Hypromellose ( INN), short for hydroxypropyl methylcellulose (HPMC), is a

semisynthetic Semisynthesis, or partial chemical synthesis, is a type of chemical synthesis that uses chemical compounds isolated from natural sources (such as microbial cell cultures or plant material) as the starting materials to produce novel compounds with ...

, inert, viscoelastic

polymer A polymer (; Greek '' poly-'', "many" + '' -mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...

used in eye drops, as well as an

excipient An excipient is a substance formulated alongside the active ingredient of a medication, included for the purpose of long-term stabilization, bulking up solid formulations that contain potent active ingredients in small amounts (thus often referred ...

and controlled-delivery component in oral medicaments, found in a variety of commercial products. As a

food additive Food additives are substances added to food to preserve Taste, flavor or enhance taste, appearance, or other sensory qualities. Some additives have been used for centuries as part of an effort to preserve food, for example vinegar (pickling), sal ...

, hypromellose is an

emulsifier An emulsion is a mixture of two or more liquids that are normally immiscible (unmixable or unblendable) owing to liquid-liquid phase separation. Emulsions are part of a more general class of two-phase systems of matter called colloids. Althoug ...

, thickening and suspending agent, and an alternative to animal gelatin. Its

Codex Alimentarius The Codex Alimentarius () is a collection of internationally recognized standards, codes of practice, guidelines, and other recommendations published by the Food and Agriculture Organization of the United Nations relating to food, food productio ...

code (

E number E numbers ("E" stands for "Europe") are codes for substances used as food additives, including those found naturally in many foods such as vitamin C, for use within the European Union (EU) and European Free Trade Association (EFTA). Commonly ...

) is E464.

Chemistry

Hypromellose is a solid, and is a slightly off-white to beige powder in appearance and may be formed into granules. The compound forms

colloid A colloid is a mixture in which one substance consisting of microscopically dispersed insoluble particles is suspended throughout another substance. Some definitions specify that the particles must be dispersed in a liquid, while others extend ...

s when dissolved in water. This non-toxic ingredient is combustible and can react vigorously with

oxidizing agent An oxidizing agent (also known as an oxidant, oxidizer, electron recipient, or electron acceptor) is a substance in a redox chemical reaction that gains or " accepts"/"receives" an electron from a (called the , , or ). In other words, an oxi ...

s. Hypromellose in an aqueous solution, like methylcellulose, exhibits a thermal gelation property. That is, when the solution heats up to a

critical temperature Critical or Critically may refer to: *Critical, or critical but stable, medical states **Critical, or intensive care medicine * Critical juncture, a discontinuous change studied in the social sciences. * Critical Software, a company specializing ...

, 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).

Uses

There are many fields of application for hypromellose, including: * Tile adhesives * Cement renders * Gypsum products * Pharmaceutical * Paints and coatings * Food * Cosmetics * Detergents and cleaners * Eye drops * Contact lenses

Use in whole grain breads

Agricultural Research Service The Agricultural Research Service (ARS) is the principal in-house research agency of the United States Department of Agriculture (USDA). ARS is one of four agencies in USDA's Research, Education and Economics mission area. ARS is charged with ext ...

scientists are investigating using the plant-derived HPMC as a substitute for

gluten Gluten is a structural protein naturally found in certain cereal grains. Although "gluten" often only refers to wheat proteins, in medical literature it refers to the combination of prolamin and glutelin proteins naturally occurring in all grai ...

in making all-oat and other grain breads. 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.

Use in construction materials

HPMC is used primarily in construction materials like tile adhesives and renders where it is used as a

rheology Rheology (; ) is the study of the flow of matter, primarily in a fluid ( liquid or gas) state, but also as "soft solids" or solids under conditions in which they respond with plastic flow rather than deforming elastically in response to an ap ...

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.

Ophthalmic applications

Hypromellose solutions were patented as a semisynthetic substitute for tear-film. 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. 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 Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...

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.

Excipient/tableting ingredient

In addition to its use in ophthalmic liquids, hypromellose has been used as an

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. It is also used as a binder and as a component of tablet

coatings A coating is a covering that is applied to the surface of an object, usually referred to as the substrate. The purpose of applying the coating may be decorative, functional, or both. Coatings may be applied as liquids, gases or solids e.g. Powd ...

. There is a growing body of anecdotal evidence that hypromellose can cause intestinal problems in some humans, even as far as an allergic reaction.

Test methods

Various benchmark tests are used to qualify hypromellose: *

Viscosity The viscosity of a fluid is a measure of its resistance to deformation at a given rate. For liquids, it corresponds to the informal concept of "thickness": for example, syrup has a higher viscosity than water. Viscosity quantifies the int ...

* Degree of substitution (DS) * Molar substitution (MS) * Salt content * Moisture

Viscosity test methods

Because hypromellose solution is a non-newtonian solution and exhibits pseudoplastic, more specifically,

thixotropic Thixotropy is a time-dependent shear thinning property. Certain gels or fluids that are thick or viscous under static conditions will flow (become thinner, less viscous) over time when shaken, agitated, shear-stressed, or otherwise stressed ( ...

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: *Solution concentration (1%, 2%, 1.9% bone dry, etc.) *Viscometer (RheoSense m-VROC and microVISC, Brookfield LV or RV, Höppler falling ball, Haake Rotovisco, etc.) *Viscometer spindle number (1 ~ 4 for Brookfield LV, 1 ~ 7 for Brookfield RV, etc.) *Solution Temperature (20 °C, 25 °C, etc.)

Degree of substitution

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

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.

Moisture

Since all cellulose ethers are

hygroscopic Hygroscopy is the phenomenon of attracting and holding water molecules via either absorption or adsorption from the surrounding environment, which is usually at normal or room temperature. If water molecules become suspended among the substance' ...

, 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.

References

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External links

Methylcellulose & Hydroxypropyl Methyl Cellulose for building materials
Polysaccharides Edible thickening agents Cellulose Excipients Cellulose ethers E-number additives