Names | |
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Other names Hydroxypropyl methylcellulose; hydroxypropyl methyl cellulose; HPMC; E464 | |
Identifiers | |
ChemSpider | |
ECHA InfoCard | 100.115.379 |
EC Number |
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E number | E464 (thickeners, ...) |
UNII | |
CompTox Dashboard (EPA) | |
| |
Properties | |
variable | |
Molar mass | variable |
Pharmacology | |
S01KA02 ( WHO ) | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Hypromellose (INN), short for hydroxypropyl methylcellulose (HPMC), is a semisynthetic, inert, viscoelastic polymer used in eye drops, as well as an excipient and controlled-delivery component in oral medicaments, found in a variety of commercial products. [1] [2]
The full form of HPMC is Hydroxypropyl Methyl Cellulose. It features a cellulose backbone with substituents that enhance its water solubility and stability, making it suitable for various applications. [3]
As a food additive, hypromellose is an emulsifier, thickening and suspending agent, and an alternative to animal gelatin. [4] Its Codex Alimentarius code (E number) is E464.
Hypromellose is a solid, and is a slightly off-white to beige powder in appearance and may be formed into granules. The compound forms colloids when dissolved in water. This non-toxic ingredient is combustible and can react vigorously with oxidizing agents. [5]
Hypromellose in an aqueous solution, like methylcellulose, exhibits a thermal gelation property. That is, when the solution heats up to a critical temperature, the solution congeals into a non-flowable but semi-flexible mass. Typically, this critical (congealing) temperature is inversely related to both the solution concentration of HPMC and the concentration of the methoxy group within the HPMC molecule (which in turn depends on both the degree of substitution of the methoxy group and the molar substitution). That is, the higher the concentration of the methoxy group, the lower the critical temperature. The inflexibility/viscosity of the resulting mass, however, is directly related to the concentration of the methoxy group (the higher the concentration is, the more viscous or less flexible the resulting mass is)[ citation needed ].
There are many fields of application for hypromellose, including: [6]
Agricultural Research Service scientists are investigating using the plant-derived HPMC as a substitute for gluten in making all-oat and other grain breads.[ citation needed ] Gluten, which is present in wheat, rye, and barley, is absent (or present only in trace quantities) in oat and other grains. Like gluten, HPMC can trap air bubbles formed by the yeast in bread dough, causing the bread to rise.
HPMC is used primarily in construction materials like tile adhesives and renders [8] where it is used as a rheology modifier, water retention agent and retarder, improve the workability and application performance of gypsum mixtures. [9]
Functionally HPMC is very similar to HEMC (hydroxy ethyl methyl cellulose) Trade names include Methocel and Walocel. The global leading producer is now DuPont, formerly manufactured under Dow Wolff Cellulosics GmbH. [10]
Hypromellose solutions were patented as a semisynthetic substitute for tear-film. [11] Its molecular structure is predicated upon a base celluloid compound that is highly water-soluble. Post-application, celluloid attributes of good water solubility reportedly aid in visual clarity. When applied, a hypromellose solution acts to swell and absorb water, thereby expanding the thickness of the tear-film. Hypromellose augmentation therefore results in extended lubricant time presence on the cornea, which theoretically results in decreased eye irritation, especially in dry climates, home, or work environments. [12] On a molecular level, this polymer contains beta-linked D-glucose units that remain metabolically intact for days to weeks. On a manufacturing note, since hypromellose is a vegetarian substitute for gelatin, it is slightly more expensive to produce due to semisynthetic manufacturing processes. Aside from its widespread commercial and retail availability over the counter in a variety of products, hypromellose 2% solution has been documented to be used during surgery to aid in corneal protection and during orbital surgery.
