Glycerin

1 Nonproprietary Names Table I: Uses of glycerin.

BP: Glycerol Use Concentration (%)
JP: Concentrated glycerin
PhEur: Glycerolum Antimicrobial preservative <20
USP: Glycerin Emollient 430
Humectant 430
Ophthalmic formulations 0.5–3.0
Plasticizer in tablet film coating Variable
2 Synonyms Solvent for parenteral formulations 450
Sweetening agent in alcoholic elixirs 420
Croderol; E422; glycerine; Glycon G-100; Kemstrene; Optim;
Pricerine; 1,2,3-propanetriol; trihydroxypropane glycerol.

3 Chemical Name and CAS Registry Number
Propane-1,2,3-triol [56-81-5]
8 Description
Glycerin is a clear, colorless, odorless, viscous, hygroscopic
liquid; it has a sweet taste, approximately 0.6 times as sweet as
sucrose.

4 Empirical Formula and Molecular Weight

C3H8O3 92.09 9 Pharmacopeial Specifications
See Table II. See also Section 18.

Table II: Pharmacopeial specifications for glycerin.

5 Structural Formula
Test JP 2001 PhEur 2005 USP 28

Identification þ þ þ
Characters þ þ —
Appearance of solution þ þ þ
Acidity or alkalinity þ þ —
Refractive index 41.470 1.470–1.475 —
6 Functional Category Aldehydes — 410 ppm —
Antimicrobial preservative; emollient; humectant; plasticizer; Related substances — þ —
solvent; sweetening agent; tonicity agent. Halogenated compounds — 435 ppm —
Limit of chlorinated — — þ
compounds
Sugars — þ —
7 Applications in Pharmaceutical Formulation Chloride 40.001% 410 ppm 40.001%
or Technology Heavy metals 45 ppm 45 ppm 45 mg/g
Water — 42.0% 45.0%
Glycerin is used in a wide variety of pharmaceutical formula- Sulfated ash 40.01% 40.01% 40.01%
tions including oral, otic, ophthalmic, topical, and parenteral Specific gravity 51.258 — 51.249
preparations; see Table I. Sulfate 40.002% — 40.002%
In topical pharmaceutical formulations and cosmetics, Esters — þ —
glycerin is used primarily for its humectant and emollient Ammonium þ — —
properties. In parenteral formulations, glycerin is used mainly Calcium þ — —
as a solvent.(1) Arsenic 42 ppm — —
In oral solutions, glycerin is used as a solvent, sweetening Acrolein, glucose or other þ — —
agent, antimicrobial preservative, and viscosity-increasing reducing substances
agent. It is also used as a plasticizer and in film coat- Fatty acids and esters þ þ þ
ings.(2,3) Glycerin is additionally used in topical formulations Organic volatile — — þ
such as creams and emulsions.(4) impurities
Glycerin is used as a plasticizer of gelatin in the production Readily carbonizable þ — —
of soft-gelatin capsules and gelatin suppositories. substances
Glycerin is employed as a therapeutic agent in a variety of Assay 598.0% 98.0–101.0% 99.0–101.0%
clinical applications,(5) and is also used as a food additive.
30 2 Glycerin

10 Typical Properties Table VI: Viscosity (dynamic) of aqueous glycerin solutions.

Boiling point: 2908C (with decomposition) Concentration of aqueous Viscosity at 208C (mPa s)
Density: glycerin solution (% w/w)
1.2656 g/cm3 at 158C;
1.2636 g/cm3 at 208C; 5 1.143
1.2620 g/cm3 at 258C. 10 1.311
Flash point: 1768C (open cup) 25 2.095
Freezing point: see Table III. 50 6.05
Hygroscopicity: hygroscopic. 60 10.96
Melting point: 17.88C 70 22.94
Osmolarity: a 2.6% v/v aqueous solution is isoosmotic with 83 111.0
serum.
Refractive index:
n15
D = 1.4758; 11 Stability and Storage Conditions
n20
D = 1.4746;
n25
D = 1.4730. Glycerin is hygroscopic. Pure glycerin is not prone to oxidation
Solubility: see Table IV. by the atmosphere under ordinary storage conditions but it
Specific gravity: see Table V. decomposes on heating, with the evolution of toxic acrolein.
Surface tension: 63.4 mN/m (63.4 dynes/cm) at 208C. Mixtures of glycerin with water, ethanol (95%), and propylene
Vapor density (relative): 3.17 (air = 1) glycol are chemically stable.
Viscosity (dynamic): see Table VI. Glycerin may crystallize if stored at low temperatures; the
crystals do not melt until warmed to 208C.
Glycerin should be stored in an airtight container, in a cool,
Table III: Freezing points of aqueous glycerin solutions. dry place.
Concentration of aqueous Freezing point (8C)
glycerin solution (% w/w) 12 Incompatibilities

10.0 –1.6 Glycerin may explode if mixed with strong oxidizing agents
20.0 –4.8 such as chromium trioxide, potassium chlorate, or potassium
30.0 –9.5 permanganate. In dilute solution, the reaction proceeds at a
40.0 –15.4 slower rate with several oxidation products being formed.
50.0 –23 Black discoloration of glycerin occurs in the presence of light,
60.0 –34.7 or on contact with zinc oxide or basic bismuth nitrate.
66.7 –46.5 An iron contaminant in glycerin is responsible for the
80.0 –20.3 darkening in color of mixtures containing phenols, salicylates,
90.0 –1.6 and tannin.
Glycerin forms a boric acid complex, glyceroboric acid, that
is a stronger acid than boric acid.

Table IV: Solubility of glycerin.

13 Method of Manufacture
Solvent Solubility at 208C
Glycerin is mainly obtained from oils and fats as a by-product
Acetone Slightly soluble in the manufacture of soaps and fatty acids. It may also be
Benzene Practically insoluble obtained from natural sources by fermentation of, for example,
Chloroform Practically insoluble sugar beet molasses in the presence of large quantities of
Ethanol (95%) Soluble sodium sulfite. Synthetically, glycerin may be prepared by the
Ether 1 in 500 chlorination and saponification of propylene.
Ethyl acetate 1 in 11
Methanol Soluble
14 Safety
Oils Practically insoluble
Water Soluble Glycerin occurs naturally in animal and vegetable fats and oils
that are consumed as part of a normal diet. Glycerin is readily
absorbed from the intestine and is either metabolized to carbon
dioxide and glycogen or used in the synthesis of body fats.
Table V: Specific gravity of glycerin. Glycerin is used in a wide variety of pharmaceutical
formulations including oral, ophthalmic, parenteral, and
Concentration of aqueous Specific gravity at 208C
topical preparations. Adverse effects are mainly due to the
glycerin solution (% w/w)
dehydrating properties of glycerin.(5)
10 1.024 Oral doses are demulcent and mildly laxative in action.
20 1.049 Large doses may produce headache, thirst, nausea, and
30 1.075 hyperglycemia. The therapeutic parenteral administration of
40 1.101 very large glycerin doses, 70–80 g over 30–60 minutes in adults
50 1.128 to reduce cranial pressure, may induce hemolysis, hemoglobi-
60 1.156 nuria, and renal failure.(6) Slower administration has no
deleterious effects.(7)
 Glycerin 3 03

