SK285966B6 - Effervescent tablet comprising magnesium and method for the preparation thereof - Google Patents

Abstract

Effervescent tablet comprising as active substance light magnesium oxide and as ancillary substances sodium hydrogen carbonate, anhydrous citric acid, polyvinyl pyrrolidone, anhydrous milk sugar, sorbitan, polyethylene glycol, pharmaceutically acceptable colouring agent, alternate sweetener and flavour agents. Described is also a method for the preparation of the effervescent tablet.

Description

Technical field

The invention is in the field of pharmacy, solves the composition and process for the preparation of an effervescent preparation in the form of tablets containing magnesium, the source of which is magnesium oxide. The composition is useful for the substitution therapy of magnesium body deficiency, which is a significant intracellular cation involved in a number of enzymatic processes, but most notably glycolysis in muscle tissues.

BACKGROUND OF THE INVENTION

As a source of magnesium for use in effervescent formulations, its pharmaceutically acceptable inorganic and organic salts, such as magnesium carbonate, magnesium amino acid salts, magnesium citric acid salts and magnesium pidolate, are widely used. Magnesium oxide is used as a magnesium source especially in capsule dosage form, e.g. for Magnesium - Optopan or Magnetrans forte, mixed with magnesium carbonate, Magnosolv granules are commercially available. Magnesium oxide is used for effervescent formulations limited to its relatively difficult processability into said formulations and mainly due to either too rapid sedimentation upon dissolution of the effervescent formulation or flotation with carbon dioxide resulting in suspension foam formation at the beverage level or persistent turbidity.

One preparation containing magnesium oxide and sucrose unsuitable for diabetics with one of the above mentioned properties is available on the market and contains, among other substances, 420 mg of magnesium oxide per effervescent tablet.

SUMMARY OF THE INVENTION

The described disadvantages are solved by the present invention, according to which only an oxide containing 60.29% Mg is used as the magnesium source for an effervescent mixture not containing sucrose or other substances unsuitable for diabetics. The advantage of using magnesium oxide in the effervescent mixture is the high Mg cation content, which is also advantageous for production reasons.

In the finished dosage form, there is no need to unnecessarily increase the amount of other excipients, so that the weight of the dosage form is within acceptable limits, which is economically advantageous.

The main advantage of the present invention is that the following composition and process for the preparation of an effervescent composition achieve high quality properties of the finished beverage in which no sedimentation or suspension foam of the active or excipients or the formation of a persistent haze occurs.

Another advantage is a simple technological process, feasible in conventional pharmaceutical plants equipped for producing effervescent formulations and the effervescent composition produced according to the invention can be directly adjusted according to the required amount of Mg cation into bags of combined gas and water vapor-impermeable, heat-weldable film. be compressed into effervescent tablets having the necessary Mg cation content and these can be adjusted into generally usable effervescent tablets.

The essence of the preparation of the effervescent tablet according to the invention is that in the high-speed type pharmaceutical granulator the active ingredient is mixed with magnesium oxide, preferably light magnesium oxide in an amount of 5 to 25% by weight, preferably 7 to 15% by weight, with sodium bicarbonate in an amount of 5 to 20%. %, preferably 7 to 15% by weight, and with citric acid, preferably anhydrous citric acid, in an amount of 10 to 35% by weight, preferably 20 to 30% by weight, based on the finished tablet.

Once homogeneous, the mixture is subjected to wet granules with 3-15%, preferably 5-10% polyvinylpyrrolidone solutions having a relative molecular weight of 12,000 to 90,000, preferably from 17,000 to 30,000, in an amount of 8 to 13% by weight. %, preferably 9 to 11% by weight, based on the finished tablet in a mixture of ethyl alcohol and isopropyl alcohol, the mixture of ethyl alcohol and isopropyl alcohol constituting 20 to 80% by weight, preferably 40 to 60% by weight ethyl alcohol and 20 to 80% by weight, preferably 40 to 60% % by weight of isopropyl alcohol.

