DE2020893A1 - Effervescent preparation and process for their production - Google Patents

Description

Effervescent preparation and process for their production

The invention relates to an effervescent preparation that has a or more antibiotic agents, optionally other active ingredients as well as auxiliaries and an effervescent set contains, and process for their preparation.

Oral application of antibiotics against a large The number of infectious microorganisms that are effective is known. The ones used for this are soluble in water and / or difficult to use to insoluble antibiotics are mainly in the form of capsules, tablets, syrups, oily suspensions or granules administered. However, this shows the following disadvantages:

a) The antibiotics are difficult to insoluble in water compared to the water-soluble antibiotics im general less well absorbed, so the urinary. elimination rates come to be lower in terms of value. In addition, there is a need to apply these antibiotics orally, as a rule, only in solid forms. this has, besides certain disadvantages in application, e.g. in pediatrics, also results in low and / or slow absorption.

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b) In the case of antibiotics which are soluble in water, the usually repeated inherent odor and bitter taste result often to a rejection of the aqueous form by the / patient. In addition, the active ingredients are water-soluble Forms of preparation, e.g. granules, are only stable for a short time as soon as they are dissolved in water, so that Here too, despite the known disadvantages, the solid form of administration is often used.

Effervescent preparations are also already known which, in addition to the active ingredients and auxiliary substances, such as sugar, sweet and flavorings, as an effervescent set a mixture of one

Base portion, namely COp donors, such as hydrogen carbonates or carbonates, and an acid portion, namely GO ₀ -releasing components, such as polybasic solid acids. They are produced by a corresponding mixture, if necessary, in whole or in part by heating and sieving or by moistening with solvents,. ,, like. Alcohols or volatile chlorinated aliphatic hydrocarbons, granulates, dries, sieves and compresses into tablets. According to this, however, when the antibiotics mentioned below are used as active ingredients, effervescent preparations are obtained which, with water in the acidic range, result in sticky deposits and agglomerates that are sparingly soluble or insoluble, or - due to the concentrated action of the acid component - decomposition products. The sticky products excreted from the acidic aqueous solution stick to the wall of the drinking vessel and look unsavory. In addition, part of the active ingredient is withdrawn from oral administration.

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The invention is therefore based on the object of an anti, To create effervescent preparation containing biotics, through which the above-mentioned disadvantages can be overcome.

The effervescent preparation according to the invention is marked by an effervescent set, in which the base portion and

the acid content have different grain sizes. "

The process for producing the effervescent preparation according to the invention is characterized in that powdered or granulated active ingredients, optionally together processed with other active ingredients, as well as auxiliaries with an effervescent set, in which the base portion and the Acid content have different grain sizes.

As a base component, namely COp donors or acid dulling agents Substances are, for example, hydrogen carbonates or carbonates, such as potassium hydrogen carbonate or preferably sodium hydrogen carbonate, used. Polybasic, for example, are suitable as the acid component, namely COp-releasing component Acids such as tartaric acid or, preferably, citric acid. The base content should have a grain size of 50-500 m / u, preferably 100 - 200 m / u, the acid content one grain size of 200-1000 m / u, preferably 500 m / u. In general, the ratio of base to acid should be 0.5: 2.0 to 2.0: 0.5.

The acid-stable antibiotics mentioned below are used

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used in the form of their sodium and / or potassium salts in aqueous solutions with a pH above 3.5 3.9 remain in solution, the ratio ^ of sodium hydrogen carbonate should with a suitable effervescent composition to citric acid 1: 1 to 1.25, preferably 1: 1.25, be. When using other base components, such as potassium hydrogen carbonate, and other proportions of acid, such as tartaric acid, the ratios should be changed accordingly. If pure, i.e. acid-stable antibiotics of the above type are assumed that are not present in salt form, then the base content must be increased accordingly.

According to the invention, the antibiotic active ingredients used are preferably acid-stable antibiotics which are in the form their sodium and / or potassium salts remain in solution in aqueous solutions with a pH value above 3.5 - 3.9. For this include, for example, ampicillin, cloxacillin, oxacillin, pheneticillin, phenoxymethylpenicillin, propicillin, Novobiocin, fusidic acid, chloramphenicol leucine carbamate or colistin methanesulfonic acid. Potassium phenoxymethylpenicillin is particularly preferred.

Acid-stable antibiotics, which are in the form of their acid addition salts, can also be used as antibiotic active ingredients result in stable aqueous solutions. These include, for example, colistin sulfate, lincomycin hydrochloride, Neomycin sulfate, pasomomycin sulfate, viomycin sulfate, Streptomycin sulfate, tetracycline hydrochloride, Chlortetracycline hydrochloride, oxytetraoycline hydrochloride, Methacycline hydrochloride, erythromycin lactoblonate,

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Lymecycline and cycloserine in free form. It can however, other corresponding acid addition salts can also be used.