Glycerin may also be used orally in doses of 1.0–1.5 g/kg (C3H8O3). A specification for glycerin is contained in the Food
body-weight to reduce intraocular pressure. Chemicals Codex (FCC).
When used as an excipient or food additive, glycerin is not
usually associated with any adverse effects and is generally
regarded as a nontoxic and nonirritant material. 19 Specific References
(8) 1 Spiegel AJ, Noseworthy MM. Use of nonaqueous solvents in
LD50 (guinea pig, oral): 7.75 g/kg
LD50 (mouse, IP): 8.98 g/kg parenteral products. J Pharm Sci 1963; 52: 917–927.
LD50 (mouse, IV): 4.25 g/kg 2 Kumar V, Kang J, Yang T. Preparation and characterization of
spray-dried oxidized cellulose particles. Pharm Dev Technol 2001;
LD50 (mouse, oral): 4.1 g/kg 6(3): 449–458.
LD50 (mouse, SC): 0.09 g/kg 3 Palviainen P, Heinamaki J, Myllarinen P, et al. Corn starches as
LD50 (rabbit, IV): 0.05 g/kg film formers in aqueous-based film coating. Pharm Dev Technol
LD50 (rat, IP): 4.42 g/kg 2001; 6(3): 353–361.
LD50 (rat, oral): 12.6 g/kg 4 Viegas TX, Van-Winkle LL, Lehman PA, et al. Evaluation of
LD50 (rat, SC): 0.1 g/kg creams and ointments as suitable formulations for peldesine. Int J
Pharm 2001; 219(1–2): 73–80.
5 Sweetman SC, ed. Martindale: The Complete Drug Reference,
15 Handling Precautions 34th edn. London: Pharmaceutical Press, 2005: 1694–1695.
6 Hägnevik K, Gordon E, Lins LE, et al. Glycerol-induced
Observe normal precautions appropriate to the circumstances haemolysis with haemoglobinuria and acute renal failure. Lancet
and quantity of material handled. Eye protection and gloves are 1974; i: 75–77.
recommended. In the UK, the recommended long-term (8-hour 7 Welch KMA, Meyer JS, Okamoto S, et al. Glycerol-induced
TWA) exposure limit for glycerin mist is 10 mg/m3.(9) Glycerin haemolysis. Report of three cases. [letter]. Lancet 1974; i: 416–
is combustible and may react explosively with strong oxidizing 417.
agents; see Section 12. 8 Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials,
11th edn. New York: Wiley, 2004: 1865.
9 Health and Safety Executive. EH40/2002: Occupational Exposure
16 Regulatory Status Limits 2002. Sudbury: Health and Safety Executive, 2002.
GRAS listed. Accepted for use as a food additive in Europe.
Included in the FDA Inactive Ingredients Guide (dental pastes;
buccal preparations; inhalations; injections; nasal and ophthal- 20 General References
mic preparations; oral capsules, solutions, suspensions and Grissom CB, Chagovetz AM, Wang Z. Use of viscosigens to stabilize
tablets; otic, rectal, topical, transdermal, and vaginal prepara- vitamin B12 solutions against photolysis. J Pharm Sci 1993; 82(6):
tions). Included in nonparenteral and parenteral medicines 641–643.
licensed in the UK. Included in the Canadian List of Acceptable Jungermann E, Sonntag NOV, eds. Glycerine: A Key Cosmetic
Non-medicinal Ingredients. Ingredient. New York: Marcel Dekker, 1991.
Smolinske SC. Handbook of Food, Drug, and Cosmetic Excipients.
Boca Raton, FL: CRC Press, 1992: 199–204.
17 Related Substances Staples R, Misher A, Wardell J. Gastrointestinal irritant effect of
glycerin as compared with sorbitol and propylene glycol in rats and
— dogs. J Pharm Sci 1967; 56: 398–400.

18 Comments
21 Authors
The EINECS number for glycerin is 200-289-5.
Some pharmacopeias also contain specifications for diluted JC Price.
glycerin solutions. The JP 2001 contains a monograph for
‘glycerin’ that contains 84–87% of propane-1,2,3-triol
22 Date of Revision
(C3H8O3). The PhEur 2005 contains a monograph for ‘glycerol
85 per cent’ that contains 83.5–88.5% of propane-1,2,3-triol 24 August 2005.
 Glyceryl Behenate

1 Nonproprietary Names Table I: Uses of glyceryl behenate.

BP: Glycerol dibehenate Use Concentration (%)
PhEur: Glyceroli dibehenas
USPNF: Glyceryl behenate Lipophilic matrix or coating for sustained-released >10.0
tablets and capsules
Tablet and capsule lubricant 1.0–3.0
2 Synonyms Viscosity-increasing agent in silicon gels (cosmetics) 1.0–15.0
Viscosity-increasing agent in w/o or o/w emulsions 1.0–5.0
Compritol 888 ATO; 2,3-dihydroxypropyl docosanoate; doc- (cosmetics)
osanoic acid, 2,3-dihydroxypropyl ester; E471; glycerol behe-
nate; glyceryl monobehenate.
Note that tribehenin is used as a synonym for glyceryl
tribehenate.
8 Description
Glyceryl behenate occurs as a fine white powder or hard waxy
3 Chemical Name and CAS Registry Number mass with a faint odor.
Docosanoic acid, monoester with glycerin [30233-64-8]
(glyceryl behenate)
Docosanoic acid, diester with glycerin [94201-62-4] (glyceryl 9 Pharmacopeial Specifications
dibehenate) See Table II.
Docosanoic acid, triester with glycerin [18641-57-1] (glyceryl
tribehenate) Table II: Pharmacopeial specifications for glyceryl behenate.

