Effervescent tablet or pellet and method of their preparation

 

(57) Abstract:

Usage: in medicine. The invention relates to effervescent tablets or granules containing the frame material, the main component of sipacate, the acid component of sipacate, sweetener, as well as macro - and micronutrients and possibly vitamins as active substances. Effervescent tablets and granules contain 20-50 wt.% mannitol as a frame material, 8-25 wt.% of potassium bicarbonate as the main component of sipacate, 9-27 wt.% malic acid as the acid component of sipacate, 0.4 to 2.2 wt.% aspartame as a sweetener. In addition, the invention relates to a method for producing such effervescent tablets or granules. Tablets or granules have a high chemical stability, easily pressed. 2 s and 5 C.p. f-crystals, 3 tables.

The invention relates to effervescent tablets or granules, containing no sugar and sodium, as well as the way they are received.

In particular, the invention relates to effervescent tablets and granules consisting of frame material of a component of the main character for outgassing and disintegration (hereinafter sipacate), the acid component of sipacate, sweetener, as well as macro and Mick is l

It is known that at the present time one of the most popular pharmaceutical forms for introduction into the body of medicines, vitamins and minerals is the so-called effervescent tablet [1]. In addition to commercial reasons, the spread of this form from the point of view of the pharmaceutical activity contributes to a number of factors: the reduction of irritation of the stomach, improving the absorption and so on, When the dissolution of these tablets in water get fizzy or carbonated beverage containing carbon dioxide.

The observed disintegration effervescent tablets due to the presence of a mixture containing an acid and a base; when interacting with water this mixture destroys the tablet with carbon dioxide.

In the production and packaging of effervescent tablets requires great caution; accordingly, in practice, the method of direct compression is preferable to "wet" methods.

Most effervescent tablets contains, in addition to the active agents, the three main components: the binder and the frame material, the acid component of sipacate and basic component of sipacate.

Usually as a binder and frame material use sugars (lactose, sucrose, glucose), Sorbi the Yu acid or adipic acid, but as a main component of sipacate - sodium bicarbonate, sodium carbonate and magnesium carbonate.

Among other components typically used in effervescent tablets, you can specify preferably applied such agents as sweeteners, like sugar, saccharin, sodium cyclamate and aspartame; flavourings and flavouring agents; lubricating agents, for example, glycols, silicone oils, stearates and adipic acid.

In the literature [2] described effervescent tablets containing lactose as a frame material, citric acid as the acidic agent sipacate, a mixture of the carbonates of sodium and potassium as the primary agent sipacate and aspartame as a sweetener. In addition to water and fat-soluble vitamins, these tablets contain as active agents, inorganic substances which are biologically better assimilated in the form of chelates. However, such tablets do not allow the exclusion of compounds of sodium, which is a disadvantage, since it is well known that the introduction into the body of excess sodium causes a number of undesirable physiological effects. Another disadvantage of known composition is the presence of lim is P> In the literature [3] described effervescent tablets containing a mixture of carbonates of calcium and potassium as the primary agent sipacate. A significant disadvantage of this composition is unpleasant soapy taste of potassium bicarbonate. In addition, the use of calcium carbonate affects the time of dissolution of the tablets.

In the literature [4] described effervescent tablets containing potassium bicarbonate as the main component of sipacate, malic acid and citric acid as the acid component of sipacate, a mixture of sorbitol and maltodextrin as a frame and a binder material, and saharat calcium as a sweetener. This composition is used as a means of lowering the acidity and pain; its disadvantage is poor low shelf life due to the presence of sorbitol. In addition, sorbitol is not recommended for wide use in soft drinks, as some people have a bad stomach to tolerate [5].

The task of the invention to provide chemically stable, easily moldable effervescent tablets and granules with improved physical properties, without sodium and sugar containing uniformly distributed macro completely solve by using to obtain effervescent tablets and granules of the following main ingredients: mannitol as a frame material, malic acid as the acid component of sipacate, potassium bicarbonate as the main component of sipacate and aspartame as a sweetener.

