Glycofurol

Basic Information

Name: Glycofurol

CAS No: a-[(Tetrahydro-2-furanyl)methyl]-o-hydroxy-poly(oxy-1,2-ethanediyl) [31692-85-0]

Functional Categories

Penetration agent Solvent

1. Nonproprietary Names

None adopted

2. Synonyms

Glycofurol 75; tetraglycol; a-(tetrahydrofuranyl)-o-hydroxy-poly(- oxyethylene); tetrahydrofurfuryl alcohol polyethylene glycol ether; THFP. Note: tetraglycol is also used as a synonym for tetrahydrofurfuryl alcohol.

3. Chemical Name & CAS Registry

a-[(Tetrahydro-2-furanyl)methyl]-o-hydroxy-poly(oxy-1,2-ethanediyl) [31692-85-0]

4. Empirical Formula & Molecular Weight

C9H18O4 (average), 190.24 (average)

5. Structural Formula

6. Applications

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.(7–11) Glycofurol has also been used at 20% v/v concentration in a rectal formulation.(12

7. Description

Glycofurol is a clear, colorless, almost odorless liquid, with a bitter taste; it produces a warm sensation on the tongue.

8. Pharmacopeial Specifications

9. Typical Properties

Boiling point 80–1008C for Glycofurol 75 Density 1.070–1.090 g/cm3 at 208C Hydroxyl value 300–400 Moisture content 0.2–5% at ambient temperature and 30% relative humidity. Refractive index n D 40 = 1.4545 Solubility see Table I.

10. Stability & Storage

Stable if stored under nitrogen in a well-closed container protected from light, in a cool, dry place.

11. Incompatibilities

Incompatible with oxidizing agents.

12. Method of Manufacture

Glycofurol is prepared by the reaction of tetrahydrofurfuryl alcohol with ethylene oxide (followed by a special purification process in the case of Glycofurol 75).

13. Safety

Glycofurol is mainly used as a solvent in parenteral pharmaceutical 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(1,2)

14. Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled.

15. Regulatory Status

Included in parenteral medicines licensed in Europe.

16. Related Substances

17. 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.