Antacid Tablet Formulation
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Patentamt JEuropâischesEuropean Patent Office © Publication number: O 003 589 Office européen des brevets B 1 @ EUROPEAN PATENT SPECIFICATION @ Date of publication of patent spécification: 11.04.84 @ Int. Cl.3: A 61 K 9/20 @ Application number: 79100337.9 @ Date offiling: 05.02.79 (54) Antacid tablet formulation. (30) Priority: 06.02.78 GB 466978 @ Proprietor: THE WELLCOME FOUNDATION LIMITED 1 83-1 93 Euston Road (43) Date of publication of application: London NW1 2BP (GB) 22.08.79 Bulletin 79/1 7 @ Inventor: Harden, David (45) Publication of the grant of the patent: 25 Sandhurst Road 1 1 .04.84 Bulletin 84/1 5 Sidcup, Kent (GB) Inventor: Gayst, Stephen 19 Arthur Street @ Designated Contracting States: Double Bay New South Wales (AU) BE CH DE FR GB LU NL SE (74) Representative: Berg, Wilhelm, Dr. etal, (§) References cited: Dr. Berg, Dipl.-lng. Stapf, Dipl.-Ing. Schwabe, Dr. FR - A - 2 007 475 Dr. Sandmair Patentanwalte Postfach 860245 FR - A - 2 230 341 D-8000 Miinchen 86 (DE) FR - A - 2 260 993 FR - A - 2 300 550 GB-A-1 057 940 US - A - 2 550 489 US-A-2 581 035 US-A-2 912 358 Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1 ) European patent convention). Courier Press, Leamington Spa, England. The present invention relates to tablets FR-A-2,300,550, 2,260,993 and which rapidly disperse in solution and are useful 2,230,341 disclose tablets in which the for the treatment of gastric hyperacidity. The ingredient is present in high concentration and present invention also provides methods for in which a disintegrating agent having a preparing such tablets. swelling capacity of greater than 5 mg/g. Formulations used to combat gastric However the disclosures are concerned with the hyperacidity conventionally contain an insoluble provision of tablets having good disintegration base or an alkaline salt with a weak acid of times (eg less. than 15 minutes) and are not magnesium or aluminium or a mixture of such dispersible tablets nor would they exhibit the bases or salts. Occasionally insoluble bases or properties of a dispersible tablet. alkaline salts with weak acids of sodium, cal- It is usual to include a mixture of insoluble cium and bismuth are also included in the metal compounds in the tablets of the present formulations together with the said magnesium invention but the invention also includes the and/or aluminium bases or salts. Thus typical case where only one such compound is formulations often contain aluminium included. The tablets contain 50 to 90%, hydroxide, magnesium hydroxide or magnesium preferably 60 to 70% of the antacid carbonate. These antacid formulations act by component(s). neutralising excess acidity in the stomach. To Suitable insoluble metal compounds include give rapid relief of gastric hyperacidity it is those of calcium, such as calcium carbonate, of necessary that antacid formulations give rapid bismuth, such as bismuth carbonate and release of the active ingredients on dismuth subnitrate, of aluminium, such as administration. aluminium hydroxide, aluminium oxide, Unfortunately, the formulations at present aluminium phosphate and aluminium glycinate, marketed are often deficient in this respect. and of magnesium, such as magnesium Antacid formulations currently available are hydroxide, magnesium carbonate and normally in tablet or suspension form and of magnesium silicate. Mixed bases and/or alkaline these the suspension form gives the most rapid salts, that is to say bases and/or salts formed release of active ingredients. A new form of from more than one metal such as sodium poly- antacid tablet has now been developed which hydroxy-aluminium monocarbonate, sodium not only gives a far more rapid release of magnesium aluminium silicate, magnesium ingredient than those antacid tablets which aluminium hydroxide and magnesium have gone before but also gives a more rapid aluminate, are also suitable. release of ingredients than some antacid Particularly suitable insoluble metal suspensions presently available. Such tablets compounds are those of aluminium and contain a disintegrating agent that has a magnesium. Thus, aluminium hydroxide is capacity to swell substantially in the presence of preferred compound for inclusion in the tablets water. of the present invention. Preferred magnesium Accordingly, the present invention provides a compounds include magnesium carbonate and, dispersible tablet for the treatment of gastric in particular, magnesium hydroxide. It has been hyperacidity, which comprises 50-90% of a found that a combination of aluminium conventional antacid component and 5-15% of hydroxide and magnesium hydroxide provides a a disintegrating agent having a swelling particularly