In addition to its use in ophthalmic liquids, hypromellose has been used as an excipient in oral tablet and capsule formulations, where, depending on the grade, it functions as controlled release agent to delay the release of a medicinal compound into the digestive tract. [13] It is also used as a binder [14] and as a component of tablet coatings. [15] [16]
Various benchmark tests are used to qualify hypromellose:
Because hypromellose solution is a non-newtonian solution and exhibits pseudoplastic, more specifically, thixotropic behavior, various test methods are available, and the results of different methods and viscosimeters do not necessarily correspond to each other. Also, due to viscometer acceptable ranges of error, viscosity is typically given as a mean, or as a range. Typical viscosity test will specify the following:
Degree of substitution is the average level of methoxy substitution on the cellulose chain. Since there are maximum three possible sites of substitution with each cellulose molecule, this average value is a real number between 0 and 3. However, degree of substitution is often expressed in percentages.
Molar substitution is the average level of hydroxypropoxy substitution on the cellulose chain. Since hydroxypropoxy base can be attached to each other on side chains and does not each require a base substitution site on the cellulose molecule, this number can be higher than 3. However, molar substitution is also often expressed in percentages.
Since all cellulose ethers are hygroscopic, they will absorb moisture from surroundings if left exposed from original packaging. Thus, moisture must be tested and weight corrected to ensure adequate amount of dry active material are apportioned for usage. Moisture is tested by weighing a sample of X grams on an analytic scale, and drying the sample in an oven at 105 °C for 2 hours, then weighing the sample again on the same scale.
Guar gum, also called guaran, is a galactomannan polysaccharide extracted from guar beans that has thickening and stabilizing properties useful in food, feed, and industrial applications. The guar seeds are mechanically dehusked, hydrated, milled and screened according to application. It is typically produced as a free-flowing, off-white powder.
A tablet is a pharmaceutical oral dosage form or solid unit dosage form. Tablets may be defined as the solid unit dosage form of medication with suitable excipients. It comprises a mixture of active substances and excipients, usually in powder form, that are pressed or compacted into a solid dose. The main advantages of tablets are that they ensure a consistent dose of medicine that is easy to consume.
In biochemistry, cellulose acetate refers to any acetate ester of cellulose, usually cellulose diacetate. It was first prepared in 1865. A bioplastic, cellulose acetate is used as a film base in photography, as a component in some coatings, and as a frame material for eyeglasses; it is also used as a synthetic fiber in the manufacture of cigarette filters and playing cards. In photographic film, cellulose acetate film replaced nitrate film in the 1950s, being far less flammable and cheaper to produce.
Xanthan gum is a polysaccharide with many industrial uses, including as a common food additive. It is an effective thickening agent and stabilizer that prevents ingredients from separating. It can be produced from simple sugars by fermentation and derives its name from the species of bacteria used, Xanthomonas campestris.
An excipient is a substance formulated alongside the active ingredient of a medication. They may be used to enhance the active ingredient’s therapeutic properties; to facilitate drug absorption; to reduce viscosity; to enhance solubility; to improve long-term stabilization ; or to add bulk to solid formulations that have small amounts of potent active ingredients. During the manufacturing process, excipients can improve the handling of active substances and facilitate powder flow. The choice of excipients depends on factors such as the intended route of administration, the dosage form, and compatibility with the active ingredient.
A diluent is a diluting agent. Certain fluids are too viscous to be pumped easily or too dense to flow from one particular point to the other. This can be troublesome, because it might not be economically feasible to transport such fluids in this state. To ease this restricted movement, diluents are added. This decreases the viscosity of the fluids, thereby also decreasing the pumping/transportation costs.
Dimethylacetamide (DMAc or DMA) is the organic compound with the formula CH3C(O)N(CH3)2. This colorless, water-miscible, high-boiling liquid is commonly used as a polar solvent in organic synthesis. DMA is miscible with most other solvents, although it is poorly soluble in aliphatic hydrocarbons.
Hydroxypropyl cellulose (HPC) is a derivative of cellulose with both water solubility and organic solubility. It is used as an excipient, and topical ophthalmic protectant and lubricant.
A thickening agent or thickener is a substance which can increase the viscosity of a liquid without substantially changing its other properties. Edible thickeners are commonly used to thicken sauces, soups, and puddings without altering their taste; thickeners are also used in paints, inks, explosives, and cosmetics.