The antibiotics or their salts can be used individually or in groups as well as together with other, non-antibiotic Active ingredients are used.

The two parts of the effervescent set should be in the inventive Effervescent preparation also in a certain ratio to the total amount of antibiotic active ingredients. It is useful to use 5 * 5 - 15 parts, preferably 8.5 parts, shower set used for one part each of antiblotisehem active ingredient.

In particular, additives such as sugar, cyclamates or saccharin, tableting base substances such as binders, glidants and / or lubricants, dyes, flavorings or pharmaceutical additives such as polyethylene glycol, stearates, ethyl cellulose or polyvinyl {

pyrrolidone, can be used.

The antibiotic agents and any existing ones other, non-antibiotic active ingredients are expediently in a particle size of 40-500 m / u, preferably 100 - 200 m / u, used.

The use of base components and acid components of certain Grain sizes for the production of the effervescent preparation according to the invention, in particular the acid-stable antibiotics

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of the former type has the advantage that when this effervescent preparation is added to water, no pH value lower than 3.5 - 3.9 occurs at any point and the antibiotics therefore go into solution in the form of their salts. This ensures that the antibiotic Active ingredients when dissolving the pharmaceutical effervescent preparation in water as a result of the buffer effect of the base set never come into contact with an environment that is more acidic than the finished solution. Conditional this effect is thus through the control of the speed and dependent on the particle size of the effervescent composition thus also the pH conditions during the dissolution process in water. The above favorable solution ratios can also be influenced by changing the diffusion, for example by coating the acid component with hydrophobic Coating materials, preferably methyl, ethyl and / or Acetyl cellulose, can be achieved.

In order to keep the losses of antibiotic active ingredients as low as possible during production, the Components of the shower set are expediently used separately.

The production of the effervescent preparation according to the invention can be carried out in detail, for example, as follows : -. ■ ·. ■■

All constituents are made up to a negligible one Moisture content dried. Then the antibiotic components, the sweeteners, coloring agents and the

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other pharmaceutical additives and then with mixed with the other ingredients using standard pharmaceutical techniques.

A cheaper way of manufacturing is that the antibiotic agents together with the base portion the effervescent set, the sweeteners and coloring agents mixed, the mixture is then granulated and the granules with the other auxiliaries and the acid content of the shower set mixed.

According to a preferred production method, however, is initially a granulate from the base portion of the effervescent set, the

; -o3tofien and the dyes and this then with the other components, namely the acid content of the effervescent set, the aromatic substances and the antibiotics Active ingredient.

The granulate is expediently produced by moistening, preferably with anhydrous granulating liquids, for example alcohols such as isopropanol, which may also contain binders such as polyvinylpyrrolidone or polyethylene glycol of various degrees of polymerization. The granulate is then either to Effervescent tablets pressed or ground homogeneously used as an effervescent powder.

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Effervescent tablets are expediently produced using a tabletting machine, the punch and die of which contain elastic working surfaces, ie, discs made of Vulkollan. The mixing of the components, the grinding and tabletting of the granules and the packaging of the finished commercial forms should take place at a relative humidity of less than 35 % .

The effervescent pharmaceutical preparations produced according to the invention are characterized by their easy solubility in water and give stable aqueous solutions, which are independent of the amount of water. This advantage relates in particular to the first-mentioned type of acid-stable Antibiotics, namely those which are in the form of their sodium and / or potassium salts in aqueous solutions with a pH above 3 * 5 - 3 * 9 remain in solution because the previously known effervescent preparations of these antibiotics when they are introduced into water, precipitates of the antibiotics result, which withdraw a large part of these active ingredients from use.

The advantage of administering antibiotics with the aid of the effervescent preparations according to the invention lies in particular in that this makes it possible to administer larger amounts of antibiotics with a single administration Body and also with many antibiotics, e.g. with potassium penicillin V, occurring taste

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To correct disadvantages. At the same time it is possible to supply the body with the large amounts of water that are often desired in very cold conditions.

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Example I s

Each effervescent tablet contains:

K-penicillin V

Sodium hydrogen carbonate, fine (grain size 10 ~ 200nyu) cane sugar
Sodium cyclamate

Citric Acid, Grless (Grain size 500m / u) polyvinylpyrrolidone Polyethylene Glycol 6000 colors and flavors

400,000 IE ft 1.50 G 2.52 G 0.25 S. 1.90 G 0.05 G 0.25 G q. S,

Each effervescent tablet contains;

Example 2 ;

K-Fenicillin-V sodium hydrogen carbonate, fine (Grain size 100-200 m / u) cane sugar

Sodium cyclamate Sodium saccharin

Citric acid, semolina (grain size 500 .nyu) Polyvinylpyrrolidone Polyethylene Glycol 6000 Colors and Flavors

600,000 IE G G 1.50 G G 2.40 G G o, 3o G 0.015 1.90 0.05 0.25 q. s.