Test PhEur 2005 USPNF 23

4 Empirical Formula and Molecular Weight (Suppl. 5.1)
The PhEur 2005 (Suppl. 5.1) describes glyceryl dibehenate as a Identification þ þ
mixture of diacylglycerols, mainly dibehenoylglycerol, together Characters þ —
with variable quantities of mono- and triacylglycerols (see Acid value 44.0 44
Section 9). The USPNF 23 describes glyceryl behenate as a Iodine value 43.0 43
mixture of glycerides of fatty acids, mainly behenic acid. It Saponification value 145–165 145–165
specifies that the content of 1-monoglycerides should be Residue on ignition 40.1% 40.1%
12.0–18.0%. Nickel 41 ppm —
Water 41.0% —
Heavy metals — 40.001%
5 Structural Formula Melting point 65–778C —
See Section 4. Content of 1-monoglycerides — 12.0–18.0%
Content of acylglycerols (glycerides) þ —
Monoacylglycerols 15.0–20.0% —
Diacylglycerols 40–60% —
6 Functional Category
Triacylglycerols 21–35% —
Coating agent; tablet binder; tablet and capsule lubricant. Free glycerin 41.0% 41.0%
Organic volatile impurities — þ
Composition of fatty acids þ —
7 Applications in Pharmaceutical Formulation Arachidic acid 410.0% —
or Technology Behenic acid 583.0% —
Erucic acid 43.0% —
Glyceryl behenate is used in cosmetics, foods, and oral
Lignoceric acid 43.0% —
pharmaceutical formulations. In cosmetics, it is mainly used
Palmitic acid 43.0% —
as a viscosity-increasing agent in emulsions; see Table I.
Stearic acid 45.0% —
In pharmaceutical formulations, glyceryl behenate is mainly
used as a tablet and capsule lubricant(1–3) and as a lipidic
coating excipient. It has been investigated for the encapsulation
of various drugs such as retinoids.(4) It has also been
10 Typical Properties
investigated for use in the preparation of sustained release
tablets; (5–10) as a matrix-forming agent for the controlled Melting point: 65–778C
release of water-soluble drugs;(10) and as a lubricant in oral Solubility: soluble, when heated, in chloroform and dichloro-
solid dosage formulations, and it can also be used as a hot-melt methane, practically insoluble in ethanol (95%), hexane,
coating agent sprayed onto a powder.(11) mineral oil, and water.
 Glyceryl Behenate 3 05

11 Stability and Storage Conditions Measurement of physical parameters (compaction, ejection and
residual forces) in the tabletting process and the effect on the
Glyceryl behenate should be stored in a tight container, at a dissolution rate. Drug Dev Ind Pharm 1986; 12: 1329–1346.
temperature less than 358C. 2 Baichwal AR, Augsburger LL. Variations in the friction coefficients
of tablet lubricants and relationship to their physicochemical
properties. J Pharm Pharmacol 1988; 40: 569–571.
12 Incompatibilities 3 Brossard C, Ratsimbazafy V, des Ylouses DL. Modelling of
— theophylline compound release from hard gelatin capsules contain-
ing Gelucire matrix granules. Drug Dev Ind Pharm 1991; 17:
1267–1277.
13 Method of Manufacture 4 Jenning V, Gohla SH. Encapsulation of retinoids in solid lipid
nanoparticles (SLN). J Microencapsul 2001; 18(2): 149–158.
Glyceryl behenate is prepared by the esterification of glycerin 5 El-Sayed GM, El-Said Y, Meshali MM, Schwartz JB. Kinetics of
by behenic acid (C22 fatty acid) without the use of catalysts. In theophylline release from different tablet matrices. STP Pharma Sci
the case of Compritol 888 ATO (Gattefossé), raw materials 1996; 6; 390–397.
used are of vegetable origin, and the esterified material is 6 Prinderre P, Cauture E, Piccerelle P, et al. Evaluation of some
atomized by spray-cooling. protective agents on stability and controlled release of oral
pharmaceutical forms by fluid bed technique. Drug Dev Ind
Pharm 1997; 23: 817–826.
14 Safety 7 Achanta AS, Adusumilli PS, James KW. Thermodynamic analysis
of water interaction with excipient films. Drug Dev Ind Pharm
Glyceryl behenate is used in cosmetics, foods and oral 2001; 27(3): 227–240.
pharmaceutical formulations and is generally regarded as a 8 Achanta AS, Adusumilli PS, James KW, Rhodes CT. Hot-melt
relatively nonirritant and nontoxic material. coating: water sorption behaviour of excipient films. Drug Dev Ind
Pharm 2001; 27(3): 241–250.
LD50 (mouse, oral): 5 g/kg(12) 9 Hariharan M, Wowchuk C, Nkansah P, Gupta VK. Effect of
formulation composition on the properties of controlled release
15 Handling Precautions tablets prepared by roller compression. Drug Dev Ind Pharm
2004; 30(6): 565–572.
Observe normal precautions appropriate to the circumstances 10 Obaidat AA, Obaidat RM. Controlled release of tramadol
and quantities of material handled. Glyceryl behenate emits hydrochloride from matrices prepared using glyceryl behenate.
acrid smoke and irritating fumes when heated to decomposi- Eur J Pharm Biopharm 2001; 52(2): 231–235.
tion. 11 Jannin V, Berard V, N’Diaye A, et al. Comparative study of the
lubricant performance of Compritol (R) 888 ATD either used by
blending or by hot melt coating. Int J Pharm 2003; 262(1–2): 39–
16 Regulatory Status 45.
12 Sweet DV, ed. Registry of Toxic Effects of Chemical Substances.
GRAS listed. Accepted for use as a food additive in Europe. Cincinatti: US Department of Health, 1987.
Included in the FDA Inactive Ingredients Guide (capsules and
tablets). Included in the Canadian List of Acceptable Non-
medicinal Ingredients. 20 General References
Gattefossé. Technical literature: Compritol 888 ATO, 2000.
17 Related Substances Hamdani J, Moes AJ, Anighi K. Physical and thermal characterization
Glyceryl palmitostearate. of Precirol and Compritol as lipophilic glycerides used for the
preparation of controlled-release matrix pellets. Int J Pharm 2003;
260(1): 47–57.
18 Comments
The EINECS numbers are: 250-097-0 for glyceryl behenate;
303-650-6 for glyceryl dibehenate; 242-471-7 for glyceryl 21 Authors
tribehenate. LME McIndoe.

19 Specific References
22 Date of Revision
1 Shah NH, Stiel D, Weiss M, et al. Evaluation of two new tablet
lubricants – sodium stearyl fumarate and glyceryl behenate. 12 August 2005.
 Glyceryl Monooleate

1 Nonproprietary Names Glyceryl monooleate gels in excess water, forming a highly

BP: Glycerol mono-oleates
PhEur: Glyceroli mono-oleates
USPNF: Glyceryl monooleate
2 Synonyms
Aldo MO; Atlas G-695; Capmul GMO; glycerol-1-oleate;
glyceryl mono-oleate; Kessco GMO; Ligalub; monolein;
Monomuls 90-O18; mono-olein; a-mono-olein glycerol;
Peceol; Priolube 1408; Stepan GMO; Tegin.
3 Chemical Name and CAS Registry Number
9-Octadecenoic acid (Z), monoester with 1,2,3-propanetriol
[25496-72-4]
4 Empirical Formula and Molecular Weight
C21H40O4 356.55 (for pure material)
Glyceryl monooleate is a mixture of the glycerides of oleic
acid and other fatty acids, consisting mainly of the monooleate;
see Section 8.
ordered cubic phase that can be used to sustain the release of
various water-soluble drugs.(3–6) It is also the basis of
mucoadhesive drug delivery systems.(7,8)
Glyceryl monooleate is reported to enhance transdermal(9)
and buccal penetration.(10)
8 Description
The PhEur 2005 (Suppl. 5.1) describes glyceryl monooleate as
being a mixture of monoacylglycerols, mainly mono-oleoylgly-
cerol, together with variable quantities of di- and triacylglycer-
ols. They are defined by the nominal content of
monoacylglycerols (see Table I) and obtained by partial
glycerolysis of vegetable oils mainly containing triacylglycerols
of oleic acid or by esterification of glycerol by oleic acid, this
fatty acid being of vegetable or animal origin. A suitable
antioxidant may be added.
Glyceryl monooleates occur as amber oily liquids, which
may be partially solidified at room temperature and have a
characteristic odor.
Table I: Nominal content of acylglycerols in glycerol monooleate
defined in the PhEur 2005 (Suppl. 5.1).

