DE2553444B2 - Process for the production of largely anhydrous granules consisting of sodium citrate and citric acid for use in effervescent preparations - Google Patents

Description

The present invention relates to a new process for producing a substantially anhydrous Granules, consisting of sodium citrate and citric acid, which are used in the production of effervescent preparations can be used.

It is already known to use granules made from sodium citrate and citric acid for use in effervescent tablets to use. In this case, granulation was previously carried out with non-aqueous systems in order to ensure that after the granulation To obtain largely anhydrous granules. Such anhydrous granules are necessary to the To give the shower preparation sufficient stability in relation to the other shower components and in particular, to prevent hydrolysis-sensitive drugs such as acetylsalicylic acid in the mixture from decomposition to protect.

For these reasons, granulation takes place in non-aqueous systems, in particular in methanol, ethanol or isopropanol as granulating liquids. Due to the flammability of these solvents, granulation must be carried out for safety reasons in explosion-proof rooms with appropriate equipment shafts such as planetary mixers or kneaders, rasps and vacuum drying cabinets. All work equipment that comes into contact with the alcohol-dampened product must meet the safety requirements. Thus the bis require _{-) (|} take precedence granulation an elaborate apparatus to the risk of explosion and environmental pollution largely off by the solvent vapors.

It has been found that a largely anhydrous granules consisting of sodium citrate and Citric acid is obtained when you mix a mixture of sodium citrate and citric acid with water in one Fluid bed granulator, granulated.

The subject of the application is the method and _b0 the use according to claims 1 and 2.

The granulation according to the invention is preferably carried out under the following conditions:

a) Supply air temperature: 120 ° C, _b5

b) Duration of the granulation process: 60 to 90 minutes,

c) Mixing ratio of sodium citrate to citric acid: 5-17.5: 1,
d) Water content based on the mixture: 1: 2.

With the mixing ratio of sodium citrate to citric acid, the proportion of citric acid is thereby determines whether the desired effervescent preparation contains other acid components, such as e.g. ascorbic acid.

The granules obtained by the process according to the invention surprisingly show the same positive product properties such as granulated with flammable liquids such as alcohols Product. The granules produced by the process according to the invention can be mixed with other Compress active ingredients and excipients into effervescent tablets. Due to the high porosity of the fluidized bed granulated In addition to being firm, these tablets have very good redissolving properties. The achievable degree of dryness in the water granulation according to the invention is a water content of <0.05% and thus just as low as with granulation with anhydrous organic solvents.

If the granules produced according to the invention are to be used, an effervescent powder is used To prepare from acetylsalicylic acid and granules, preferably 17.5 parts of sodium citrate are granulated with a part of citric acid. If you want to make an effervescent powder, consisting of acetylsalicylic acid / ascorbic acid and granules, preferably 5 parts of sodium citrate and 1 part of citric acid are used for the production of the granules. This Mixing ratio can vary within the limits given above, depending on the intended use will.

The fluidized bed granulation according to the invention with water as the granulating liquid offers a number of options of advantages:

a) Production can take place in normal rooms and using normal equipment take place without explosion protection.

b) The process offers greater safety by avoiding the risk of fire and explosion in manufacturing and storage rooms.

c) The time-consuming drying in the vacuum cabinet is not necessary.

d) The process is much more environmentally friendly due to the sole use of water and avoids the health risk of the workforce through toxic solvent vapors.

e) The method enables a larger throughput by the more efficient fluidized bed process and saves additional costs because water is used instead of the more expensive solvents is used.

According to the prior art it was to be expected that the use of water in the granulation process is unsuitable for the production of largely anhydrous granules. It was with that to be expected that the water content of the process product would be higher than 0.05% and that at the same time the good redissolubility of the granulate would disappear, which is a use of this Excludes granules in the manufacture of effervescent preparations.

The granules produced according to the invention represent the acidic component of an effervescent preparation. This is done with the appropriate alkaline compo-

such as carbonates and / or hydrogen carbonates of metals such as B. sodium or calcium and the desired active ingredient such as acetylsalicylic acid mixed. Other dry substances can be added to the mixture, e.g. B. Flavors, Sweeteners or vitamins. The finished mixture produced in this way can be tabletted in the usual way, all common types of tabletting machines can be used. Furthermore, this mixture can also be filled directly as effervescent granules.

The following exemplary embodiments describe the granulation process according to the invention by way of example:

example 1

150 kg primary sodium citrate and 8.5 kg citric acid wer.Jen put in a fluidized bed granulator and poured hot water in the amount of one

Liters per minute sprayed. At the same time, the powder mixture is swirled through with heated supply air of 120 ° C. The spraying and whirling are interrupted at regular intervals to shake off the product retention filters. The granulation process is completed after about 80 minutes. The fluidized bed granulate is then dried without further spraying for about 30 to 45 minutes with a supply air of 120 ° C. and then sieved to a maximum particle size of 1 mm in diameter. The granulate produced in this way shows a water content of 0.03% _{above P, O 5.}

Example 2

53 kg of the sodium citrate-citric acid granules produced according to the invention are mixed with 38 kg of sodium bicarbonate and 10 kg of powdered acetylsalicylic acid mixed and compressed on a tablet machine to give tablets weighing 3.2 g.

Claims (2)

Patent claims: 1. Process for the production of largely anhydrous granules, consisting of sodium citrate and citric acid, characterized in that a mixture of sodium citrate and citric acid with water in a mixing ratio of sodium citrate to citric acid of 3-30: 1 and a proportion of water, based on this mixture, of 1: 1-4 in a fluidized bed granulator granulated at a supply air temperature of 80 to 140 ° C for a period of 40 to 240 minutes. 2. Use of the largely anhydrous granules produced according to claim 1 for the production of effervescent powder and tablets.