BG1069U1 - Combined preparation medicinal form - Google Patents

Abstract

The utility model relates to the composition of a combined preparation medicinal form, containing metamizole sodium, triacetoneamine-4-toluene-sulphonate, and auxiliary substances. The medicinal formensures a fast general therapeutic effect as a result of the improved dissolution of the triacetoneamine-4-toluene-sulphonate, preserving at the same time the optimal value of the dissociability and mechanical strength indices, the stability of the active substances and of the medicinal form.

Description

Technical field

The utility model relates to a dosage form of a combination preparation containing the medicaments metamizole sodium and triacetonamine-4-toluene sulfonate with analgesic and antipyretic action.

BACKGROUND OF THE INVENTION

A preparation in the form of film-coated tablets having analgesic, antipyretic and antispasmodic action (Ki 2235544) is known, with an average mass of 0.76 § containing active substances in wt. % from 59.0 to 72.0 metamizole sodium and from 2.4 to 2.9 tempidone, as well as excipients: from 8.5 to 11.0 microcrystalline cellulose, from 7.0 to 9.0 polyvinylpyrrolidone, from 1.0 to 1.5 sodium starch glycolate, from 1.5 to 2.5 talc, from 0.9 up to 1.5 magnesium stearate and the remaining amount of corn starch. According to the description, the preparation was prepared by mixing the active substances with part of corn starch, microcrystalline cellulose and part of sodium starch glycolate, followed by granulation with a mixture of 1.5% corn starch based binder and 25% aqueous polyvinylpyrrolidone solution, drying, powdering and tableting.

Also known is a dosage form containing the drug substances by weight. % metamizole sodium 45 to 85 and triacetonamine 4-toluene sulfonate 2 to 4 (BC 63147) and excipients such as wheat starch, microcrystalline cellulose, talc, magnesium stearate and povidone (polyvidone) in a concentration of 4.6 to 9, as appropriate and pregelatinized starch from 1 to 15 wt. % or starch from 1 to 20. According to the disclosure in the description, the dosage form contains the following amounts in tablets per tablet: metamizole sodium 300 to 800, triacetonamine-4-toluene sulfonate (Tempidone®) 10 to 50, microcrystalline cellulose 40 to 200, pregelatinized or wheat starch 20 to 120, magnesium stearate 3 to 50, talc 5 to 80 and povidone 20 to 80.

The object of the known solution is to provide a stable formulation with a high dissolution rate of triacetonamine-4-toluenesulfonate. Because metamizole sodium dissolves very well in water (1: 1 ratio), it is absorbed quickly and completely through the gastric mucosa, while tempidone dissolves in water in a ratio of 1:10 to 1: 3, essential for the therapeutic action of the medicinal product is the dissolution profile of tempidone, i. faster release of the tranquilizer from the dosage form would lead to a more rapid manifestation of the general analgesic effect of the combination of metamizole sodium and triacetonamine-4-toluene sulfonag.

This dosage form achieves stability but does not rapidly achieve a high dissolution rate of triacetonamine-4-toluenesulfonate, which has an effect on the pharmacological properties of the combination preparation. According to the company specification of the combined preparation (batch 7C0802) obtained in BO 63147, the dissolution rate of triacetonamine-4-toluene sulfonate is not less than 80% after 45 m. According to an analytical analysis of the same preparation, the dissolution rate of triacetonamine-4-toluene sulfonate is as follows:

Time (Vols) 10 15 20 30 45 Dissolution rate (%) of triacetonamine-4-toluene- sulfonate of the dosage form Xsr. 33.1 60.8 74.5 90.8 98.9 δϋ 1.50 3.68 2.89 2.25 1.46

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The technical problem facing the present utility model is to improve the dissolution profile of triacetonamine-4-toluene sulfonate and to ensure a rapid overall therapeutic effect, while maintaining the 5 optimum degradability and mechanical strength of the tablets obtained, as well as stability of the active substances and of the dosage form.

The technical nature of the utility model

A dosage form of a combination preparation containing metamizole sodium drug in weight by weight has been developed. % from 45 to 85, triacetonamine-4-toluene sulfonate from 2 to 4 and excipients: wheat starch from 12.0 to 13.5, microcrystalline cellulose from 9.0 to 10.5, povidone from 5.0 to 6.5, magnesium stearate from 0.6 to 1.3 and talc from 1.3 to 2.6. The dosage form can be any oral dosage form, for example tablets, capsules and powders. Tablets and in particular film-coated tablets are preferred.

