DE1800727A1 - Method of making tablets - Google Patents

Description

The present invention relates to a lubricant for tablet production, the one to be tabletted Powder substance can be mixed, and this makes it slippery when pressing tablets. In detail concerns the invention relates to the use of a lubricant which consists of dry-miscible particles which have a Have lubricating oil containing core and a coating of an oil-insoluble, film-forming substance.

Lubricants for tabletting are intended to make the mass 1. slidable against the punch surfaces come into contact with the pressed mass and

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2. freeze over the surfaces of the die walls, between which the tablet is formed ^ make conductive. That Lubricant must fulfill both functions if the powdery tablet substance in the technical Scale is to be pressed in high-performance tableting machines. Some lubricants that have been used up to now meet only one of the two necessary lubricant functions and must therefore be used together with other lubricants will. A common problem with these known lubricants is their insolubility, which leads to that when the tablets containing these lubricants disintegrate in water, foam and an uneven, flaky suspension forms. Examples for such lubricants are talc and magnesium tearate, other known lubricants are due their toxicity excluded from some areas of application, for example. Boric Acid and Benzoic Acid, Some Lubricants such as sodium benzoate are themselves therapeutically effective and therefore change the pharmacological one Capacity for tablets in which they are included. ■

One lubricant that has found use in low volume manufacturing is corn oil. Of the The main disadvantage of using such an oil as a lubricant is that it only contains small amounts of the

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substance to be tabletted or added to the mixture because it tends to dampen the hatred and therefore the mingling is worthwhile about the distribution to relieve the small amounts of oil, attempts have been made to dilute it with various solvents; therefor however, special devices and additional work steps are necessary. As a result, corn oil have lubricants not found widespread use.

It has now been found that lubricating oil particles are coated with an oil-insoluble film-forming substance can be used to make these particles dry miscible; this allows them to be powdered and tabletted Substances are added to prevent these substances from sliding when tableting in high-speed machines to effect. If these coated oil particles are mixed with a dry substance, they are obtained Mixtures essentially free-flowing and can easily be tabletted, f

An object of the present invention is therefore an improved tableting process in which coated Oil particles are mixed with a powdered substance to be tabletted before pressing into tablets.

Another object of the present invention is a tablet which consists of a mixture of a tabletting-

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powdered material and a tabletting slide in the form of dry-miscible particles of a lubricant oil, coated with an oil-insoluble one film-forming substance, is pressed.

The lubricant in the form of coated oil particles is used together with powdered, tablettable substances to ensure the even flow of the pressed material during tableting. For tablettable substances that were previously only tabletted on slow-running machines or hand presses, the lubricant according to the invention, if added before pressing, has both internal pressure-lubricity and a certain surface-lubricity and thus enables tableting in high-speed machines that run at high speed, It is true that different amounts of lubricant can be mixed with the substances to be tabletted, depending on whether they are still other _; contain ingredients acting as lubricants and, depending on the desired tableting speed j in general "", however, it is sufficient to use at least about 0.5 % lubricant, based on the weight of the lubricated tablettable material. If necessary, the lubricant can also be added in larger amounts up to a limit of about 50 % _t based on the total weight of the tablet; if this limit value is exceeded

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steps, excess lubricating oil becomes visible on the tablet surface and this is generally undesirable. Preferably less than 5 % lubricant is used,

The amount of film-forming substance used is less than necessary to remove the oil particles with a continuous, thick resinous layer to coat. A minimum amount of film-forming agent that can be processed is preferred Substance related to the oil used. This is not a critical feature of the present invention, it it is found, however, that the relatively thin coating produced in this way allows improved sliding.

A major advantage of the tablet lubricant of the present invention lies in the fact that it can be mixed dry and thus with the various types of powdered, to tablettie rend materials can be easily mixed and homogenized. This property can be defined as the Ability of the lubricant to be mixed homogeneously with dry powders as if it were a complete itself dry powder. This feature does not mean that the particles alone are completely free-flowing, but rather rather, that when mixed with at least the same weight of dry powder for tablet manufacture the resulting mixture is free flowing. Will

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If the lubricant particles are dispersed in water, no foam forms on the surface and it will get an even solution.

The substances to be tabletted, which can be made lubricious with the coated oil particles, can be any substances that hold together sufficiently that they take on a tablet shape when pressed and keep this. Such substances are e.g. disinfectants, germicides or oral hygienic products that - once put in water - disintegrate and form solutions of various kinds. The addition of quaternaries is particularly useful Ammonium compounds such as Cetylpyridiniurnchiorid due to their surface tension lowering and bactericidal Properties. Preferred substances are water-soluble, Tablettable substances that dissolve into clear solutions, especially effervescent mixtures that contain an alkali carbonate or bicarbonate and an acid such as malic acid, citric acid or tartaric acid and which quickly release carbon dioxide when water is added. If that Carbon dioxide has been released, the solution formed is because of its alkalizing properties suitable for oral intake. Uniform appearance is a desirable feature of such solutions.

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Various therapeutic preparations can also be tabletted with the aid of the coated oil particles will. Xh Such preparations can consist of at least a drug, a water-soluble excipient and the necessary coloring, flavors, Diluents, binders or disintegrants exist. If necessary, binders are added to the substance to be tabletted or to the mixture to demand cohesion. There can also be substances or Mixtures for the production of effervescent tablets from which beverages with added flavor are prepared with the coated oil lubricants can be made lubricious. All of these currently known substances can be tabletted insofar as they hold together in the compressed state. very However, many of these substances can only be tabletted in hand presses because they power the punches and dies Tableting machines stick together and erode. In order to achieve the speeds required for technical production To achieve this, a tabletting lubricant such as that of the present invention must be added to reduce surface friction between Hasse and device and the internal friction in the mass that occurs when it is pressed together to reduce.

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Water-soluble disinfectant tablets can also can be made by an effervescent combination, a tablet lubricant, an antibacterial substance and, preferably, a flavor and / or color mixed together and the powder mixture into a cohesive one Tablet form is pressed. The tablet obtained, after being dissolved in water, can be used as a des « Infectious solution find application. It can be scheduled that way be that it is particularly suitable for disinfecting the oral cavity, i.e. an agent after dissolving in water for gargling and mouth rinsing.

