Hypromellose60 RT50

Category

Binder Excipients

Molecular Formula

C8H15O8-(C10H18O6 ) n- C8H15O8

Molecular Weight

10000-1500000

Grade

Pharmceutical Excipients

Description

Hypromellose is an odorless and tasteless, white or creamy-white fibrous or granular powder.

UNII

3NXW29V3WO

Chemical Name

Cellulose hydroxypropyl methyl ether

CAS Number

9004-65-3

Synonyms

Benecel MHPC; E466; hydroxypropyl methylcellulose; HPMC; hypromellosum; Methocel; methylcellulose propylene glycol ether; methyl hydroxypropylcellulose; Metolose; MHPC; Pharmacoat; Tylopur; Tylose MO.

Administration route

Oral

Dosage Form

Ophthalmic and nasal preparations; oral capsules, uspensions, syrups, and tablets; topical and vaginal preparations

Stability and Storage Conditions

Hypromellose powder is a stable material, although it is hygroscopic after drying. Solutions are stable at pH 3-11. Hypromellose undergoes a reversible sol-gel transformation upon heating and cooling, respectively. The gelation temperature is 50-90℃, depending upon the grade and concentration of material. For temperatures below the gelation temperature, viscosity of the solution decreases as temperature is increased. Beyond the gelation temperature, viscosity increases as temperature is increased. Aqueous solutions are comparatively enzyme-resistant, providing good viscosity stability during long-term storage.However, aqueous solutions are liable to microbial spoilage and should be preserved with an antimicrobial preservative: when hypromellose is used as a viscosity-increasing agent in ophthalmic solutions, benzalkonium chloride is commonly used as the preservative. Aqueous solutions may also be sterilized by autoclaving; the coagulated polymer must be redispersed on cooling by shaking. Hypromellose powder should be stored in a well-closed container, in a cool, dry place.

Source and Preparation

A purified form of cellulose, obtained from cotton linters or wood pulp, is reacted with sodium hydroxide solution to produce a swollen alkali cellulose that is chemically more reactive than untreated cellulose. The alkali cellulose is then treated with chloromethane and propylene oxide to produce methyl hydroxypropyl ethers of cellulose. The fibrous reaction product is then purified and ground to a fine, uniform powder or granules.Hypromellose can then be exposed to anhydrous hydrogen chloride to induce depolymerization, thus producing low viscosity grades.

Applications

Hypromellose is widely used in oral, ophthalmic, nasal, and topical pharmaceutical formulations.In oral products, hypromellose is primarily used as a tablet binder, in film-coating, and as a matrix for use in extended-release tablet formulations. Concentrations between 2% and 5% w/w may be used as a binder in either wet- or dry-ranulation processes. High-viscosity grades may be used to retard the release of drugs from a matrix at levels of 10-80% w/w in tablets and capsules. Hypromellose is also used in liquid oral dosage forms as a suspending and/or thickening agent at concentrations ranging from 0.25-5.0%.Depending upon the viscosity grade, concentrations of 2-20% w/w are used for film-forming solutions to film-coat tablets. Lowerviscosity grades are used in aqueous film-coating solutions, while higher-viscosity grades are used with organic solvents. Examples of film-coating materials that are commercially available include AnyCoat C, Spectracel, Pharmacoat, and the Methocel E Premium LV series. Hypromellose is also used as a suspending and thickening agent in topical formulations. Compared with methylcellulose, hypromellose produces aqueous solutions of greater clarity, with fewer undissolved fibers present, and is therefore preferred in formulations for ophthalmic use. Hypromellose at concentrations between 0.45-1.0% w/w may be added as a thickening agent to vehicles for eye drops and artificial tear solutions. It is also used commercially in liquid nasal formulations at a concentration of 0.1%. Hypromellose is used as an emulsifier, suspending agent, and stabilizing agent in topical gels and ointments. As a protective colloid, it can prevent droplets and particles from coalescing or agglomerating, thus inhibiting the formation of sediments. In addition, hypromellose is used in the manufacture of capsules, as an adhesive in plastic bandages, and as a wetting agent for hard contact lenses. It is also widely used in cosmetics and food products.

Safety

Hypromellose is widely used as an excipient in oral, opthalmic, nasal, and topical pharmaceutical formulations. It is also used extensively in cosmetics and food products. Hypromellose is generally regarded as a nontoxic and non-irritating material, although excessive oral consumption may have a laxative effect.The WHO has not specified an acceptable daily intake for hypromellose since the levels consumed were not considered to represent a hazard to health.In fact, high dosages of hypromellose are being investigated for treating various metabolic syndromes.
LD50 (mouse, IP): 5 g/kg
LD50 (rat, IP): 5.2 g/kg

Incompatibilities

Hypromellose is incompatible with some oxidizing agents. Since it is nonionic, hypromellose will not complex with metallic salts or ionic organics to form insoluble precipitates.