Nominal content of acylglycerol (%)

5 Structural Formula
40 60 90

Monoacylglycerols 32.0–52.0 55.0–65.0 90.0–101.0

Diacylglycerols 30.0–50.0 15.0–35.0 <10.0
Triacylglycerols 5.0–20.0 2.0–10.0 <2.0

9 Pharmacopeial Specifications
See Table II.

6 Functional Category
Bioadhesive; emollient; emulsifying agent; emulsion stabilizer; 10 Typical Properties
gelling agent; mucoadhesive; nonionic surfactant; sustained- Boiling point: 238–2408C
release agent. Density: 0.942 g/cm3
Flash point: 2168C
HLB value: 3.3 (n/e); 4.1 (s/e).
7 Applications in Pharmaceutical Formulation Melting point: 358C (see also Section 13)
or Technology Refractive index: 1.4626
Glyceryl monooleate is a polar lipid that swells in water to give Solubility: soluble in chloroform, ethanol (95%), ether, mineral
several phases with different rheological properties.(1) It is oil, and vegetable oils; practically insoluble in water. The
available in both nonemulsifying (n/e) and self-emulsifying (s/e) self-emulsifying grade is dispersible in water.
grades, the self-emulsifying grade containing about 5% of an Viscosity (kinematic): 100 m2/s (100 cSt) at 408C
anionic surfactant.
The nonemulsifying grade is used in topical formulations as
an emollient and as an emulsifying agent for water-in-oil
11 Stability and Storage Conditions
emulsions. It is also a stabilizer for oil-in-water emulsions. The
self-emulsifying grade is used as a primary emulsifier for oil-in- Glyceryl monooleate should be stored in an airtight container,
water systems.(2) protected from light in a cool, dry place.
 Glyceryl Monooleate 3 07

Table II: Pharmacopeial specifications for glyceryl monooleate. 17 Related Substances

Test PhEur 2005 USPNF 23 Glyceryl monostearate.
(Suppl. 5.1)

Identification þ þ 18 Comments
Characters þ þ
A specification for glyceryl monooleate is included in the Food
Acid value 46.0% 46.0%
Chemicals Codex (FCC).
Iodine value 65.0–95.0 65.0–95.0
The EINECS number for glyceryl monooleate is 247-038-6.
Peroxide value 412.0% 412.0%
Saponification value 150–170 150–170
Free glycerol 46.0% 46.0%
19 Specific References
Composition of fatty acids
Palmitic acid 412.0% 412.0% 1 Engstrom S, Lindahl L, Wallin R, Engblom J. A study of polar lipid
Stearic acid 46.0% 46.0% drug carrier systems undergoing a thermoreversible lamellar-to-
Oleic acid 560.0% 560.0% cubic phase transition. Int J Pharm 1992; 86: 137–145.
Linoleic acid 435.0% 435.0% 2 Ganem-Quintanar A, Quintanar-Guerro D, Burri P. Mono-olein: a
review of the pharmaceutical applications. Drug Dev Ind Pharm
Linolenic acid 42.0% 42.0%
2000; 26(8): 809–820.
Arachidic acid 42.0% 42.0% 3 Wyatt DM, Dorschel D. Cubic-phase delivery system composed of
Eicosenoic acid 42.0% 42.0% glyceryl monooleate and water for sustained release of water-
Content of acylglycerol see Table I — soluble drugs. Pharm Technol 1992; 16: 116–130.
Water 41.0% 41.0% 4 Burrows R, Collett JH, Attwood D. The release of drugs from
Total ash 40.1% 40.1% monoglyceride-water liquid crystalline phases. Int J Pharm 1994;
111: 283–293.
5 Longer M, Tyle P, Mauger JW. A cubic-phase oral drug delivery for
controlled release of AG 337. Drug Dev Ind Pharm 1996; 22: 603–
12 Incompatibilities 608.
Glyceryl monooleate is incompatible with strong oxidizing 6 Chang CM, Bodmeier R. Low viscosity monoglyceride based drug
agents. The self-emulsifying grade is incompatible with cationic delivery systems transforming into a highly viscous cubic phase.
Int J Pharm 1998; 173: 51–60.
surfactants.
7 Neilson LS, Schubert L, Hansen J. Bioadhesive drug delivery
systems. 1. Characterization of mucoadhesive properties of
13 Method of Manufacture systems based on glyceryl monooleate and glycerol monolinoleate.
Eur J Pharm Sci 1998; 6(9): 231–239.
Glyceryl monooleate is prepared by the esterification of 8 Lee J, Young SA, Kellaway IW. Water quantitatively induces the
glycerol with fatty acids, chiefly oleic acid. As the fatty acids mucoadhesion of liquid crystalline phases of glyceryl monooleate.
are not pure substances, but rather a mixture of fatty acids, the J Pharm Pharmacol 2001; 53(5):629–636.
product obtained from the esterification will contain a mixture 9 Ogiso T, Iwaki M, Paku T. Effect of various enhancers on
of esters, including stearic and palmitic. Di- and tri-esters may transdermal penetration of indomethacin and urea, and relation-
ship between penetration parameters and enhancement factors. J
also be present. The composition and, therefore, the physical
Pharm Sci 1995; 84: 482–488.
properties of glyceryl monooleate may thus vary considerably 10 Lee J, Kellaway IW. Buccal permeation of (D-Ala(2), D-leu(5))en-
from manufacturer to manufacturer; e.g., the melting point kephalin from liquid crystalline phases of glyceryl monooleate. Int
may vary from 10–358C. J Pharm 2000; 195(1–2): 29–33.

14 Safety
20 General References
Glyceryl monooleate is used in oral and topical pharmaceutical
Eccleston GM. Emulsions and Microemulsions. In: Swarbrick J, Boylan
formulations and is generally regarded as a relatively non-
JC, eds. Encyclopaedia of Pharmaceutical Technology, 2nd edn, vol.
irritant and nontoxic excipient. 2. New York: Marcel Dekker, 2002: 1066–1085.
Weiner AL. Lipid excipients in pharmaceutical dosage forms. In:
15 Handling Precautions Swarbrick J, Boylan JC, eds. Encyclopaedia of Pharmaceutical
Technology, 2nd edn, vol. 2. New York: Marcel Dekker, 2002:
Observe normal precautions appropriate to the circumstances 1659–1673.
and quantity of material handled.

