Hypromellose acetate succinate

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

Cellulose, 2-hydroxypropylmethyl ether, acetate hydrogen butanedioate [71138-97-1] 

Hypromellose acetate succinate is a mixture of acetic acid and monosuccinic acid esters of hydroxypropylmethyl cellulose. It is available in several grades, which vary in extent of substitution, mainly of acetyl and succinoyl groups, and in particle size (fine or granular). When dried at 105°C for one hour, it contains 12.0-28.0% of methoxy groups 4.0-23.0% of hydroxypropoxy groups 2.0-16.0% of acetyl groups and 4.0-28.0% of succinoyl groups. 

The molecular weight of hypromellose acetate succinate is approximately 55 000-93 000 Daltons, measured hy gel permeation chromatography using polyethylene oxide as a relative reference standard. 

Where -OR represents one of the following functional groups -hydroxyl, methoxyl, 2-hydroxypropoxyl, acetyl, or succinoyl. 

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Tanno, F., Y. Nishiyama, H. Kokubo, and S. Obara. 2004. Evaluation of hypromellose acetate succinate (HPMCAS) as a carrier in solid dispersioifi nug Development and Industrial Pharmacy. 30 9-17. 

Hypromellose acetate succinate is commonly used in oral pharmaceutical formulations as a film coating, as well as enteric coating material for tablets or granules.It is insoluble in gastric fluid but will swell and dissolve rapidly in... 

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 extru-... 

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). 

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 liquid is produced. Hypromellose acetate succinate can be dissolved in buffers of pH greater than 4.5 with the rank order of solubility for the various grades (see Section 8) increasing with the ratio of acetyl over succinoyl substitution. The exact pH value at which the polymer dissolves depends on the buffer type and ionic strength, although the rank order for the different grades is independent of the buffer used. 

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. It is stable for four years after manufacturing. 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. 

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

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. 

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 2500mg/kg. ... 

A new accurate and robust analytical method based on liquid chromatography has been developed for the analysis of free organic acids, and acetyl and succinoyl substitutions in hypromellose acetate succinate. It provides efficient separation and sensitive quantitation of free acetic and succinic acids. Another new analytical method based on liquid chromatography has also been developed for the analysis of methoxyl and 2-hydroxypropoxyl substitutions in hypromellose acetate... 

Observe normal precautions appropriate to the circumstances and quantity of material handled. Hypromellose acetate succinate dust may be irritant to the eyes. Excessive dust generation should be avoided to minimize the risks of explosions. Avoid contact with open flame, heat, or sparks. Avoid contact with acids, peroxides, and other oxidizing materials. Eye protection is recommended. 

Included in the EDA Inactive Ingredients Guide 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. 

A specification for hypromellose acetate succinate is also included in the Japanese Phatmaceutical Excipients (JPE) see Table II. 

New monograph for Hypromellose Acetate Succinate (In-Process Revision). Pharmaceutical Forum 2003 29(1) 142-146. 

Denatonium Benzoate (for monohydrate) 224 55000-93000 Hypromellose Acetate Succinate 350... 

Hydroxypropyl Starch Hypromellose Acetate Succinate Inulin... 

Hypromellose acetate succinate (HPMCAS) is also frequently leveraged for use in solubilization methodologies with examples demonstrated in Table 27.3. HPMCAS is unique in that it is enteric in nature and contains both hydrophilic and hydrophobic substituents. The enteric nature is advantageous in that the ASD does not dissolve until it encounters the higher pH values associated with the upper intestine and thus release the API in an environment more suitable for maintaining supersaturation of the drug compound. 

Conveniently, many of the polymers that most effectively stabilize supersaturation also provide suitable thermoplastic characteristics for extrusion. Two of the most commonly used materials are copovidone and hypromellose acetate succinate, which are non-ionic and enteric materials, respectively. 

Cellulose esters or ethers such as methylcellulose (MC), ethylcellulose (EC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose/hypromellose (HPMC), hypromeUose phthalate (HPMCP), hypromellose acetate phthalate (HPMCAP), hypromellose acetate succinate (HPMCAS), cellulose acetate (CA) and derivates Poly (methyl) methacrylates (Eudragit L, S, E, RS/ RL)... 

Hypromellose acetate succinate (HPMCAS) Cellulose ethers anionic 130°C 50,000 g/mol Above pH 5.0 Low 29.1 200 °C Hot melt extrusion Spray drying Solvent-controlled precipitation Eluid bed spraying... 

Hypromellose acetate succinate AQOAl -L aqoat -m aqoat -h 120-135 1. Easily extruded without plasticizer 2. Process temperatures >140°C 3. Stable up to 190 °C depending on processing conditions... 

HPMCAS is also known as hypromellose acetate succinate and is commercially available from Shin-Etsu Chemical Company and The Dow Chemical Company. 

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