Hydroxypropyl methyl cellulose

Toxicity

LD 50 (Rat): > 5 g/kg .
Hypromellose is considered low toxicity to non-toxic .
Adverse events may include blurred vision and contact dermatitis . Hypersensitivity and intolerance reactions may occur (for example, eye burning, pain, increased lacrimation, a sensation of foreign body, conjunctival hyperemia, eyelid swelling, pruritus). The stickiness sensation of the eyelids, the decreased sense of smell, photosensitivity .

Chemical properties

Hypromellose is an odorless and tasteless, white or creamy-white fibrous or granular powder. This product is soluble in water (10 mg/ml). However, it is very important to thoroughly disperse the particles in water with agitation before they will dissolve. Otherwise, they will lump and form a gelatinous membrane around the internal particles, preventing them from wetting completely. There are four dispersion techniques commonly used to prepare solutions of hydroxypropylmethylcellulose: dispersion in hot water, dry blending, dispersion in non-solvent medium, and dispersion of surface-treated powders.

The Uses of Hydroxypropyl methyl cellulose

Hydroxypropyl Methylcellulose is a gum formed by the reaction of propylene oxide and methyl chloride with alkali cellulose. it will gel as the temperature is increased in heating and upon cooling will liquefy. the gel temperature ranges from 60°c to 90°c, forming semifirm to mushy gels. it is used in bakery goods, dressings, breaded foods, and salad dressing mix for syneresis control, texture, and to provide hot viscosity. usage level ranges from 0.05 to 1.0%.

Background

Hypromellose, or hydroxypropyl methylcellulose (HPMC) , is a semisynthetic, inert, and viscoelastic polymer that forms a colloid solution when dissolved in water. It acts as a thickening agent, coating polymer, bioadhesive, solubility enhancer in solid dispersions, and binder in the process of granulation and in modified release formulations . It is a commonly used as a delivery component in oral pharmaceutical products that provides the release of a drug in a controlled fashion, effectively increasing the duration of release of a drug to prolong its therapeutic effects . Hypromellose is also found in eye drops as a lubricant .

Production Methods

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.

What are the applications of Application

Hydroxypropyl methyl cellulose is used as an ophthalmic lubricant, an emulsifier and a thickening and suspending agent. It is widely used as an excipient in pharmaceutical formulations. It acts as a food additive. Its eye drops are known as artificial tears, which are used to relieve eye dryness and soreness. It finds applications in various fields as emulsifier, film former, protective colloid, stabilizer, suspending agent, or thickener in foods. Pharmaceutic aid (suspending agent; tablet excipient; demulcent; viscosity increasing agent); hydrophilic carrier in drug delivery systems. In adhesives, asphalt emulsions, caulking compounds, tile mortars, plastic mixes, cements, paints.

Indications

Hydroxypropyl methylcellulose belongs to the group of medicines known as artificial tears. It is used to relieve dryness and irritation caused by reduced tear flow. It helps prevent damage to the eye in certain eye diseases. Hydroxypropyl methylcellulose may also be used to moisten hard contact lenses and artificial eyes. In addition, it may be used in certain eye examinations.

General Description

Hydroxypropylmethylcelluloses are water soluble polymers derived from cellulose. They are typically used as thickeners, binders, film formers, and water retention agents. They also function as suspension aids, surfactants, lubricants, protective colloids, and emulsifiers. In addition, solutions of these polymers thermally gel.
These polymers are prepared by reacting wood or cotton cellulose fibers with propylene oxide and methyl chloride in the presence of caustic soda. This product has a methoxyl content of 28-30% and a hydroxypropoxyl content of 7-12%.

Pharmacokinetics

Hypromellose is the most commonly used in hydrophilic matrix fabrication. It allows for controlled release of drug substances, increasing duration of therapeutic effects . The physical characteristics of this drug resemble natural tears, providing lubrication to the ocular surface and maintaining corneal hydration in dry eye syndromes.

Side Effects

Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug.
Major & minor side effects for Hydroxypropyl Methylcellulose
Blurred vision
Decrease/loss of vision
Eye pain
Excessive tearing of the eye
Redness in and around the eyes

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 nonirritating 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(20) LD50 (rat, IP): 5.2 g/kg

Structure

Hydroxypropyl methyl cellulose (HPMC) is a propylene glycol ether of methylcellulose. In this compound, hydroxypropyl and methyl groups are attached to the anhydrous glucose rings of cellulose through ether linkages. HPMC is synthesized from methyl cellulose through the reaction with alkali and propylene oxide. This process produces a water-soluble ether derivative of cellulose that contains both methoxy and hydroxypropyl groups. The degree of substitution for HPMC ranges from 1.08 to 1.83, with hydroxypropyl groups being the minor constituent.

storage

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°C, 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.

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.

Regulatory Status

GRAS listed. Accepted for use as a food additive in Europe. Included in the FDA Inactive Ingredients Database (ophthalmic and nasal preparations; oral capsules, suspensions, syrups, and tablets;topical and vaginal preparations). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.