DE1937133A1 - Pharmaceutical fizzy preparation - Google Patents

Description

Sterllng-Wlnthrop Group (British 35060/68 - prio 23.7.1968

"" ¹ ^ 3665 - 6421)

London. S.W. 1 / England Hamburg, July 21, 1969 Fizzy pharmaceutical preparation

Pharmaceutical fizzy supplements come in tablet form or as granules for better or more refreshing administration produced by painkillers or vitamin preparations · The soda preparations known up to now have the Disadvantage that they have a short shelf life and do not dissolve quickly enough undissolved particles of the preparation on the surface and thus impair appetite or remain on The edge of the glass adhere and are therefore not removed from the body included ο

The object of the present invention is to provide a pharmaceutical To propose a soda preparation which dissolves quickly and has an excellent shelf life and in which the substances causing the fizzy effect do not interfere with the active ingredients.

To solve this problem, a pharmaceutical fizzy preparation is proposed which is characterized in that it is an aoylaminophenol and a non-toxic polyvalent metal salt of stearic acid in an amount of 0.001 to Contains 0.2% by weight of the total solution.

The pharmaceutical fizzy preparation according to the invention has excellent solubility in water, which lasts up to

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50 % shorter than with known preparations. So you get in a short time. A solution of the active ingredient or, in the case of insoluble active ingredients, an extremely well distributed dispersion or suspension of the same.

Although it is known »metal stearates, especially magnesium, Calcium or aluminum stearates as lubricants in the Manufacture of pharmaceutical tablets, sometimes in Mixture of old natural wax, such as paraffin or bee

wax, to be used in order to facilitate the flowability of granules in the feeder or in the tabletting devices and the emergence of the tablets from the molds Oesamtad extinction, used. For effervescent preparations to Hetallstearate has not been used because of this there was no need and there Stearatevon polyvalent metals as water-insoluble or are considered water-repellent _o In ordinary water-soluble tablets, it is known that the addition of. Stearates increases the dissolution time considerably or adversely affects the dissolution of pharmaceutical mixtures, as is described in the American Pharmaceutical Association, Scientific Edition, 46, 4, pp. 236 to 239 and in the Journal of Pharmaceutical Sciences, £ 2, 12, December 1963, rare 1139 to 239 1144 described 1st. In contrast, it is surprising that the use of metal stearates in much smaller amounts than before and in such a small amount that practically no lubricating effect is to be expected, the dissolution of certain fizzy preparations in water leads to a considerable reduction in the dissolution rate. This surprising effect occurs particularly strongly when acylaminophenols, which are particularly suitable as anaigetics, as

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Active ingredients are used. When making tablets Ik is generally the intimate mixture of all components Bit an AHfeuehtslttel, mostly haters, processed into chunks " which are then ground into granules, which are then initially compressed into tablets in molds. Allegedly reduce the metal stearates in the case of the invention Fizzy preparation the attachment of the individual particles within the orangulate and the adhesion of the granulate within the tablet, so that the tablet or, similarly, the orangulates file apart more quickly when water is penetrated and because of the larger surface available, it dissolves or disperses more quickly will.

If less than O, © 01 Jf stearate is used, occurs only a slight effect on and at the same time it is difficult to put together a bit of that kind small additives manufacture & su At very than $ 0.2 stearate the hydrophobic effect of the stearate becomes noticeable and prevents the binding of water into the tablet, so that the solution or dispersion time is increased will.

For these reasons, the pharmaceutical fizzy preparation according to the invention preferably contains up to 0.1 and in particular 0.001 to 0.004 and in particular 0.01 to 0.02 % stearate.

AIa stearates are in general aluminum, calcium or NagnesluB stearate, either as mono-, DI- or Tristearate used. Commercially available stearates, which still contain paloltetes or sometimes even oleates, can also be used be used. -

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Pie in the pharmaceutical fizzy preparation according to the invention Aoylaminophenols used are preferably N-acyl-p-aminophenol, in particular N-acetyl-p-aminophenol or an ester or ether thereof, in particular the salicylic acid or aoetylsalicylic acid ester. As an ether derivative the p-Xthoxyacetane IIIide can also be used.

