Opinion | What Does the Recent Pig-to-Human Kidney Transplant Mean for Tissue Therapeutics?
In a pioneering procedure, a team of surgeons at New York University Langone Health Grossman School of Medicine in New...
Methacrylic Acid-Ethyl Acrylate Copolymer (1:1) Dispersion 30% is a colloidal suspension of the anionic copolymer Methacrylic acid and Ethyl acrylate (molecular weight 320,000 g/mol) in water at a solids content of 30%. The ratio of free carboxyl groups to ester groups is approx. 1:1. It is used as an enteric coating (trigger pH 5.5). It is commonly known as EUDRAGIT® L30 D 55 (Evonik) or KOLLICOAT MAE 30 DP (BASF). Methacrylic Acid-Ethyl Acrylate Copolymer (1:1) Dispersion 30% is supplied as a milky liquid with a faint acrylic odour.
Synonyms and Trade Names: Methacrylic Acid–Ethyl Acrylate Copolymer (1:1) Dispersion 30%; Methacrylic Acid Copolymer Dispersion; Methacrylic Acid Copolymer LD; Eudragit L30 D-55; Acrycoat L30D-55; Acrylates Copolymer; Polyacrylate Dispersion 30%; Acryl-EZE; Kollicaot MAE 30DP; Eastacryl 30D
Pharmacopoeial Compliance: USP-NF; Ph.Eur; JP; B.P, and IP
Uses and Applications: Film Forming Agent; Tablet Binder; and Tablet Coating Agent
Methacrylic Acid Ethyl Acrylate Copolymer (1:1) Dispersion 30% is a colloidal suspension of the anionic copolymer Methacrylic acid and Ethyl acrylate (molecular weight 320,000 g/mol) in purified water. As well as the copolymer, it also contains Sodium lauryl sulphate (0.7%), and Polysorbate 80 (2.3%). Methacrylic Acid Ethyl Acrylate Copolymer (1:1) Dispersion 30% is the premier poly(methacrylate) copolymer system for use as an enteric coating agent (trigger pH 5.5). It is commonly known as EUDRAGIT® L30 D 55 (Evonik) or KOLLICOAT MAE 30 DP (BASF).
Methacrylic Acid–Ethyl Acrylate Copolymer (1:1) contains between 46% and 56% m/m methacrylic acid units. The ratio of carboxylic groups to ester groups is approximately 1:1. Thus, due to the presence of carboxylic acid groups in its structure, Methacrylic Acid–Ethyl Acrylate Copolymer (1:1) is insoluble in acidic media but soluble in neutral to alkaline fluids, making it ideal as an enteric film coating agent.
Poly(methacrylate) copolymers have a long history of use in the pharmaceutical industry having been introduced in 1955 following on from the work of the famed scientist, Otto Rohm (of Rohm & Haas), who also invented PLEXIGLASS®, a material that is chemically related to, and shares many chemical properties with poly(methacrylate) copolymers. Their introduction marked a step-change in the field of drug delivery and pharmaceutical technology owing to their reproducibility and versatility compared with naturally derived polymers based on cellulose.
Basics of Poly(methacrylate) Copolymers
The structural basis of all Poly(methacrylate) copolymers, such as Methacrylic Acid–Ethyl Acrylate Copolymer, is Methacrylic acid, an alpha, beta-unsaturated monocarboxylic acid, that is, acrylic acid having the hydrogen at C2 substituted by a methyl group:
To synthesise poly(methacrylate) polymers, acrylic and methacrylic acid esters are combined via free radical polymerisation. Long polymer chains are then formed by chain grow reactions from various acrylate or methacrylate derivatives. The polymerisation reaction can be performed in a solvent, bulk, suspension or emulsion:
Variations in chain lengths can be obtained via termination and transfer reactions, while the functional properties of methacrylic copolymers and the final polymers are adjusted by selecting from a variety of monomers. Generally, non-functional comonomers determine the polymer’s properties while functional comonomers determine the solution profile.