21 Authors
16 Regulatory Status
NA Armstrong.
GRAS listed. Included in the FDA Inactive Ingredients Guide
(oral capsules, oral powder, oral tablets; creams, controlled-
release transdermal films). Included in nonparenteral medicines
22 Date of Revision
licensed in the UK. Included in the Canadian List of Acceptable
Non-medicinal Ingredients. 15 August 2005.
 Glyceryl Monostearate

1 Nonproprietary Names
BP: Glyceryl monostearate 40–55
JP: Glyceryl monostearate
PhEur: Glyceroli monostearas 40–55
USPNF: Glyceryl monostearate
Note that the USPNF 23 also includes a specification for mono-
and di-glycerides that corresponds to glyceryl monostearate
40–55 in the PhEur 2005.
2 Synonyms
Capmul GMS-50; Cutina GMS; 2,3-dihydroxypropyl octa-
decanoate; glycerine monostearate; glycerin monostearate;
glycerol monostearate; glycerol stearate; glyceryl stearate;
GMS; Imwitor 191; Imwitor 900; Kessco GMS; Lipo GMS
410; Lipo GMS 450; Lipo GMS 600; monoester with 1,2,3-
propanetriol; monostearin; Myvaplex 600P; Myvatex; 1,2,3-
propanetriol octadecanoate; Protachem GMS-450; Rita GMS;
stearic acid, monoester with glycerol; stearic monoglyceride;
Stepan GMS; Tegin; Tegin 503; Tegin 515; Tegin 4100; Tegin
M; Unimate GMS.
polar and nonpolar compounds that may form water-in-oil or
oil-in-water emulsions.(1,2) These properties also make it useful
as a dispersing agent for pigments in oils or solids in fats, or as a
solvent for phospholipids, such as lecithin.
Glyceryl monostearate has also been used in a novel
fluidized hot-melt granulation technique for the production of
granules and tablets.(3)
Glyceryl monostearate is a lubricant for tablet manufactur-
ing and may be used to form sustained-release matrices for solid
dosage forms.(4–6) Sustained-release applications include the
formulation of pellets for tablets(7) or suppositories(8) and the
preparation of a veterinary bolus.(9) Glyceryl monostearate has
also been used as a matrix ingredient for a biodegradable,
implantable, controlled-release dosage form.(10)
When using glyceryl monostearate in a formulation, the
possibility of polymorph formation should be considered. The
a-form is dispersible and foamy, useful as an emulsifying agent
or preservative. The denser, more stable, b-form is suitable for
wax matrices. This application has been used to mask the flavor
of clarithromycin in a pediatric formulation.(11)

3 Chemical Name and CAS Registry Number 8 Description

Octadecanoic acid, monoester with 1,2,3-propanetriol While the names glyceryl monostearate and mono- and di-
[31566-31-1] glycerides are used for a variety of esters of long-chain fatty
acids, the esters fall into two distinct grades:
40–55 percent monoglycerides: the PhEur 2005 describes
4 Empirical Formula and Molecular Weight glyceryl monostearate 40–55 as a mixture of monoacylgly-
C21H42O4 358.6 cerols, mostly monostearoylglycerol, together with quanti-
ties of di- and triacylglycerols. It contains 40–55% of
monoacylglycerols, 30–45% of diacylglycerols, and 5–15%
5 Structural Formula of triacylglycerols. This PhEur grade corresponds to mono-
and di-glycerides USPNF, which has similar specifications
(not less than 40% monoglycerides).
90 percent monoglycerides: the USPNF 23 (Suppl. 1) describes
glyceryl monostearate as consisting of not less than 90% of
monoglycerides, chiefly glyceryl monostearate (C21H42O4)
and glyceryl monopalmitate (C19H38O4).
The commercial products are mixtures of variable
proportions of glyceryl monostearate and glyceryl mono-
palmitate.
Glyceryl monostearate is a white to cream-colored,
waxlike solid in the form of beads, flakes, or powder. It is
waxy to the touch and has a slight fatty odor and taste.

6 Functional Category
Emollient; emulsifying agent; solubilizing agent; stabilizing
agent; sustained-release ingredient; tablet and capsule lubri-
cant.
7 Applications in Pharmaceutical Formulation
or Technology
The many varieties of glyceryl monostearate are used as
nonionic emulsifiers, stabilizers, emollients, and plasticizers in a
variety of food, pharmaceutical, and cosmetic applications. It
acts as an effective stabilizer, that is, as a mutual solvent for
9 Pharmacopeial Specifications
Table I compares the specifications for the 40–55% grades.
Glyceryl monostearate PhEur and mono- and di-glycerides
USPNF. PhEur divides glyceryl monostearate 40–55 into three
types according to the proportion of stearic acid ester in the
mixture, and those specifications are presented in Table II.
Table III presents the specifications for glyceryl monostearate
USPNF (90% monoglycerides). Since the JP specifications are
broad enough to encompass both grades, JP is included in both
Table I and Table III.
 Glyceryl Monostearate 3 09

Table I: Pharmacopeial specifications for glyceryl monostearate HLB value: 3.8

(40–55%). Flash point: 2408C
Melting point: 55–608C
Test JP 2001 PhEur 2005 USPNF 23(a) Polymorphs: The a-form is converted to the b-form when
heated at 508C.(12)
Identification þ þ —
Solubility: soluble in hot ethanol, ether, chloroform, hot
Acid value 415.0 43.0 44.0
acetone, mineral oil, and fixed oils. Practically insoluble in
Iodine value 43.0 43.0 43.0
water, but may be dispersed in water with the aid of a small
Hydroxyl value — — 300–330
amount of soap or other surfactant.
Saponification value 157–170 158–177 155–165
Specific gravity: 0.92
Melting point 5558C — —
Residue on ignition 40.10% 40.10% 40.1%
Acidity or alkalinity þ — — 11 Stability and Storage Conditions
Free glycerin — 46.0% 47.0%
Composition of fatty — see Table II — If stored at warm temperatures, glyceryl monostearate increases
acids in acid value upon aging owing to the saponification of the ester
Heavy metals — — 40.001% with trace amounts of water. Effective antioxidants may be
Nickel — 41 ppm — added, such as butylated hydroxytoluene and propyl gallate.
Water — 41.0% — Glyceryl monostearate should be stored in a tightly closed
Organic volatile — — þ container in a cool, dry place, and protected from light.
impurities
Assay (monoglycerides) — 40.0–55.0% 440.0%(b)
12 Incompatibilities
(a)
mono- and di-glycerides
(b)
90.0–110.0% of labeled amount
The self-emulsifying grades of glyceryl monostearate are
incompatible with acidic substances.
Table II: Specifications for the composition of fatty acids in glyceryl
monostearate 40–55.
13 Method of Manufacture
Glyceryl Fatty acid used in Composition of fatty acids Glyceryl monostearate is prepared by the reaction of glycerin
monostearate manufacturing with triglycerides from animal or vegetable sources, producing
Stearic acid Sum of palmitic a mixture of monoglycerides and diglycerides. The diglycerides
and stearic may be further reacted to produce the 90% monoglyceride
acids grade. Another process involves reaction of glycerol with
stearoyl chloride.
Type I Stearic acid 50 40.0–60.0% 490.0%
The starting materials are not pure substances and therefore
Type II Stearic acid 70 60.0–80.0% 490.0%
the products obtained from the processes contain a mixture of
Type III Stearic acid 95 90.0–99.0% 496.0%
esters, including palmitate and oleate. Consequently, the
composition, and therefore the physical properties, of glyceryl
monostearate may vary considerably depending on the
Table III: Pharmacopeial specifications for glyceryl monostearate manufacturer.
(90%).