The mixture is mixed for the time necessary to form a granule of suitable structure. The granulate is dried in a chamber, vacuum, preferably floating, so that the product temperature reaches 30 to 50 ° C, preferably 36 to 48 ° C and the residual moisture content of the product reaches 0.2 to 0.6% by weight, preferably 0.25 to 0 % By weight. The dried granulate is subjected to an oscillating particle size adjustment through a sieve so that the resulting product contains 50 to 85% by weight, preferably 65 to 80% by weight, of a particle size of 0.18 mm to 0.63 mm.

Sodium bicarbonate in an amount of 5 to 15% by weight, preferably% to 13% by weight, citric acid, preferably anhydrous citric acid, in an amount of 10 to 35% by weight, preferably 20 to 30% by weight, is successively admixed to the granulate of the above-mentioned properties in a volume homogenizer. milk sugar, preferably anhydrous milk sugar, in an amount of 1 to 8% by weight, preferably 2.5 to 6% by weight, sorbitol, preferably sorbitol for direct tabletting, in an amount of 3 to 12% by weight, preferably 5 to 9% by weight, polyethylene glycol relative molecular weight 4000 to

000, preferably 5000 to 7000, the particle size of which ranges from 40 micrometers to 500 micrometers, preferably from 100 micrometers to 355 micrometers in an amount of 1 to 3.5% by weight, preferably of 1.8 to 2.6% by weight, groups of natural, naturally identical or permitted synthetic and combinations thereof in an amount of 0.01 to 0.03% by weight, preferably 0.018 to 0.029% by weight, sweeteners and combinations thereof, preferably potassium acesulfame in an amount of 0.2 to 0 5% by weight, preferably 0.35 to 0.45% by weight, of a taste-correcting substance from the group of natural and / or natural identical and / or synthetic permitted flavorings and combinations thereof in an amount of 0.5 to 3% by weight, preferably 0.7 up to 1.5% by weight per finished tablet.

Experimentally it has been found and confirmed by stability tests that the above mentioned method of preparation of effervescent tablet has a significant influence on the quality of the finished product, its stability during the specified shelf life and especially the formation of a clear or almost clear solution after dissolution of the effervescent tablet in recommended amount of drinking water. is illustrated in the figure (Figure 1) where the degree of turbidity of the finished beverage of the composition of the invention and of a commercially available composition with the same Mg cation content in 1 tablet is compared.

DETAILED DESCRIPTION OF THE INVENTION

The subject matter of the invention is illustrated in the examples without being limited thereto.

Example 1.

(a) Effervescent tablet composition:

Magnesium oxide light 11.052 wt. Sodium bicarbonate 21,973% Citric acid anhydrous 51,314% polyvinylpyrrolidone 0,789% Milk sugar, anhydrous 3,921% sorbitol 7,243% Polyethylene glycol 2,236% Acesulfame potassium 0,394% Red synthetic dye 0,026% Strawberry aroma natural identical 1,052%

(b) Method of preparation:

In a high-speed pharmaceutical homogenizer, e.g. Diosna, is sieved through a sieve with a mesh size of 1.25 mm sieved light magnesium oxide in an amount of 11.052% by weight per 1 tablet with a sieve with a mesh size of 1.25 mm sieved with sodium bicarbonate in an amount of 10.526% by weight with 1 citric acid. sieved through a sieve with a mesh size of 1.25 mm in an amount of 25.657% by weight per tablet. Upon reaching homogeneity, the mixture is moistened with stirring with a 7.89% solution of polyvinylpyrrolidone having a relative molecular weight of 25,000 dissolved in a mixture of 50% by weight of ethyl alcohol and 50% by weight of isopropyl alcohol. The amount of solution used is 10.0% by weight per tablet. The wet mixture is agitated until the necessary degree of grain is reached, transferred to the flask of a fluidized bed drying apparatus, and dried at an inlet air temperature of 70 ° C until the residual moisture is 0.25% by weight.