The invention, moreover, is based on the fact that the use of mannitol can be entered into the composition of the salt tablets macro - and micronutrients with a high content of water of crystallization. Accordingly, the invention allows to overcome the technical difficulties, in virtue of which so far as we know, not been able to get effervescent tablets and granules with such substances as the high content of water in them preventing them from pressing and at the same time caused a premature dissolution.

The basis of the invention also expected that when using mannitol tablets or granules macro - and micronutrients form complexes with mannitol, making it possible to resolve the incompatibility of the components in the process, the final product is chemically stable, and the resulting complexes with mannitol will be easier assimilated by the body, it is better to be used.

The invention is also based on the fact that when used together, mannitol, malic acid and aspartame can Kacha is possible to exclude from the tablets sodium ions. In addition, in this combination there is no inherent potassium bicarbonate poor compressibility, i.e., its high adhesion to the surface of dies and matrices, which does not allow it to be pressurized with a relative moisture content of 45% or higher. Therefore, even in this respect the invention is based on overcoming technical stereotype. This is confirmed by the fact that in the literature [3] column 1, lines 27 to 32 States that "the Use of a single potassium bicarbonate and potassium carbonate does not lead to the desired results, because, firstly, potassium compounds give the composition an unpleasant soapy taste, and secondly, high sensitivity to moisture with the introduction of potassium causes serious technical difficulties".

The basis of the invention is also based on the fact that when the joint use of malic acid as the acid component of sipacate with mannitol obtained composition can sufficiently good to extrude. This fact is unexpected because it is known that one malic acid poorly pressed, and it is technically difficult to process, as a result of low melting point, it melts when grinding. On the other hand, established by the authors fact gives vozmojnoe malic acid to improve the taste, as well as the possibility of optimizing it with the help of pH.

Finally, the invention is based on the fact that when used together, mannitol, potassium bicarbonate, malic acid and aspartame becomes possible to obtain a composition with a low energy content, which does not cause gastro-intestinal disorders. Tablets of this composition have a very high tensile fault, they are quickly dissolved with gas and form a clear solution, though the composition contains incompatible vitamins, macro - and trace elements and components (potassium bicarbonate, malic acid, salts of macro - and micronutrients with a high content of water of crystallization), each of which by itself has poor compressibility.

The invention based on the above facts, relates to effervescent tablets and granules containing frame material, the main component of sipacate, the acid component of sipacate and sweetener, as well as macro - and micronutrients and possibly vitamins as active substances. In accordance with the invention, effervescent tablets and granules contain 20 to 50 wt.%, preferably 30 to 40 wt.% mannitol as a frame material, 8 to 25 wt. %, preferably 14 to 18 mcnay acid as the acid component of sipacate and 0.4 - 2.2 wt.%, preferably from 0.6 to 1.5 wt.% aspartame as a sweetener, and, if necessary, taste, wetting and other additives commonly used in the manufacture of effervescent tablets, in amounts necessary to ensure that the sum of the components is 100%.

The invention, furthermore, relates to a method of obtaining effervescent tablets or granules. In accordance with the invention by blending and granulation prepare four types of granules: vitaminstores granules, granules containing acid component sipacate, granules, containing the main component of sipacate, granules, containing trace elements, and homogenized containing substances external phase, with subsequent joint homogenization of the resulting four types of pellets and substances external phase and pelletizing the obtained granules. Upon receipt of the tablets in aggregate use 20 - 50 wt.%, preferably 30 to 40 wt.% mannitol, 8 to 25 wt.%, preferably 14 to 18 wt.% bicarbonate of potassium, 9 - 24 wt.%, preferably 15 to 21 wt.% malic acid, 0.4 to 2.2 wt.%, preferably from 0.6 to 1.5 wt.% aspartame, as well as necessary for the introduction of macro - and micronutrients and vitamins, and possibly taste, lubricant, and other additives, usually use the Ohm, as macro - and micronutrients preferably contain cations of magnesium, zinc, iron (II), copper (II), manganese (II), chromium (III), and also the anions of molybdenum (VI) and selenium (IV).

