DK151770B - PROCEDURE FOR THE PREPARATION OF A POWDER-SHAPED BASIC PREPARATION - Google Patents

Description

DK 151770 B

in

The invention relates to a process for preparing a powdered bismuth-containing composition. The powdered compositions prepared by the method of the invention are active against ulcer 5 and novel.

Liquid compositions prepared from bismuth salts are known, such as bismuth citrate or bismuth subnitrate. Such liquid preparations have the disadvantage that they are less convenient to store and transport than solid preparations. They can be difficult to transfer into an effective powdered product, e.g. not by simple heating and drying.

The process of the invention is characterized by converting an aqueous, colloidal solution containing bismuth citrate, ammonia and a polyol / dry powder by spray drying. The liquid starting material may optionally contain pepsin, a coloring agent such as carmine, an alkali metal hydroxide (e.g., of sodium or potassium), and a preservative such as the mixture of soluble salts of esters of p-hydroxybenzoic acid which is negotiated under the trade name "Nipacombin A". The known liquid compositions sometimes contain volatile liquids such as ethanol and chloroform. Such 25 fluids may be present in the starting material of the process according to the invention in an amount not exceeding 15%, but in fact they have no effect on the process or on the product obtained. In general, the commercially available aqueous, colloidal solutions containing bismuth citrate, ammonia and a polyol can be used to practice the process of the invention. It is unknown whether bismuth citrate, ammonia and polyol are present as such in the liquid or whether they form a new molecule or a new ion.

The bismuth citrate can be used as such or it can be formed in situ, e.g. from citric acid and a bismuth salt with a physiologically acceptable anion.

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DK 151770 B

The liquid is most stable at a pH of approx. 9. If the pH is significantly below or above this value, a precipitate is formed. Especially if the liquid is to be stored for some time before spray drying, it is therefore advisable to use so much ammonia and alkali metal hydroxide that this pH is reached. The amount of ammonia must at least be sufficient to keep the bismuth in solution. Preferred polyols are disaccharides such as sucrose or maltose. The fact that the liquid ammonia preparations 10 are only stable within a limited pH range and that the pH may become too low in loss of ammonia constitute another disadvantage of these preparations.

The dry powder prepared by the process of the invention can be prepared from the colloidal liquid in a conventional spray drying plant.

Suitably, the liquid starting material contains between 11 and 16% dissolved solids. The solution is preferably preheated to a temperature of 60-65 ° C. The heating time is chosen such that no undesirable reaction occurs. For example, when If sucrose is used, the heating time should preferably not exceed 20 minutes to avoid inversion. The solid product produced by the process of the invention is very hygroscopic. It is therefore recommended to remove the moisture from the spray drying system by preheating, e.g. 30-60 minutes with a temperature of the supplied air of approx. 200-250 ° C and to perform the drying with low moisture air.

During the drying process, the temperature of the supplied air is preferably between 150 and 260 ° C, with one temperature between 170 and 190 ° C being particularly preferred and the outlet temperature between 50 and 110 ° C.

It will be appreciated that the liquid should preferably be fed to the system at such a rate that the atomizing capacity 35 is sufficient to form a dry powder.

Tablets containing the powdered bismuth-containing preparation may be formulated in the usual manner with one or more pharmaceutically acceptable diluents.

DK 151770 B

agents or excipients, e.g. lactose or starch, and include materials of a lubricating nature, e.g. calcium stearate or magnesium stearate. Capsules made of absorbable materials such as gelatin may contain the active substance alone or in admixture with a solid or liquid diluent.

The compositions of the invention are therapeutically effective in the treatment of ulcer peptic ulcer, including gastric ulcer, duodenal ulcer and post-operative ulcer and ulcer peptic ulcer in association with 10 hiatus hernias. Appropriate daily doses for adult humans are equivalent to 450-1000 mg Bi20. · The dose for children depends on their weight and age and can be calculated according to the methods commonly used in medical practice. The daily dose for children under 10 years is 15 to 150-400 mg 15120 ^ · Therefore, the pharmaceutical preparations have a bismuth content of 50-250 mg 6120 ^ in dosage form.

The following example further explains the method of the invention.

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Example 1 1500 liters of liquid are prepared from 180,360 kg of bismuth citrate 25 118,279 liters of 25% ammonia 7,125 kg of pepsin 1: 1000 23,700 kg of anhydrous citric acid 0.990 liters of carmine acarate 8.051 liters of glycerol 330,000 kg of sucrose 39,900 kg of potassium hydroxide 3,000 kg 0.2% "Nipacombin A" 8,700 liters of chloroform 94,050 liters of ethanol 35 and purified water to obtain the desired volume.

The resulting solution is diluted with water to a solids content of 12% and the diluted liquid

Claims (1)

A process for preparing a powdery bismuth-containing composition, characterized by converting an aqueous, colloidal solution 25 containing bismuth citrate, ammonia and a polyol into a dry powder by spray drying. 30 35