Methyl cellulose

Outline

Methylcellulose ether, abbreviated MC, is a kind of long-chain substituted cellulose, in which 27% to 32% of the hydroxyl group exists in the form of methoxy. The substitution degree affects the physical properties of methyl cellulose such as solubility. Methylcellulose has an average molecular weight of 10,000 to 220,000. At room temperature, it exhibits as a white powder or fibrous material, and is non-toxic, non-irritating with non-allergic effect. Its apparent relative density is 0.35 to 0.55 (with the real density being 1.26 to 1.30). It swells in water into a translucent viscous colloidal solution which is neutral to litmus, insoluble in ethanol, ether and chloroform, but soluble in glacial acetic acid. It is tolerant to the effects of acid, alkali, microorganisms, heat, and light and is also not affected by oil and grease, but will burn upon reaching ignition point. Methyl cellulose is a product composed of cellulose glucose with all or part of three hydroxyls getting methylated. General products contain a methoxy fraction of 26% to 33% with degree of substitution being 1.7 to 2.2. Product with substitution degree being 1.3 to 2.6 is soluble in water, pyridine, and acetic acid. This product is widely used for architecture, such as being used as the adhesive of cement, mortar, and for mudding off the seam. It is also used for making film an adhesive in cosmetics, medicine, and food industry. It can be also used as a textile sizing agents, synthetic resin dispersing agent, paint film formers and thickeners. The production method is that: use pulp to produce the alkali cellulose; alkali cellulose is reacted with methyl chloride or dimethyl sulfate in an autoclave and then further refined with warm water to obtain the final product.

Herbs and Applications

Methyl cellulose is widely applied in a variety of orally administrated or topical formulations; it is also widely used in cosmetics and food. After oral administration, methyl cellulose can’t be digested or absorbed so that it is a calorie-free material. Excessive intake of methyl cellulose may temporarily increase flatulence and even cause esophageal obstruction upon insufficient water intake. However, methyl cellulose has a laxative effect.
Methyl cellulose is a hydrophilic colloid and is the high-viscosity cellulose derivatives. It is non-toxic and caustic, hygroscopic and can expand into a colloidal suspension in cold water. It is also insoluble in hot water, alcohol, ether, chloroform and saturated salt solution but is soluble in glacial acetic acid and the mixture of equal amount of alcohol and chloroform solution. Its solution may be agglomerated by salts, polybasic acid, phenol and tannin with adding ethanol being able to prevent this agglomeration effect. Methyl cellulose can’t be digested, absorbed in the intestine. It can absorb moisture, mixed with water to form a large volume of hydrophilic gum, and increase the stool volume and soften it, and also stimulate the gut peristalsis to promote the defecation. In patients with diarrhea, because the product can absorb moisture, so it reduces the intestine liquidity to take the antidiarrheal effect.
Oral administration: 1~4g/d together with taking large amounts of water as a bulk laxative for the treatment of constipation. The product has been worked as anorectic agents for controlling appetite and inducing weight loss. But it doesn’t have a reliable effect. Methyl cellulose can also be used as: adhesives which are suitable for choosing low or moderate viscosity grade plastic with both adding powder and solution working well. It is used for improving drug dissolution rate or disintegration rate; the general concentration is 1% to 2%. For gels, thickening gels and creams: it is appropriate to choose high-viscosity grade. Suspending agents and thickening agents, solutions can replace syrup; for thickening, use a concentration of up to 5%. For Tablet coating: we can choose the high-level replacement & low viscosity product as film coating; it can also be used for coating for surrounding the outer nuclear layer for isolation. For disintegrating agents, it is commonly used at a concentration of 2% to 10%. For emulsifier, it is generally recommended to use low-viscosity grade at a concentration of 1% to 5%. For eye drops, we should use high-viscosity grade.

Stability and storage conditions

Methyl cellulose powder is stable and slightly hygroscopic; it should be placed in an airtight container and stored in a cool dry place.
Methyl cellulose solution is sable in diluted acid or base with pH 3 to 11 at room temperature, and is easy to be destroyed by microbes to be corrupted. Therefore, the solution should be added into preservatives or subject to autoclaving. After autoclaving, the change of the solution viscosity is related with pH value. For solution of pH <4, the viscosity will decrease by more than 20% after autoclaving.

Incompatibility

Methylcellulose is incompatible for combination with ammonia acridine hydrochloride, chlorine cresol, mercury chloride, phenol, resorcinol, 4-aminobenzoic acid. Inorganic acid, phenol, and tannic acid cause the agglomeration of methyl cellulose; and can also forms complex with tetracaine; it can also bind with parabens so we should increase the amount of parabens upon application.
The above information is edited by the chemicalbook of Dai Xiongfeng.

