Compression lactic and method thereof

 

(57) Abstract:

The invention relates to medicine, in particular directly the compression of the granulate of lactate and to tablets prepared on its basis. The granulate contains lactic and physiologically acceptable nicaraguense binder, which can serve as necrogenic sugar alcohol, polymerized restored sugar, alkaline carboxymethyl cellulose, hydrolyzed hydrogenating starch, hydroxypropylcellulose, physiologically acceptable derivatives of cellulose, polyvinylpyrrolidone, gum Arabic and other physiologically acceptable resin. The most preferred binder is lactic. The invention relates also to a method for producing a directly compressible granulate of lactate, which can be used for preparing tablets. Get tablets find high hardness and low friability. They necrogen and have the taste profile Loctite and its metabolic properties. 4 C. and 19 C.p. f-crystals, 4 tab., 2 Il.

The technical field to which the invention relates

The present invention relates to a directly compressible to granulate Loctite. The granulate contains lactic and physiologically p which is necrogenic sugar alcohol, such as lactic. The invention relates also to a method for producing a directly compressible granulate of lactate, which can be used as part of the process of tabletting; the resulting granulate finds acceptable characteristics of fluidity and favorable curve pressing. The granulate has a taste, metabolic and necardiogenny properties inherent in Loctite. The invention relates also to tablets that contain lactic and have high hardness and are non-fragile and necardiogenny and have a taste and metabolic properties Loctite.

Art

Sweetener, the most widely used with food and pharmaceutical products, is sucrose. Sucrose is used due to its well-known sweetening properties, and also as a filler. Although there are a large number of alternative sweeteners, sucrose is generally regarded as the best sweetener with regard to its taste and technology parameters. However, it was found the effect of sucrose as a contributing factor in many diseases, including hypertension, diseases of the coronary system, atherosclerosis and brown the Arosa and its important role as a component of food.

Lactic is a dimeric sugar alcohol with a sweet taste, which is produced by the catalytic hydrogenation of lactose. Commercially available lactic is either a mixture of mono - and dehydraton lactate anhydrous lactitol or purely monohydrate and pure anhydrous form.

Using Loctite seems attractive due to sustained taste and technological characteristics. In particular, lactic has the following (non-exhaustive) set of properties that make it potentially very useful as an excipient for tablets:

1. clean monohydrate form essentially nephroscopy that enhances its properties as a stable, free of the current product, which is potentially suitable for the production of tablets with a long shelf life;

2. its solubility in water lactic close to sucrose, which helps to obtain a homogeneous sensations in the mouth (i.e., the absence of feelings of grains), as well as the effective release of the active ingredient;

3. the energy content of lactate is only 2 kcal/g;

4. lactic metabolized without requiring the presence of insulin and glycemic pokazateli lactic has minimal negative heat of dissolution (a cooling effect), which may affect the desired taste.

The combination of properties inherent Loctite (nephroscopes, solubility, energy value, metabolism, dental and organoleptic parameters), explicitly allocate lactic of other crystalline sugar alcohols and other alternative sweeteners-fillers. For example, although mannitol (widely used in the preparation of tablets) is essentially non-hygroscopic, has an energy content of 1.6 kcal/g, is not carcinogenic and is metabolized independently of insulin, it creates a noticeable cooling effect and has a low solubility, which often creates a sense of presence of grains. Sorbitol and xylitol create significant cooling effect and have moderately hygroscopic properties. ▫ Maltitol, moderately hygroscopic, requires a moderate level of insulin and has an energy value of 3 kcal/g Isomalt as mannitol, exhibits low solubility, which can affect the perception of the tablet in the mouth.

The area in which previously lactic used only with limited success, is its use as a component of the tablets. In U.S. patent US 5534555 discusses the use of dstone compression". However, this mixture does not possess such properties free of fluidity, as a granulate, and not so easy to handle, it karyagina and not fully realizes the advantages of Loctite as material for the preparation of tablets.

In a pharmacological context tablets are used to make the active substances of size, shape and texture that allow them to dose, chewing, sucking, swallowed whole, or dissolved in the water while drinking. In the food context tablets can be in the form of compressed candy with fruit or mint flavor, consisting of sweetening agents (sweeteners), flavorings and possibly dye and acid.