Classification of Poly(methacrylate) Copolymers
Depending on the functional group attached to the polymer chain backbone, poly(methacrylate) copolymers can be categorised into two broad different groups:
In reality, there is some overlap and the most ideal method of classifying poly(methacrylate) copolymers is to use both schemes as shown below:
Anionic poly(methacrylate) polymers contain -COOH (methacrylic acid) functional groups, which allows them to dissociate and dissolve at the higher pH of the small intestine and colon. These polymers offer enteric protection to many active ingredients in oral solid formulations in the gastric environment and can trigger drug release at a selected pH for targeted drug delivery. They are available in a wide range of physical forms (aqueous dispersions, organic solvent, granules, and fine powders).
Cationic polymethacrylate polymers are based on dimethyl amino ethyl methacrylate, butyl methacrylate, and methyl methacrylate residues. These grades are cationic and soluble in gastric fluid below pH 5 but become swellable and permeable, but not soluble, above pH 5. For this reason, cationic poly(methacrylate) copolymers can be used for taste-masking and moisture -protection applications. They are available in a wide range of physical forms, including aqueous dispersions, organic solvent, granules, and fine powders.
Neutral poly(methacrylate) copolymers are further divided into two broad groups:
A summary of various poly(methacrylate) copolymer grades and their application scope in pharmaceuticals is shown in the table below:
R = COOH, Alkyl = -CH2CH3
|Chemical Name||Poly(methacrylic acid co-methyl methacrylate) 1:1|
|CAS Registration Number||[25212-88-8]|
|Molecular weight||320 000|
|UNII Code (FDA)||T967IEU43C|
Methacrylic Acid–Ethyl Acrylate copolymer (1:1) 30% Dispersion is an approved pharmaceutical excipient. It is listed in the Ph.Eur (Methacrylic Acid–Ethyl Acrylate Copolymer (1:1)) 30% Dispersion, USP-NF (Methacrylic Acid Copolymer, Type C) and the J.P (Methacrylic Acid Copolymer LD). It is included in the FDA Inactive Ingredients Database (oral capsules and tablets). It is, however, not approved for food use.
|Physical state||Milky-white aqueous dispersion|
|Density (true)||1.06 – 1.07 g/cm3|
|Density (relative)||1.06 – 1.07 g/cm3|
|Refractive index||index = 1,39-1.|
|Solubility||Miscible in water, soluble in Acetone, Ethanol & intestinal fluids ³6.0|
|Viscosity (Brookfield)||3-10 mPa.s|
|Viscosity (Kinematic)||3-15 mm2/s|
|Official name||Ethyl Acrylate and Methacrylic Acid-Copolymer Dispersion||Methacrylic Acid-Ethyl Acrylate Copolymer (1:1) Dispersion 30%|
|Identification||A, B||A, B|
|Appearance of a film||n/a||specified|
|Apparent viscosity||≤15 mPa.s||≤15 mPa.s|
|Ethyl acrylate and methacrylic acid||n/a||≤0.1%|
|Loss on Drying||68.5-71.5%||≤5.0%|
|Residue on ignition||≤0.2%||n/a|
|Limit of total monomers||≤0.01%||n/a|
Key: n/a Specification is not listed
*All claims with respect to conformity are subject to our Terms and Conditions. No express or implied warranty is made for specific properties or fitness for any particular application or purpose.
Methacrylic Acid –Ethyl Acrylate Copolymer (1:1) 30% dispersion is the most-widely used enteric film-forming agent and tablet binder. It is used in oral capsule and tablet formulations as film-coating agents. Methacrylic acid –Ethyl Acrylate Copolymer (1:1) dispersion may additionally be used to form the matrix tablet systems, alone or in combination with other polymeric resins.