Content Analysis

Measure the methoxy content according to the GT-14 method.

Toxicity

ADI does not make special provision (FAO/WHO, 2001).
GRAS (FDA, §182.1480, 2000).

Limited application

FAO /WHO (1984) Citrus canned; 10Mg/kg (as an anti-haze agent); cold drinks 10g/kg.
According to Japanese regulations (1990), the maximum amount is 2% (used alone or the combination amount together with calcium carboxymethyl cellulose, sodium carboxymethyl cellulose, sodium carboxymethyl starch, sodium starch phosphate).
It can also be used as the emulsion stabilizer of ice cream with the amount being 0.05%; salad sauces being 0.75%; for bread corruption prevention and surface homogenization, use 0.2% to 0.3%.
For application in citrus canned to prevent precipitation of hesperidins and the anti-clounding agent in the juice, use 10~30mg/kg.

Chemical Properties

It is a kind of methyl ether of cellulose. It is white or pale yellow or light gray small particles (95% through a 40 mesh sieve), filaments like or powder. It is odorless, tasteless and has hygroscopicity with an apparent density of 0.3~0.7g/mL.
When all the R in the structure is methyl, the substitution degree is equal to 3, and the methoxy content is 45.57%. For methylcellulose used as the food additive, the methoxy content should be around 26%~33% which corresponds to a degree of substitution of 1.7 to 2.2. When the substitution degree is lower than 1.3, it can be dissolved in alkaline. While methylcellulose with substitution degree higher than 2.6 is soluble in an organic solvent. When the degree of substitution is less than 1.3, it can be dissolved in alkali; for those with substitution degree higher than 2.6, it is soluble in organic solution. At the range between 1.3 and 2.6, it is soluble in cold water, pyridine, aniline, trimethyl formamide, benzyl alcohol and acetic acid.
Aqueous solution is stable at neutral and room temperature; but it can generate gelation effect and be precipitated at high temperature. Gelation temperature is dependent on the absolute viscosity and concentration of the solution; solution of large viscosity and high concentration has a relative low gelling temperature. In the presence of inorganic salts, viscosity can be increased. Due to that it belongs to a non-ionic solution, the polyvalent metal is not able to precipitate it; Gelation will only occur when the concentration of the electrolyte and other dissolved substances exceeds a certain limit.
Aqueous solution has surfactant activity and dried to form a thin film; upon heating and cooling, it will orderly go through the reversible transition from the sol to gel.

Uses

It can be used as thickeners; stabilizer; emulsifier; excipients; dispersant; binders; substitutes of film-forming agent hydrosol. It can also be used in mayonnaise, shortenings and some other foods. Because of that the materials can’t digested in the body, it can maintain several times amount of water, resulting in satiety; it can be used in crackers, waffles and other food for taking effect. For application, first 1/5 of the required amount of water for moistening the powder, together with cold water (necessary, to add ice) for mixing well. EEC: approved for using at frozen foam products, potato chips, soft drinks, special dietary foods, baked goods filling, the top material for foaming, sauces, and sauces.
It can also be used in mayonnaise, shortenings and some other foods.
Because of that the materials can’t digested in the body, it can maintain several times amount of water, resulting in satiety; it can be used in crackers, waffles and other food for taking effect.
For application, first 1/5 of the required amount of water for moistening the powder, together with cold water (necessary, to add ice) for mixing well. EEC: approved for using at frozen foam products, potato chips, soft drinks, special dietary foods, baked goods filling, the top material for foaming, sauces, and sauces.
The product is widely used in the architecture industry such as the mixture agent for cement, plaster, and clay seams. It can also be used as adhesive film-forming agent in cosmetics, medicine, and food industry; also can be used as sizing agents for spinning, and printing and dyeing, synthetic resin dispersing agent, paint film formers and thickeners. Methyl cellulose is a very stable material which is resistant to acid, alkalis, microorganisms, and heating. It can be excrete out from the human body without any change. It is used for synthetic resin dispersing agent, film-forming agent of painting, thickener, binder materials, textile sizing agent, and the film-forming agent in the pharmaceutical and food industries.