The effervescent combination of the powdery tablet mixture consists of at least one solid acid and one solid basic substance j which when dissolved in water become ,, together with the formation of carbon dioxide COp that causes the shower or bubbling to occur. The acid can be an organic acid, e.g. malic acid, Fumaric acid, tartaric acid, itaconic acid, maleic acid, citric or mesaconic acid or a corresponding anhydride such as itaconic anhydride and citraconic anhydride or it is an inorganicxacid, e.g. a sulfamic acid or phosphorous acid derivative as described in the United States patent 3,325,357. The basic one Substance can be any metal carbonate, for example an alkali or alkaline earth carbonate and bicarbonate. Examples for such substances are lithium, sodium, potassium,

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Magnesium and calcium carbonates or - "bicarbonate. The Combining certain of these acids and bases with each other ~ leads to a much faster effervescence and foaming, though the mixture is given in water than with other individual acids or bases of the groups indicated above. The combination of citric acid and sodium bicarbonate is particularly preferred because of their rapid and subsequent reaction Shower and foam.

As stated above, the Tablettier ™

.Lubricant made from particles of a liquid lubricant consist of a water-soluble film-forming substance are coated.

The antibacterial substance in these according to the invention Water soluble tablets can be any substance from the wide range of microbiοstatic or be microbiocidal compounds or substances,

Common antimicrobial and antibacterial agents that can be used include Phenol and its homologues and derivatives, e.g. alkylphenols, halogenated phenols, polyhydric phenols, Diphenyl derivatives and like aryl derivatives. Synthetic phenolic substances such as chloroxylenol can also be used Find a use. Various soaps e.g. fatty acid

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find soaps or soaps made from naturally occurring oils also application; such as various solid alcohols, especially chlorinated benzyl alcohols. Other substances than Antimicrobial substances are effective, are dyes, surface-active compounds, halogenated compounds, heavy metal salts and substances that release a gas that is deadly to microbes. Antimicrobial dyes are e.g. triphenylmethane dyes such as malachite green, brilliant green and crystal violet, acridine dyes and the various substituted acridine dyes. Surface-active compounds with antimicrobial effectiveness, which can be used are, in general, the quaternary ammonium compounds such as getylpyridinium bromide or chloride, tetradecylpyridinium bromide, alkyldimethylbenzylammonium chloride, ß-Phenoxyäthyldimethyldodecylammoniumbromid, Di- (n-octyl) -dimethylammonium bromide, p-tert-octylphenoxyethoxyethyldimethyldecylammonium chloride and N- (acylcolaminoformylmethyl) pyridinium chloride. From this list it can be seen that the four quaternary substituents can be very versatile. Among the numerous Halogen compounds with antimicrobial activity come e.g. hypochlorites, inorganic chloramines, organic chlorine-releasing compounds such as sodium ptoluenesulfonchloramide, p-sulfonedichloraminobenzoic acid and dichloroisocyanuric acid in question. The heavy metal compounds are generally mercury ", silver,

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Copper and tin compounds. Suitable salts are, for example, mercury (II) chloride, sodium dibromoxymercurifluorescein (Mercurochrome), merthiolate and phenyl mercurine nitrate, Silver nitrate, silver citrate, silver lactate, copper naphthenate, Copper oleate and copper pentachlorophenate. The most common deadly gases are oxygen and chlorine, the former can from a perborate, anhydrous perborate or a monopersulphate The latter is released by combining a chloride with a persulfate in an acidic medium set.

Among the above antimicrobial compounds, the surface-active compounds are preferred, especially the United States Food + Drug Administration (FDA) -approved compounds. For Gurgel " tablets and mouthwash tablets is cetyldimethylbenzylammonium chloride preferred.

As colorings and flavorings, the too Any substances can be added to tableting mixtures that are compatible with the intended use of the finished tablet are compatible. Should the disinfectant solution prepared by dissolving the tablet for cleaning u of unpopular surfaces are used, so can if necessary a coloring material such as a water-soluble dye can be used. In general, any

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the FD · + C dyes are used. The addition of a flavoring agent is only required when a solution is intended for gargling or mouth rinse or for a similar internal use. "Various flavors z, _e B, spray dried fragrance oils and edible esters can be used as flavor additives used. If desired, these components of the oil be added before the coated particles α are formed. Indispensable (essential) oils are particularly suitable for this.

If a tablet is to be used for brushing teeth, a substance can be added to the mixture to be tabletted with anti-caries activity are added in an amount that gives the tooth surfaces some protection against Gives tooth decay. Anticarious active substances that can be used for this are e.g. stannous fluoride, Stannous chlorofluoride, sodium monofluorophosphate, sodium fluoride, Ρ · pyridoxine, pyridoxine »HC.l, dipyridoxine fluorophosphate, as well their mixtures. In particular, tin (l! 0-fluoride and Sodium monofluorophosphate preferred. The amount of added anticarious substances can be increased Range}. 'For example 1 to 100 mg of this Substances can be contained in a 4 g tablet, preferably about 8 mg.

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Tablets that contain such anticarious substances form solutions when dissolved in water with repeated use as a mouthwash and gargle give tooth surfaces protection against tooth decay.

The above-mentioned lubricant made of coated oil particles, with which these various tablettable mixtures are made lubricious during pressing, can have a particle size of about 1 to 200 λα. Preferred lubricant particles produced by the spray drying procedure described above have a particle size in the range from about 1.0 to about 50 / U with a mean diameter of about 15.6 ai.

The coated oil particles of the present invention can can be used as the sole lubricant or together with other lubricants if they are in the one to be tabletted Mixture are included because the coated oil particles are compatible with other lubricants. Besides that The coated oil particles acting as lubricants can be wholly or partly in place of various other substances which act as a tablet lubricant when pressed. Also, the coated lubricant oil particles can be made from non-toxic materials, generally aa are approved for use in pharmaceutical and food preparations.