The effervescent effect can on any catfish, usually , can be achieved by an alkali carbonate or alkali bicarbonate with an "aliphatic polycarboxylic acid. Particularly Sodium and potassium carbonate or bicarbonates and citric acid or tartaric acid are suitable. Further it is of advantage if the pharmaceutical effervescent preparation according to the invention also contains sorbitol, which according to British Patent 1 002-93 describes the rate of absorption increased by N-acetyl-p-aminophenol. Though However, sorbitol generally delays the dissolution time due to its sticky nature when wet this disadvantage becomes with the fizzy preparations according to the invention eliminated. The pharmaceutical according to the invention Fizzy products can contain other ingredients,} such as codeine or coffees and lauryl sulfate as surface-active ingredients Substance as well as sweeteners, saccharin or glutamic acid, which is particularly important in the case of bitter-tasting Active ingredients is expedient.

example

For the production of a pharmaceutical fizzy preparation the following substances were intimately mixed with one another after sieving:

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Components mg per tablet kg per 6 ^, 000 _____ " tablets

N-acetyl ~ aminophenol 500.0. 32,500 Sorbitol powder 50.0 5 * 250 Saccharin sodium 10.0 0.650 C od «3 in phosphate 8.0 0.520

Caffeine 30.0 1,950

Glutamic acid 0.9 0.059 Sodium Lauryl Sulphate 0.1 0.0065 Sodium carbonate 1346.2 87.500

This mixture was moistened with water and then mixed with 923.0 mg per tablet corresponding to 60,000 kg per 65,000 tablets of anhydrous citric acid. The mass was spread out on Bleohen and dried at 80 ⁰ C and then sieved into a mixing device, into which 153.8 per tablet mg according to 10.000 kg per 65c000 tablets approach settled and was mixed until homogeneous "The obtained Qranulat was g to about 3 heavy Compressed tablets. It was then dried at low humidity.

These approaches were treated with different stearates, with due S & easefc susaaaen »it most recently added sodium" The tablet weight, the Dicks of the tablets and the molding pressure were was blcarbonat processed _o kept same in all cases "" this hard and brittle tablets were glelchmässlg received. The dissolution times in water of these comparative experiments were measured in seconds. These values are listed in Table I below as the average dissolution rate in seconds as a function of the amount of stearate in weight of the various stearates A to I.

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In the further table II, the maximum total temporal Lusllchkeltsreduction is given in % ,

In particular, the following stea? A £ e were used:

A) Magnesium stearafe, presumably a distearate according to U.3.P.ρ of which 99.9 % passed through a No. _a 300 sieve according to the British Standard (BSS). "The product was suitable up to an addition of 0.07% stearate , at higher concentrations foam formed, the

W settled on the container. With increasing stearate concentration the bitter caffeine taste became noticeable, which was noticeable unpleasantly with additions of more than 0.1 ^,

B) magnesium stearate, presumably Dlstearat according BP, with a Schüttdlohte of 4.54 kg The 28.517 liters, with 99.9% of the material passed through a # "{60 BSSO) and 97 to 100 f> through a slab 200 (» » SS) happened. The solution obtained was suitable up to an addition of 0.05 % stearate without deposits; which become noticeable with increasing stearate concentration

The bitter oeso taste of the caffeine that made barable was more than 0.05 % no longer acceptable _{or the like}

C) Magnesium tea rat, presumably distearate, of which 100 % passed through a 100 sieve (BoSoS.) And at least £ 95 through a 300 sieve (BoS = S ₁ ). The solution was suitable up to additions of £ 0.05; the bitterness of the caffeine was unpleasantly noticeable above £ 0.08.

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D) Magnealumetearat "probably Dietearat, which differs from the stearate type C only in terms of liability and the grip differed · Up to 0.05 f> Additional gave good solutions at higher additions took a significant foaming on. The bitter taste of the caffeine was unpleasantly noticeable over 0.05%,

E) Aluainlumetearate, a dietearate with 6.9 % aluminum oxide, 1.5 % water, 14.8% by weight fatty acid and 9.5% by weight asobe content. 90 % of the material "passed a sieve 36 (BS S ^ and 60 % a sieve 200 (BoS.S.)". The solution showed no foam and no deposits in the entire area observed over 0.05 # resulted in an unacceptable product.

F) aluminum stearafc, presumably a. Üiafcearate with 8 free molten acid and a bulk density of _{8-16 kg per 28 tons of} 517 liters. 100 f dec ffefcerißJo passed through a sieve J6 (BSS) and 99.1% a sieve 20 (BSS), the LösuB ^ who excellent in total beobscihteteii ifoRsentretionsbereinh and vi r & aucli geoohrnacklicli not objectionable.

