Pharmaceutical Preparation Containing Ibuprofen and a Process for Its Preparation

This invention relates to an ibuprofen containing pharmaceutical preparations. More particularly, this invention relates to an ibuprofen containing pharmaceutical preparation in which the unpleasant taste of ibupofen is avoided, and in which the tendency of the ibuprofen to irritate the esophagus and the gastrointestinal tract is reduced by coating the ibuprofen particles with a hydro-colloid and fumaric acid. This invention further relates to a process for manufacturing the ibuprofen containing pharmaceutical preparation.

Pharmaceutical preparations are known which contain as inactive agents substances having an acid or an acid radical. Such substances have a tendency to irritate strongly the mucous membrane of the mouth and throat. One such active agent which is known to irritate strongly the mucous membranes of the mouth and throat is ibuprofen (2-(4-isobutyl phenyl) propionic acid).

Ibuprofen is an active agent which has become increasingly important for the treatment of rheumatism and arthritis. It is relatively insoluble in water. It also has a very unpleasant taste, and, as mentioned above, causes irritation of the mucous membranes of the esophagus. It is also known from the literature that, like aspirin, ibuprofen can cause gastrointestinal bleeding. This occurs if the substance arrives at the stomach wall in a relatively high concentration, such as in the form of a tablet or a capsule.

This problem can be alleviated if the ibuprofen were suspended in water prior to its being taken orally, thus preventing local over-concentration from developing in the gastrointestinal tract. However, because of the relative insolubility of ibuprofen, such water suspensions are difficult to prepare.

Known water suspensions of ibuprofen contain discrete particles of ibuprofen . These particles may become trapped in the mouth and esophagus where they may cause scratching and irritating sensations. They also impart an unpleasant taste to the suspension. There have thus been difficulties heretofore associated with the oral administration of ibuprofen containing substances.

It is therefore an object of the present invention to provide an ibuprofen containing pharmaceutical preparation which does not irritate the mucous membranes of the throat and gastrointestinal tract.

It is also an object of the present invention to provide an ibuprofen containing pharmaceutical preparation which does not have the unpleasant taste effects of prior art ibuprofen containing preparations.

It is also an object of the present invention to prepare an effervescent mixture of an ibuprofen containing pharmaceutical preparation.

It is yet another object of the present invention to provide a process for the manufacture of the ibuprofen containing pharmaceutical preparation.

These and other objects are achieved by means of an ibuprofen containing pharmaceutical preparation wherein the ibuprofen particles are coated with a hydro-colloid and with fumaric acid. Desirably, the hydro-colloid contains xanthan gum and/or maltodextrin.

The ibuprofen containing pharmaceutical preparation of the present invention can be prepared, if desired, in the form of an effervescent mixture. Such a mixture can be manufactured by adding citric acid and calcium carbonate to the previously prepared ibuprofen coated preparation. In such an effervescent mixture, the calcium carbonate envelops the citric acid and a bonding layer is formed by the reaction of the calcium carbonate with the surface adjacent layer of the citric acid crystal.

In accordance with a different aspect of the present invention, a process for the manufacture of the ibuprofen containing pharmaceutical preparation is provided. In accordance with this process, ibuprofen particles under vacuum conditions are coated with a hydro-colloid and fumaric acid in a vacuum mixing machine, and the resulting mixture is then vacuum-dried. More particularly, a process is provided wherein ibuprofen particles and a hydro-colloid are mixed with water in a vacuum mixing machine at a pressure of about 0.1 bar. The mixture is then partially dried to about 0.2 bar. Fumaric acid is added to the mixture, and the mixture is then completely dried.

The ibuprofen containing preparation pharmaceutical preparation of the present invention does not suffer from the shortcomings of prior art preparations due to the envelopment of the ibuprofen crystals by the hydro-colloid in the presence of fumaric acid . The fumaric acid has a higher pH than the ibuprofen and prevents the negative taste effects. The pseudo-colloid performs the function of connecting the water insoluble ibuprofen particles to the sparingly soluble fumaric acid .

The process by which the ibuprofen containing pharmaceutical preparation of the present invention is prepared may be conveniently and advantageously carried out in a vacuum mixing machine by a process which is generally described in German patent application P 3434774.7, which is incorporated herein by reference.

The present invention will be more fully illustrated by reference to the following examples.

200 parts of ibuprofen were treated with a solution of 10 parts xanthan gum and 10 parts maltodextrin in 50 parts of water. 20 parts fumaric acid were added to the mixture prior to complete drying in vacuo at about 200 mbar. After complete drying, a granulate was obtained which was ground to a grain size of about 0.3 mm.

These particles were then combined with crystalline sugar and citric acid by an instantaneous technology. The amount of sugar used was equal to 10 to 15 times the quantity of the pharmaceutical preparation, while the amount of citric acid was equal to twice the quantity of the pharmaceutical preparation.

The resulting mixture could be made into a pleasant tasting beverage having a dosage of 200 mg ibuprofen and which no longer irritated the mucous membranes.

The mixture of example 1 was successfully prepared as an effervescent mixture by adding citric acid and calcium carbonate.

50 parts citric acid were reacted with 50 parts calcium carbonate in vacuo, 5 parts of 50% ethanol being added. This effervescent mixture was dried and added to the ibuprofen containing pharmaceutical preparation of Example 1 in an amount equal to 5 times the amount of the ibuprofen.

A product thus prepared comprised a slowly effervescing mixture in which the calcium carbonate exerted an additional pleasant tasting effect on the ibuprofen.

While the invention has been described by reference to specific embodiments, this was for purposes for illustration only and should not be construed to limit the spirit or the scope of the invention.