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The coated oils of the invention become particles as a lubricant in an amount from about 0.5 to 2 wt .- ^, based on the total weight used, so Tableting speeds can be set from the low speeds of manual operation up to around 5,000 Tablets per minute on rotary machines with 4-9 punch and apply die sets. In these machines, each punch and die set makes about 102 tablets each Minute ago. On rotary machines with 33 stamps and

™ die sets the tablets can be compressed at a speed of -76 tablets per minute and set, corresponding to a total production of around 2,500 tablets per minute. Generally, amounts of at least about 0.5 % are coated oil particles; Based on the total weight of the lubricated tablet mixture, sufficient for tablet production in high-speed machines. If the lubricant is used in quantities of up to about 5 % , the oil

The amount is so small that the oil is completely dispersible in the solution formed and, as a result, a uniform solution is obtained. However, quantities of up to about 50 _t based on the total weight can also be used. If the lubricant according to the invention is used as one of two or more tablet lubricants, a proportionally smaller proportion is used, \

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The coated oil particles can be beneficial and together with a siloxane polymer, which has the surface lubricating effect of the combined lubricant, incorporated into the powdered tablet raw materials ! herds. The polysiloxane also enhances free flow the lubricant itself. If this combined lubricant is mixed with a dry substance, thus the mixtures obtained are essentially free-flowing.

The main advantage of such an inventive Combined lubricant for tablet production is that the lubricant is almost free-flowing and gives the tablet raw materials to which it is added good surface lubrication. The addition of this combined lubricant to tablet raw materials Before the pre-compression, the molding compound also helps to flow into the dies of the tableting machines and contributes to the fact that after pressing and subsequent stripping of the tablets, the stamping surface and Hatrizen surface remain free of retained substance, which otherwise, if it sticks, will result in faulty tablets. The combined The lubricant itself can be mixed dry and can be easily mixed and homogenized with the various powder pots to be processed into tablets.

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This property can be defined as ability the lubricant to be mixed homogeneously with dry powders as if it were a complete itself dry powder. This property makes the tablet raw materials mixed with lubricant free-flowing. Another advantage of the inventive combined The main thing about lubricant is that when it is dissolved in water, foam does not form, and that the resulting foam Solution has a uniform appearance «

The lubricant in the form of coated oil particles is produced in the following individual work steps:

1. At room temperature it becomes an oil-in-water emulsion of the lubricating oil produced, which contains an oil-insoluble film-forming substance in the aqueous phase in an amount of about 1-9 parts by weight per 1 part of lubricating oil contains j

2. the emulsion is held at about 15 ° C or above;

3. The emulsion is sprayed into an air stream, the initial temperature before coming into contact with the emulsion of about 150 - 29o C ⁰ beträgtj ^. the emulsion is dried to a moisture content of about 2-10 % ; and 5. the dried, coated oil particles are collected. The ratio of 2 - k parts by weight of film-forming substance to 1 part by weight of lubricant oil is preferred in order to remain well below the 9: 1 limit below which the 01 content is no longer sufficient. A final water content of about 3 - 5 % and temperatures in the range of about 15 - about kO ° Q for step 2 are preferred.

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It has also been found that the higher air temperatures in the range from about 2 ^ 10 to about 265 ^° C. are preferred. During the drying process, the emulsion can be sprayed into the air stream with a small pressure difference from a rotating spray disc or nozzle.

The moisture content of the coated oil particles can be easily adjusted by varying the flow rate of the emulsion at constant air temperature and air flow velocity being controlled. The flow rate of the emulsion can also be kept constant and the flow velocity of the air can be varied. The airflow does not need to be specially dried, to have a low humidity because of the humidity equilibrium at temperatures in the range given above is sufficiently low to allow rapid drying of the excess water from the emulsion formed cause.

The drying is preferably carried out in a conventional spray drying device in which the The discharge opening for the emulsion is connected to a distributor disc that feeds the emulsion into the from the device hurls out the enclosed gas space. In such a The device turns the disk at a speed of

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about ^ O 000 RPM driven by an electric motor or by applying compressed air to a turbine connected to the disc. The inlet points for the heated air stream are located near the distributor disc and the dry-miscible coated oil particles are collected as a powder at the bottom of the device. A cyclone separator can optionally be used to separate the particles from the air stream. The temperature of the air when leaving φ the pressure with the particles is about 70 to 115 ⁰ C.

Spray drying is preferred, but it can other working methods, e.g. freeze-drying, are also used to dry the emulsion.

The emulsion for the above process can be prepared by first creating a solution of a water-soluble, oil-insoluble, film-forming substance ^ in the absolutely necessary for the formation of the solution

Minimum amount of water prepared, the lubricant oil added and the mixture is emulsified by vigorous stirring. Of course, the order of the additions can also be different be. The emulsion formed can also be mixed with water be added in order to obtain the desired spray properties with the proviso that the water is not up to

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to the point where the ability is added to drive off this water is exceeded. Non-aqueous continuous phases can also be used for the production of emulsions, provided that these are compatible with all components.

The film-forming substance can be selected from a variety be selected from substances such as water-soluble rubbers, modified celluloses, proteinaceous substances, polymers Sea plant derivatives, agar or synthetic film-forming substances such as polyvinylpyrblidone, examples for water-soluble vegetable gums are gum arabic (gum acacia), pectin, tragacanth, gum karaya, guar gum, Locust bean gum and starch gum (dextrin) in either natural or modified form, e.g. carboxylated Dextrin. The modified celluloses can Ethers or esters, e.g. Hydroxypropylmethylcellulose or garboxymethyl cellulose. Protein-containing substances, that are used include gelatine, albumin and casein. Various polymeric sea plant derivatives such as algines, alginates and carrageenates are also useful. The synthetic film-forming substances can be either water soluble or water dispersible.

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These substances are generally high-molecular substances and when dry they form resinous layers over the Particles of oil. They are also insoluble in lubricant oil, with which they are used and are preferably water soluble so that the emulsion can be formed more easily can.

