Hypromellose acetate succinate

• JPHypromellose Acetate Succinate
• USP–NFHypromellose Acetate Succinate

Affinisol HPMCAS; Aqoat (AS-L, AS-M, AS-H grades); AquaSolve HPMCAS; HPMCAS; hydroxypropyl methylcellulose acetate succinate

Cellulose, 2-hydroxypropyl methyl ether, acetate hydrogen butanedioate (mixed acetic and monosuccinic esters of hypromellose) · [71138-97-1]

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

Coating agent, film former, Release-modifying polymer

Typical concentrations: — · Dosage forms: Solid

Used as an enteric film coating applied from organic solutions or aqueous dispersions, and widely as a carrier for amorphous solid dispersions of poorly water-soluble drugs made by spray drying or hot-melt extrusion, where it maintains drug supersaturation and inhibits crystallisation. It is also used in modified-release matrices and granules.

A white to off-white, odourless or faintly acetic-smelling powder or granules. Grades (L, M and H) differ in their acetyl-to-succinoyl ratio, which determines the pH at which they dissolve; fine (F) and granular (G) particle-size forms are available.

Dissolution pH

L grade ≥ 5.5; M grade ≥ 6.0; H grade ≥ 6.8

Substituent content

methoxy 12–28%, hydroxypropoxy 4–23%, acetyl 2–16%, succinoyl 4–28% (pharmacopoeial ranges)

Glass transition temperature

≈ 120 °C

Solubility

insoluble in water and acidic media; soluble in aqueous media above the grade's threshold pH, and in acetone and methanol–dichloromethane mixtures

Hygroscopic. Under high temperature and humidity the ester groups slowly hydrolyse, increasing the content of free acetic and succinic acids. Store in a tightly closed container in a cool, dry place.

Incompatible with strong oxidising agents. Its acidic carboxyl groups can interact with basic drugs or alkaline excipients, which may affect enteric performance or the stability of solid dispersions.

Made by esterifying hypromellose with acetic anhydride and succinic anhydride in acetic acid with sodium acetate as catalyst. The product is precipitated with water, washed, dried and milled.

Used in oral products and regarded as non-toxic and non-irritant; it is not absorbed from the gastrointestinal tract.

Observe normal precautions for the quantity handled; eye protection, gloves and a dust mask are recommended. Dust explosions are possible with fine powders.

Included in the FDA Inactive Ingredient Database (oral capsules and tablets) and in oral medicines marketed in the USA, Europe and Japan.

Hypromellose; hypromellose phthalate; cellulose acetate phthalate; methacrylic acid copolymers.

For aqueous enteric coating, the micronised (F) grade is dispersed in water with a plasticiser such as triethyl citrate and kept cool during spraying, since the polymer coalesces into a film only after application. For solid dispersions, the grade is chosen by balancing drug–polymer interaction (hydrophobic acetyl groups) against dissolution in the small intestine (succinoyl groups).