Note that for enteric applications, there are several anionic Poly(methacrylate) copolymers that possess carboxyl groups in varying amounts, and therefore, are suitable for use, either alone or in combination with Methacrylic acid-ethyl acrylate copolymer (1:1), as enteric coatings. When the dissolution pH is reached, the polymers dissolve by salt formation, allowing the drug substance to be released at the desired rate or location in the GI tract.
|Pharmacopoeial name||Brand||Solubility||Release site|
|Methacrylic acid-ethyl acrylate copolymer (1:1)||EUDRAGIT®L30 D-55
|Methacrylic acid-methyl acrylate copolymer (1:1)||EUDRAGIT® L 100
EUDRAGIT® L 12.5
|Methacrylic acid-methyl acrylate copolymer (1:2)||EUDRAGIT® S 100
EUDRAGIT® S 12.5
|Poly(methyl acrylate-co-methyl methacylate-co-methacrylic acid) 7:3:1||EUDRAGIT® FS30D||≥Ph 7.0||Ileum/colon|
If the interest is in simple enteric coatings that dissolve quickly in the small intestine, the aqueous dispersion, Methacrylic acid-ethyl acrylate copolymer (1:1) 30% dispersion or the same polymer in spray-dried form, Methacrylic acid-ethyl acrylate copolymer (1:1) are more than adequate.
If the drug is to be released lower down in the small intestines, poly(methacrylate) copolymers with higher trigger pH, such as Methacrylic acid-methyl acrylate copolymer (1:1) or Methacrylic acid-methyl acrylate copolymer (1:2) can be used in different mixtures to create specific dissolution profiles.
For release in the colon, grades with a dissolution pH of 7 are used. Methacrylic acid-methyl acrylate copolymer (1:2) (e.g EUDRAGIT® S), is the choice for coating tablets while the Poly(methyl acrylate-co-methyl methacrylate-co-methacrylic acid) 7:3:1 (e.g EUDRAGIT® FS 30D) is recommended for coating multiparticulates due to its greater flexibility.
Preparation Basics for Enteric Coatings
All anionic poly(methacrylate) copolymers, with the exception of Poly(methyl acrylate-co-methyl methacrylate-co-methacrylic acid) 7:3:1 (e.g EUDRAGIT® FS 30D), have high glass transition temperature (Tg) and are brittle in nature. Their aqueous dispersions have high minimum film-forming temperatures, which reduces their film-forming abilities at normal tablet coating temperatures. For this reason, a plasticiser is needed when using these polymers for coating solid dosage forms. Commonly used plasticisers include Triethyl citrate, Polyethylene Glycol 6000, and Propylene Glycol at a concentration of 10-20% (polymer dry basis).
The reduction of the polymer’s Tg has the effect of increasing its tackiness during processing. To prevent this, it is necessary to add a suitable antitacking agent. Traditionally, talc has been used for this purpose at 50% (polymer dry basis) however, Glyceryl monostearate (at 5% polymer dry basis) is preferred since it reduces spray thickness without impacting on weight gain growth.
Once a suitable antitacking agent has been added, it may be desirable to add pigments. Anionic Poly(methacrylate) copolymers permit the use of pigments and colourants in a single coating dispersion (as opposed to using a separate coloured top-coat). The only caveat is that pigments and colourants should be used moderately as they can alter the permeability of the film, reducing its acid resistance.
Anionic Poly(methacrylate) copolymers can be used individually or in combination with other polymers to match virtually any target release profile including immediate, delayed, sustained, pulsatile, accelerated and zero-order release.
For standard enteric coatings, Methacrylate acid ethyl acrylate copolymers, such as EUDRAGIT® L 30 D-55, is the clear option due to its ease of use and global acceptability. Recently, Evonik has launched an improved formulation of EUDRAGIT® L 30 D-55 which incorporates plasticisers for increased flexibility and reduced brittleness. This system is known as EUDRAGIT® FL 30 D-55.
For specific guidance on the use of Poly(methacrylate) copolymers, consult the manufacturer’s technical team.