favourable antacid component for capacity of between 5 and 100 ml/g. the tablets of the present invention. Suitably the All percentages herein are expressed as aluminium hydroxide and the magnesium weight/weight unless otherwise stated. hydroxide are in weight ratio of from 4:1 to 1:4 Antacid components suitable for inclusion in and preferably in a weight ratio of from 4:1 to the tablets of the present invention are, for 1:2. Tablets containing these ingredients may example, pharmaceutically acceptable metal suitably contain from 200 to 1000 mg of these bases or alkaline salts with weak acids conven- compounds per tablet, for example 400 to tionally used in antacid formulations (see, for 500 mg per tablet. A suitable dose for the example, Martindale, the Extra Pharmacopoeia, treatment of gastric hyperacidity in man is 1 to 27th Ed., for a list of conventional antacid 4 tablets repeated as required. formulations and their ingredients), which have As used herein, the swelling capacity of a a solubility in water of less than 1 part in 70 disintegrating agent is defined as the volume under neutral conditions. (ml) to which 1 g. of a test tablet containing GB-A-1,269,987 (=FR-A-2,007,475) 95% of the dry, disintegrating agent and 5% of discloses inter alia, solid antacid formulations polyvinylpyrollidone (K30) will swell when in which are claimed to revert to suspensions on contact with an excess of water at a contact with water. However the only disclosure temperature of 21°C. It is determined by of a compressed tablet formulation provides granulating the disintegrating agent (2 g) with products with unacceptable physical properties 10% polyvinylpyrollidone (K30) (1 ml) and and, in as far as could be determined, would drying the resultant granules at 60°C. not be a dispersible tablet. Compression of the granules to a hardness value of 12 kg. provides test tablets having a the antacid component will normally be diameter of 15 mm and a weight of below 100 pm and preferably below 50 µm. As approximately 900 mg. Each tablet is then used herein, the particle size of the antacid accurately weighed and placed on the bottom of component is defined in terms of the "weight a 25 ml. measuring cylinder. A nylon disc of median diameter" hereinafter referred to as 8 mm thickness and having two grooves W.M.D. Thus, each particle is considered as a provides a close, but sliding, fit in the measuring sphere having a volume identical with the actual cylinder, resting on the top of the tablet. The particle and the W.M.D. is that "diameter", grooves are disposed opposite each other on wherein 50% of these hypothetical spheres the circumference of the disc in a direction at have a larger diameter than that figure and 50% right angles to the plane thereof and allow for a a smaller diameter than that figure. The W.M.D. thin hypodermic needle to be inserted between may be determined using a Coulter counter in the disc and the glass wall of the measuring which the antacid component dispersed in an cylinder. A 5 g. weight is placed on the nylon electrolyte comprising an aqueous solution of, disc and water injected through one of the for example, sodium chloride, saturated with the grooves into the space surrounding the tablet; antacid component is passed through a small the other groove allowing for air to be displaced. orifice in a tube on either side of which is When the water level is above the top of the immersed an electrode. The changes in disc, the needle can be removed and water resistance as particles pass through the orifice added until it is in excess, e.g. 25 ml. The generate voltage pulses whose amplitudes are volume under the disc is then noted at periodic proportional to the volume of the particles. The intervals until there is no further increase in pulses are amplified, and the numbers counted absorption. In some cases, disintegrating agents at different threshold levels. From this data the absorb water to form viscous gels, and this distribution of the suspended particles and slows down the rate of absorption necessitating hence the W.M.D. may be determined. a longer interval, such as 48 hours, before The particle size of the antacid component maximum swelling is achieved. may readily be reduced, if desired, by On completion of swelling, the final volume is precipitation techniques or by grinding the read and corrected to the corresponding value particles with any apparatus or by any other for 1 g. of the tablet, i.e. the value for the method known in the art suitable for such swelling capacity. The whole operation should purposes. In particular, the hammer mill, which preferably be performed at an approximately can be used with either the rigid or the swing constant room temperature, for example 21 °C.