The dextrins or starch gums are considered to be film-forming Substances are particularly preferred because they are highly oil-insoluble and are water-soluble and quickly release bound water when spray-dried.

The lubricant oil that comes with the above fum-forming Any of the common viscous vegetable, animal, synthetic or mineral oils, including oils previously used as lubricants in tabletting became. Examples of vegetable oils are those obtained from the following plants or parts of plants oils: corn, cottonseed, coconuts, peanuts, olives, Soybeans, sunflower seeds, flax seeds, palm kernels, saffron flower seeds and more, examples of animal oils are: seal strands, whale fat, cod liver feran and neat oil. Examples of synthetic oils are polyethylene glycols in the molecular weight range of 250 to 2,000. Useful Mineral oils are the highly pure oils, e.g. refined pe- ' troleum distillate. These oils can optionally be hydrogenated so that the fatty acid content is more saturated,

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Hydrogenated oils are generally preferred,. whose viscose ibäb in the range of 120 to I4o ci ^J He ^ t and die- #ut heat-resistant and oxydationsbesbündip · are. Sole oils are microbial and do not change chemically during spray drying. White or refined oils in the pale viscous range are also preferred because their egg sheep parts can be reproducibly determined.

In both inventions: sp: emässen combined lubricants, the siloxane polymer can be combined with the lubricant oil in the coated particles or the siloxane polymer can be applied to the surface of the. overzoprene. ·. If the polysiloxane is combined with the lubricant oil in the coated particles, then the individual stages in the preparation are the same as above for the particles without polysiloxanes ,

If the polysiloxane is to be applied to the surface of the coated oil particles, it is not added to the oil-in-water emulsion of stage 1, but first to the collected, dried uterine oil particles by spraying in such a way that the surfaces have a thickness of Io - ^ G Qevi.-fa Polysiloxane , based on the total weight of lubricant oil coated vierden. Neither procedure can be used. continuous

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Phases are used for tile emulsion, that these are compatible with "all components.

In accordance with the invention, polysiloxanes which can be used are any polysiloxanes with a viscosity in the range from-250 - -12 50U c * ¹ + 5 / i> »-those of the formula - ■.-.-.

R ¹

Si- U

R.
Si

si - ir

in which each substituent R is hydrogen atom, an alkyl, aryl, ar alkyl or. Allcaryl group and each substituent R can be one of these groups, with the exception of hydrogen and in which the individual substituents R can be identical or different and the individual substituents R can likewise be identical or different. Siloxane cream mix are also useful. Preferred polymers are the linear dialkylpolysiloxanes,

Examples of useful polysiloxanes are the polymers of dihydroprensiloxane, diethylhydrofrensiloxane, Dimethylsiloxane, propylhydrofensiloxane, dipropylsiloxane, Phenylhydrofensiloxane, ßenzylhydroprensiloxane, Toluylhydrop: ensiloxane and mixtures of DimethylsiLoxane and

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Methylhydrofrensiloxane. All of these polysiloxanes are terminated Groups in which R of the obipen formula is an alkyl-aryl, Can be alkaryl and / or aralkyl group.

According to a further embodiment of the present invention, any desired flavor additives are added to the oil prior to the formation of the coated particles . Essential oils are particularly suitable for this inclusion in the lubricant oil particles.

Example 1 follows

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example 1

Ingredients Parts by Weight, g wt -.%

1. Sodium bicarbonate 6th 780 52.5 2. Citric acid (anhydrous) 5 712 44.3 3. coated oil particles 180 1.4 4th Flavor additive 150 1.2- 5. Sodium cyclohexyl sulfamate 60 0.5 6th Nat r iumeacehar in 6th 0.05 7th Cetyldimethylbenzylammonium chloride . 15th 0.12

total 12 903 100.0?

Ingredients 1 and 2 were mixed together, passed through a sieve and dried. The remaining ingredients were mixed with this dry mixture and the mixture obtained was compressed into tablets on a Golton T-12 single-punch tablet machine at commercial speed. The tablets were 2.54 cm (1 in.) In diameter and weighed about 4.3 g on average. They contained 1.4 % coated oil particles (lubricant) based on the weight of the tablet,

The tablets made about 135 cirr when dissolved Tap water is a pleasant-tasting mouthwash.

The coated oil particles were formed by spray drying as described above using a refined vegetable oil having good heat resistance and air resistance and microbe resistance. The content of free fatty acids was a maximum of 0.05 % _t the oxygen resistance 450 to 500 h, measured according to the active oxygen method

L.

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(Tentative Method Gd 12-57, revised 1959, published in "Official and Tentative Procedures of the American Oil Chemists Society"; 3rd edition, 1966, Chicago, Ill.) And the Wiley melting point -5.56 ± 1.1 ⁰ C (22 + 2 ⁰ F). The most important fatty acids were palmitic acid 8-10 %, stearic acid 2-4 %, oleic acid 43-47 %, elaidic acid 39-43 % and linoleic acid 1-3 %. A vegetable oil of this type is supplied by Durkee Famous Foods, Inc. of Cleveland, Ohio under the tradename "DUHKEX 500".

The film-forming substance was used in a weight ratio of 2: 1, based on the lubricant oil; a starch was used with the following properties: viscosity 120-14G cP; Particle size 98 % <0.42 mm; Color light tan. This starch was a consistent shark dextrin. A dextrin of this specification is sold by National Starch and Chemical Company, Inc. of New York, HY under the tradename "MDEX 772".

A spray-dried oil, coated with the same dextrin used.