Test JP 2001 USPNF 23 14 Safety

Identification þ — Glyceryl monostearate is widely used in cosmetics, foods, and
Acid value 415.0 46.0 oral and topical pharmaceutical formulations and is generally
Iodine value 43.0 43.0 regarded as a nontoxic and nonirritant material.
Hydroxyl value — 300–330 LD50 (mouse, IP): 0.2 g/kg(13)
Saponification value 157–170 155–165
Melting point 5558C 5558C
Residue on ignition 40.10% 40.5% 15 Handling Precautions
Acidity or alkalinity þ —
Limit of free glycerin — 41.2% Observe normal precautions appropriate to the circumstances
Composition of fatty acids — — and quantity of material handled.
Heavy metals — 40.001%
Organic volatile impurities — þ
Assay (monoglycerides) — 490.0% 16 Regulatory Status
GRAS listed. Included in the FDA Inactive Ingredients Guide
(oral capsules and tablets; ophthalmic, otic, rectal, topical,
transdermal, and vaginal preparations). Included in nonpar-
10 Typical Properties
enteral medicines licensed in the UK. Included in the Canadian
A wide variety of glyceryl monostearate grades are commer- List of Acceptable Non-medicinal Ingredients.
cially available, including self-emulsifying grades that contain If glyceryl monostearate is produced from animal fats
small amounts of soap or other surfactants. Most grades are (tallow), there may be additional regulatory requirements that
tailored for specific applications or made to user specifications the source be free of contamination from bovine spongiform
and therefore have varied physical properties. encephalopathy.
31 0 Glyceryl Monostearate
17 Related Substances
Glyceryl monooleate; glyceryl palmitostearate; self-emulsifying
glyceryl monostearate.
Self-emulsifying glyceryl monostearate
Comments: a specification for self-emulsifying glyceryl mono-
stearate was previously included in the PhEur. Self-
emulsifying glyceryl monostearate is a grade of glyceryl
monostearate to which an emusifying agent has been added.
The emulsifier may be a soluble soap, a salt of a sulfated
alcohol, a nonionic surfactant, or a quaternary compound.
It is used primarily as an emulsifying agent for oils, fats,
solvents, and waxes. Aqueous preparations should contain
an antimicrobial preservative.
18 Comments
Glyceryl monostearate and other fatty acid monoesters are not
efficient emulsifiers. However, they are useful emollients that
are readily emulsified by common emulsifying agents and by
incorporation of other fatty materials into the formulation.
Addition of the monoester materials provides the creams with
smoothness, fine texture, and improved stability.
In topical applications, glyceryl monostearate is less drying
than straight stearate creams, and is not drying when used in
protective applications. A specification for glyceryl monostea-
rate is contained in the Food Chemicals Codex (FCC).
19 Specific References
1 O’Laughlin R, Sachs C, Brittain H, et al. Effects of variations in
physicochemical properties of glyceryl monostearate on the
stability of an oil-in-water cream. J Soc Cosmet Chem 1989; 40:
215–229.
2 Rafiee-Tehrani M, Mehramizi A. In vitro release studies of
piroxicam from oil-in-water creams and hydroalcoholic gel topical
formulations. Drug Dev Ind Pharm 2000; 26(4): 409–414.
3 Kidokoro M, Haramiishi Y, Sagasaki S, et al. Application of
fluidized hot-melt granulation (FHMG) for the preparation of
granules for tableting; properies of granules and tablets prepared
by FHMG. Drug Dev Ind Pharm 2002; 28(1): 67–76.
4 Peh KK, Yuen KH. Development and in vitro evaluation of a novel
multiparticulate matrix controlled release formulation of theophyl-
line. Drug Dev Ind Pharm 1995; 21: 1545–1555.
5 Peh KK, Yuen KH. In vivo perfomance of a multiparticulate
matrix, controlled release theophylline preparation. Drug Dev Ind
Pharm 1995; 22: 349–355.
6 Peh KK, Wong CF, Yuen KH. Possible mechanism for drug
retardation from glyceryl monostearate matrix system. Drug Dev
Ind Pharm 2000; 26: 447–450.
7 Thomsen LJ, Schaefer T, Sonnergaard JM, Kristensen HG.
Prolonged release matrix pellets prepared by melt pelletization. I.
Process variables. Drug Dev Ind Pharm 1993; 19: 1867–1887.
8 Adeyeye CM, Price J. Development and evaluation of sustained-
release ibuprofen-wax microspheres. II. In vitro dissolution
studies. Pharm Res 1994; 11: 575–579.
9 Evrard B, Delattre L. In vitro evaluation of lipid matrices for the
development of a sustained-release sulfamethazine bolus for
lambs. Drug Dev Ind Pharm 1996; 22: 111–118.
10 Peri D, Bogdansky S, Allababidi S, Shah JC. Development of an
implantable, biodegradable, controlled drug delivery system for
local antibiotic therapy. Drug Dev Ind Pharm 1994; 20: 1341–
1352.
11 Yajima T, Itai S, Takeuchi H, Kawashima Y. Optimum heat
treatment conditions for masking the bitterness of clarithromycin
wax matrix. Chem Pharm Bull 2003; 51(11): 1223–1226.
12 Yajima T, Itai S, Takeuchi H, Kawashima Y. Determination of
optimum processing temperature for transformation of glyceryl
monostearate. Chem Pharm Bull 2002; 50(11): 1430–1433.
13 Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials,
11th edn. New York: Wiley, 2004: 2757–2758.
20 General References
Eccleston GM. Emulsions. In: Swarbrick J, Boylan JC, eds. Encyclo-
pedia of Pharmaceutical Technology, vol. 5. New York: Marcel
Dekker, 1992: 137–188.
Rieger MM. Glyceryl stearate: chemistry and use. Cosmet Toilet 1990;
105(Nov): 51–54, 56–57.
Schumacher GE. Glyceryl monostearate in some pharmaceuticals. Am J
Hosp Pharm 1967; 24: 290–291.
Wisniewski W, Golucki Z. Stability of glycerylmonostearate. Acta Pol
Pharm 1965; 22: 296–298.
21 Authors
AK Taylor.
22 Date of Revision
20 May 2005.
 Glyceryl Palmitostearate

1 Nonproprietary Names 8 Description

None adopted. Glyceryl palmitostearate occurs as a fine white powder with a
faint odor.

