Hydroxyethyl Cellulose

Category

Coating Agents; Suspending Agents; Tablet Binder; Thickening Agents; Viscosity-increasing Agents

Grade

Pharmceutical Excipients

Description

Hydroxyethyl cellulose occurs as a white, yellowish-white or grayish-white, odorless and tasteless, hygroscopic powder.

UNII

T7SWE4S2TT

Chemical Name

Cellulose, 2-hydroxyethyl ether

CAS Number

9004-62-0

Synonyms

Cellosize HEC; cellulose hydroxyethyl ether; cellulose 2-hydroxyethyl ether; cellulose hydroxyethylate; ethylhydroxy cellulose; ethylose; HEC; HE cellulose; hetastarch; 2-hydroxyethyl cellulose ether; hydroxyethylcellulosum; hydroxyethyl ether cellulose; hydroxyethyl starch; hyetellose; Natrosol; oxycellulose; Tylose H; Tylose PHA

Administration route

Ophthalmic; oral; otic and topical

Dosage Form

Ophthalmic preparations; oral syrups and tablets; otic and topical preparations

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.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.

Source and Preparation

A purified form of cellulose is reacted with sodium hydroxide to produce a swollen alkali cellulose, which is chemically more reactive than untreated cellulose. The alkali cellulose is then reacted with ethylene oxide to produce a series of hydroxyethyl cellulose ethers. The manner in which ethylene oxide is added to cellulose can be described by two terms, the degree of substitution (DS) and the molar substitution (MS). The DS designates the average number of hydroxyl positions on the anhydroglucose unit that have been reacted with ethylene oxide. Since each anhydroglucose unit of the cellulose molecule has three hydroxyl groups, the maximum value for DS is 3. MS is defined as the average number of ethylene oxide molecules that have reacted with each anhydroglucose unit. Once a hydroxyethyl group is attached to each unit, it can further react with additional groups in an end-to-end formation. This reaction can continue and there is no theoretical limit for MS.

Applications

Hydroxyethyl cellulose is a nonionic, water-soluble polymer widely used in pharmaceutical formulations. It is primarily used as a thickening agent in ophthalmic and topical formulations, although it is also used as a binder and film-coating agent for tablets. It is present in lubricant preparations for dry eye, contact lens care, and dry mouth.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.

Safety

Hydroxyethyl cellulose is primarily used in ophthalmic and topical pharmaceutical formulations. It is generally regarded as an essentially nontoxic and nonirritant material.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. 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.

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 water soluble antimicrobial preservatives.