Due to its taste and other described properties lactic represents a potentially attractive component constituting tablets both for food and for pharmaceutical purposes. Although other high molecular weight alcohols used in the preparation of tablets as diluents, flavoring agents or binders, lactic not found wide application in the field.

Tablets can be molded by extrusion or casting. The simplest method of compaction has been known for centuries. In 1577 Hieronyma "pills" sugar for the first time in 1606 attributed to Jean de Renou, and one of the first patents for the production of pills and medical patch" was issued in 1843, in the UK some Thomas Bracelona. There are many types of tablets, including chewable tablets, cake, effervescent tablets, tablets, film-coated, coated tablets, tablets with prolonged action (release of ingredients for some time), multilayer tablets, etc.

Modern technology of tablets pressed, regardless of their nature (and the final form of the final product) use of the device piston type with three stages in each cycle: (1) filling, i.e., the input components of the tablets into the pressing chamber; (2) forming tablets by pressing; (3) ejection, i.e. the destruction of the tablets. Then the cycle repeats. A typical example of the means of pressing (tabletiruemogo press) is a rotary press model MANESTY EXPRESS 20, manufactured by Manesty Machines Ltd. (Liverpool, UK); there are also many other models.

In order to produce tablets, preferably all of the ingredients, or at least the carrier, or diluent, which is usually sostavlyauschuu free to yield and acceptable cohesion (or compressibility). In this context, "free turnover" means that the particles to be pressed should be sent to the pressing chamber in the form of discrete particles. If in the preparation of tablets particles do not possess the property "free turnover", they can only be used subject to the availability of power feeding devices or other mechanical means for moving particles. "Compressibility" means that after pressing, the particles form a tablet, and not remain in powdered or almost powdery phase. Since many materials do not have or have only partially specified properties should be designed in ways that make these properties of the constituent components of the tablets. The use of such methods increases the cost of the process and greatly reduces its effectiveness; therefore, they are rarely used.

Two metrics that are critical to quality tablets are crushing strength (or hardness) and fragility. Hardness determines properties such pills as resistance to chipping, abrasion or breakage under conditions of storage, transportation and preparation for use. The firmness of the units strong-Cobb, where 7 N=1 E. C. K.), corresponding to the force applied to a single tablet at the time of rupture. A representative device for testing is the device model HT-300, manufactured by Key International, Inc. Acceptable hardness value depends on the desired mouth feel, the expected forms of use and the nature of the packaging of tablets, however, in most situations to ensure that the tablet had a commercial value, its hardness must be greater than about 10 E. C. K.

For fragility there is also a standard test known to specialists in this field. Fragility is measured under standard conditions by weighing a certain number of tablets (usually 20 or more), placing them in a rotating Plexiglas drum, inside which they are in the process of re-spins rise through the radial grid, and then discharged from the height of the diameter of the drum. After repeated spins pills again weighed and calculated the proportion of "erased" material or atlamillia pieces. The fragility in the interval from 0 to 3% is considered acceptable for most pharmaceutical or food applications. Particularly preferred fragility, priblijayushim easy to break down or fall apart under normal conditions of packaging or handling. Tablets with insufficient hardness cannot be used for the manufacture of peppermint candy or such medical tablets, want to suck, with the gradual release of ingredients, active in the medical or taste. In addition, these tablets in the mouth can cause undesirable feeling of poroshkoobraznoe or grain.

Lactic is not considered a directly compressible material, i.e. crystalline lactic cannot be compressed into tablets of sufficient hardness and low friability. In this regard, in order to apply lactic for tablets, we tested different ways of giving the desired characteristics, but was not successful.

