Gastro-resistant tablet

Enteric tablets are pharmaceutical forms with delayed release of active ingredient, which (also by a coating Coating called) is achieved. These dosage forms are resistant to the acidic environment of the gastric juice . The coating only dissolves after passing through the gastric porter . The dissolving behavior of the coating depends on the pH value, so that the active substance is only released in a targeted manner in the section of the intestine whose milieu corresponds to this value.

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In addition to tablets, which can be coated in an enteric coating in all possible shapes and sizes, the following forms of administration can also be coated in an enteric coating: coated tablets, hard capsules, soft capsules, pellets and granules. In the case of very fine-grained powders (<100 µm), successful coating is difficult because they have a very large total surface area and tend to agglomerate.
Tablets with an enteric coating are assigned to the "film-coated tablets" category in the pharmacopoeias.
The following substances are used as components that give the coating gastric juice resistance:

Poly (meth) acylates
Cellulose acetate phthalate (CAP)
Cellulose acetate succinate
Hydroxypropyl methyl cellulose phthalate
Hydroxypropyl methyl cellulose acetate succinate
Polyvinyl acetate phthalate (PVAP)
shellac
Cellulose acetate trimellitate
Sodium alginate

In addition, depending on the coating formulation, other auxiliaries are used, such as release agents, plasticizers, stabilizers, gloss / polishing agents, emulsifiers and / or pigments / coloring substances.
The functional components and the required auxiliaries are in principle added to a solvent in which they are dispersed or dissolved in this. Both water and organic solvents can be used as solvents. The solution / suspension obtained in this way is then applied to the dosage form, the solvent evaporating.

Indications

Enteric coated tablets are stable in the acidic environment of the stomach, but disintegrate relatively quickly in the small intestine, which has a weakly acidic, neutral or alkaline environment, and thus release the active ingredient.

This principle is used in the following cases:

If there is a risk of inactivation or destruction of the medicinal substance in the stomach due to the acidic environment in the gastric juice (e.g. antibiotics , pancreatin and other enzymes, organ preparations)
For drugs that cause nausea or vomiting, irritate or damage the stomach lining (such as NSAIDs such as acetylsalicylic acid, diclofenac)
If a high drug concentration in the intestine is to be achieved, e.g. B. for local treatment (anthelmintics, antiseptics , probiotics )
When drugs impede digestion ( tannin , astringent heavy metals, formation of insoluble compounds with pepsin and peptones ).
If optimal absorption concentrations are to be achieved in the duodenum and jejunum by releasing the entire amount of drug.

Polymethacrylate for coating gastro-resistant tablets

Eudragit L-55

Eudragit L-55 is an anionic copolymer of methacrylic acid and ethyl acrylate in an acid-ester ratio of 1: 1. This Eudragit type is enteric-coated and easily soluble in the duodenum from pH 5.5. Eudragit L 30 D-55 (30% aqueous dispersion) or L 100-55 (powder) are available as commercial products.

Eudragit L

Eudragit L is an anionic copolymer made from methacrylic acid and methyl methacrylate. The acid-ester ratio is 1: 1. In the acidic gastric environment, the carboxylic acid is protonated. In the section of the small intestine following the duodenum, the jejunum , the carboxylic acid is deprotonated and can therefore be solvated as an ion and dissolve. Eudragit L 100 (powder) and Eudragit L 12.5% (organic solution 12.5%) are commercially available.

Eudragit S.

Eudragit S is an anionic copolymer of methacrylic acid and methyl methacrylate in an acid-ester ratio of 1: 2. Eudragit is gastric juice-resistant and only soluble in the rear part of the small intestine, the ileum or in the transition to the colon . The commercial products are Eudragit S 100 (powder) and Eudragit L 12.5% (organic solution 12.5%).

Eudragit FS 30 D

The Eudragit FS is an aqueous dispersion of an anionic copolymer of methyl acrylate, methyl methacrylate and methacrylic acid. The acid-ester ratio is 1:10. The polymethacrylate is flexible, gastric juice-resistant and, like the Eudragit S, soluble in the ileum / colon .

Summary on polymethacrylates

Film maker	Type	Mark	Soluble in	application
Eudragit L-55	anionic	Acid-ester ratio 1: 1	Intestinal juice> pH 5.5	Enteric-coated coating
Eudragit L	anionic	Acid-ester ratio 1: 1	Intestinal juice> pH 6	Enteric-coated coating
Eudragit S.	anionic	Acid-ester ratio 1: 2	Intestinal juice> pH 7	Enteric-coated Coating / Colon Targetting
Eudragit FS	anionic	Approx. 10% free acid	Intestinal juice> pH 7.2	Enteric coating / colon targetting

The gastro-resistant Eudragit types shown have different acid-ester ratios. The higher the ester content, the more difficult it is for the coating to come off in the small intestine. The carboxylic acid function is essential for the dissolution, as it is deprotonated in the slightly acidic, neutral small intestine, can then be solvated and finally it comes to dissolution. This dissolution mechanism is the same for all enteric coated Eudragit types. The acid content of the Eudragit FS 30D is only 10%, which is why the coating dissolves at the highest pH value and therefore later.

Tests for gastro-resistant tablets from the pharmacopoeia

Disintegration time (Ph.Eur. Monograph 2.9.1)

The test for disintegration takes place in the “test apparatus A” or “test apparatus B” described in the European Pharmacopoeia, whereby either 6 or 3 tablets can be tested at the same time, depending on the apparatus. When testing gastro-resistant tablets, the apparatus must be kept in operation for 2 hours in hydrochloric acid (0.1 M), whereby the tablet must not disintegrate in this medium.

The duration of resistance of the tablets in an acidic environment varies depending on the tablet being tested and is usually at least 2 to 3 hours, but it must not be less than an hour even with permitted deviations. The tablets must not show any signs of disintegration, other than fragments of the coating, or cracks which could lead to the release of the contents. The acidic solution is then replaced by a phosphate buffer solution pH 6.8 R and the test items (tablets) are each weighted with a disk. The apparatus is kept in operation for 60 minutes, after which time the tablets must have disintegrated.

If the tablets fail the test because they stick to the disc, the results will be invalid. In this case, the test is repeated with six more tablets without discs.

literature

(Source: European Pharmacopoeia Edition 8)

Individual evidence

↑ ^a ^b ^c ^d M. Kumpugdee-Vollrath et al .: Coatings in the pharmaceutical industry. In: Easy Coating - Basics and trends in coating pharmaceutical products. Vieweg + Teubner Verlag, Wiesbaden 2011, p. 53 ISBN 978-3-8348-0964-3

[CPI-1] M. Kumpugdee-Vollrath et al .: Coatings in the pharmaceutical industry. In: Easy Coating - Basics and trends in coating pharmaceutical products. Vieweg + Teubner Verlag, Wiesbaden 2011, p. 53 ISBN 978-3-8348-0964-3