Methacrylic Acid –Ethyl Acrylate Copolymer (1:1) 30% dispersion is the most widely used enteric film-coating material today. It is generally regarded as a non-toxic and non-irritant material. 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 is recommended, depending on the grade.
Toxicology: LD50 (rat. IP) 1.33 g/kg, LD50 (rat, SC): 75g/kg
Acute and chronic adverse effects have been observed in workers handling the related substances methyl methacrylate and poly(methyl methacrylate) (PMMA). In the UK, the workplace exposure limit for methyl methacrylate has been set at 208 mg/m3 (50ppm) long-term (8-hour TWA), and 416mg/m3 (100ppm) short-term.
Methyacrylic Acid Ethyl Acrylate Copolymer dispersions are sensitive to extreme temperature 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.
Observe normal precautions appropriate to the circumstances and quantity of material handled. Additional measures should be taken when handling organic solutions of polymethacrylates. Eye protection, gloves, and a dust mask or respirator are recommended. Ensure there is adequate ventilation.
Click here to read more about recommended storage conditions for EUDRAGIT L100-D and EUDRAGIT L30 D-55 aqueous dispersions here:
EUDRAGIT® L100-55 Storage Stability Information Sheet (Evonik)
A sustainability score for Methacrylic Acid–Ethyl acrylate copolymer (1:1) 30% Dispersion has not been provided.
Evonik Operations GmbH (ex DEGUSSA/Rohm)
 C.G. Cameron, J.W. McGinity, Controlled-Release Theophylline Tablet Formulations Containing Acrylic Resins, III. Influence of Filler Excipient, Drug Development and Industrial Pharmacy, 13 (1987) 303-318.
 M.Z.I. Khan, Ž. Prebeg, N. Kurjaković, A pH-dependent colon targeted oral drug delivery system using methacrylic acid copolymers. I. Manipulation Of drug release using Eudragit L100-55 and Eudragit S100 combinations, Journal of Controlled Release, 58 (1999) 215-222.
 A. Ceballos, M. Cirri, F. Maestrelli, G. Corti, P. Mura, Influence of formulation and process variables on in vitro release of theophylline from directly-compressed Eudragit matrix tablets, Farmaco, 60 (2005) 913-918.
 Evonik Industries, EUDRAGIT® L 100, Technical Information, (2012).
 S. Thakral, N.K. Thakral, D.K. Majumdar, Eudragit®: a technology evaluation, Expert Opinion on Drug Delivery, 10 (2013) 131-149.
 R. Wulff, C.S. Leopold, Coatings of Eudragit® RL and L-55 blends: investigations on the drug release mechanism, AAPS PharmSciTech, 17 (2016) 493-503.
In a pioneering procedure, a team of surgeons at New York University Langone Health Grossman School of Medicine in New...
PharmaCentral.com may on occasion publish user-generated content. Any information provided on our platform is for general informational and educational purposes only. All information is provided in good faith to enable collaboration and sharing of know-how among our community of users. Authors who submit content retain copyright to it.
PharmaCentral.com does not make any representation or warranty of any kind regarding its accuracy, adequacy, or legality. Any references to particular product names, brands, descriptions, formats, styles, corporate entities, tests, applications, technologies, uses, standardisations, medical conditions, and treatments are for illustration purposes and should not be considered complete or binding. All respective intellectual property, such as trademarks and logos, are properties of their owners
Under Section 107 of the Copyright Act 1976, allowance is made for ‘Fair Use’ for purposes such as criticism, comment, news, reporting, scholarship, education, and research.
Fair use is a use permitted by copyright statute that might otherwise be infringing.
Some information contained on PharmaCentral.com may contain copyrighted material, the use of which may not have been specifically authorised by the respective copyright owners. Some material is made available to help explain and relay complex phenomena, formulae, physical and chemical constants, and other concepts that are scientifically incontestable but relevant to the use of products, and/or to illustrate, transmit, and teach pharmaceutical science principles. Some material is published to support research and user education, and for the public good.