Example 2
Components

1. Sodium bicarbonate

2. Citric acid (anhydrous)

3. Fumaric acid ■

4. Flavor additive

5. Sodium cyclohexyl sulfamate

6. Sodium saocharin

7. Cetyldimethylbenzylamine ammonium chloride or id

Parts by weight, g Wt .- ^ o 6 780 53.3 4,284 33.7 1 428 11.2 150 1.2 · . 60 0.47 6th 0.04 ■ - 15 0.12

insß-it. 12 723 100, u3

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Ingredients 1–3 were mixed together, sieved and dried. The mixture was mixed with the other constituents and the molding compound obtained ^; Compressed into tablets according to Example "1. The diameter of the tablets was 2.54 cm, their average weight about 4.2 g. They contained 11.2 % fumaric acid as a lubricant, based on the tablet weight. ■ -

These tablets dissolve in water under strong pressure Showers become an effective disinfectant solution. There' all components -non-toxic .would be, the solution as round water use. .: ■■ -. '■

The flavor additive was the same as in ^examples: play first

Example 3

Ingredient e parts by weight,% wt .- ^

1. Sodium bicarbonate 1 909 '58.5

2. Citric acid (anhydrous) 1 206 36.9

3. Coated Oil Particles 100 3, O6 ^ J-. Flavor additive 20 O, 6'5

5. Sodium cyclohexyl sulfamate '24 0.73

6. Sodium saodiarin 2.4 0.07

7. Getyldimethylbenzylammonium

chloride 0 * 5- " ^: - 0.02

8. stannous 2.0 '\ u, 06

total, 3,263.9 9% .99 ■■: ■, -,

The components are mixed together and put together through hand sieves with a clear mesh size of 1.4 mm and 0.59 mm. The mixture was then in a single-punch CoIton T-12 tablet machine Compressed tablets. The made tablets were

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appropriately sliding, made; pitting at the edges only occurred at high speeds.

The coated oil particles used for this tablet formulation were formed by spray drying an emulsion of 250 grams of dry gelatin, 1,450 grams of gum acacia, 425 grams of corn oil, 80 grams of polydimethylsiloxane, and 3,000 cm. Deionized water. The emulsion was maintained at Haumtemperatur (25 °) and into the air stream of a spray dryer eingesprühtj the temperature of the air stream was 265 + 3 ⁰ C on entry into the dryer 110 and + 5 ° C at the outlet from the dryer. The individual particles are composed of 4 parts by weight of film-forming substances (gelatin and gum acacia) to 1 part by weight of lubricant oil.

The tablets disintegrated quickly in water to form a mouthwash and gargle solution.

Example 4 Components

1. Sodium bicarbonate

2. Citric acid

3. Coated oil particles

4. Flavor additive ","

5. Sodium Cyclohexyl Sulphamate 24 0.67 "

6. Hatriumsaeharin

7. Cetyldimethylbenzylammonium chloride

8. Liatric perborate

total, 3,561.9 100.05

The press mix was prepared according to Example 3 and then in a single punch Colton T-12 tableting machine Tablets are pressed with the diameter of the punch 2.54 om (1 in *) The mixture flowed as desired

Weight Parts, g 4th Wt .- ^ 1 909 5 53.6 1 206 33.9 200 5.6 20th 0.6 24 0.67 2, 0.07 0, 0.01 200

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into the dies and was "when pressing and subsequent Strip off the tablets with a smooth slide. The tablets dissolved in water to form a disinfectant solution, those for cleaning solid surfaces, e.g. the surfaces of dentures or for controlling certain gum diseases could be used. Component 7 has a killing effect on microorganisms that live on such surfaces are located; component 8 releases oxygen as soon as it comes into contact with water, which in turn releases oxygen the metabolism of the microorganisms intervenes and in this way supports the disinfecting effect. Applied internally, the perborate also has a changing effect the protein of the attacked gum tissue makes it stronger and less susceptible to it further irritation.

The coated oil particles were dried by spray drying an emulsion made of the following composition; 200 g dry gelatin, 1,000 g gum acacia, 200 g Olive oil, Jjo g polydimethylsiloxane and 240 g deionized Water. The emulsion was spray dried under the same conditions as in Example 3. In the received dry particles the ratio of film-forming substance to lubricant oil was 6: 1,

Example 5

Ingredients by weight «« parts, g by weight 5

1. Sodium bicarbonate

2. Citric acid

3. Coated oil particles H-. Flavor additive

5. Dye (light green) 6 “Sodium cyclohexyl sulfamate 7 ", sodium saccharin

8. Cetyldimethylbenzylammonium chloride_

total k 07 ^, 9 100.01

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2,200.0 5 ^, 0 1 5 ^ 2.0 37.9 20OjO 100.0 2.5 0.9 0.02 20.0 0.4-9 2.0 0.05 rid 10.0 .0.25

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The ingredients are mixed with one another according to Example 2 and tabletted. The tablets glided well and were therefore made on the single-punch machine at commercial speed. They disintegrated quickly at room temperature (25 ^° C.) in water with the formation of a gargle and mouthwash solution.

The coated oil particles were obtained by spray-drying an emulsion of the following composition: 900 g starch according to Example 1, 100 g refined vegetable oil according to Example 1, 20 g polydimethylsiloxane and 1,500 g deionized water. The emulsion was kept at tree temperature and blown into the air flow of a spray dryer. Temperature of the air flow on entry into the dryer 250 + 10 ⁰ C, temperature on exit 110 + 5 ⁰ G, the composition of the particles obtained was 9 parts by weight of film-forming agent ( Starch) to 1 part by weight of lubricant oil.

Example 6 Components

1. Sodium bicarbonate

2. Citric acid (anhydrous)

3. coated © oil particles 4, - flavor additive

5. dye (light blue)

6, sodium cyclohexyl sulfamate

7. Sodium saccharin

8, cetyldimethylbenzylammonium chlorine id

total 4 14-9.9 100.00

The ingredients became in the order of decreasing amounts, i.e. in the order of ingredient

- 30 -

Parts by weight, g Gew _f - / & 2,200.0 53 1,742.0 42 75.0 1.81 100.0 2.4 0.9 0.02 20.0 0.48 2.0 0.05 10.0 0.24

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No. 1, 2, ^ -, 3 »6, 8, 7 and 5 mixed together. The dry molding compound was tabletted on a single-punch machine, the punch diameter 2.5 cm. The tablets were 0.5 cm (0.2 in.) Thick and had a hardness of about 3 - ^ kg, they dissolved at 23 ⁰ C in a mean time of ^ 2 seconds.

The lubricant corresponded to Example 1 with the addition of 22 % polydimethylsiloxane in the lubricant oil, based on the weight of the oil.