Preferably, the iron ions in the composition of the tablets used in the form of sulfate heptahydrate iron (II), zinc ions in the form of heptahydrate zinc sulfate, copper ions in the form of the pentahydrate of copper sulfate, manganese ions in the form of a monohydrate, manganese sulfate, molybdenum ions in the form of the tetrahydrate heptamolybdate ammonium ions selenium in the form of se acid, magnesium ions in the form of sulfate heptahydrate magnesium, chromium ions in the form of uranyl chloride chromium (III).

The vitamins in the composition is added preferably in the following amounts: 0.01 to 0.5 wt.% vitamin B1, 0.01 to 0.25 wt.% vitamin B2, 0.01 to 0.5. % vitamin B6, 0.001 to 0.01 wt.% vitamin B12, 0.1 to 2 wt.% nicotinamide, 0.01 to 0.5 wt.% vitamin A, 0,0015 - of 0.015 wt.% vitamin D, 0.1 to 5 wt.% vitamin C, 0.01 to 0.1 wt.% folic acid, 0.1 to 0.5 wt.% Pantothenic acid, 0.01 to 7 wt.% vitamin E and 0.001 to 0.01 wt.% vitamin H.

Tablets obtained by the proposed method, along with macro - and micronutrients and vitamins may contain flavouring and aromatic additives, e.g. is of asle, stearates or adipic acid, agents increase absorption, for example, tartaroo acid and glycerin, as well as any other additives commonly used in the manufacture of effervescent tablets.

The main advantages of the invention are as follows.

1. Tablets are chemically stable, easily subjected to pressing and have excellent physical properties.

2. Tablets and granules contain uniformly distributed active substances, i.e. macro - and micronutrients, and vitamins.

3. After dissolving the tablets in water is transparent drink a pleasant taste, not a draught.

4. In the presence of mannitol, the possibility of using malic acid as the acid component of sipacate in relatively large quantities, thus increasing the useful action of this acid as antioxidant, flavor additives and substances that optimizes pH.

5. When using mannitol can be obtained effervescent tablets with low-calorie diets and enriched with macro - and micronutrients and vitamins, the use of these tablets is also possible and people suffering from diabetes.

6. In previously known effervescent tablets the ionic water, or in the form of small content. On the other hand, the invention is able to use substances with a high content of water of crystallization, which themselves have poor compressibility, or impossible to extrude, but they are the most stable forms of inorganic compounds and therefore can be acquired at a lower price and with a high degree of purity.

7. When used together, mannitol, malic acid and aspartame is possible to achieve uniform distribution of macro - and micronutrients and vitamins, even if their number is very small relative to the weight of the finished tablet. Uniform distribution of vitamins achieved without adverse effects on the properties of these metastability substances during manufacturing operations.

8. The invention allows to obtain effervescent tablets containing incompatible active substances, for example vitamins, and macro - and microelements.

9. In the production of tablets of macro - and micronutrients form with mannitol complexes, more preferred from the viewpoint of chemical stability of tablets, as well as absorption and biological effect of the active substances is potassium and malic acid) and inorganic substances with a high content of water of crystallization (sources of macro - and micronutrients), who in their properties previously could not be used in the manufacture of effervescent tablets. In addition, the resulting effervescent tablets have high mechanical strength, and when the dissolution is rapid evolution and formed a clear solution.

The invention is further illustrated by the examples, without limiting its scope.

Example 1.

Ready-to-press the granules are four types of granules and the so-called external phase.

The pellets I

Vitamin B1- 7,29 g

Vitamin B2- 7.50 g

Vitamin B6- 10,94 g

Ca-Pantothenate - 38,215 g

Nicotinamide - 85,00 g

Mannitol - 500,00 g

After sifting substances homogenized, mixed with ethanol, granularit, then wet granules are dried and again granularit.

Granules II

The sulfate heptahydrate iron (II) - 99,55 g

Malic acid - 1500,00 g

Mannitol - 1500,00 g

After sifting substances homogenized, mixed with ethanol, granularit, dried, and then re-granularit and dried.