When pelletizing ground monohydrate lactate with an average particle size of about 65 microns to press Manesty F3 using as lubricants 1% of magnesium stearate were obtained tablets with acceptable hardness and friability. However, the coefficient of variation of weight of tablets was unacceptably high (> 4%). Significant variations in weight were attributed to poor flow characteristics of milled Loctite. Adding to molotow Loctite to 8% talc significantly improved the flow CLASS="ptx2">

When the press Manesty F3 using as the lubricant of 1% magnesium stearate was tabletirovanija crystalline monohydrate of lactate with an average particle size of about 500 μm were observed to have acceptable characteristics of fluidity and stable weight of the tablets, However, the hardness of the tablets at best was on the border of acceptable values, and the fragility is unacceptably high.

Attempts to combine ground and crystalline monohydrate of lactate in a weight ratio of 1:1 resulted in tablets with a hardness on the verge acceptable, fragility, exceeds the allowable value, and with a high enough flow characteristics and uniformity of tablet weight.

When tabletirujut crystalline anhydrous lactic with different average particle size may be obtained tablets, the values of hardness and fragility which initially are acceptable. However, presumably due to the tendency of anhydrous lactate to absorb moisture from the atmosphere with a gradual transformation in monohidrato the form of tablets during storage even under mild ambient conditions noticeably softened.

The invention

Thus, objective,current granulate of lactate with an average particle size of up to 500 microns. The granulate contains lactic and physiologically acceptable nicaraguense binder. Acceptable binders include sugar alcohols, polymerized restored sugar, alkaline carboxymethyl cellulose, hydrolyzed hydrogenating starch, hydroxypropylcellulose, physiologically acceptable derivatives of cellulose, polyvinylpyrrolidone (PVP), gum Arabic and other physiologically acceptable resin. The most preferred sugar alcohol to the binder is lactic. The most preferred binder based on the recovered sugars are maltodextrin and modified Polydextrose, and the most preferred binders based on alkali carboxymethyl cellulose is sodium carboxymethyl cellulose. GRANULAT may include other sweeteners.

One of the embodiments of the invention contains a directly compressible, necrogenic, free current granulate of lactate, which consists of ground lactic and Loctite binder. Binder is present in the granulate at a level from about 2% to about 30% by weight, preferably are level from 5% to 15%, and especially preferred is from about 10% to about 15%.

Sobri, formed directly by the compression agents, including lactic and physiologically acceptable nicaraguense binder. The tablet may also include other components, including microcrystalline cellulose, physiologically acceptable derivatives of cellulose, starch, food additives, starch-based, and nicaraguense sugar alcohols. The tablet may also include intense sweeteners. Preference is given to intensive sweeteners, taken from the group consisting of dipeptide sweeteners, saccharin, Acesulfame K, reveal, cyclamate, Sucralose, neohesperidin of dihydrochalcone.

The present invention also aims at creating a method of producing a directly compressible, free of the current, necardiogennogo granulate of Loctite consisting of granulated milled lactate with an average particle size less than about 300 microns with physiologically acceptable nicaraguensis binder. Binders include the above compounds, particularly preferred binder is lactic. According to a preferred variant of the method lactic used in aqueous solution at concentrations of from about 30% to about 60% of the list of figures

The invention hereinafter will be described in more detail with reference to the accompanying drawings, on which:

Fig. 1 illustrates the stability of tablets prepared from granules of lactate, in comparison with the tablets of commercially available mannitol intended for tabletting;

Fig. 2 shows the results of the research on pressing, namely the comparison of hardness of tablets prepared from granules of lactate of the present invention, and tablets of commercially available mannitol intended for tableting, and lactose.

Information confirming the possibility of carrying out the invention

The granulate according to the present invention shows excellent fluidity and compressibility when using typical compaction equipment, such as rotary tabletroute press Manesty Express 20 or other tabletiruemye the media, who are known experts in this field. A preferred form of Loctite used to obtain a granulate, is lactic, milled to obtain an average particle size of less than about 300 microns, preferably about 30-200 μm, particularly preferably from about 50 to about 90 microns. To obtain particles with the pre is the manual. Crystalline lactic can be applied in the form of anhydrous lactate, in the form of a monohydrate, dihydrate and three-hydrate in pure crystalline form or in the form of solid mixtures of these hydrated and anhydrous forms. The preferred form is a monohydrate Loctite.

Lactic for the purpose of granulation can be combined with other necardiogenny high molecular weight alcohols, such as xylitol.