The tablets were then tested for shelf life and strength. To do this, they were layered in glass bottles that were closed with lined, metal screw caps. Half the bottles were stored for 2 weeks at * K) ° C, the other half of the bottles 2 weeks at 50 ⁰ G. After this time, various properties of the tablet with the original properties were compared before the test. The results are shown in Table I below.

The first property measured was the appearance * The rating unchanged or slightly yellowed relates to the original appearance of the tablets before the start of the test. »The hardness of the tablets was measured in a Stokes hardness tester. The disintegration times were measured in 135 cmr of water at Α · 3 ° 0 and the pH * · value of the solutions obtained was determined. Finally, the tablets were analyzed to determine the amount of active substances. ner connection (component no, 8) to be determined.

A modified phenol coefficient test was carried out using S. aureus carried. For this purpose, the tablets stored under spilled conditions were each in 135 cnr

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Dissolved water at 43 ° C. The method used is described in Horwits, W .: Official Methods of Analysis of the AOAC, 10th edition, Association of Official Agricultural Chemists, Washington, D.C. (1965), pp. 80-94. The test results were reported as the time it took for the complete killing of the bacteria is required.

Table I.

Cere- active bacteria falls- quaternary completely

Time-hardship time connection killed

Temperature Appearance kg see pH g / tablet after min

Start -

22 ^e c - 6, 4 33 6.4 9.98 5

2 weeks - without

40 ° C changes 8.7 33 6.6 9.54 10

2 weeks - easy

5O ° G yellowed 10.7 33 6.8 8.67 10

The results show that accelerated aging does not significantly change the properties of these tablets, that the tablets are rather stable and than mouthwash tablets remain effective.

Example 7

Emulsion constituents parts by weight g wt. -%

Gum acacia peanut oil

demineralized water

8,000 in total

The demineralized water became the gum acacia

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1 600 20th 400 5 6,000 75

9 0 9 8 19/1125

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, The solution-with offset aera peanut oil and ^·: mixture emulsified in a laboratory mixer at tree temperature ^". Yaws The emulsion was in a conventional spray" tumble dried, wherein the Zerstauberscheibe centrally in the upper part of the drying chamber, the air supply ' - ¹ with an air heater directly under the atomizer ^: and the outlet opening for drawing off the particles and the air were arranged at the bottom of this chamber. The emulsion was fed from a storage tank to the atomizer disk and the coated oil particles were collected in a cyclone separator connected to the outlet opening

ner
collected. The dry used was a NERCO-NIRO portable spray dryer manufactured by Nichols Engineering and Research Corporation, New York, NY.

The emulsion was used at about room temperature and stirred in the storage tank until it fell on the atomizer disk ' was fed.

The temperature of the air when entering the dryer was 220-230 ⁰ C, the flow rate was sufficient to reduce the moisture of the dried lubricant particles to about 2 - ^ wt .- ^. The temperature of the exhaust air was: 70 - 80 ⁰ C.

The atomizer disk was operated at about k0,000 rpm by means of a connected turbine, which carries compressed air at 5 »8 - 6.

Drive turbine, the compressed air supplied at 5-8-6.2 kg / cm.The weight of the coated oil particles collected at the bottom of the spray dryer was 1,880 gj this indicates a weight loss of 76.5 % , based on the emulsion weight. The moisture content of the dried particles was ^, ^ 5 % (determined by toluene

9098 19/1125

.-. ■ ■ "- 33 - iA-35

distillation) due to the retained bound from acacia gum and partially bound water "The moisture content of the particles was determined by 16-hour drying at about .50 ⁰ G in an oven mitZwangsluftführung further to about; reduced 4%. The ratio of gum acacia to lubricant oil in these. Particle was about 4: 1,

The spray dried coated oil parts were then for making the molding compound for effervescent beverage tablets glide following recipe used *

Parts by weight, g

1, coated oil parts are 819.0

2 »Citric acid (anhydrous) 4 368.0

3, sodium bicarbonate 2,910.0

4 _.; Kirs char oma 45.0

5. Hoter dye (FD and G Eed No.2) 56.1

6. Tartaric acid 330.0

7. Ascorbic acid 50.0

8. Sodium cyclohexyl sulfamate 342.0 9 «Sodium saccharin 84.0

inspres. 8,984.1

The lubricated molding compound was made by adding all of the ingredients except for the citric acid dried separately and then the coated oil particles were mixed with ingredients 3 and 4, The remaining ingredients were then mixed with this premix and the molding compound at commercial speed compressed into tablets in a single-punch tableting machine. The tablets, gliding well, had a diameter of 2.54 cm and became to a hardness of about 3 - 3 * 5 kg, measured with a Stokes hardness tester, compressed. The mean tablet weight was about 3 g for a total of about 3,000 tablets.

- 34 909819/1125

022

Another smaller batch was made to the recipe with oil particles coated in the same manner, with the exception that the ingredients were not dried. The molding compound was also tabletted on a single-punch press at commercial speed, average hardness of the tablets "" about \ "", 3.9 kg * The diameter of the tablets was 2.54 cm, the average thickness about k mm (0.156 in ») . The molding compound flowed evenly from the filling funnel into the die filling. It contained 9% coated oil particles for a total of 273 mg, based on the weight of the individual tablet,

Some tablets were dissolved at a temperature of about 3 _ 5 ⁰ C in water, the disintegration time was about 150 see. When dissolved, the tablets gave an effervescent drink with a cherry flavor. The oil content in these tablets was about 5.6 mg of oil per tablet. It is important that the lubricant particles cause the molding compound to slide or pour adequately into the molding compound for effervescent beverages, which in the absence of the coated oil particles If at all, it could only be tabletted by hand. In addition, the coating with the film-forming gum acacia made the oil particles dry-mixable and they could therefore be mixed directly with the other dry ingredients of the recipe and the mass can be tabletted without difficulty, _ ...

Example 8 ..