Production methods

1. Use Pulp to prepare the base fiber; then have etherification reaction to obtain methyl chloride. According to different sources, pulp can be classified into cotton pulp, wood pulp, straw pulp, etc., It is commonly used in industrial of wood pulp and cotton pulp (cotton linters). The cellulose in the pulp itself is difficult to have reaction with methyl chloride; it must first be made into alkali cellulose. Use 1 part of cellulose to be combined with 0.9-1.2 parts of sodium hydroxide and 0.9 to 1.2 parts (all by weight) of water for soak at 30 °C for 1-2h. Then compress to remove excess alkali to obtain the bulk-like alkali cellulose. Break it into pieces to loosen the alkali cellulose and make it more uniform; with the reaction with the oxygen in the air, alkaline cellulose is degraded and its polymerization is also reduced to achieve the purpose of regulating the viscosity. The alkali cellulose which has undergone the above aging process is further suspended in an excess of methyl chloride (typically 10-15 times of the weight of pulp) for taking reaction for about 5h at 60-70 °C to complete the etherification reaction with the corresponding pressure of about 1.7MPa . Post-processing of the products includes washing and drying of the finished product. Is generally washed in hot water of 80-90 °C; add an appropriate amount of hydrochloric acid (or sulfuric acid) for neutralization, and further add it into oxalic acid to make it form complex with iron and heavy metal which is removed together with sodium chloride during the washing step by water. The product was washed and dehydrated, dried to obtain methyl cellulose products.
2. Use alkali to treat wood pulp or cotton, further use methyl chloride to methylate the alkali to obtain the final product. Some industrial products contain small amounts (up to 5%) hydroxyethyl and/or cellulose displaced by hydroxypropyl. For these products, the calculation of content index should follow the percentage of methoxy group plus percentage of ethoxy group and/or percentage of propoxy with "total alkoxy" representing the content.

Chemical Properties

Methyl cellulose is a water soluble, gel-like substance with no odor and no taste.

Chemical Properties

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).

Chemical Properties

white powder or (often) 2% solution in water, properties

Uses

Thickener for aqueous and non-aqueous systems, clear films with grease resistance, binders, lubricants, steric stabilizer and water retention aid.

Uses

Methyl cellulose is used as a thickener and an emulsifier in various food and cosmetic products; as a gel in advanced cookery and as a lubricant. It is also involved in the treatment of constipation. It acts as a buffer additive in capillary electrophoresis to control electoosmotic flow for improved separations. In paper and textile industries, it is used as a sizing, thereby protecting the fibers from water or oil.

Uses

Methylcellulose is a gum composed of cellulose in which the meth- oxyl groups replace the hydroxyl groups. it is soluble in cold water but insoluble in hot water. solutions increase in viscosity upon heating, gel at 50–55°c, and liquefy upon cooling. it is used in baked goods for moisture retention, and in fruit pie fillings for the reduction of water absorption into the pie crust during baking. it is also used in breaded shrimp where it functions to form an oil barrier film.

Uses

As a substitute for water-soluble gums; to render paper greaseproof, in adhesives, as thickening agent in cosmetics, as protective colloid in emulsions, as binder and stabilizer in foods. As fat replacer in the formulation of dietetic foods. Pharmaceutic aid (suspending agent).

Production Methods

Methylcellulose is prepared from wood pulp (cellulose) by treatment with alkali followed by methylation of the alkali cellulose with methyl chloride. The product is then purified and ground to powder form.

Preparation

Prepared from wood pulp or cotton by treatment with alkali and methylation of alkali cellulose with methyl chloride.

brand name

Cologel (Lilly); Methocel A (Dow Chemical).

General Description

Odorless white or creamy white fibrous powder. Tasteless.

Air & Water Reactions

Methyl cellulose is hygroscopic. Swells in water to a viscous, colloidal solid. Slightly water soluble.

Reactivity Profile

Methyl cellulose is incompatible with strong oxidizing agents. Methyl cellulose is also incompatible with aminacrine HCl, chlorocresol, mercuric chloride, phenol resorcinol, tannic acid and silver nitrate.

Fire Hazard

Flash point data for Methyl cellulose are not available; however, Methyl cellulose is probably combustible.

Pharmaceutical Applications

Methylcellulose is widely used in oral and topical pharmaceutical formulations;
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.Highviscosity grades of methylcellulose may also be incorporated in tablet formulations as a disintegrant.Methylcellulose may be added to a tablet formulation to produce sustained-release preparations.
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. 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.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.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.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.

Biochem/physiol Actions

Methyl cellulose is known to have a molecular size that might pass through placenta. It is useful in visualizing small bowel loops through its overlaps.

Safety Profile

A poison by intraperitoneal route. When heated to decomposition it emits acrid smoke and irritating fumes.

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.
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.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.
LD₅₀ (mouse, IP): 275 g/kg

storage

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.On heating, solution viscosity is reduced until gel formation occurs at approximately 50°C;
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.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.

Incompatibilities

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.

Regulatory Status

GRAS listed. Accepted as a food additive in the USA, Europe and Japan. Included in the FDA Inactive Ingredients Database (sublingual tablets; IM injections; intrasynovial injections; nasal preparations; ophthalmic preparations; oral capsules, oral suspensions, and oral tablets; topical and vaginal preparations). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.Reported in the EPA TSCA inventory.