Example 3 ;

K-penicillin V

Sodium hydrogen carbonate, fine (grain size 100-200nyu)

Cane sugar

Sodium cyclamate Sodium saccharin

'Citric acid, in powder form, coated with methyl cellulose 1,000,000 IU 1.60 g

2.70 g 0.40 g 0.04 g

2.00 g

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Polyvinylpyrrolidone polyethylene glycol 6000 Colors and flavors 0.05 g 0.25. G

q s.

Example 4 :

Propicillin - K

Sodium hydrogen carbonate, fine (grain size 100-20OnJM-)

Cane sugar

Sodium cyclamate sodium saccharin

Citric acid, semolina (grain size), polyvinylpyrrolidone Polyethylene glycol 6OOO dyes and flavors

600,000 IE 1.50 S. 2.00 ε 0.30 S. 0.03 S. 1.90 G 0.05 ε 0.25 ε q. s.

Example fi t
Chloramphenicol Leucine Carbamate Na

Cane sugar

Sodium hydrogen carbonate, fine (grain size l00-200ip / u)

Citric acid, semolina (grain size 500m / u) Polyvinylpyrrolidone polyethylene glycol 6000 Colorings and flavors mg based on chloramphenicol

2.00 g 1.80 ε

1.70 g

0.05 g. P, 25 εΛ

et- ·. · s ·

The production of the effervescent tablets according to the formulations given in Examples 1-5 is carried out using one of the two methods given below:.

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Procedure 1 :

All components are processed in a dried and / or anhydrous form. The antibiotics are mixed with the sodium hydrogen carbonate, the cane sugar, the artificial sweeteners and the coloring agents, moistened with a solution of polyvinylpyrrolidone in anhydrous isopropanol and then granulated. The dry granulate is mixed with the aromas, citric acid and polyethylene glycol 6000, mixed homogeneously and pressed into tablets. The procedures are carried out according to the usual pharmaceutical technology with the usual suitable apparatus. Mixing, granulating, tabletting and packaging take place in special rooms, the relative humidity of which is less than 35 % »

The tablets are placed in suitable moisture-proof containers closed with desiccant stoppers. packed directly after pressing.

Procedure 2:

The mixture of sodium hydrogen carbonate, cane sugar and artificial Sweeteners are made with a polyvinylpyrrolldon-isopropanol solution granulated, dried and after homogeneously mixing with the citric acid, the pre-granulated antibiotics, the Coloring and flavoring substances and after adding polyethylene glycol pressed into tablets.

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Claims (11)

- & - 970-9608 P atent claims: 1. effervescent formulation, containing one or more anti * biotic substances, optionally other active ingredients, and Hilfss-tQffe and an effervescent composition, marked λ is characterized by an effervescent composition, wherein welohem the base moiety and the acid moiety different Korngröseen have '. 2. Effervescent preparation according to claim 1, characterized in that the base portion has a grain size of 50 - 500 m / u, preferably 100 - 200 m / u, and the acid portion has a grain size of 200 - 1000 m / u, preferably 500 τα / α, owns. 3. Effervescent preparation according to one of the preceding Claims, characterized in that the base | portion of sodium bicarbonate and the acid portion of citric acid used. 4. Effervescent preparation according to one of the preceding Claims, characterized in that one part of sodium bicarbonate 1 - 1.25 parts, preferably ^ 1.25 parts, citric acid used. 5. Effervescent preparation according to one of the preceding Claims, characterized in that the acid content 009847/1 U2 970r9608 is covered with hydrophobic substances. 6. - Brewing preparation according to one of the previous ones Claims, characterized in that they have an acid-stable contains antibiotic active substance, its sodium and / or potassium salt in aqueous solutions with a pH value remains in solution above 3.5-3.9. 7. Effervescent preparation according to one of the preceding claims, characterized in that the antibiotic active ingredient has a particle size of 40-500 μm yes, preferably 100-200 myu ^. 8. Shower preparation according to one of the preceding Claims, characterized in that they are for one part of antibiotic active ingredient 5.5-15 parts, preferably 8.5 parts, contains a shower set. 9. Effervescent preparation according to one of the preceding claims, characterized in that it is as acid-stable contains the antibiotic active ingredient phenoxymethylpenicillin. 10. A method for producing an effervescent preparation according to one of the preceding claims, the one or more antibiotic active ingredients, optionally other active ingredients, as well as auxiliaries and an effervescent ingredient, characterized in that powdered or granulated active ingredients, optionally together with 009847/1 U2 other active ingredients, as well as auxiliaries with an effervescent set processed, in which the base portion and the acid portion have different grain sizes. 11. A method for producing an effervescent preparation according to claim 10, characterized in that one first produces a granulate from the base portion of the effervescent set, the sweeteners and the coloring agents and then this with the acid content of the effervescent set, the flavoring substances as well as the antiblotlschen active ingredient. The patent attorney: 009847/1142