HYDROXYPROPYL METHYL CELLULOSE ACETATE SUCCINATE Chemical Properties

Melting point:

>203°C (dec.)

storage temp. 

Hygroscopic, -20°C Freezer, Under inert atmosphere

solubility 

Practically insoluble in ethanol (95%), hexane, unbuffered water, and xylene. On the addition of acetone, or a mixture of ethanol (95%) and dichloromethane (1 : 1), a clear or turbid viscous solution is produced. Hypromellose acetate succinate also forms a clear or turbid solution in buffers of pH greater than 4.5 with the rank order of solubility for the various grades increasing with the ratio of acetyl over succinoyl substitution. The exact pH value at which the polymer starts to swell and dissolve depends on the buffer type and ionic strength, although the rank order for the different grades is independent of the buffer used. No solvent has been found to completely dissolve hypromellose acetate succinate polymer; the resulting clear or turbid solutions significantly scatter light in both static and dynamic light scattering experiments, indicating that the polymer may exist as colloids or aggregates. The data is collated from the Shin-Etsu Chemical Co. Ltd and the research work of the authors (R Chen, BC Hancock, and RM Shanker).

form 

Solid

color 

White to Off-White

Stability:

Hygroscopic

LogP

-0.591 (est)

Safety Information

HS Code 

3912390000

HYDROXYPROPYL METHYL CELLULOSE ACETATE SUCCINATE Usage And Synthesis

Chemical Properties

soluble in organic solvents, including acetone, methanol, aqueous ethanol

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).

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.

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