2 Synonyms
9 Pharmacopeial Specifications
Glycerin palmitostearate; glycerol palmitostearate; 2-[(1-oxo-
hexadecyl)-oxy]-1,3-propanediyl dioctadecanoate and 1,2,3- —
propane triol; Precirol ATO 5.
10 Typical Properties

3 Chemical Name and CAS Registry Number Acid value: <6.0

Boiling point: 2008C
Octadecanoic acid, 2,3-dihydroxypropyl ester mixed with Color: <3 (Gardner scale)
3-hydroxy-2-[(1-oxohexadecyl)-oxy] propyl octadecanoate Free glycerin content: <1.0%
[8067-32-1] Heavy metals: <10 ppm
Hydroxyl value: 60–115
Iodine value: <3
4 Empirical Formula and Molecular Weight Melting point: 52–558C
Glyceryl palmitostearate is a mixture of mono-, di-, and 1-Monoglycerides content: 8.0–17.0%
triglycerides of C16 and C18 fatty acids. Peroxide value: <3.0
Saponification value: 175–195
Solubility: freely soluble in chloroform and dichloromethane;
5 Structural Formula practically insoluble in ethanol (95%), mineral oil, and
water.
See Sections 3 and 4. Sulfated ash: <0.1%
Unsaponifiable matter: <1.0%
Water content: <1.0%
6 Functional Category
Biodegradable material; coating agent; gelling agent; release 11 Stability and Storage Conditions
modifying agent; sustained-release agent; tablet and capsule
diluent; tablet and capsule lubricant; taste-masking agent. Glyceryl palmitostearate should not be stored at temperatures
above 358C. For storage for periods over 1 month, glyceryl
palmitostearate should be stored at a temperature of 5–158C in
7 Applications in Pharmaceutical Formulation an airtight container, protected from light and moisture.
or Technology
Glyceryl palmitostearate is used in oral solid-dosage pharma- 12 Incompatibilities
ceutical formulations as a lubricant.(1,2) Disintegration times Glyceryl palmitostearate is incompatible with ketoprofen(15)
increase(3) and tablet strength decreases(4) with increase in and naproxen.(16)
mixing time.
It is used as a lipophilic matrix for sustained-release tablet
and capsule formulations.(5,6) Tablet formulations may be 13 Method of Manufacture
prepared by either granulation or a hot-melt technique,(7,8) the Glyceryl palmitostearate is manufactured, without a catalyst,
former producing tablets that have the faster release profile. by the direct esterification of palmitic and stearic acids with
Release rate decreases with increased glyceryl palmitostearate glycerol.
content.(5)
Glyceryl palmitostearate is used to form microspheres,
which may be used in capsules or compressed to form 14 Safety
tablets,(9,10) pellets,(11) coated beads,(12) and biodegradable
Glyceryl palmitostearate is used in oral pharmaceutical
gels.(13) It is also used for taste-masking.(14) See Table I.
formulations and is generally regarded as an essentially
nontoxic and nonirritant material.
Table I: Uses of glyceryl palmitostearate.(14)
LD50 (rat, oral): >6 g/kg(14)
Use Concentration (%)

Matrix for sustained release 10.0–25.0 15 Handling Precautions

Tablet masking 2.0–6.0
Tablet lubricant 1.0–3.0 Observe normal handling precautions appropriate to the
circumstances and quantity of material handled.
31 2 Glyceryl Palmitostearate
16 Regulatory Status
GRAS listed. Included in the FDA Inactive Ingredients Guide
(oral suspension, oral tablet). Included in nonparenteral
preparations licensed in Europe. Included in the Canadian
List of Acceptable Non-medicinal Ingredients.
17 Related Substances
Glyceryl behenate; glyceryl monostearate.
18 Comments
— vivo evaluation. Pharm Res 1995; 12: 864–868.
19 Specific References
1 Holzer AW, Sjogren J. Evaluation of some lubricants by the
comparison of friction coefficients and tablet properties. Acta
Pharm Suec 1981; 18: 139–148.
2 Allen LV. Featured excipient: capsule and tablet lubricants. Int J
Pharm Compound 2000; 4(5): 390–392.
3 Sekulovic D. Effect of Precirol ATO 5 on the properties of tablets.
Pharmazie 1987; 42(1): 61–62.
4 Velasco V, Munoz-Ruiz A, Mondero C, Jimenez-Castellanos R.
Force–displacement parameters of maltodextrins after the addition
of lubricants. Int J Pharm 1997; 152: 111–120.
5 Saraiya K, Bolton S. Use of Precirol to prepare sustained release
tablets of theophylline and quinidine gluconate. Drug Dev Ind
Pharm 1990; 16(13): 1963–1969.
6 Bodmeier R, Paeratakul O, Chen H, Zhang W. Formation of
sustained release wax matrices within hard gelatin capsules in a
fluidised bed. Drug Dev Ind Pharm 1990; 16: 1505–1519.
7 Malamataris S, Panagopoulou A, Hatzipantou P. Controlled
release from glycerol palmito-stearate matrices prepared by dry-
heat granulation and compression at elevated temperature. Drug
Dev Ind Pharm 1991; 17(13): 1765–1777.
8 Evrard B, Arnighi K, Beten D, et al. Influence of melting and
rheological properties of fatty binders in the melt granulation
process in a high sheer mixer. Drug Dev Ind Pharm 1999; 25(11):
1177–1184.
9 Shaikh NH, De Yanes SE, Shukla AJ, et al. Effect of different
binders on release characteristics of theophylline from compressed
microspheres. Drug Dev Ind Pharm 1991; 17: 793–804.
10 Edimo A, Leterme P, Denis J, et al. Capacity of lipophilic auxiliary
substances to give spheres by extrusion-spheronisation. Drug Dev
Ind Pharm 1993; 19: 827–842.
11 Pongjanyakul T, Medlicott NJ, Tucker IG. Melted glyceryl
palmitostearate (GPS) pellets for protein delivery. Int J Pharm
2004; 271(1–2): 53–62
12 Mount DL, Schwortz JB. Formulation and compaction of non-
fracturing deformable coated beads. Drug Dev Ind Pharm 1996;
22(7): 609–621.
13 Gao ZH, Shukla AJ, Johnson JR, Crowley WR. Controlled release
of contraceptive steroids from biodegradable and injectable gel: in
14 Gattefossé. Technical literature: Precirol ATO 5, 2004.
15 Botha SA, Lotter AP. Compatibility study between ketoprofen and
tablet excipients using differential scanning calorimetry. Drug Dev
Ind Pharm 1989; 15: 415–426.
16 Botha SA, Lotter AP. Compatibility study between naproxen and
tablet excipients using differential scanning calorimetry. Drug Dev
Ind Pharm 1990; 16: 673–683.
20 General References
Chan HK, Chew NYK. Excipients-powder and solid dosage forms. In:
Swarbrick J, Boylan JC, eds. Encyclopedia of Pharmaceutical
Technology, 2nd edn, vol. 2. New York: Marcel Dekker, 2002:
1132–1142.
Armstrong NA. Tablet manufacture. In: Swarbrick J, Boylan JC, eds.
Encyclopedia of Pharmaceutical Technology, 2nd edn, vol. 3. New
York: Marcel Dekker, 2002: 2713–2732.
21 Authors
NA Armstrong.
22 Date of Revision
16 August 2005.
 Glycofurol

