Chemical Properties
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).
Chemical Properties
soluble in organic solvents, including acetone, methanol, aqueous ethanol
Uses
Hypromellose Acetate Succinate HPMCAS;is a pharmaceutical compound comprising enzalutamide.
Production Methods
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.
Pharmaceutical 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
storage
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.
Incompatibilities
Hypromellose acetate succinate is incompatible with strong acids or
bases, oxidizing agents, and sustained levels of elevated humidity.
Regulatory Status
Included in the FDA Inactive Ingredients Database for use in oral
preparations (capsules, and delayed-action preparations). Hypromellose
acetate succinate has been approved for use in commercial
pharmaceutical products in the USA and in Japan.
