Food additives Europe numbers: E1525
Functional Category
Coating agent; suspending agent; tablet binder; thickening agent; viscosity-increasing agent.
Applications in Pharmaceutical Formulation
Hydroxyethyl cellulose is a nonionic, water-soluble polymer widely used in pharmaceutical formulations. It is primarily used as a thickening agent in ophthalmic(1) and topical formulations,(2) although it is also used as a binder(3) and film-coating agent for tablets.(4) It is present in lubricant preparations for dry eye, contact lens care, and dry mouth.(5) The concentration of hydroxyethyl cellulose used in a formulation is dependent upon the solvent and the molecular weight of the grade. Hydroxyethyl cellulose is also widely used in cosmetics.
Description
Hydroxyethyl cellulose occurs as a white, yellowish-white or grayish-white, odorless and tasteless, hygroscopic powder.
Stability and Storage Conditions
Hydroxyethyl cellulose powder is a stable though hygroscopic material. Aqueous solutions of hydroxyethyl cellulose are relatively stable at pH 2–12 with the viscosity of solutions being largely unaffected. However, solutions are less stable below pH 5 owing to hydrolysis. At high pH, oxidation may occur.Increasing the temperature reduces the viscosity of aqueous hydroxyethyl cellulose solutions. However, on cooling, the original viscosity is restored. Solutions may be subjected to freeze–thawing, high-temperature storage, or boiling without precipitation or gelation occurring. Hydroxyethyl cellulose is subject to enzymatic degradation, with consequent loss in viscosity of its solutions.(6) Enzymes that catalyze this degradation are produced by many bacteria and fungi present in the environment. For prolonged storage, an antimicrobial preservative should therefore be added to aqueous solutions. Aqueous solutions of hydroxyethyl cellulose may also be sterilized by autoclaving. Hydroxyethyl cellulose powder should be stored in a well-closed container, in a cool, dry place
Incompatibilities
Hydroxyethyl cellulose is insoluble in most organic solvents. It is incompatible with zein and partially compatible with the following water-soluble compounds: casein; gelatin; methylcellulose; polyvinyl alcohol, and starch. Hydroxyethyl cellulose can be used with a wide variety of watersoluble antimicrobial preservatives. However, sodium pentachlorophenate produces an immediate increase in viscosity when added to hydroxyethyl cellulose solutions. Hydroxyethyl cellulose has good tolerance for dissolved electrolytes, although it may be salted out of solution when mixed with certain salt solutions. For example, the following salt solutions will precipitate a 10% w/v solution of Cellosize WP-09 and a 2% w/v solution of Cellosize WP-4400: sodium carbonate 50% and saturated solutions of aluminum sulfate; ammonium sulfate; chromic sulfate; disodium phosphate; magnesium sulfate; potassium ferrocyanide; sodium sulfate; sodium sulfite; sodium thiosulfate; and zinc sulfate. Natrosol is soluble in most 10% salt solutions, excluding sodium carbonate and sodium sulfate, and many 50% salt solutions with the exception of the following: aluminum sulfate; ammonium sulfate; diammonium phosphate; disodium phosphate; ferric chloride; magnesium sulfate; potassium ferrocyanide; sodium metaborate; sodium nitrate; sodium sulfite; trisodium phosphate; and zinc sulfate. Natrosol 150 is generally more tolerant of dissolved salts than is Natrosol 250. Hydroxyethyl cellulose is also incompatible with certain fluorescent dyes or optical brighteners, and certain quaternary disinfectants which will increase the viscosity of aqueous solutions.
Safety
Hydroxyethyl cellulose is primarily used in ophthalmic and topical pharmaceutical formulations. It is generally regarded as an essentially nontoxic and nonirritant material.(7,8) Acute and subacute oral toxicity studies in rats have shown no toxic effects attributable to hydroxyethyl cellulose consumption, the hydroxyethyl cellulose being neither absorbed nor hydrolyzed in the rat gastrointestinal tract. However, although used in oral pharmaceutical formulations, hydroxyethyl cellulose has not been approved for direct use in food products; see Section 16. Glyoxal-treated hydroxyethyl cellulose is not recommended for use in oral pharmaceutical formulations or topical preparations that may be used on mucous membranes. Hydroxyethyl cellulose is also not recommended for use in parenteral products.