1 Nonproprietary Names Moisture content: 0.2–5% at ambient temperature and 30%

relative humidity.
None adopted.
Refractive index: n40
D = 1.4545
Solubility: see Table I.
2 Synonyms
Table I: Solubility of glycofurol.
Glycofurol 75; tetraglycol; a-(tetrahydrofuranyl)-o-hydroxy-
poly(oxyethylene); tetrahydrofurfuryl alcohol polyethylene Solvent Solubility at 208C
glycol ether.
Note: tetraglycol is also used as a synonym for tetra- Arachis oil Immiscible
hydrofurfuryl alcohol. Castor oil Miscible(a)
Ethanol (95%) Miscible in all proportions
Glycerin Miscible in all proportions
3 Chemical Name and CAS Registry Number Isopropyl ether Immiscible
a-[(Tetrahydro-2-furanyl)methyl]-o-hydroxy-poly(oxy-1,2- Petroleum ether Immiscible
ethanediyl) [31692-85-0] Polyethylene glycol 400 Miscible in all proportions
Propan-2-ol Miscible in all proportions
Propylene glycol Miscible in all proportions
4 Empirical Formula and Molecular Weight Water Miscible in all proportions(a)
C9H18O4 (average) 190.24 (average) (a)
Cloudiness may occur.

5 Structural Formula Viscosity (dynamic): 8–18 mPa s (8–18 cP) at 208C for Glyco-
furol 75.

11 Stability and Storage Conditions

Stable if stored under nitrogen in a well-closed container
protected from light, in a cool, dry place.
Glycofurol 75: n = 1–2
12 Incompatibilities
6 Functional Category
Incompatible with oxidizing agents.
Penetration enhancer; solvent.

7 Applications in Pharmaceutical Formulation 13 Method of Manufacture

or Technology
Glycofurol is used as a solvent in parenteral products for
intravenous or intramuscular injection in concentrations up to
50% v/v.(1–5) It has also been investigated, mainly in animal
studies, for use as a penetration enhancer and solvent in
topical(6) and intranasal formulations.(7–10) Glycofurol has also
been used at 20% v/v concentration in a rectal formulation.(11)
8 Description
Glycofurol is a clear, colorless, almost odorless liquid, with a
bitter taste; it produces a warm sensation on the tongue.
9 Pharmacopeial Specifications
—
Glycofurol is prepared by the reaction of tetrahydrofurfuryl
alcohol with ethylene oxide (followed by a special purification
process in the case of Glycofurol 75).
14 Safety
Glycofurol is mainly used as a solvent in parenteral pharma-
ceutical formulations and is generally regarded as a relatively
nontoxic and nonirritant material at the levels used as a
pharmaceutical excipient. Glycofurol can be irritant when used
undiluted; its tolerability is approximately the same as
propylene glycol.(1,2)
Glycofurol may have an effect on liver function and may
have a low potential for interaction with hepatoxins or those
materials undergong extensive hepatic metabolism.(4)
LD50 (mouse, IV): 3.5 mL/kg(2)

10 Typical Properties
15 Handling Precautions
Boiling point: 80–1008C for Glycofurol 75
Density: 1.070–1.090 g/cm3 at 208C Observe normal precautions appropriate to the circumstances
Hydroxyl value: 300–400 and quantity of material handled.
31 4 Glycofurol
16 Regulatory Status
Included in parenteral medicines licensed in Europe.
17 Related Substances
— 8 Bechgaard E, Gizurarson S, Hjortkjaer RK. Pharmacokinetic and
18 Comments
Grades other than Glycofurol 75 may contain significant
amounts of tetrahydrofurfuryl alcohol and other impurities.
Glycofurol 75 meets an analytical specification which includes
a requirement that the fraction in which n = 1 or 2 amounts to a
minimum of 95%; see Section 5.
19 Specific References
1 Spiegelberg H, Schläpfer R, Zbinden G, Studer A. A new injectable
solvent (glycofurol) [in German]. Arzneimittelforschung 1956; 6:
75–77.
2 Spiegel AJ, Noseworthy MM. Use of non-aqueous solvents in
parenteral products. J Pharm Sci 1963; 52: 917–927.
3 Anschel J. Solvents and solubilisers in injections. Pharm Ind 1965;
27: 781–787.
4 Bury RW, Breen KJ, Desmond PV, et al. Disposition of intravenous
glycofurol: effect of hepatic cirrhosis. Clin Pharmacol Ther 1984;
36(1): 82–84.
5 Taubøll E, Lindström S, Klem W, Gjerstad L. A new injectable
carbamazepine solution: antiepileptic effects and pharmaceutical
properties. Epilepsy Res 1990; 7(1): 59–64.
6 Lashmar UT, Hadgraft J, Thomas N. Topical application of
penetration enhancers to the skin of nude mice: a histopathological
study. J Pharm Pharmacol 1989; 41(2): 118–122.
7 Bindseil E, Bechgaard E, Jørgensen L, Larsen R. Morphological
examination of rabbit nasal mucosa after exposure to acetyl-
salicylic acid, glycofurol 75 and ephedrine. Int J Pharm 1995;
119(1): 37–46.
pharmacodynamic response after intranasal administration of
diazepam to rabbits. J Pharm Pharmacol 1997; 49(8): 747–750.
9 Nielson HW, Bechgaard E, Twile B, et al. Intranasal administration
of different liquid formulations of bumetanide to rabbits. Int J
Pharm 2000; 204: 35–41.
10 Bagger MA, Nielsen HW, Bechgaard E. Nasal bioavailability of
peptide T in rabbits: absorption enhancement by sodium
glycocholate and glycofurol. Eur J Pharm Sci 2001; 14(1): 69–74.
11 Dale O, Sheffels P, Khorasch ED. Bioavailabilities of rectal and oral
methadone in healthy subjects. Br J Clin Pharmacol 2004; 58(2):
156–162.
20 General References
Mottu F, Laurent A, Rufenacht DA, Doelker E. Organic solvents for
pharmaceutical parenterals and embolic liquids: a review of toxicity
data. PDA J Pharm Sci Technol 2000; 54(6): 456–469.
21 Authors
PJ Weller.
22 Date of Revision
14 August 2005.