Granules III

The potassium bicarbonate - 3800,00 g

Mannitol - 3800,00 g

After sieving and homogenization of the mass is mixed with an aqueous-ethanolic see what that magnesium - 1571,50 g

Glycine - 150,00 g

Succinic acid - 250,00 g

Mannitol - 75,00 g

Se acid - 0,1635 g

Tetrahydrate heptamolybdate ammonium 0,690 g

Monohydrate, manganese sulfate (II) - 15,38 g

The pentahydrate of copper sulfate (II) - 29,47 g

Heptahydrate zinc sulfate - 219,95 g

After grinding, homogenizing, and pulp washing her granularit with distilled water, then dried, re-granularit and finally dried.

Substances external phase

Vitamin C - 300,00 g

Malic acid - 3000,00 g

The glycol - 710,00 g

Aspartame - 200,00 g

Lemon flavor - 1000,00 g

After sifting and grinding substances external phase homogenized. This mixture is then mixed with the pellets I, II, III and IV and again homogenized. From the thus obtained pellets were oppressively about 5000 tablets with a diameter of 32 mm, weighing about 4.5,

Example 2.

Repeating the same operation as in example 1 with the difference that the vitamins added vitamin E, and the number of components changed as follows:

Component Amount (g)

Sulphate of iron (II) (FeSO47H2O) - 99,56

Sulphate of zinc (II) (ZnSO47H2O) - 109,97

Sulphate of copper (II) (CuSO45H2247H2O) - 608,34

Vitamin B1(HCl) - 3

Vitamin B2(Riboflavin) - 3,5

Vitamin B6(HCl) - 4

Nicotinamide - 40

Vitamin C [L-(+)-ascorbic acid] - 175

Pantothenic acid (Ca-Pantothenate) - 15

Vitamin E (DL-alpha-tocopherol) - 25

Succinic acid - 100

Glycine - 75

Malic acid - 2750

The potassium bicarbonate (KHCO3) - 2300

Mannitol - 6500

Aspartame - 200

Pineapple flavor - 1000

The polyethylene glycol - 750

From ready for pressing pellets obtained about 5000 tablets with a diameter of 25 mm, weighing about 3 g

Example 3.

Repeating the operations described in example 1 with the difference that the trace elements added chromium, and vitamins - vitamin B12A , D, H, and folic acid, and the number of components changed as follows:

Component Amount (g)

Sulphate of iron (II) (FeSO47H2O) - 373,35

Sulphate of zinc (II) (ZnSOt47H2O) - 329,97

Sulphate of copper (II) (CuSO45H2O) - 39,29

Manganese sulfate (II) (MnSO4H2O) - 38,46

The ammonium molybdate [(NH4)6Mo7O247H2O) - 5069,5

Chloride chromium (III) (CrCl36H2O) - 1,28

Vitamin B1(t (cyanocobalamin) - 0,01

Nicotinamide - 95

Vitamin A - 5

Vitamin D - 0,05

Vitamin C [L-(+)-ascorbic acid] - 450

Folic acid - 1

Pantothenic acid (Ca-Pantothenate) - 35

Vitamin E (DL-alpha-tocopherol) - 50

Vitamin H (Biotin) - 325

Succinic acid - 300

Glycine - 180

Malic acid - 6000

The potassium bicarbonate (KHCO3) - 5000

Mannitol - 11500

Aspartame - 300

Orange flavor - 1500

The polyethylene glycol - 2000

From ready for pressing pellets obtained about 5000 tablets with a diameter of 35 mm, a weight of 6.6 g

Example 4.

Repeating the operations described in example 3 with the difference that the amount of malic acid was reduced to 3500 g of potassium bicarbonate to 2800 g, aspartame - up to 150 g, and the amount of mannitol was increased to 16000, ready for pressing pellets obtained about 5000 tablets with a diameter of 32 mm, a weight of 6.6 g

Example 5.

