid dispersions
of indometacin with PEG 6000, Myri 52, lactose, sorbitol, dextrin, and
Eudragit (R) E100. Drug Dev Ind Pharm 2004; 30(3): 303–317.
14 Lindvall S, Andersson NSE. Studies on a new intramuscular haematinic,
iron–sorbitol. Br J Pharmacol 1961; 17: 358–371.
15 Burggraaf J et al. Sorbitol as a marker for drug-induced decreases of
variable duration in liver blood flow in healthy volunteers. Eur J Pharm
Sci 2000; 12: 133–139.
16 Bundgaard H. Drug allergy: chemical and pharmaceutical aspects.
Florence AT, Salole EG, eds. Formulation Factors in Adverse Reactions.
London: Wright, 1990; 23–55.
17 Jain NK et al. Sorbitol intolerance in adults. Am J Gastroenterol 1985;
80: 678–681.
18 Brown AM, Masson E. ‘Hidden’ sorbitol in proprietary medicines – a
cause for concern? Pharm J 1990; 245: 211.
19 Greaves RRSH et al. An air stewardess with puzzling diarrhoea. Lancet
1996; 348: 1488.
Soybean Oil
S
1 Nonproprietary Names
BP: Refined Soya Oil
JP: Soybean Oil
PhEur: Soya-Bean Oil, Refined
USP: Soybean Oil
2 Synonyms
Aceite de soja; Calchem IVO-114; Lipex 107; Lipex 200; Shogun
CT; soiae oleum raffinatum; soja bean oil; soyabean oil; soya bean
oil.
3 Chemical Name and CAS Registry Number
Soybean oil [8001-22-7]
4 Empirical Formula and Molecular Weight
A typical analysis of refined soybean oil indicates the composition
of the acids, present as glycerides, to be: linoleic acid 50–57%;
linolenic acid 5–10%; oleic acid 17–26%; palmitic acid 9–13%;
and stearic acid 3–6%. Other acids are present in trace quantities.(1)
20 Ayers CS, Abrams RA. Noncariogenic sweeteners: sugar substitutes for
caries control. Dental Hygiene 1987; 61: 162–167.
21 Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th
edn. New York: Wiley, 2004; 3292.
22 Chen M-L et al. A modern view of excipient effects on bioequivalence:
case study of sorbitol. Pharm Res 2007; 1: 73–80.
23 Food Chemicals Codex, 6th edn. Bethesda, MD: United States
Pharmacopeia, 2008; 919.
20 General References
Barr M et al. The solubility of sorbitol in hydroalcoholic solutions. Am J
Pharm 1957; 129: 102–106.
Blanchard J et al. Effect of sorbitol on interaction of phenolic preservatives
with polysorbate 80. J Pharm Sci 1977; 66: 1470–1473.
Burgess S. Sorbitol instant: a unique excipient. Manuf Chem 1987; 58(6): 55,
57, 59.
Cargill Pharmaceutical Excipients. Product literature: C*PharmSorbidex,
2008.
Collins J. Metabolic disease: time for fructose solutions to go. Lancet 1993;
341: 600.
Rabinowitz MP et al. GLC assay of sorbitol as cyclic n-butylboronate. J
Pharm Sci 1974; 63: 1601–1604.
Roquette Frères. Technical literature: Neosorb, 2004.
Shah DN et al. Mechanism of interaction between polyols and aluminum
hydroxide gel. J Pharm Sci 1981; 70: 1101–1104.
SPI Pharma. Technical literature: Sorbitab SD 250/500, 2007.
Zatz JL, Lue R-Y. Flocculation of suspensions containing nonionic
surfactants by sorbitol. J Pharm Sci 1987; 76: 157–160.
21 Author
J Shur.
22 Date of Revision
11 February 2009.
5 Structural Formula
See Sections 4 and 8.
6 Functional Category
Oleaginous vehicle; solvent.
7 Applications in Pharmaceutical Formulation or
Technology
In pharmaceutical preparations, soybean oil emulsions are primar-
ily used as a fat source in total parenteral nutrition (TPN)
regimens.(2) Although other oils, such as peanut oil, have been
used for this purpose, soybean oil is now preferred because it is
associated with fewer adverse reactions. Emulsions containing
soybean oil have also been used as vehicles for the oral and
intravenous administration of drugs;(3,4) drug substances that have
been incorporated into such emulsions include amphotericin,(5–7)
diazepam, retinoids,(8) vitamins,(9) poorly water-soluble ster-
oids,(10,11) fluorocarbons,(12,13) ibuprofen,(14) and insulin.(15) In
addition, soybean oil has been used in the formulation of many drug
delivery systems such as liposomes,(16) microspheres,(17) dry
emulsions,(18) self-emulsifying systems,(19,20) microemulsions,(21,22)