Emulsions emulsi on em ily starch gum (dextrin) refined vegetable oil distilled water

Parts by weight, g wt .- /

222 , 2 22nd , 22. "111 , 2 - ■ 11th , 12 666 , 6 . 66 , 66

1,000.0

100.00

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9819/1125

^ν "' ^: - 35 -' 1Α-35 022

Starch gum and vegetable oil were the same as in Example 1.

The starch was placed in a planetary mixer, the oil added and the resulting mixture at a higher rate Stirring at speed »As soon as the oil appeared to be evenly dispersed, 2/3 water was added and xtfeiter mixed. As soon as there is a uniform dispersion had formed, the remaining water was added and the mixture as a whole in another Mixer processed into a homogeneous emulsion.

The emulsion was spray dried in a manner similar to Example 7. The temperature of the air when entering the dryer was 210 + 5 ° G, the Liett el temperature 212 - 213 ° C. The atomizer was operated with ho ÜÜÜ UpH and collected the coated oil particles at the bottom of the dryer as a relatively dry powder. The temperature of the exhaust air was 110 + 5 ° C. The particles did not need to be dried any further. The weight ratio of starch to vegetable oil in these coated particles was 2: 1. The coated oil particles were then used as lubricants for the following tablet formulation:

Parts by weight

1. Coated Oil Particles x 37.5

2. Citric acid (anhydrous) 1 Jj-56.0

3. Sodium bicarbonate 970.0

4. Lemon and citrus flavor ^ 0.0

5. blue dye (PDfG Blue No.1) 0.5

6. Yellow dye (FDrC Yellow No.5) 5.0

7. Tartaric acid 110.0

8. Ascorbic acid 10.0

9. Sodium cyclohexyl sulfamate 11 ^, 0 10. Sodium saccharin 28.0

inspres. 2,771.0

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To produce the molding compound, all components with the exception of No. 1 and k were dried. Ingredients 1, ^, 5 and 6 were mixed together and passed through a sieve until uniform. Components 3 and 7-10 were then added in the order of the decreasing parts by weight and the mixture obtained was mixed with citric acid (component no. 2). The molding compound was "tabletted" on a single-punch machine at commercial speed.

The strength of the tablets produced was very high at 1.5 - 5 »5 kg, measured on a standard Stokes hardness tester. The average weight of the; Tablets were 2.771 g, their diameter 2.5 ^. cm, its thickness is about 3.6 mm (0.1 ^ 5 in.) The tablets disintegrated in water of 16 ⁰ G in 6o -. see 6.5. The dissolved tablets produced an effervescent drink with a pleasant lemon taste. Five test persons, each of whom propped drinks made with different tablets, did not perceive any oily taste in the drink.

The concentration of the coated oil particles in the molding compound before tableting was about 1.36 %, based on the weight of the ingredients without lubricant, or about 37 »5 mg per tablet. The oil concentration in the tablets was 12.5 mg per tablet and was thus deep enough that this amount was dispersible in the volume of water used to dissolve the individual beverage tablets.

The tablets produced were made to slide well and the. Compound could be handled easily} -that Thus, lubricant in the form of the coated oil particles exerted an adequate lubricating effect on them with difficulty tabletting mixture of,

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Example 9

Emulsion consisted of 11 e wt. - »parts g wt. %

refined vegetable oil 1 000 11.11

Starch gum (dextrin) 2,000 22.22

distilled water 6,000 66.67

9,000 100.00

The vegetable oil was placed in a planetary mixer and the iSbärke was added. The ingredients were the same as described in Example 7 above. The mixture was stirred until smooth, combined with k OQO g of water and stirring was continued at higher speed until a uniform suspension had formed. The remaining water was added with continued stirring. Then x \ jurde the mixture in a homogenizer; spent and processed there into a homogeneous emulsion.

The emulsion was spray-dried by being sprayed into the air stream of a spray dryer. The temperature of the air at the inlet was 210 ± 5 ° C. It took 9 hours to dry the entire emulsion batch. The coated oil particles obtained weighed 2,225 g, corresponding to 7-1 / 8 % of the original 3,000 g solid constituents. This weight loss indicates that some of the normally retained water had been withdrawn from the starch, the cyclone separator of the dryer did not remove the smaller particles and / or that some of the particulate matter was volatilized. The final moisture content of the particles was about 2% by weight.

From a second emulsion of the same composition coated oil particles were produced for 1 year

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tested for stability and shelf life. The results are shown in Table II below listed! the percentage water content was determined according to the Karl Fischer method. The other evaluations have the same meaning as in Table I. above"

Table II

Tablet
age Appearance
RT kO ° G SD Taste / smell a
RT kö ^a G ^{/ o} NSD ^{1 H} 2 ° ■ RT oil*
kO ° G fresh here NC NSD posed C- * M. NC 2 _s k 26.7 - 1 month NC <- NSD - 25.2 2k _t k 3 months NC NSD - 2 ^, 5 2k, 1. 6 months SD - 25.9 1 year NC - 26.7 -

κ determined by ether extraction RT = room temperature

NC = unchanged

From Table II it can be seen that the coated oil particles described in this example have a Appearance, taste and smell and oil content are persistent and therefore an excellent lubricant for represent tablettable mixtures. The lubricant was added to a tablet molding compound of the following recipe :

1. Coated oil particles

2 »citric acid (anhydrous)

3. Sodium carbonate.

il ·, MonoealciumphOsphat

inis ges ♦ 4-7

- 3f

Ge w * parts, g 300 619 17th , 250 26, 315 3

- 39 - '1A' 35 022

The ingredients 2 ~ h were dried separately from one another in the oven and then mixed with ingredient 1. The molding compound was tabletted on a rotary machine. The tablets obtained were very hard, their mean disintegration time in water at room temperature was about 45 seconds. During the tablet-making process, the molding compound showed good pleating and tablet-making properties; this indicates that the lubricant of the invention can be used in the form of coated oil particles at a concentration of only about 0.63% by weight, based on the weight of the remaining tablet components. The tablets disintegrated in water to form an alkalizing solution which was suitable for internal use. A.