Binder provided by the present invention is physiologically acceptable and nicaraguensis. Surprisingly and unexpectedly, but an aqueous solution of lactate acts as an excellent binder that meets these conditions. Lactic not very widely known as a binder. However, it was found that an aqueous solution of lactate at concentrations of about 30-60% (by weight) is an excellent binder for the purposes of the present invention. Preferred is an aqueous solution of lactate with a concentration of 45-55% (by weight), and particularly preferred is a solution with a concentration of 49-51% (by weight). Thus, the resulting granulate consists only of Loctite that allows you to fully use its taste and technological advantages. Crystalline form of lactate as connecting some of the carboxymethylcellulose. Sodium carboxymethylcellulose can be used in a wide range of cosmetic, food, pharmaceutical and industrial applications, but it is not found use as a binder for lactate in the context of tableting. Sodium carboxymethylcellulose is supplied by the company Aqualon Company (USA). Sodium carboxymethyl cellulose is a cellulose ether obtained by reaction of alkali cellulose with monochloracetate sodium in controlled conditions. Offers food, pharmaceutical and standard grades of sodium carboxymethylcellulose with different substitution levels (from 0.38 to 1.4) and different viscosities of aqueous solution.

Other acceptable binders include restored polymeric sugars such as maltodextrin and modified Polydextrose described, for example, in the application for the European patent EP 90300577.5. Another possible binder is hydrolyzed hydrogenating starch. The hydrolysate hydrogenating starch is a product of the catalytic hydrogenation of a syrup with a high content of maltose; it is commercially available from many suppliers. Other functionally acceptable binder may include hydroxypropyl logicheskie acceptable resin.

Content lactitol binder in the final dry product (expressed as a percentage of dry weight) is in the range from about 2% to about 30% with a preferred range from about 5% to about 15%, and especially preferred is the range from about 10% to about 15%.

Granulation of lactate with a binder may be implemented using any available standard equipment. Available on the market appropriate granulators or granulating systems are, for example, horizontal Lodige mixer (Gebruder Lodige GmbH) in combination with desiccant fluidized bed (Glatt GmbH, Germany), vertical granulator Aeromatic fluidized bed (Aeromatic AG, Switzerland), Schugi (Schugi, BV, the Netherlands). For the implementation of the present invention can be applied to other granulators, well known to specialists in this field.

Manufactured and dried granulate is usually subjected to particle size analysis to remove large particles. Suitable for this purpose room sieve corresponds to 16 mesh (1.2 mm). Large particles can be recycled, crushed, or dissolved for further use.

The granulate may be using whitesky applications alone or in combination with other sweeteners (such as intense sweeteners), other high molecular weight alcohols and/or other binding agents.

The granulate in accordance with the present invention can be used as filler for tablets, alone or in combination with other fillers, lubricating agents, flavoring agents and/or diluents. The content of the granulate can be from approximately 5% to approximately 99.5% by dry weight; other fillers may include microcrystalline cellulose, derivatives of cellulose, starch, derivatives of starch and nicaraguense sugar alcohols.

Example 1

Using a granulator SWG 15 Glatt Fluid Bed Granulator with a fluidized bed equipped with a sieve mounted on the bottom of the camera, and with the mill Quadro Comil, Model 197-1-064 using a grid of size 2A-. 04R031/37, monohydrate lactate, milled to a particle size of about 65 microns, was granulated using water lactitol binder (containing lactate 50% by weight) and maintained under normal conditions. There were prepared three granular lactinex product: (A) containing 6% binder (dry weight, PSV); B) is of atur input about 80oC; pressure spraying air 5105PA; performance spraying a binder of about 110 ml/min; temperature of the air exiting from about 34oIn the process, and about 44oWith the end of the drying cycle. Products B and C were obtained by the air flow rate of about 5.6 m3/min, while the product was obtained at a flow rate of air is about 7.0 m3/min. Each product showed satisfactory flow properties, moisture content of about 4.6%, bulk density in the free state was about 0,58 g/ml using a rotary tabletiruemogo press Manesty Express 20 with a working pressure of 2.0 tons and a capacity of 1000 tablets/min of each product were prepared tablets with a weight of approximately 550 mg, diameter 11 mm, flat, beveled. Tablet from all of the food was tasty and had good properties in terms of hardness and acceptable friability. The values of hardness for tablets of various products amounted to: And about 231 N (33 E. C.); B - near 238 N (34 E. C.); about 154 N (22 E. C. K.).

