Hydroxypropyl methylcellulose; hydroxypropyl methyl cellulose; HPMC; E464
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Hypromellose (INN), short for hydroxypropyl methylcellulose (HPMC), is a semisynthetic, inert, viscoelastic polymer used as eye drops, as well as an excipient and controlled-delivery component in oral medicaments, found in a variety of commercial products.
As a food additive, hypromellose is an emulsifier, thickening and suspending agent, and an alternative to animal gelatin. 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.
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).
There are many fields of application for hypromellose, including:
- Tile adhesives
- Cement renders
- Gypsum products
- Paints & coatings
- Detergents & cleaners
- Eye drops
- Contact lenses
Use in whole grain breads
Agricultural Research Service scientists are investigating using the plant-derived HPMC as a substitute for gluten 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 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.
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 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. It is also used as a binder and as a component of tablet coatings.
Various benchmark tests are used to qualify hypromellose:
- Degree of substitution (DS)
- Molar substitution (MS)
- Salt content
Viscosity test methods
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:
- 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 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.
Society and culture
The cost of this medication in the U.S. is $24 (USD) for 15 ml ophthalmic solution 2.5% 
- ↑ de Silva DJ, Olver JM (July 2005). "Hydroxypropyl methylcellulose (HPMC) lubricant facilitates insertion of porous spherical orbital implants". Ophthal Plast Reconstr Surg. 21 (4): 301–2. doi:10.1097/01.iop.0000170417.19223.6c. PMID 16052145.
- ↑ Williams RO, Sykora MA, Mahaguna V (2001). "Method to recover a lipophilic drug from hydroxypropyl methylcellulose matrix tablets". AAPS PharmSciTech. 2 (2): 29–37. doi:10.1208/pt020208. PMC 2750474. PMID 14727883.
- ↑ "NOSB TAP Review Compiled by OMRI: Hydroxypropyl Methylcellulose" (PDF). Archived (PDF) from the original on 2008-07-20. Retrieved 2008-10-16.
- ↑ Safety data for hydroxypropyl methyl cellulose[permanent dead link]
- ↑ "Example properties and applications of hydroxypropyl methyl cellulose". Archived from the original on 2010-05-04. Retrieved 2008-10-16.
- ↑  Archived December 31, 2008, at the Wayback Machine
- ↑ "About Us". Dow.com. Archived from the original on 2013-01-04. Retrieved 2013-01-01.
- ↑ "US Pat. No. 5,679,713". Archived from the original on 2016-12-22. Retrieved 2022-03-14.
- ↑ Koroloff N, Boots R, Lipman J, Thomas P, Rickard C, Coyer F (June 2004). "A randomised controlled study of the efficacy of hypromellose and Lacri-Lube combination versus polyethylene/Cling wrap to prevent corneal epithelial breakdown in the semiconscious intensive care patient" (PDF). Intensive Care Med. 30 (6): 1122–6. doi:10.1007/s00134-004-2203-y. PMID 15014864. S2CID 28523038. Archived (PDF) from the original on 2017-08-08. Retrieved 2020-01-06.
- ↑ Ali Nokhodchi; Shaista Raja; Pryia Patel; Kofi Asare-Addo (Nov 2012). "The Role of Oral Controlled Release Matrix Tablets in Drug Delivery Systems". Bioimpact. 2 (4): 175–87. doi:10.5681/bi.2012.027. PMC 3648939. PMID 23678458.
- ↑ Weiner, Myra L.; Lois A. Kotkoskie (1999). Excipient Toxicity and Safety. p. 8. ISBN 9780824782108.
- ↑ Reddy, Indra K.; Riz̤ā Miḥvar (2004). Chirality in Drug Design and Development. p. 21. ISBN 9780824750626.
- ↑ Niazi, Sarfaraz (2004). Handbook of Pharmaceutical Manufacturing Formulations. pp. 275–276. ISBN 9780849317460.
- ↑ "Gonak Hypromellose Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 29 August 2021. Retrieved 15 April 2021.
- ↑ "Hypromellose 2910 (4000 mPa.S) | DrugBank Online". go.drugbank.com. Archived from the original on 16 July 2021. Retrieved 15 April 2021.
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