Hypromellose Acetate Succinate

Category

Controlled-release Agents; Coating Agents; Film-forming Agents; Sustained-release Agents

Grade

Pharmceutical Excipients

Description

Hypromellose acetate succinate is a white to off-white powder or granules. It has a faint acetic acid-like odor and a barely detectable taste. Hypromellose acetate succinate is available in several grades, according to the pH at which the polymer dissolves (low, L; medium, M; and high, H) and its predominant particle size (cohesive fine powder, F; or free-flowing granules, G).

UNII

NA

Chemical Name

Cellulose, 2-hydroxypropylmethyl ether, acetate hydrogen butanedioate

CAS Number

71138-97-1

Synonyms

Aqoat; Aqoat AS-HF/HG; Aqoat AS-LF/LG; Aqoat AS-MF/MG; cellulose, 2-hydroxypropyl methyl ether, acetate succinate; HPMCAS

Administration route

Oral

Dosage Form

Capsules, and delayed-action preparations

Stability and Storage Conditions

Hypromellose acetate succinate should be stored in a well-closed container, in a cool, dry place. In such storage conditions, hypromellose acetate succinate is a stable material. Hypromellose acetate succinate is hygroscopic. It is hydrolyzed to acetic acid and succinic acid, and the hypromellose polymer starts to form if dissolved in 1 mol/L sodium hydroxide for more than two hours. The hydrolysis is the main degradation pathway that is responsible for increasing amounts of free acids in storage, especially upon exposure to moisture.

Source and Preparation

Hypromellose acetate succinate is produced by the esterification of hypromellose with acetic anhydride and succinic anhydride, in a reaction medium of a carboxylic acid, such as acetic acid, and using an alkali carboxylate, such as sodium acetate, as catalyst.The fibrous reaction product is precipitated out by adding a large volume of water to the reaction medium. Purification is achieved by thorough washing with water. The granular grade of hypromellose acetate succinate that is so obtained can be pulverized to a fine powder if required.

Applications

Hypromellose acetate succinate is commonly used in oral pharmaceutical formulations as a film coating, as well as an enteric coating material for tablets or granules.It is a solubility enhancing agent via solid dispersion. Hypromellose acetate succinate is insoluble in gastric fluid but will swell and dissolve rapidly in the upper intestine. For aqueous film-coating purposes, a dispersion of hypromellose acetate succinate fine powder and triethyl citrate (as a plasticizer) in water is commonly utilized.Organic solvents can also be used as vehicles for applying this polymer as a film coating. Hypromellose acetate succinate may be used alone or in combination with other soluble or insoluble binders in the preparation of granules with sustained drug-release properties; the release rate is pH-dependent. Dispersions of poorly soluble drugs with hypromellose acetate succinate are prepared using techniques such as mechanical grinding, solvent evaporation, and melt extrusion.

Safety

The safety and pharmacological profiles of hypromellose acetate succinate are similar to those of other ether and ester derivatives of cellulose. All nonclinical studies reported in the literature identify no target organs for toxicity by hypromellose acetate succinate.It has also been reported that hypromellose acetate succinate does not alter fertility in rats, does not produce any developmental anomalies in rats and rabbits, and does not alter perinatal and postnatal development in rats when assessed up to 2500 mg/kg body-weight.

Incompatibilities

Hypromellose acetate succinate is incompatible with strong acids or bases, oxidizing agents, and sustained levels of elevated humidity.