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]
As a food additive, hypromellose is an emulsifier, thickening and suspending agent, and an alternative to animal gelatin. [3] 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. [4]
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: [5]
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 [7] where it is used as a rheology modifier and water retention agent.
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. [8]
Hypromellose solutions were patented as a semisynthetic substitute for tear-film. [9] 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. [10] 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. [11] It is also used as a binder [12] and as a component of tablet coatings. [13] [14]
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.
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.
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).
Pharmaceutical formulation, in pharmaceutics, is the process in which different chemical substances, including the active drug, are combined to produce a final medicinal product. The word formulation is often used in a way that includes dosage form.
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.
Brookfield Engineering is an engineering and manufacturing company with headquarters in Middleboro, Massachusetts. It is a subsidiary of the conglomerate Ametek. Its product line includes laboratory viscometers, rheometers, texture analyzers, and powder flow testers as well as in-line process instrumentation. These instruments are used by research, design, and process control departments.
Thin-film drug delivery uses a dissolving film or oral drug strip to administer drugs via absorption in the mouth and/or via the small intestines (enterically). A film is prepared using hydrophilic polymers that rapidly dissolves on the tongue or buccal cavity, delivering the drug to the systemic circulation via dissolution when contact with liquid is made.
Hydrophilization is a process used for hydrophobic drugs to increase their release rate from capsules, which is dependent on the rate of dissolution, by covering the surface of the drug particles with minute droplets of a hydrophilic polymer solution.
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.
High-maltose corn syrup (HMCS) is a food additive used as a sweetener and preservative. The majority sugar is maltose. It is less sweet than high-fructose corn syrup and contains little to no fructose. It is sweet enough to be useful as a sweetener in commercial food production, however. To be given the label "high", the syrup must contain at least 50% maltose. Typically, it contains 40–50% maltose, though some have as high as 70%.
Ophthalmic viscosurgical devices (OVDs) are a class of clear gel-like material used in eye surgery to maintain the volume and shape of the anterior chamber of the eye, and protect the intraocular tissues during the procedure. They were originally called viscoelastic substances, or just viscoelastics. Their consistency allows the surgical instruments to move through them, but when there is low shear stress they do not flow, and retain their shape, preventing collapse of the anterior chamber. OVDs are available in several formulations which may be combined or used individually as best suits the procedure, and are introduced into the anterior chamber at the start of the procedure, and removed at the end. Their tendency to remain coherent helps with removal, as the cohesive variants tend to be drawn into the aspiration orifice without breaking up.
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.