Repeating the operations described in example 3 with the difference that the amount of malic acid was increased to 10000 g, potassium bicarbonate up to 9000 grams of aspartame up to 800 g, and the amount of mannitol was reduced to 8000, ready for pressing pellets obtained about 5000 tablets with a diameter of 32 mm, weighing approximately the x games tablets (1, 2 and 3) on the stability of the composition and properties when stored for 3 months under the following conditions, conventionally denoted (A), (B) and (C):

(A) temperature 25oC2oC, Rel. humidity 605%;

(B) temperature 25oC2oC, Rel. humidity 855%;

(C) temperature 30oC2oC, Rel. humidity 605%.

Literature

1. Pharmaceutical Dosage Form: Tablets, Vol.1, 2nd edition, A. Lieberman ed., 1989, Marcel Dekker, Inc.

2. Pat. USA 4725427.

3. Pat. USA 4678661.

4. Pat. USA 4704269.

5. Martindale. The Extra Pharmacopoeia, 19th ed, London, 1989, p. 1274.

1. Effervescent tablet or granule containing frame material, the main component of sipacate, the acid component of sipacate, sweetener, as well as macro - and micronutrients and possibly vitamins as active substances, characterized in that it contains 20 to 50 wt.% mannitol as a frame material, 8 to 25 wt.% of potassium bicarbonate as the main component of sipacate, 9 - 27 wt.% malic acid as the acid component of sipacate, 0.4 to 2.2 wt.% aspartame as a sweetener, and possibly taste, lubricant, and other additives commonly used in the manufacture of effervescent tablets, in amounts necessary to bring the amount of the component is a, 14 to 18 wt.% bicarbonate of potassium, 15 - 21 wt.% malic acid and 0.6 - 1.5 wt.% aspartame.

3. Effervescent tablet or pellet under item 1, characterized in that it contains as macro - and micronutrients cations of magnesium, zinc, iron (II), copper (II), manganese (II), chromium(III) and the anions of molybdenum (VI) and selenium (IV).

4. Effervescent tablet or pellet under item 1, characterized in that it contains iron ions in the form of iron sulfate heptahydrate, zinc ions in the form of heptahydrate zinc sulfate, copper ions in the form of the pentahydrate of copper sulfate, manganese ions in the form of a monohydrate, manganese sulfate, molybdenum ions in the form of the tetrahydrate heptamolybdate ammonium ions selenium in the form of se acid, magnesium ions in the form of sulfate heptahydrate magnesium, chromium ions in the form of uranyl chloride chromium (III).

5. Effervescent tablet or pellet under item 1, characterized in that it contains vitamins in the following amounts in relation to the weight of the composition: 0.01 to 0.5 wt.% vitamin b1, 0.01 to 0.25 wt.% vitamin b2, 0.01 to 0.5. % of vitamin b6, 0.001 to 0.01 wt.% vitamin b12, 0.1 to 2 wt.% nicotinamide, 0.01 to 0.5 wt.% vitamin a, 0,0015 - of 0.015 wt.% vitamin D, 0.1 to 5 wt.% vitamin C, 0.01 to 0.1 wt.% folic acid, 0.1 to 0.5 wt.% pantat is or granules, characterized in that by blending and granulation prepare four types of granules: vitaminstores granules containing acid component sipacate, granules, containing the main component of sipacate, granules, containing trace elements, and homogenized containing substances external phase, with subsequent joint homogenization of the resulting four types of pellets and substances external phase and pelletizing the obtained granules.

7. The method according to p. 6, characterized in that at reception of tablets in aggregate use 20 - 50 wt.%, preferably 30 to 40 wt.%, mannitol, 8 to 25 wt.%, preferably 14 to 18 wt.%, bicarbonate of potassium, 9 - 24 wt. %, preferably 15 to 21 wt.%, malic acid, 0.4 to 2.2 wt.%, preferably from 0.6 to 1.5 wt.%, aspartame and input macro - and micronutrients, vitamins, and possibly taste, lubricant, and other additives commonly used in the manufacture of effervescent tablets.

 

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