Example 10

Emulsion constituents parts by weight, g wt. ~ $>

Polyvinylpyrrolidone 1 000 33, ^

refined vegetable oil 500 16.6

Water 1,500 50.0

a total of 3,000 100.00

The water was heated to about 5O ⁰ G, and polyvinylpyrrolidone (PVP) with stirring. The lubricant oil was then added to the PVP solution in a mixer with stirring. The emulsion was stirred further and fed into a spray dryer operating according to Example 8.

10 parts by weight of the coated oil particles thus prepared were mixed with 500 parts by weight of dicalcium phosphate containing some sugar and corn oil, and the mixture obtained was passed through a sieve having an open mesh size of 0.72 mm. The tablet mass was tabletted on a single punch machine. The punch was 11.9 mm

9 0 9 8 19/1125

- KO - LA-35 022

(15/32 in.) Ο The tablets obtained were of excellent quality, maintaining lubricity during their Education was very good. The tablets could be used as a placebo.

Example 11

Emulsion components Qew «-Teilet g Ge w» - /

Starch gum 500 .19.2 refined vegetable oil 500 19.2 Polydimethylsiloxane 92 3.5 nonionic surfactants substance 12th 0, ^ demineralized water 1,500 57.7

total of 2 60k 1OQ0

The weight ratio of rubber to oil was of this formulation 1: 1. When siloxane was added to the oil, the actual weight ratio for the combined lubricant was (1: 1. The nonionic surfactant Substance was a polyoxyethylene derivative, namely Polysorbate 80, USP XVII, trade name "TWEEN 80" the Atlas Powder Company.

^ The water was ^{heated to 1} Ki ⁰ G and the gum was dispersed in it. The polysiloxane was heated together with the vegetable oil, formed to sich.eine clear solution hattet6O ⁰ C) the heated oil mixture i'jurde with the nonionic emulsifier and the mixture added to the starch solution. The mixture was made into a permanent emulsion in a high-performance mixer.

The emulsion was made in a common laboratory ~ Spray dryer, whose atomizer disc is central was located in the upper part of the drying chamber | The air inlet with the air heater was located directly below the atomizer disk and the outlet opening on the bottom of the chamber

- kl -

9 0 9 8 19/1125

- kl -. LA-35 022

which the particles and air were withdrawn. The emulsion was poured into the atomizer disk from a reservoir and fell to the ground a distance of approximately four feet by the air stream of the dryer. The obtained dried and coated polysiloxane oil particles were collected in a cyclone separator collected. The dryer was a portable one Spray dryer, brand NEECO-NIRO. The temperature of the supply air was kept at about 265 ° C with in equilibrium standing moisture content at that temperature. The temperature of the exhaust air was around 115 ° C.

The atomizer disk was operated at about 40,000 rpm with the aid of a drive turbine connected to it, the air under a pressure of 5 »8 - 6.2 kg / cm was fed.

The moisture content of the collected polysiloxane oil particles was about 2% by weight .

Example 12 Emulsion ingredients

Gelatine olive oil gum acacia Polydimethylsiloxane water

Weight - parts, g wt -.% 100 2.6 200 5.2 1 100 28.6 40 1.1 2 400 62.5

a total of 3,840 100.0

The gelatin was heated in 300 g. Dissolved water, The polydimethylsiloxane was added to the olive oil and this scaffold was added while stirring the gelatin solution. The mixture was then stirred into a homogeneous emulsion in a high-speed mixer. That

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Gum acacia was suspended in the remaining water (2,100 g) and an equal amount of this solution added to the homogeneous emulsion. The resulting mixture was emulsified with the aid of a hand-held homogenizer. The remaining acacia solution was then added without further stirring. The relationship of film-forming Means to oil was 6: 1.

Tablet formulation parts by weight, g

Sodium bicarbonate citric acid (waterless) coated oil particles flavoring agent

Sodium perborate

Sodium cyclohexyl sulfamate Sodium saccharin C etyldimethylbenzylammonium chloride

a total of 3,761.9

These ingredients were mixed by them repeated through US Standard Sieve No. I ^ and No. 30 (clear mesh size 1.18 mm and 0.59 mm) were given. The molding compound was processed into tablets on a single-punch tableting machine. The powdery one Mixture flowed evenly and freely and the tablets were made to slide appropriately. By dissolving the Tablets was obtained from an acidic mouthwash.

1 909 k 1 206 5 200 20th 200 Zk 2, O,

claims 7223

9 0 9 8 19/1 125

Claims (6)

DR.ING. F. WtTESTHOFF 8 MUNICH 9O DIPL. ING. G. PULS J. ^ SCHWEIGEBSTHASSKi DR.E.V.PEOHMANN «i» J tümpok 22 0OiSl DR. ING. D. BEHRENS telequammadbessei PATENTANWJtLTE PnOTECTPATENT ΜβΚΟΒΙΚ P IB 00 727.7 lA-35 022 November 13, 1968 claims 1. Method of making tablets by pressing a powdery tablettable substance into Presence of an oil-containing lubricant, characterized in that the lubricant used is fine divided oil droplets coated with an oil-insoluble, water-soluble, film-forming substance are used. 2. The method according to claim 1, characterized in that a lubricant is used in which the ratio of film-forming substance to oil 1: 1 to 9: 1, vzw. Is 2: 1 to 4-: 1. 3. The method according to claim 1 or 2, characterized in that a lubricant is used, which also contains a polysiloxane. ^. Method according to claim 1 to 3 »characterized in that that the lubricant in a particle size of about 1 to 20U, u, preferably from approx. 1 to 50 / rev. 5. The method according to claim 1 to ^, characterized in that the lubricant in an amount from 0.5 to 50% by weight, preferably from 0.5 to 909819/1125 - t- 5 wt -.% Is added, based on the pressing massee 6. The method according to claim 1 to 5, characterized in that a tablettable mixture is used, which is an effervescent combination, preferably a metal carbonate and a polycarboxylic acid and a
Microbicidal substance, preferably containing a quaternary ammonium salt 7, the method according to claim 1 to 6, characterized in that one tablettable Mixture used that contains at least one anticarious substance. 909819/1125.