Dosage form containing pantoprazole as active ingredient

Abstract

Dosage forms for the oral administration of the magnesium salt of pantoprazole are described.

Description

TECHNICAL FIELD [0001] The present invention relates to the field of pharmaceutical technology and describes a dosage form for oral administration of the magnesium salt of pantoprazole. The invention additionally relates to proces-ses for producing the dosage form. PRIOR ART [0002] It is generally known to coat peroral administration forms, e.g. tablets or pellets which contain an acid-labile active compound, with an enteric coating which, after passage through the stomach, rapidly dissolves in the alkaline medium of the intestine. Examples of such acid-labile active compounds are acid-labile proton pump inhibitors (H+ / K+ ATPase inhibitors), in particular pyridin-2-ylmethylsulfinyl-1H-benzimidazoles, such as are disclosed, for example, in EP-A-0 005 129, EP-A-0 166 287, EP-A-0 174 726 and EP-A-0 268 956. On account of their H+ / K+ ATPase-inhibiting action, these are of importance in the therapy of diseases, which are due to increased gastric acid secretion. Examples of active compoun...

AI Technical Summary

Benefits of technology

[0011] It is an object of the present invention to provide a dosage form for oral administration of pantoprazole magnesium salt, which dosage form can be produced without great technical complexity, which takes account of the acid lability of pantoprazole and which makes available the pantoprazole magnesium salt effectively for the body in such a way that an optimal active ingredient profile and thus action profile is achieved.

[0014] Surprisingly it has also been found now that oral dosage forms for pantoprazole magnesium salt comprising low molecular weight polyvinylpyrrolidone as excipient show stability and a distinctly improved release profile for the active ingredient as compared to oral dosage forms for pantoprazole magnesium salt known from the art.

[0019] Because of a great tendency to decompose in a neutral and, in particular, acidic environment, which also results in highly colored decomposition products, for oral compositions, it is preferred on the one hand to keep the magnesium salt of pantoprazole in an alkaline environment and, on the other hand, to protect it from exposure to acids. It is generally known to coat tablets or pellets, which contain an acid-labile active ingredient with an enteric coating which, after passage through the stomach, rapidly dissolves in the alkaline medium in the intestine. In the case of pantoprazole, which is very acid-labile, it is preferred to process it in the tablet core or in pellets in the form of its alkaline salts, and preferably together with alkaline substances. Since the substances suitable for enteric coatings contain free carboxyl groups, a problem arises when the enteric coating is partly or even completely dissolved from the inside because of the alkaline medium in the interior, and the free carboxyl groups promote decomposition of the active ingredients. It is therefore preferred to provide a sealing intermediate layer (subcoating) between the enteric coating and an alkaline tablet or pellet core. EP-A 0244380 proposes to coat cores, which contain the active ingredient together with alkaline compounds or as alkaline salt with at least one layer, which is soluble in water or rapidly disintegrates in water, of nonacidic, inert pharmaceutically-acceptable substance before the enteric layer is applied. The intermediate layer or intermediate layers act as pH-buffering zones in which hydrogen ions, which diffuse in from the outside, are able to react with the hydroxyl ions which diffuse out of the alkaline core. In order to increase the buffer capacity of the intermediate layer, it is proposed to incorporate buffer substance into the intermediate layer(s). It is possible in practice by this method to obtain rather stable compositions.

Problems solved by technology

Since the substances suitable for enteric coatings are those having free carboxyl groups, the problem results that the enteric coating is partly dissolved or even dissolved from inside because of the alkaline medium in the interior and the free carboxyl groups promote the decomposition of the active compounds.

Moreover, a considerable effort is to be made in the preparation to avoid traces of moisture.

As the abovementioned prior art shows, the production of peroral administration forms for acid-labile active compounds requires technically complicated processes.

Images