Example 2

The granulate of Loctite for Example 1B and commercially available granulated mannitol were merged using 1% of magnesium stearate as a lubricating ve.With.K). Tablets were kept for 23 days at a temperature of about 20oC and a relative humidity of 75% with the control of increasing moisture content. As shown in Fig.1, for tablets from lactate increase in moisture content was only about 0.1%, while in the tablet of mannitol, the moisture content increased approximately 1.0%.

Example 3

The granules of lactate according to Examples 1A-had an average particle size less than about 200 microns. With the aim of obtaining a higher average particle size of the granulate of Loctite ground monohydrate lactate was granulated with a solution of lactate (50% by weight) using the same equipment as in Example 1 under the following conditions: air consumption 7.0 m3/min; inlet temperature of about 85oC; pressure spraying air 2,5105PA; performance spraying a binder of about 250 ml/min; duration spraying about 11 min; temperature of the air exiting from about 38oIn the process, and about 45oSince during the drying cycle. The binder content in the final product amounted to about 12% by dry weight. The resulting granules had excellent yield and was practically free from dust. The average particle size was about 390 μm. Kokolo 0.45 g/ml

Example 4

Was prepared granulate as described in Example 3. The average particle size of the granules was approximately 300 μm. The granules had excellent properties for yield, moisture content is about 5%, bulk density in the free state of about 0.55 g/ml Were carried out various tests granulate and available on the market directly compressible mannitol and directly compressible lactose. Comparative tests included: 1) research profile extrusion; 2) preparation of tablets of ascorbic acid (vitamin C), and 3) assessment of the potential dilution of the filler using as diluent powder in the form of acetaminophen (ARAR).

Research profile extrusion was carried out on a flat tablets with a diameter of 11 mm beveled with an average weight of about 600 mg of magnesium Stearate in the amount of 0.5% was used as lubricants during pelletizing. Tablets were prepared on a rotary press Manesty Express 20. The results of the study of pressuemosti, which are illustrated in Fig. 2, indicate that the characteristics of the granulate of Loctite better or similar features of the two maps fillers available in piano above, using a 10% (by weight) of ascorbic acid, 87.5% of filler, and 2.0% component Ac-di-sol and 0.5% magnesium stearate. The pressing force was 1.3 tons Each filler was possible to obtain tablets with acceptable quality, as is evident from Table 1.

Assessment of the potential dilution of each filler was carried out using as diluent a 10% or 30% ARAR. As the lubricant was used stearate content of 0.5%. Tablets were prepared as described above, when the effort of pressing in the range of 1.3 to 2.0 so All the fillers had similar potential dilution, as is evident from Table 2.

Example 5

Was a commercial batch of granules of lactate using a granulator WSG500 Glatt Fluid Bed Granulator with a grid of wire 16 mm, installed at the bottom of the camera. The granulate was razmalyvanija mill Quadro Comil installed in the granulator and having a mesh size of 0,N/60. Ground monohydrate Loctite (with an average particle size of about 65 μm) was used with a binder solution lactate (50% by weight) containing 12% of Loctite on a dry weight basis. The granulation conditions were as follows: air flow rate of about 73 m3/min at the beginning and about 78 m3/min at econanic spray about 3 l/min; the final temperature when cooled to about 29oC. the Average particle size of the granules was about 280 μm; the granulate well was flushed and was practically free from dust. The moisture content of the granules was approximately 5%. Bulk density in the free state was about 0,57 g/ml Flat tablets with beveled edge weight of 600 mg and a diameter of 11 mm were merged on a rotary press Manesty Express 20 with a pressing force of about 1.5 t using magnesium stearate as the lubricant. The resulting tablets had a pleasant taste and creating a pleasant feeling in the mouth without residual taste. The hardness of the tablets was about 25 Kr, variation of weight of tablets was characterized by a standard deviation of 1%, friability of tablets was less than 1%.