Carboxymethyl cellulose (CMC) or cellulose gum is a cellulose derivative with carboxymethyl groups (-CH2-COOH) bound to some of the hydroxyl groups of the glucopyranose monomers that make up the cellulose backbone. It is often used in its sodium salt form, sodium carboxymethyl cellulose. It used to be marketed under the name Tylose, a registered trademark of SE Tylose.
An enteric coating is a polymer barrier applied to oral medication that prevents its dissolution or disintegration in the gastric environment. This helps by either protecting drugs from the acidity of the stomach, the stomach from the detrimental effects of the drug, or to release the drug after the stomach. Some drugs are unstable at the pH of gastric acid and need to be protected from degradation. Enteric coating is also an effective method to obtain drug targeting. Other drugs such as some anthelmintics may need to reach a high concentration in a specific part of the intestine. Enteric coating may also be used during studies as a research tool to determine drug absorption. Enteric-coated medications pertain to the "delayed action" dosage form category. Tablets, mini-tablets, pellets and granules are the most common enteric-coated dosage forms.
In the manufacture of pharmaceuticals, encapsulation refers to a range of dosage forms—techniques used to enclose medicines—in a relatively stable shell known as a capsule, allowing them to, for example, be taken orally or be used as suppositories. The two main types of capsules are:
Methyl cellulose is a compound derived from cellulose. It is sold under a variety of trade names and is used as a thickener and emulsifier in various food and cosmetic products, and also as a bulk-forming laxative. Like cellulose, it is not digestible, non-toxic, and not an allergen. In addition to culinary uses, it is used in arts and crafts such as papier-mâché and is often the main ingredient of wallpaper paste.
An Ubbelohde type viscometer or suspended-level viscometer is a measuring instrument which uses a capillary based method of measuring viscosity. It is recommended for higher viscosity cellulosic polymer solutions. The advantage of this instrument is that the values obtained are independent of the total volume. The device was developed by the German chemist Leo Ubbelohde (1877-1964).
Cellulose acetate phthalate (CAP), also known as cellacefate (INN) and cellulosi acetas phthalas, is a commonly used polymer phthalate in the formulation of pharmaceuticals, such as the enteric coating of tablets or capsules and for controlled release formulations. It is a cellulose polymer where about half of the hydroxyls are esterified with acetyls, a quarter are esterified with one or two carboxyls of a phthalic acid, and the remainder are unchanged. It is a hygroscopic white to off-white free-flowing powder, granules, or flakes. It is tasteless and odorless, though may have a weak odor of acetic acid. Its main use in pharmaceutics is with enteric formulations. It can be used together with other coating agents, e.g. ethyl cellulose. Cellulose acetate phthalate is commonly plasticized with diethyl phthalate, a hydrophobic compound, or triethyl citrate, a hydrophilic compound; other compatible plasticizers are various phthalates, triacetin, dibutyl tartrate, glycerol, propylene glycol, tripropionin, triacetin citrate, acetylated monoglycerides, etc.
Solution polymerization is a method of industrial polymerization. In this procedure, a monomer is dissolved in a non-reactive solvent that contains a catalyst or initiator.
Microcrystalline cellulose (MCC) is a term for refined wood pulp and is used as a texturizer, an anti-caking agent, a fat substitute, an emulsifier, an extender, and a bulking agent in food production. The most common form is used in vitamin supplements or tablets. It is also used in plaque assays for counting viruses, as an alternative to carboxymethylcellulose.
Capsugel is a company that manufactures and sells two-piece hard gelatin drug capsules. Capsugel also sells equipment for filling empty and liquid capsules, as well as equipment for sealing liquid capsules.
Topical gels are a topical drug delivery dosage form commonly used in cosmetics and treatments for skin diseases because of their advantages over cream and ointment. They are formed from a mixture of gelator, solvent, active drug, and other excipients, and can be classified into organogels and hydrogels. Drug formulation and preparation methods depend on the properties of the gelators, solvents, drug and excipients used.