The particle size of the dry, green mixture is adjusted in an oscillating manner through a sieve with a mesh size of 0.8 mm. Citric acid, sieved through a sieve with an aperture of 1.25 mm in an amount of 25.657% by weight per tablet, sodium bicarbonate sieved through a sieve with an aperture of 1.25 mm in an amount of 11.447, was added successively to the treated mixture in a dry homogenizer. % by weight per tablet, sorbitol for direct tabletting with a residual moisture content of 0.2% by weight sieved through a 1.25 mm sieve at 7.243% by weight per tablet, acesulfame potassium sieved through a 0.45 mm sieve in an amount of 0.394% by weight per tablet, polyethylene glycol with a relative molecular weight of 6000, its particle size is from 100 micrometers to 350 micrometers in an amount of 2.236% by weight per tablet, anhydrous milk sugar for direct tabletting sieved through a 1-mesh screen, 5 mm in an amount of 3.921% by weight per tablet, natural identical powder Strawberry flavor sieved through a sieve with a 0.45 mm sieve in an amount of 1.052% by weight and permissible synthetic dye E 124 sieved through a sieve with a sieve with 0.45 mm sieve in an amount of 0.026% by weight per tablet.

The mixture is mixed until homogeneous and is thus ready for the tabletting process.

On a rotary tablet press for effervescent tableting, tablets are prepared from a mixture of 25 mm diameter, 3.80 g, height up to 5.30 mm, which are adjusted into metal or polypropylene tablet tubes and sealed with an active silica gel cap.

Example 2

(a) Effervescent tablet composition:

11.052 wt.

Sodium bicarbonate 21,973%

Citric acid anhydrous 51,315%

Polyvinylpyrrolidone 0.789%

Milk sugar anhydrous 3,947%

Sorbitol 7.649%

Polyethylene glycol 2,236%

Acesulfame potassium 0,050%

Aspartame 0,200%

Red synthetic dye 0,026%

Strawberry aroma natural identical 0,500%

Strawberry aroma synthetic 0,263%

(b) Method of preparation:

In a high-speed pharmaceutical granulator, a sieve with a mesh size of 1.25 mm was sieved with 11.052% by weight per 1 tablet along with a sieve with a mesh size of 1.25 mm with sieved sodium bicarbonate in an amount of 10.526% by weight per tablet. citric anhydrous, sieved through a sieve with a mesh size of 1.25 mm in an amount of 25.658% by weight per tablet.

After reaching homogeneity, the mixture is wetted with stirring with a 7.89% solution of polyvinylpyrrolidone with a relative molecular weight of 25,000 dissolved in a mixture of 50% by weight of ethanol and 50% by weight of isopropanol. The amount of solution used is 10.0% by weight per tablet. The wet mixture is agitated until the necessary degree of grain is reached, transferred to the flask of a fluidized bed drying apparatus, and dried at an inlet air temperature of 70 ° C until the residual moisture is 0.25% by weight.

The particle size of the dry, green mixture is adjusted in an oscillating manner through a sieve with a mesh size of 0.8 mm. Citric acid, sieved through a sieve with an aperture of 1.25 mm in an amount of 25.657% by weight per tablet, sodium bicarbonate sieved through a sieve with an aperture of 1.25 mm in an amount of 11.447, was added successively to the treated mixture in a homogenizer for dry homogenization. % by weight per tablet, sorbitol for direct tabletting with a residual moisture of 0.2% by weight sieved through a sieve with a mesh size of 1.25 mm in an amount of 7.649% by weight per tablet, acesulfame potassium sieved through a sieve with a mesh size of 0.45 mm in an amount of 0.05% by weight per tablet, aspartame sieved through a 0.45 mm aperture sieve in an amount of 0.2% by weight per tablet, polyethylene glycol having a molecular weight of 6000, its particle size is from 100 microns to 350 microns in an amount of 2.236% by weight per tablet, anhydrous milk sugar intended for direct tabletting sieved through a sieve mesh size 1,5 mm at 3,947% by weight per tablet, natural identical powdered strawberry flavor sieved through a sieve with 0,45 mm aperture at 0,5% by weight per tablet, synthetic strawberry sieve sieved through a sieve with aperture size 0.45 mm in an amount of 0.263% by weight per tablet and the permissible synthetic dye E 124 is sieved through a sieve with a mesh size of 0.45 mm in an amount of 0.026% by weight per tablet.

The mixture is mixed until homogeneous and is thus ready for the tabletting process. On a rotary tablet press for effervescent tableting, 25 mm diameter tablets weighing 3.8 g, height up to 5.3 mm are prepared from the mixture, which are adjusted into metal or polypropylene tablet tubes and sealed with an active silica gel cap.