Example 6

Simple household multifunctional mixer (Moulinex) was used to prepare pellets of lactate small batches (200 g) using different binders. The cooking process was comparable with the use of commercially available high-speed mixer/granulators.

There were prepared aqueous solutions of the following binders:

- lactate, 60% by weight;

Different binder solutions were slowly added to Loctite before the formation of granules. The granules were dried in a thermostat at 60oC.

The dispersible granules was assessed visually by dispersion teaspoon of granules in 100 ml of tap water.

The granules obtained using solution lactate as a binder, had the best dispersibility; their flavouring properties have also been the best. For parties, obtained using a binder, giving the granules with low solubility in water (e.g., gelatin), dispersibility was worse than for pellets with lacticum binder.

For the preparation of tablets the granules were mixed in the turbula mixer for 2 minutes with 1% magnesium stearate. Tableting lubricated granules were produced on dropwinsonde machine (Manesty) using a punch with a diameter of 12.7 mm Solid granules lactate was tabletirovanii very good, and most durable happened tablets with PVP.

Example 7

Crystalline lactic (brand Lactitol CM50, firm Xyrofin Oy, Finland), milled to an average particle size of 50 μm, was placed in the mixing chamber multifunctional mixer Moulinex.

Estestvoznaniya 20 g maltodextrin brand C*Pur01915 (company Cerestar) in 180 g of water. 150 g of milled Loctite took of 8.2 g of this solution. 3% PVP solution was obtained by dissolving 6 g of PVP marks CO (ISP) and 194 g of water. 10.0 g of this solution was taken in 200 g of milled Loctite. 60% solution of lactate was obtained by dissolving 120 g of Loctite brand MS (manufactured by Xyrofin Oy) in 80 g of water. 30.0 g of this solution was taken in 200 g of milled Loctite.

The binder solution was added to lactic via syringe while stirring Loctite. The mixture is then sieved through a household sieve (mesh size about 1 mm) on the foil, which was covered baking sheet. The mixture is then drying was placed overnight in a thermostat configured on the 40oC. Prior to pelletizing the dried granulate was sieved through a household sieve.

As the lubricant was added 1% of magnesium stearate. Then the granulate alloy preformed on dropwinsonde press Manesty 2C using a flat punch with a diameter of 15 mm with a beveled edge.

The pressing force was regulated by adjustment of the height of the stroke of the upper punch. The hardness of the tablets was measured using instrument company Key Instruments for testing of tablets hardness, which measures the load required to break the tablet in diameter. Tested on 10 what was the average result. The weight of the tablets was recorded as the average of the 10 individual tablets.

Friability of the tablets was measured using instrument company Key Instruments for assessing fragility. Ten tablets were thrown 100 times and record the mass loss percentage. All the tablets that are badly cracked, were removed before weighing.

Results

All of these pellets gave the tablets of acceptable quality when the maximum hardness values above 350 N. All the tablets gave satisfactory results in fragility.

The concrete results of the tablets are shown in Table 4.

Example 8

A 50/50 blend of lactate and xylitol was granulated with stirring a mixture containing 6 kg of each component in the cell pellet. Used pellet mill WSG 15 Glatt; as a binder at a temperature of 60oWith used sodium carboxymethylcellulose with a concentration of 1.5%.

The properties of the granulate according to pressuemosti was determined using a rotary press Manesty Express 20. Two kilograms of granulated product was sifted through a 20 mesh and mixed for 5 minutes in a Hobart mixer with 10 g of magnesium stearate.

The pressing was carried out of priority with a diameter of 11 mm with beveled edge

Weight tablets 550 mg

The pressing force is 1,0-3,0 t

The hardness of tablets consistent with approximately 237 N (33,9 E. C. K.).

Describes in General and experimental examples are intended to illustrate the present invention and should not be construed as limiting it. There are various modifications that do not go beyond the boundaries of the ideas and scope of the invention, and specialists in this field will be able to imagine.

