Hypromellose (HPMC)

• BPHypromellose
• JPHypromellose
• Ph. Eur.Hypromellose
• USP–NFHypromellose

Benecel MHPC; HPMC; hydroxypropyl methylcellulose; methylhydroxypropylcellulose; Methocel; Metolose; Pharmacoat; Tylopur; E464

Cellulose, 2-hydroxypropyl methyl ether · [9004-65-3]

Polymer, mixture or material of variable composition — no single molecular formula applies.

Binder, Coating agent, film former, Gelling agent, viscosity modifier

Typical concentrations: 2–5% binder · 10–80% matrix · 2–20% film coat · Dosage forms: Solid, Liquid, Semi-solid

One of the most widely used polymers in oral, ophthalmic, nasal and topical products. Typical uses: tablet binder in wet or dry granulation, about 2–5% w/w; film coating, using 2–20% w/w solutions depending on viscosity grade; hydrophilic matrix former for extended release, about 10–80% w/w of high-viscosity grades; thickener in eye drops and artificial tears, 0.45–1.0%. It is also used to make capsule shells, as a suspending and stabilising agent, as a precipitation inhibitor in amorphous solid dispersions and in hot-melt extrusion.

An odourless and tasteless, white or creamy-white fibrous or granular powder. Pharmacopoeias classify it by substitution type, a four-digit number giving the approximate methoxy and hydroxypropoxy percentages (for example 2910, 2208, 1828, 2906), and by the nominal viscosity of a 2% w/w aqueous solution.

Substitution (type 2910 / 2208)

2910: methoxy 28–30%, hydroxypropoxy 7–12%; 2208: methoxy 19–24%, hydroxypropoxy 4–12%

Viscosity

grades from about 3 mPa·s to 100 000 mPa·s or more (2% w/w aqueous solution, 20 °C)

pH

5.0–8.0 (2% w/w aqueous solution)

Thermal gelation

aqueous solutions gel reversibly on heating, at about 50–90 °C depending on substitution type and concentration

Solubility

soluble in cold water; practically insoluble in hot water, ethanol and chloroform; soluble in mixtures of ethanol and dichloromethane and in some aqueous alcohols

The powder is stable, although slightly hygroscopic; store in a well-closed container in a cool, dry place. Aqueous solutions are stable over about pH 3–11 but are susceptible to enzymatic and microbial degradation and should be preserved. Viscosity falls as temperature rises until the gel point is reached.

Incompatible with some oxidising agents. Being non-ionic, it does not form insoluble complexes with metal salts or ionic organic compounds, but high concentrations of electrolytes or other solutes lower its gelation temperature and can salt it out.

Prepared by treating alkali cellulose with chloromethane and propylene oxide to introduce methoxy and hydroxypropoxy groups. The product is purified in hot water, in which it is insoluble, then dried and milled.

Widely used and regarded as non-toxic and non-irritant; it is not absorbed after oral administration. Excessive oral intake may have a laxative effect.

Observe normal precautions for the quantity handled. The dust may irritate the eyes and is combustible; use eye protection and avoid generating dust.

Accepted as a food additive in Europe (E464). Included in the FDA Inactive Ingredient Database (ophthalmic, nasal, oral, rectal, topical and vaginal preparations) and in non-parenteral medicines licensed in Europe.

Hypromellose acetate succinate; hypromellose phthalate; hydroxypropyl cellulose; methylcellulose.

To dissolve it without lumps, disperse the powder in about a third of the water heated above about 80 °C, then add the rest as cold water or ice with stirring. In hydrophilic matrices, drug release is controlled by the formation of a gel layer, and type K (2208) grades are generally preferred because they hydrate fastest.