DK143436B - PROCEDURE FOR PREPARING TABLETS WITH A HIGH CONTENT OF ANTIOB LD OF ANTIBIOTICS - Google Patents

Description

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The invention relates to a process for the preparation of tablets having a high content of penicilin and cephalosporin antibiotics.

In the oral therapy with antibiotics, 5 are used to treat infections at increasingly higher doses to rapidly obtain a sufficiently high blood level of the drug in the patient.

Not infrequently, single doses of up to several grams of antibiotic are administered.

10 It is therefore necessary to develop oral drug:

forms of these antibiotics that exhibit a content of the antibiotic that is as large as possible. As antibiotics usually have a very unpleasant bitter taste, only drug forms can be selected that can be sucked whole without difficulty. The 15 may optionally have a further coating. : M

These tablets, after ingestion in the digestive tract, must rapidly decompose to release the active substance for resorption.

In certain molding (eg in oval or oblong form) the visibility of also tablets with a high content of active substance can be facilitated.

Pharmaceutical forms which, irrespective of size, can be fully aspirated, have - corresponding to the volume of the tablet mixture - maximum weights of approx. 0.25 to 3 g.

25 In order to ensure optimal properties of the tablets and their manufacture on modern, fast-running machines, the active substances are added to the active substances according to their known flowing and pressing conditions, which do not infrequently exceed the amount of active substance several times. In normal 30 cases, amounts of adjuvant of 30% and more are needed to ensure that the drug can be tableted and the drug form is of good quality.

As auxiliary substances, for example. Mention is made of diluents such as milk sugar and sugar, binders such as starch and cellulose derivatives, disintegrants such as starch and ultra amylopectin, and lubricants such as talc and magnesium stearate.

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In the development of tablet preparations, the selection of suitable excipients must be such as to produce flowable mixtures or granules from which tablets with optimum properties with respect to degradation, release of active substance, hardness, fragility and appearance can be produced. rational manufacture.

For high doses of active substance it is especially important to keep the amount of excipients low so that the tablets do not become too large. On the other hand, however, these tablets must also exhibit satisfactory properties, especially good decay and good release of the active substance.

A variety of antibiotics, particularly penicillins and cephalc-sporins, as well as their derivatives, exhibit very poor flow conditions. Due to electrostatic charge, they already exhibit a tendency for aggregate formation and aggregation when moving in a bottle, so that the skilled artisan can produce sufficient tabletable mixtures or granules only by the addition of high amounts of excipients.

20 On the other hand, the rational production of tablets on high-capacity machines requires active ingredient blends and granules that also flow sufficiently at the high speed of the tableting machine. Also, large matrices in oblong form must be filled uniformly to ensure uniform dosing. Lid formation and other mechanical damage to the tablets, which occur especially at high press speeds, must be avoided. These disadvantages are overcome by adding large quantities of well-flowing auxiliaries.

Thus, it was completely surprising to one skilled in the art that an impeccably rational production of such tablets, i. high content of active substance and low amounts of excipients would be possible.

The present process enables the rational preparation of tablets having a high content of anti-biotic and as small as possible from a poorly flowing antibiotic powder, namely penicillin or

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The type of cephalosporin type and the method is characterized in that the antibiotic constituting 85-95% of the weight of the tablets is mixed with at least three excipients selected from crystalline cellulose, starch, starch derivatives, ultraamylopectin, talc and magnesium stearate, after which the mixture, if desired, granulation, pressed into tablets.

The proportions of the mentioned active substances and excipients relate, e.g. as follows; Antibiotic 85-93%

Crystalline cellulose 8-4%

Ultraamylopectin 5-2%

Magnesium stearate 2-1% Particularly good flow properties and thereby the most rational production of the process according to the invention are achieved by mixing the antibiotic with 10-2.5% crystalline cellulose, 3-1% ultra-amylopectin and 2-1.0% magnesium stearate, or by mixing the antibiotic with 8-2.6% starch or starch derivative, 5-2.0% talc and 2-0.4% magnesium stearate.

As antibiotics, derivatives of penicillin, e.g. penicillin-V potassium, ampicillin, oxacillin or cephalosporin derivatives.

Crystalline cellulose is a product obtained by reprocessing of cellulosic materials.

Starch and starch derivatives are known as explosives. As starch derivatives, e.g. For example, carboxy-methyl starch or "STAR RX 1,500", which is corn starch, is 30 which is physically modified so that its water-soluble content is raised to approx. 20%.

Ultraamylopectin is a starch product obtained by the action of sodium alcoholate and halogen fatty acids on starch. It serves because of its swelling ability 35 as a tablet explosive.

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Magnesium stearate and talc are described in the pharmacopoeia as lubricants and anti-adhesives.

These auxiliary compositions may be added, if necessary, to other commonly known tablet adjuvants.

Of course, from the mixtures in question, smaller tablets can also be pressed, cf. claim 1 (eg for children) or larger tablets cf. Claim 1 (for example, for vaginal or animal administration).

The mixtures possibly formed after granulation with the above-mentioned compositions flow freely and can be made with immaculate quality on fast-running machines in an amount of approx. 2000 to approx. 3000 tablets per day minute.

Depending on the water solubility of the active substance, the tablets decay into water or artificial gastric juice at a temperature of 37 ° C for a few minutes to a maximum of 6 minutes.

The tablets formed can be coated in a conventional manner with a (optionally flavored) film or dragee coating for protection against external influences, e.g. humidity and light, and for taste masking.

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Example 1

Tablets with 1000 mg ampicillin

composition:

Ampicillin trihydrate 92.5% corresponding to 1000 mg of ampicillin

Crystalline cellulose 6.0%

Ultraamylopectin 1.0%

Magnesium stearate 0.5% 100.0% 30

Preparation: In a quick mixer, a mixture is prepared from the above substances and a granule having a grain size between 2.0 and 0.3 mm is prepared.

35 The granulated mixture is pressed onto a tablet runner for vaulted oblorg tablets (eg 21 mm x 9 mm) with rupture groove at a rate of 2000 to 3000 tablets per minute. minute.

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The tablets decay into artificial gastric juice at 37 ° C for a maximum of 3 minutes.

The shaped bodies may be provided with an optionally flavored film or dragee coating.

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Example 2

Tablets with 1.2-mega units of penicillin-V potassium. composition:

Penicillin-V potassium + 10% overdose 93.0% 10 corresponding to 1,320,000 I.E.

Corn starch 3.5%

Talc 3.0%

Magnesium stearate 0.5% 100.0% 15

Preparation: In a quick mixer, a mixture is prepared from the above substances and a granule having a grain size between 2.0 and 0.3 mm is prepared.

20 The granulated mixture is pressed onto a tablet round for vaulted oblong tablets (e.g., 19 x 8 mm) with rupture groove at a speed of approx. 2000 to 3000 tablets per minute.

The tablets decay into artificial gastric juice at 37 ° C for a maximum of 5 to 6 minutes.

The shaped bodies may be provided with an optionally flavored film or dragee coating.