Poly(methyl acrylate)

Chemical Properties

Polymethacrylates are synthetic cationic and anionic polymers of dimethylaminoethyl methacrylates, methacrylic acid, and methacrylic acid esters in varying ratios. Several different types are commercially available and may be obtained as the dry powder, as an aqueous dispersion, or as an organic solution. A (60 : 40) mixture of acetone and propan-2-ol is most commonly used as the organic solvent.
Eudragit E is a cationic polymer based on dimethylaminoethyl methacrylate and other neutral methacrylic acid esters. It is soluble in gastric fluid as well as in weakly acidic buffer solutions (up to pH≈5). Eudragit E is available as a 12.5% ready-to-use solution in propan-2-ol–acetone (60 : 40). It is light yellow in color with the characteristic odor of the solvents. Solvent-free granules contain ≈98% dried weight content of Eudragit E. Eudragit E PO is a white free-flowing powder with at least 95% of dry polymer.
Eudragit L and S, also referred to as methacrylic acid copolymers in the USP32–NF27 monograph, are anionic copolymerization products of methacrylic acid and methyl methacrylate. The ratio of free carboxyl groups to the ester is approximately 1 : 1 in Eudragit L (Type A) and approximately 1 : 2 in Eudragit S (Type B). Both polymers are readily soluble in neutral to weakly alkaline conditions (pH 6–7) and form salts with alkalis, thus affording film coats that are resistant to gastric media but soluble in intestinal fluid. They are available as a 12.5% solution in propan-2-ol without plasticizer (Eudragit L 12.5 and S 12.5); and as a 12.5% ready-to-use solution in propan-2-ol with 1.25% dibutyl phthalate as plasticizer (Eudragit L 12.5 P and S 12.5 P). Solutions are colorless, with the characteristic odor of the solvent. Eudragit L - 100 and Eudragit S-100 are white free-flowing powders with at least 95% of dry polymers.
Eudragit FS 30 D is the aqueous dispersion of an anionic copolymer based on methyl acrylate, methyl methacrylate, and methacrylic acid. The ratio of free carboxyl groups to ester groups is approximately 1 : 10. It is a highly flexible polymer, designed for use in enteric-coated solid-dosage forms, and dissolves in aqueous systems at pH >7.
Eudragit RL and Eudragit RS, also referred to as ammonio methacrylate copolymers in the USP32–NF27 monograph, are copolymers synthesized from acrylic acid and methacrylic acid esters, with Eudragit RL (Type A) having 10% of functional quaternary ammonium groups and Eudragit RS (Type B) having 5% of functional quaternary ammonium groups. The ammonium groups are present as salts and give rise to pH-independent permeability of the polymers. Both polymers are water-insoluble, and films prepared from Eudragit RL are freely permeable to water, whereas, films prepared from Eudragit RS are only slightly permeable to water. They are available as 12.5% ready-to-use solutions in propan-2-ol–acetone (60 : 40). Solutions are colorless or slightly yellow in color, and may be clear or slightly turbid; they have an odor characteristic of the solvents. Solvent-free granules (Eudragit RL 100 and Eudragit RS 100) contain 597% of the dried weight content of the polymer.
Eudragit RL PO and Eudragit RS PO are fine, white powders with a slight amine-like odor. They are characteristically the same polymers as Eudragit RL and RS. They contain 597% of dry polymer.
Eudragit RL 30 D and Eudragit RS 30 D are aqueous dispersions of copolymers of acrylic acid and methacrylic acid esters with a low content of quaternary ammonium groups. The dispersions contain 30% polymer. The quaternary groups occur as salts and are responsible for the permeability of films made from these polymers. Films prepared from Eudragit RL 30 D are readily permeable to water and to dissolved active substances, whereas films prepared from Eudragit RS 30 D are less permeable to water. Film coatings prepared from both polymers give pH-independent release of active substance. Plasticizers are usually added to improve film properties.
Eudragit NE 30 D and Eudragit NE 40 D are aqueous dispersions of a neutral copolymer consisting of polymethacrylic acid esters. The dispersions are milky-white liquids of low viscosity and have a weak aromatic odor. Films prepared from the lacquer swell in water, to which they become permeable. Thus, films produced are insoluble in water, but give pH-independent drug release.
Eudragit NM 30 D is an aqueous dispersion of a neutral copolymer based on ethyl acrylate and methyl methacrylate, and is of identical monomer composition to Eudragit NE 30 D.
Eudragit L 30 D-55 is an aqueous dispersion of an anionic copolymer based on methacrylic acid and ethyl acrylate. The copolymer corresponds to USP32–NF27 methacrylic acid copolymer, Type C. The ratio of free-carboxyl groups to ester groups is 1 : 1. Films prepared from the copolymers dissolve above pH 5.5, forming salts with alkalis, thus affording coatings that are insoluble in gastric media but soluble in the small intestine.
Eastacryl 30D and Kollicoat MAE 30 DP are also aqueous dispersions of the anionic copolymer based on methacrylic acid and ethyl acrylate. The copolymer also corresponds to USP32–NF27 methacrylic acid copolymer, Type C. The ratio of free-carboxyl groups to ester groups is 1 : 1. Films prepared from the copolymers dissolve above pH 5.5, forming salts with alkalis, thus affording coatings that are insoluble in gastric media but soluble in the small intestine.
Eudragit L 100-55 (prepared by spray-drying Eudragit L 30 D- 55) is a white, free-flowing powder that is redispersible in water to form a latex that has properties similar to those of Eudragit L 30 D- 55.
Acryl-EZE and Acryl-EZE MP are also commercially available as redispersible powder forms, which are designed for enteric coating of tablets and beads, respectively.

