Enteric coating acid copolymers

Shellac is the oldest known material that has been used as enteric coating material. However, as a natural material, it lacks a crucial quality criterion of more modern polymers (i.e., batch-to-batch reproducibility). Hence, the most commonly used polymers today are the synthetic methacrylate copolymers or semisynthetic derivatives of cellulose. The main structural element of these polymers is an acidic function (either phthalate or methacrylic acid), which is responsible for the pH-dependent dissolution. 

A survey of the German market showed that more than 50% of enteric formulations were coated with methacrylate copolymers, about 40% with cellulose derivatives, 5% with shellac, and 3% with other materials [1], Enteric coating materials (Table 1) are described in various publications [21, 22], In addition to polymers mentioned in Table 1, others are being studied (e.g., to obtain release at lower pH) [23], Polymers with a dissolution at lower pH are intended for the protection of drugs in acidic medium and not for the protection of the gastric mucosa. 

To achieve enteric protection of the core, at least 3-4 mg/cm2 of polymer have to be applied (Figure 4). The precise amount of film coating depends on the type of polymer that is applied. Cellulose derivatives usually require higher amounts of polymer to obtain the same protection as methacrylic acid copolymers. A thin layer of 4 mg/cm2 of methacrylate copolymer will dissolve within approximately 10 minutes. However, if increasing layers of polymer are applied, the dissolution time will be prolonged, which can be used to delay the dissolution of the dmg in the small intestine (Figure 5). 

The enteric protection properties of a methacrylate polymer were investigated with the use of naproxen tablets [56] enteric coated with an aqueous dispersion of methacrylic acid copolymer (EUDRAGIT L 30 D-55, USP NF type C). 

As previously discussed, food effects are an important parameter for enteric-coated systems, especially for drugs, that are sensitive to food. Pancreatic enzyme-containing products fail when they come in contact too early with lipids, proteins, and carbohydrates present in food. The clinical efficacy of pancreatic enzymes formulated as enteric-coated tablets was investigated in man and dog [44], The enteric materials examined were hydroxypropyl methylcellulose phthal-ate (HPMCP), cellulose acetate phthalate (CAP), and the methacrylic acid copolymer USP/NF Type C. In vivo behavior monitored by x-ray scintigraphy showed clear differences between the three coating formulations. HPMCP-coated products adhered to the gastric mucosa, whereas CAP and methacrylate copolymer... 

CGP 57813 is a peptidomimetic inhibitor of human HIV-1 protease. This lipophilic compound has been successfully entrapped in polylactic acid (PLA) and into pH-sensitive methacrylic acid copolymer particles (EUDRAGIT L 1 GO-55) [69], After the application of a film-coating, the plasma concentration was acceptable and reached similar levels as with injections of drug-loaded PLA carriers. To hinder the proteolytic degradation of a drug, two types of enteric-coated pellets were applied simultaneously. One contained the protease inhibitor coated... 

K. Lehmann, B. Brogmann, C. J. Kenyon, J. R. Wilding, The in vivo behaviour of enteric naproxen tablets coated with an aqueous dispersion of methacrylic acid copolymer, S.T.P. Pharma Sci 7(6) 403-437 (1997). 

Eastacryl 30 D, Kollicoat MAE 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. 

Eudragit PS 30D 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 has been designed for the use in enteric-coated solid-dosage forms and dissolves in aqueous systems at pH >7. 

In another aspect of the SODAS design, the secondary pellet fraction is produced as described above however, the delayed release beads are produced by coating the IR beads with an enteric polymer (methacrylic acid copolymer) rather than a sustained release polymer (81). This bi-modal release system was used in the formulation of Ritalin LA and was demonstrated to produce two distinct pla.sma concentration peaks separated by approximately 4 hours (81). This bi-modal pulsed release system was demonstrated to be bioequivalent to two immediate release tablet doses administered four hours apart. 

Table 88. Enteric coating with methacrylic acid copolymer and povidone...

The enteric materials examined were hydroxypropyl methylcellulose phthal-ate (HPMCP), cellulose acetate phthalate (CAP), and the methacrylic acid copolymer USP/NF Type C. In vivo behavior monitored by x-ray scintigraphy showed clear differences between the three coating formulations. HPMCP-coated products adhered to the gastric mucosa, whereas CAP and methacrylate copolymer... 

The first example of a surface eroding polymer was a partially esterified copolymer of methyl vinyl ether and maleic anhydride, published in 1978 [1], These polymers solubilize by ionization of carboxylic acid groups as shown in Scheme 1 and because at low pH the carboxyl groups are unionized and hence the polymer is insoluble, these materials are useful as enteric coatings to protect oral dosage forms from dissolution in the stomach [4-6]. 

Chem. Descrip. Methacrylic acid copolymer system Uses Enteric coating for pharmaceutical solid dosage forms such as tablets, granules, and beads... 

Chem. Descrip. Methacrylic acid copolymer, Type C, USP/NF aq. disp. Uses Excipient for controlled-release pharmaceutical applies., enteric coatings, coatings resist, to tropical conditions, lozenges, sealing coats Properties Aq. disp. sol. in intestinal fluid from pH 5.5 flash pt. none 30% polymer... 

Chem. Descrip. Methacrylic acid copolymer Type C USP/NF Uses Excipient tor controlled-release pharmaceutical applies., enteric coated tablets masks unpleasant taste/odors of pharmaceutical ingreds. Features Sol. in intestinal tluid above pH 5.5, but resist, to gastric tluids Properties Redispersible, spray-dried powd. sol. in intestinal tluid above pH 5.5, but resist, to gastric tluids insol. in water, acids nontlamm. anionic 95% polymer Storage 36 mos min. shell lile < 30 C Eudragit NE 30 D [Rohm GmbH Rohm Am. Rohm Tech]... 

Chem. Descrip. Methacrylic acid copolymer Type B USP/NF Uses Excipient for controlled-release pharmaceuticals, enteric coatings Features pH-dependent... 

Docosahexaenoic acid tablet mfg., enteric coated Methacrylic acid copolymer tablet ng agent... 

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