G) Alumliäiiißistec ^ at ^ and z ^ rnr Triefce & rst with an enamel

ijunkt; tftfii 105 ° C, 53 Sqm * free Pe tv acid and specific pool density of; rO and cninci * bulk density of 11 _a 8 leg each 28.317 Mtersu? -CC- % of the material passed a mm DS, Sc) sieve and 99 % a 36 (BSS) sieve. The LösuB'j was observed throughout ironsentrationebereich without Sslisum and Ablegenmgen _c DeF bitter caffeine taste was oil-J- Susätzen of more ice 0 _e 0% £ uiiengenehnic

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H) aluminum stearate, namely an oietearate with little

Monostearate, whereby 99 % of the sample passed a sieve 100 (B.8.3.) The solution was found throughout the entire concentration range and the bitter oesohaaok of the caffeine became unpleasant with an addition of 0.08%

I) Aluminum tearat, and "was a honostearate naoh USP. During the bubbling process a foam was formed which, however, quickly collapsed. The solutions were | up to xu additions of 0 * 08 pounds were acceptable and the bitter taste of the caffeine was su starte at concentrations above 0.04%.

J) Aluminum tearate, namely distearate with a bulk density of 9.07 kg. Per 28.217 liters of total observed concentration range, excellent solutions were obtained, the bitterness of the caffeine being unpleasantly noticeable at 0.04% addition, but the taste improved In the range of concentrations of 0.08 Ji

The various Nagneslumstearate behave SiOH Similarly, \ where jedooh types A and B was the most suitable% n. The aluminum stearates differ significantly, but Types X and J were the best. Oils stearate concentrate depends essentially on how the aqueous solution is assessed in terms of appearance and taste. In the case of magnesium stearates, the preferred upper concentration limit of stearate was £ 0.04; with aluminum tearate concentration limits of up to 0.1 % led to excellent results, provided that one disregards the influence on the taste of the caffeine. In practical cases, therefore, a compromise must be made

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with regard to the decrease in the solution time and the deterioration in the appearance and taste of the solution. Concentrations of 0.1 to 0.02 % are most suitable. In general, tablets containing aluminum stearate are better than those containing magnesium stearato

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Table I.

Q * to & S tear «fc DurotaohnlfctUoha solutions are effective
In seconds B. C D 142 B. P. Q 117 123 H I. j 0.0 A. 142 142 98 142 142 L 42 101 P34 116 142 142 142 0.005 150 103 118 101 117 I30 100.4 116 104 104 111 0.01 IO3 110 99 126 101.2 107 113 88 96 0.08 135 96 97 94 118 99 115 84 95 0.03 87 87 89 90 120 89I 98 108 78 90! 0.04 85 91 91 95 123 99 88 85! 0.05 86 79 113 90 97 82.5 88 I. 0.07 OO 77 79 0.08 έο 83 105 96 81 78! 0.1 öo

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Table II

Maximum temporary reduction in solubility of stearate in %.

A NagnesliuB stearate (distearate) 46.7 B Ma & neeirostearate (diatearate). 41.5 C Magnesia luastearate (distearate) 45.75 D Magnesium stearate (Disteernv) 44.3 E Aluffllnlunaterrat (Dietearate) 26 P aluminum alumina astearate (diatearate) 37.5

0 AluninliiiBBtearate (Tristearet) 51 ^ 0

H Alumlniunatearat (distearate and about » Monoatearate} 52.3

Σ Alumina stearate (nonostearate) 45.1 J AluBiii: unstearate (distearate) 45.1

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Claims (5)

Claims 1. A pharmaceutical fizzy preparation, characterized in that it is an aoylaminophenol and a non-toxic polyvalent · Metal than stearic acid in an amount of Contains 0.001 to 0.2 Qewjf of the Oeeamtaisohung. 2. A pharmaceutical fizzy preparation according to claim 1 »thereby characterized in that it is up to 0.1 and in particular 0.001 contains up to 0.0 *, preferably 0.01 to 0.02 Oewji stearate, 3 · FbarBaEeutisohes fizzy preparation according to claim 1 to 2, characterized in that it contains aluminum, calcium or magnesium, mono-, di- or tristearate. 4 · Pharmaceutical fizzy preparation according to claim 1 to 2, daduroh marked «that it is an N-aoyl-p-aminophenol, preferably N-aoetyl-p-aminophenol or an ester or. Xther, especially the salicylic acid or aoetyl alloylic acid ester or p-Äthoxyaoetanilid contains. 5. Pharmaceutical-based fizzy preparation according to claim 1 to #, daduroh characterized in that it is an alkali metal carbonate or hydrogen carbonate, in particular sodium «or potassium and an aliphatic polycarbonic acid, in particular Citric or tartaric acid, contains 6 · Pharmaceutical-based fizzy preparation according to claims 1 to 5, daduroh marked * that there is still sorbitol «codeine» Coffees, lauryl sulfate sweeteners, saccharin and / or Contains glutamic acid. ueisoh. 009840/2202