The dosage form is characterized by a dissolution profile of triacetonamine-4-toluene sulfonate as follows:

Time (Vols) 10 15 20 30 45 Degree of dissolution (%) on triacetonamines-4- toluene sulfonate from the dosage form no less than: 60.0 80.0 90.0 90.0 90.0

The dosage form of the present utility provides the rapid onset of the general therapeutic effect due to the rapid dissolution of triacetonamine-4-toluenesulfonate. The required degree of dissolution is achieved by reducing the amount of lubricant (magnesium stearate) and finding a specific ratio between the other excipients. The new composition allows for faster release of triacetonamine-4-toluene sulfonate from the dosage form, while maintaining optimum degradability and mechanical strength, stability of the active substances and the dosage form. The new solution avoids the breakdown of metamizole sodium and the release of monomethylaminoantipyrine, as in BC 63147.

Explanation of the annexed figure 35

Figure 1 is a graphical representation of the results of a comparative study of the dissolution rate of triacetonamine-4-toluene sulfonate of the drug formulation obtained according to BC 63147 (lot 7C0802) and the combined product; obtained according to example 1 of the present utility model (batch 30503).

Exemplary embodiments of the utility model

The utility model is explained, without limitation, by the following exemplary formulations of the dosage form in the amounts given in mg per tablet core.

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Metamizole sodium

Triacetonamine-4-toluene sulfonate

Povidone

Microcrystalline cellulose Wheat starch Magnesium stearate Talc

The dosage form is obtained by mixing metamizole sodium and triacetonamine-4-toluenesulfonate with 1/3 part of the required amount of microcrystalline cellulose and 4/5 parts of the intended wheat starch and sieving through a sieve with a 0.7 m bright hole. The weighed and sieved medicinal and auxiliary substances are transferred to a granulator, homogenized in a dry manner, and then moistened with a spirit-aqueous granulation solution of povidone. The granulate is dried and calibrated 20 through a sieve with a bright opening of 1.2 mm. The granulate obtained and analyzed was homogenized (powdered) with the remaining amount of microcrystalline cellulose and wheat starch in a ratio of 2.8 to 1.0 and talc for 10 mt. Finally, magnesium stearate was added and the mixture was homogenized for another 5 ml. The resulting tabletting mixture was tableted on a rotary tablet machine with 13 µm punches and the resulting tablet cores with an average mass of 760 µm were subjected to filming.

Example 4. 3θ

Proceed as in Examples 1, 2 and 3, homogenizing the drugs and excipients in a rotary oven and then moistening with a mixture of aqueous starch glue and povidone aqueous solution.

The resulting film-coated tablets according to 35

Example 1 Example 2 Example 3 500,0 500,0 500,0 20,0 20,0 20,0 45.0 41,0 50.0 80,0 71,0 73,0 94.0 98.0 101,0 7.0 10,0 8.0 14,0 20,0 10,0

Example 1 (batch No. 30503) were observed for stability according to Table 1 and Table 2. The drug was stable at (25 ± 2) ° C for three years and six months, and under accelerated aging at (40 ± 2) ° C for one year (studies continue).

A comparative study was performed to determine the degree of dissolution of triacetonamine-4-toluene sulfonate from the dosage form prepared according to BC 63147 (batch 7C0802) and the combined product (batch No. 30503) of the present utility model. The study was carried out according to the requirement of the European Pharmacopoeia (Pb. Eig. 5., 2.9.3) under the following conditions:

Apparatus - apparatus for determining the degree of release with a rotating blade

Venue:

Solution medium - distilled water

Volume of medium - 1000 t1

Ambient temperature - (37 ± 0,5) ° C

Number of tablets in the container -1

Blades rotational speed (100 ± 2) rpm

Time for conducting - 45 tt

Sample volume - 10 t1

The following comparative results were obtained:

Time (Vols) 10 15 20 30 45 Dissolution rate (%) of triacetonamine-4-toluene sulfonate from dosage form, lot 7C0802 Xsr. 33.1 60.8 74.5 90.8 98.9 8ϋ 1.50 3.68 2.89 2.25 1.46 Dissolution rate (%) of triacetonamine-4-toluene sulfonate from dosage form, batch He 30503 Xsr. 70.9 88.1 94.3 97.4 98.3 δϋ 5.58 3.96 1.69 1.52 1.25

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Claims (3)

Claims A dosage form of a combination composition containing by weight. % metamizole sodium 45 to 85, triacetonamine-4-toluene sulfonate 2 to 4 and excipients: wheat starch, microcrystalline cellulose, talc, magnesium stearate and povidone, characterized in that it contains excipients: wheat starch of 12.0 to 13.5, microcrystalline cellulose from 9.0 to 10.5, povidone from 5.0 to 6.5, magnesium stearate from 0.6 to 1.3 and talc from 1.3 to 2.6. The dosage form of the combination preparation according to claim 1, characterized 5 in that it is a film-coated tablet. 3. The dosage form of the combination preparation according to claim 1, characterized by a dissolution profile of the triacetonamine-4-toluene-sulfonate tablet as follows: Time (Vols) 10 15 20 30 45 Degree of dissolution (%) on triacetonamines-4- toluene sulfonate from the dosage form no less than: 60.0 80.0 90.0 90.0 90.0