1. Directly compressible, necrogenic, free current granulate of lactate with an average particle size of up to 500 microns, containing lactic and physiologically acceptable nicaraguense binder in a ratio of from about 2% to about 30% by dry weight, characterized in that the binder is a sugar alcohol that represents lactic.

2. Directly compressible granulate under item 1, characterized in that the specified lactic includes ground crystalline monohydrate, dihydrate, trihydrate lactate, anhydrous lactic and/or crystalline or precipitated mixture.

3. Directly compressible granulate under item 2, characterized in that the specified ground lactic is a monohydrate Loctite.

5. Directly compressible granulate under item 1, characterized in that it additionally contains an intense sweetener selected from the group consisting of dipeptide sweeteners, saccharin, Acesulfame K, reveal, cyclamate, Sucralose and/or neohesperidin of dihydrochalcone.

6. Directly compressible granulate under item 1, characterized in that it additionally contains one sugar alcohol such as xylitol.

7. Directly compressible granulate under item 1, characterized in that the binder contained in the granulate in an amount of from 10% to about 15% by dry weight.

8. Directly compressible, necrogenic, free current granulate of lactate containing ground lactic and Loctite binder, with specified binder contained in the granulate in an amount of from about 2% to about 30% by dry weight.

9. Directly compressible granulate under item 8, characterized in that the specified ground lactic includes monohydrate, dihydrate, trihydrate lactate, anhydrous lactic or mixtures thereof.

10. Directly compressible granulate under item 9, characterized in that the specified ground lactic is a monohydrate Loctite.

11. HB granulate in an amount of from about 5% to about 15% by dry weight.

12. Relatively stable, securigera taken inside the tablet, formed by means of extrusion and containing lactic and physiologically acceptable nicaraguense binder in a ratio of from about 2% to 30% by dry weight, characterized in that the binder is a sugar alcohol that represents lactic.

13. Taken inside the tablet under item 12, characterized in that it additionally contains one or more fillers.

14. Taken inside the tablet p. 13, characterized in that the fillers selected from the group consisting of microcrystalline cellulose, physiologically acceptable derivatives of cellulose, starch, food additives based on the derivatives of starch and necrogenic sugar alcohols.

15. Taken inside the tablet p. 14, characterized in that the specified necrogenic sugar alcohol is a xylitol.

16. Taken inside the tablet under item 12, characterized in that it further contains an intense sweetener selected from the group consisting of dipeptide sweeteners, saccharin, Acesulfame K, reveal, cyclamate, Sucralose, neohesperidin of dihydrochalcones, including the milled granulation lactate having an average particle size less than about 300 microns, with physiologically acceptable nicaraguensis binder and screening thus obtained granulate, characterized in that the binder is a sugar alcohol that represents lactic.

18. The method according to p. 17, characterized in that the specified ground lactic has an average particle size of from about 30 to about 200 microns, more preferably from about 50 to about 90 microns.

19. The method according to p. 17, characterized in that the binder on the basis of lactate used in the form of an aqueous solution containing lactate from about 30% to about 60% by weight.

20. The method according to p. 17, characterized in that the binder on the basis of lactate used in the form of an aqueous solution containing lactate from about 45% to about 55% by weight.

21. The method according to p. 17, characterized in that the binder on the basis of lactate used in the form of an aqueous solution containing lactate from about 49% to about 51% by weight.

22. The method according to p. 17, characterized in that the granulate has an average particle size less than about 500 microns.

23. The method according to p. 17, characterized the

 

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The invention relates to pharmacology and about creating convenient for intravaginal application form new, not previously used in gynecological practice antiseptic plant have antibacterial, antifungal, antiviral activity and activates the reparation of damaged mucosa

FIELD: medicine, in particular composition for quick-disposable in buccal cavern tablets.

SUBSTANCE: claimed composition contains granulated product of fine dispersed long releasing particles, comprising drug and fillers selected from group including sugars and sugar alcohols together with binder, wherein content of non-granulated fine dispersed long releasing particles is 0-15 %. Method for production of such tablets is also disclosed.

EFFECT: pharmaceutical composition with accelerated degradation.

24 cl, 9 ex, 3 dwg

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