Industrial usability

The invention is useful in the pharmaceutical industry in the manufacture of dietary and medicinal preparations containing magnesium cations.

The composition of the present invention is useful in magnesium deficiency in food, some chronic diseases, inadequate absorption or excessive excretion resulting in increased neuromuscular excitability (hyperreflection, nocturnal spasm in the extremities), acoustic hypersensitivity, hallucinations, diseases, depression, depression, depression, depression i.

The recommended intake for an adult is 350 to 450 mg per day, with about 300 mg per day for a balanced diet.

Claims (6)

PATENT CLAIMS An effervescent preparation containing magnesium cation, characterized in that, in the form of an effervescent tablet, it contains, as active ingredient, light magnesium oxide in an amount of 5 to 25% by weight, and as excipients sodium hydrogen carbonate in an amount of 10 to 30% by weight, anhydrous acid. lemon in an amount of 40 to 60% by weight, polyvinylpyrrolidone in an amount of 0.3 to 1.2% by weight, anhydrous milk sugar in an amount of 1 to 8% by weight, sorbitol in an amount of 3 to 12% by weight, polyethylene glycol in an amount of 1 % to 3.5 wt.%, pharmaceutically acceptable colorant in an amount of 0.01 to 0.03 wt.%, sweetener in an amount of 0.2 to 0.5 wt. and a flavoring agent in an amount of 0.5 to 3 wt. Composition according to claim 1, characterized in that polyvinylpyrrolidone with a relative molecular weight of 12,000 to 90,000, milk sugar, anhydrous, sorbitol with a residual moisture content of at most 0.2% by weight, polyethylene glycol with a relative molecular weight of 6000 are used as excipients. and a particle size of from 100 to 350 microns, an acesulfame potassium sweetener and / or a combination of sweeteners, a red cochineal A dye, and a flavor correcting agent, which is a naturally identical powdered flavor and / or a flavor correcting agent combination. Process for the preparation of an effervescent formulation according to claims 1 and 2, characterized in that, in a first technological step, a granulate consisting of light magnesium oxide in an amount of 100% by weight, part of sodium bicarbonate in an amount of 10.526% by weight is prepared. and a portion of anhydrous citric acid in an amount of 25.658 wt. per 1 tablet, the granulate is then dried in an air-drying atmosphere at a drying air temperature of 70 ° C so that the residual moisture of the granulate reaches 0.25 to 0.6% by weight, the particle size of the dried granulate is adjusted oscillating through a sieve with a 0 8 mm, if the mixture so treated is further admixed with sodium bicarbonate, anhydrous citric acid, milk sugar, sorbitol, polyethylene glycol, coloring agent, sweeteners and combinations thereof, and a flavoring agent from the group of natural and / or natural identical and / or synthetic flavors and combinations thereof. Process for the preparation of an effervescent formulation according to claim 3, characterized in that the first portion of the granulate is prepared by a wet process, wherein a 3-15% solution of polyvinylpyrrolidone in an amount of 8 to 13% by weight is used to wet the granulate. in a 1: 1 mixture of ethyl alcohol and isopropanol. A process for the preparation of an effervescent formulation according to claims 3 and 4, characterized in that the particle size of the dried granulate is oscillated through a sieve with a mesh size of 0.8 mm so that the resulting product contains 50 to 85% by weight. particles of 0.18 mm to 0.63 mm. A process for the preparation of an effervescent formulation according to claims 3 to 5, characterized in that anhydrous citric acid 10 to 35% by weight, sodium bicarbonate in an amount of 5 to 15% by weight, anhydrous lactic acid are subsequently successively added to the dried and treated granulate. sugar for direct tabletting in an amount of 1 to 8% by weight, sorbitol for direct tabletting in an amount of 3 to 12% by weight, polyethylene glycol in an amount of 1 to 3.5% by weight, sweetener in an amount of 0.2 to 0.5% % dye in an amount of 0.01 to 0.03 wt. and a flavoring agent in an amount of 0.5 to 3 wt. on the finished tablet.