NL193821C - Pharmaceutical preparation. - Google Patents

Description

1 193821

Pharmaceutical preparation

The present invention relates to a pharmaceutical composition containing ranitidine or a physiologically acceptable salt thereof and also another active ingredient.

Such a preparation is known from British patent GB 1,565,966, Ranitidine is the approved name for N- [2 - [[[5- (dimethylamino) methyl] -2-furanyl] methyl] thio] ethyl-N '- methyl 2-nitro-1,1-ethylenediamine. Ranitidine is a strong histamine H2 antagonist and can be used in the treatment of conditions where it is beneficial to reduce gastric acidity, especially in gastric and duodenal ulcers, and in the treatment of allergic and inflammatory conditions in which histamine is a known mediator. GB 1,565,966 describes the administration of ranitidine and other furan derivatives in combination with other active ingredients in which only conventional anti-histamines, i.e. histamine Hrantagonists, are mentioned.

Systemic non-steroidal anti-inflammatory drugs such as acetosal, Indomethacin and ibuprofen are known for their unwanted side effects. In particular, it is known that these compounds are not ulcero-15 and can therefore cause stomach ulcers when administered orally. This side effect can be further enhanced when combined with other factors such as stress. Since some treatments require these compounds to be used for a long time, these effects can be a significant drawback.

It has now been found that mucose damage of the gastrointestinal tract caused by systemic non-anti-inflammatory agents can be markedly reduced by co-administration of ranitidine.

The present invention therefore provides pharmaceutical preparations as described in the preamble, characterized in that the other active ingredient is ibuprofen or indomethacin.

As the prior art, further reference is made to Chemical Abstracts 94, 24923V (1981) which relates to the effect of ranitidine and another H 2 antagonist, cymetidine, on aspirin-induced intestinal damage in the rat. In the experiments described, ranitidine and aspirin were administered separately. A pharmaceutical composition containing both substances is not described by this reference.

The pharmaceutical preparations of the invention are particularly useful in a form suitable for oral or rectal administration.

The systemic non-steroidal anti-inflammatory agents used in the invention also exhibit marked analgesic activity. They can be used in the present compositions in their usual dosage amounts, for example 10 to 100 mg of indomethacin and 100 to 500 mg of ibuprofen per unit dose, which can be administered once or several times a day according to normal therapy for the particular agent.

Preferably, the ranitidine is used in the formulation in the form of a physiologically suitable salt. Such salts include salts of inorganic or organic acids, such as the hydrochloride, hydrobromide, sulfate, acetate, maleate, succinate, and the fumarate. The hydrochloride is particularly preferred. The amount of ranitidine, preferably in the form of a physiological salt, that is used in the present compositions should be sufficient to reduce the gastrointestinal concerns caused by the anti-inflammatory agents and is preferably in the range of 10-200 mg per dosage unit.

The present compositions can be made using at least one pharmaceutical carrier or excipient. The preparation can e.g. in the form of tablets, capsules, folding powders, granules, solutions, syrups, suspensions or suppositories, which are suitably manufactured with conventional excipients. The preparation can thus be used as excipient e.g. contain: binders, tableting aids, fillers, lubricants, disintegrants and wetting agents. If desired, other active ingredients may also be present in this type of preparation. Tablets can be coated in a conventional manner, e.g. with an appropriate film-forming material, such as methyl cellulose, ethyl-50 cellulose, and / or hydroxypropyl methyl cellulose, or with sugar.

The liquid preparations can also e.g. edible oils, such as groundnut oil. Suppositories can e.g. fat-soluble or water-miscible bases.

The compositions of the invention can be prepared according to conventional techniques common in the pharmaceutical industry. For example, e.g. most preferably the anti-inflammatory agents the 55 ranitidine or the ranitidine salt mixed together, and if desired provided with suitable excipients.

Tablets can e.g. are manufactured by directly crushing such a mixture into tablets. Capsules can be prepared by filling the mixture into gelatin capsules together with suitable excipients using a suitable filling machine. t

Also, the present compositions may be in the form of an appropriate controlled release form such that the ranitidine or its salt is rapidly released for resorption and the non-steroidal anti-inflammatory agent is slowly released. The preparations thus obtained are suitable for oral or rectal administration and are often put in a controlled release form.

The present compositions can be used to treat inflammatory conditions, especially acute and chronic musculoskeletal infections, such as rheumatoid and osteoarthritis as well as ankylosis spondylitis and in conditions in which an analgesic side effect is desired, such as in dysmenorrhoea, especially if the use of the anti-inflammatory agent is limited by gastrointestinal-10 side effects.

The invention is further illustrated by the following non-limiting examples.

Example I - Tablets.

15 (a) mg / tablet ranitidine hydrochloride 168.0011 ibuprofen 400.00 lactose 387.00 hydroxypropylmethylcellulose 5.00 sodium starch glycolate 30.00 magnesium stearate 10.00 tablet weight 1000.00 x equivalent to 150 mg ranitidine base.

25

The ranitidine hydrochloride and the ibuprofen were sieved through a 250 µm sieve and mixed with the lactose. This mixture was granulated with a solution of the hydroxypropylmethylcellulose. The granules were dried, sieved and mixed with the sodium starch glycolate and the magnesium stearate. These lubricated granules were pelleted using 30 12.5 mm punches.

(b) mg / tablet ranitidine hydrochloride 168.00 indomethacin 50.00 35 microcrystalline cellulose 79.00 magnesium stearate 3.00 tablet weight 300.00

The ranitidine hydrochloride and the indomethacin were mixed with the microcrystalline cellulose and the magnesium stearate and crushed using 9.5 mm punches.

Example II - Capsules (a) mg / capsule 45 ranitidine hydrochloride 168.00 ibuprofen 400.00 starch 1500 * 228.00 magnesium stearate 4.00 fill weight 800.00 50 xx A form of a directly tabletable starch from Colorcon Ltd., Orpington, Knows

The ranitidine hydrochloride and ibuprofen were sieved through a 250 µm sieve and mixed with the starch 1500 and the magnesium stearate. The resulting mixture was filled into size 0 hard gelatin capsules using an appropriate filling machine.

Claims (3)

3 193821 (b) mg / capsule 'ranitidine hydrochloride 168.00 indomethacin 50.00 starch 1500 80.50 5 magnesium stearate 1.50 fill weight 300.00 The ranitidine hydrochloride and indomethacin were sieved through a 250 µm sieve and mixed with the starch 1500 and the magnesium stearate. The resulting mixture was filled into size 2 hard gelatin capsules using an appropriate filling machine. 15 Pharmaceutical preparation containing ranitidine or a physiologically suitable salt thereof and also another active ingredient, characterized in that the other active ingredient is ibuprofen or indomethacin. Pharmaceutical preparation according to claim 1, characterized in that it contains 10 to 200 mg ranitidine or a physiologically acceptable salt thereof and 100 to 500 mg ibuprofen or 10 to 100 mg indomethacin. Pharmaceutical preparation according to claim 1 or 2, characterized in that the ranitidine is used in the form of the hydrochloride salt