Chemical Properties

clear liquid

Uses

PMA/methylamine borane (MeAB) composites, prepared by solution blending process finds uses as a hydrogen storage material with better dehydrogenation property compared to MeAB.

Preparation

The structure of methyl acrylate is H2C=CH-COOCH3. The monomer used to prepare poly(methyl acrylate) is produced by the oxidation of propylene. The resin is made by free-radical polymerization initiated by peroxide catalysts and has the following formula:

Poly(methyl acrylate) resins vary from soft, elastic, film-forming materials to hard plastics.

Definition

ChEBI: An acrylate macromolecule composed of repeating methoxycarbonylethylene units.

Production Methods

Prepared by the polymerization of acrylic and methacrylic acids or their esters, e.g. butyl ester or dimethylaminoethyl ester

Pharmaceutical Applications

Polymethacrylates are primarily used in oral capsule and tablet formulations as film-coating agents.(1–21) Depending on the type of polymer used, films of different solubility characteristics can be produced;
Eudragit E is used as a plain or insulating film former. It is soluble in gastric fluid below pH 5. In contrast, Eudragit L, S and FS types are used as enteric coating agents because they are resistant to gastric fluid. Different types of enteric coatings are soluble at different pH values: e.g. Eudragit L is soluble at pH > 6 whereas Eudragit S and FS are soluble at pH > 7. The S grade is generally used for coating tablets, while the flexible FS 30 D dispersion is preferred for coating particles.
Eudragit RL, RS, NE 30D, NE 40D, andNM30D are used to form water-insoluble film coats for sustained-release products. Eudragit RL films are more permeable than those of Eudragit RS, and films of varying permeability can be obtained by mixing the two types together. The neutral Eudragit NE/NM grades do not have functional ionic groups. They swell in aqueous media independently of pH without dissolving.
Eudragit L 30 D-55 is used as an enteric coating film former for solid-dosage forms. The coating is resistant to gastric juice but dissolves readily at above pH 5.5.
Eudragit L 100-55 is an alternative to Eudragit L 30 D-55. It is commercially available as a redispersible powder.
Kollicoat MAE 100 P, Acryl-EZE and Acryl-EZE MP are also commercially available as redispersible powder forms, which are designed for enteric coating of tablets or beads.
Eastacryl 30 D and Kollicoat MAE 30 DP are aqueous dispersions of methacrylic acid–ethyl acrylate copolymers. They are also used as enteric coatings for solid-dosage forms. Polymethacrylates are also used as binders in both aqueous and organic wet-granulation processes. Larger quantities (5–20%) of dry polymer are used to control the release of an active substance from a tablet matrix. Solid polymers may be used in directcompression processes in quantities of 10–50%.
Polymethacrylate polymers may additionally be used to form the matrix layers of transdermal delivery systems and have also been used to prepare novel gel formulations for rectal administration.

Safety

Polymethacrylate copolymers are widely used as film-coating materials in oral pharmaceutical formulations. They are also used in topical formulations and are generally regarded as nontoxic and nonirritant materials.
Based on relevant chronic oral toxicity studies in rats and conventionally calculated with a safety factor of 100, a daily intake of 2–200 mg/kg body-weight depending on the grade of Eudragit may be regarded as essentially safe in humans.

Solubility in organics

Aromatic hydrocarbons, esters, ketones, THF

storage

Dry powder polymer forms are stable at temperatures less than 30°C. Above this temperature, powders tend to form clumps, although this does not affect the quality of the substance and the clumps can be readily broken up. Dry powders are stable for at least 3 years if stored in a tightly closed container at less than 30°C.
Dispersions are sensitive to extreme temperatures and phase separation occurs below 0°C. Dispersions should therefore be stored at temperatures between 5 and 25°C and are stable for at least 18 months after shipping from the manufacturer’s warehouse if stored in a tightly closed container at the above conditions.

Purification Methods

Precipitate it from a 2% solution in acetone by addition of water.

Incompatibilities

Incompatibilities occur with certain polymethacrylate dispersions depending upon the ionic and physical properties of the polymer and solvent. For example, coagulation may be caused by soluble electrolytes, pH changes, some organic solvents, and extremes of temperature. For example, dispersions of Eudragit L 30 D, RL 30 D, L 100-55, and RS 30 D are incompatible with magnesium stearate. Eastacryl 30 D, Kollicoat MAE 100 P, and Kollicoat MAE 30 DP are also incompatible with magnesium stearate.
Interactions between polymethacrylates and some drugs can occur, although solid polymethacrylates and organic solutions are generally more compatible than aqueous dispersions.

Regulatory Status

Included in the FDA Inactive Ingredients Database (oral capsules and tablets). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.