International Numbering System (INS) for Food Additives: 461
Food additives Europe numbers: E461
Functional Category:
Coating agent; emulsifying agent; suspending agent; tablet and capsule disintegrant; tablet binder; viscosity-increasing agent.
Applications in Pharmaceutical Formulation
Methylcellulose is widely used in oral and topical pharmaceutical formulations; see Table I. In tablet formulations, low- or medium-viscosity grades of methylcellulose are used as binding agents, the methylcellulose being added either as a dry powder or in solution.(1–3) Highviscosity grades of methylcellulose may also be incorporated in tablet formulations as a disintegrant.(4) Methylcellulose may be added to a tablet formulation to produce sustained-release preparations.(5) Tablet cores may also be spray-coated with either aqueous or organic solutions of highly substituted low-viscosity grades of methylcellulose to mask an unpleasant taste or to modify the release of a drug by controlling the physical nature of the granules.(6) Methylcellulose coats are also used for sealing tablet cores prior to sugar coating. Low-viscosity grades of methylcellulose are used to emulsify olive, peanut, and mineral oils.(7) They are also used as suspending or thickening agents for orally administered liquids, methylcellulose commonly being used in place of sugar-based syrups or other suspension bases.(8) Methylcellulose delays the settling of suspensions and increases the contact time of drugs, such as antacids, in the stomach. High-viscosity grades of methylcellulose are used to thicken topically applied products such as creams and gels. In ophthalmic preparations, a 0.5–1.0% w/v solution of a highly substituted, high-viscosity grade of methylcellulose has been used as a vehicle for eye drops.(9) However, hypromellose-based formulations are now preferred for ophthalmic preparations. Methylcellulose is also used in injectable formulations. Therapeutically, methylcellulose is used as a bulk laxative; it has also been used to aid appetite control in the management of obesity, but there is little evidence supporting its efficacy
Description
Methylcellulose occurs as a white, fibrous powder or granules. It is practically odorless and tasteless. It should be labeled to indicate its viscosity type (viscosity of a 1 in 50 solution).
Stability and Storage Conditions
Methylcellulose powder is stable, although slightly hygroscopic. The bulk material should be stored in an airtight container in a cool, dry place. Solutions of methylcellulose are stable to alkalis and dilute acids at pH 3–11, at room temperature. At pH less than 3, acid-catalyzed hydrolysis of the glucose–glucose linkages occurs and the viscosity of methylcellulose solutions is reduced.(10) On heating, solution viscosity is reduced until gel formation occurs at approximately 508C; see Section 10. Methylcellulose solutions are liable to microbial spoilage and antimicrobial preservatives should therefore be used. Solutions may also be sterilized by autoclaving, although this process can decrease the viscosity of a solution.(11,12) The change in viscosity after autoclaving is related to solution pH. Solutions at pH less than 4 had viscosities reduced by more than 20% subsequent to autoclaving.(11)
Incompatibilities
Methylcellulose is incompatible with aminacrine hydrochloride; chlorocresol; mercuric chloride; phenol; resorcinol; tannic acid; silver nitrate; cetylpyridinium chloride; p-hydroxybenzoic acid; paminobenzoic acid; methylparaben; propylparaben; and butylparaben. Salts of mineral acids (particularly polybasic acids), phenols, and tannins will coagulate solutions of methylcellulose, although this can be prevented by the addition of ethanol (95%) or glycol diacetate. Complexation of methylcellulose occurs with highly surface-active compounds such as tetracaine and dibutoline sulfate. High concentrations of electrolytes increase the viscosity of methylcellulose mucilages owing to the ‘salting out’ of methylcellulose. With very high concentrations of electrolytes, the methylcellulose may be completely precipitated in the form of a discrete or continuous gel. Methylcellulose is incompatible with strong oxidizing agents.
Safety
Methylcellulose is widely used in a variety of oral and topical pharmaceutical formulations. It is also extensively used in cosmetics and food products, and is generally regarded as a nontoxic, nonallergenic, and nonirritant material.(13) Following oral consumption, methylcellulose is not digested or absorbed and is therefore a noncaloric material. Ingestion of excessive amounts of methylcellulose may temporarily increase flatulence and gastrointestinal distension. In the normal individual, oral consumption of large amounts of methylcellulose has a laxative action and medium- or high-viscosity grades are therefore used as bulk laxatives. Esophageal obstruction may occur if methylcellulose is swallowed with an insufficient quantity of liquid. Consumption of large quantities of methylcellulose may additionally interfere with the normal absorption of some minerals. However, this and the other adverse effects discussed above relate mainly to the use of methylcellulose as a bulk laxative and are not significant factors when methylcellulose is used as an excipient in oral preparations. Methylcellulose is not commonly used in parenteral products, although it has been used in intra-articular and intramuscular injections. Studies in rats have suggested that parenterally administered methylcellulose may cause glomerulonephritis and hypertension.(13) Methylcellulose is considered to be toxic by the intraperitoneal route of administration. The WHO has not specified an acceptable daily intake of methylcellulose since the level of use in foods was not considered to be a hazard to health.(14) LD50 (mouse, IP): 275 g/kg(15)