NL194154C - Pharmaceutical water-soluble preparation containing N-acetylcysteine and aspartame. - Google Patents

Description

1 194154

Pharmaceutical water-soluble preparation containing N-acetylcysteine and aspartame

The invention relates to a pharmaceutical water-soluble preparation containing N-acetylcysteine (NAC) and aspartame.

5 Such a preparation is known from the No. 4 (April) 1986 publication in the 86th edition of the "Bollettino mensile deirülCM", Bern, Switzerland. It mentions effervescent tablets called "Fluimucil" with a composition of 100 mg, 200 mg or 600 mg of acetylcysteine, as well as aspartame and pressing aid, or a composition of 150 mg of acetylcysteine, sodium saccharin, dye E110 and pressing aid.

The exact composition of the preparation is not disclosed. Available on the market is a 10 effervescent formulation called Fluimicil containing 600 mg NAC, 975 mg citric acid, 1035 mg sodium bicarbonate, 20 mg sodium saccharin, 770 mg sucrose and 100 mg lime flavor.

Non-effervescent preparations are also available under the name of Fluimicil, such as a water-soluble granulate from 100 mg NAC, 8 mg sodium saccharin, 4341 mg sucrose, 550 mg orange flavor and 15 1 mg colorant E110, as well as a water-soluble granulate consisting of 200 mg NAC , 8 mg sodium saccharin, 2241 mg sucrose, 550 mg orange flavor and 1 mg dye E110. (Cl: 15985).

The NAC present in the above preparations has mucolytic activity and can be taken orally as an aqueous solution, which is created by dissolving a granulate. However, the organoleptic properties of the drug can be subjectively perceived as unpleasant, due to the typical unpleasant taste of the NAC. To soften or mask this taste, the existing preparations generally contain sucrose. However, the use of sucrose is objectionable for several reasons, for example for diabetics, or because it is a caries-causing sugar.

Replacement of sucrose by artificial sweeteners and / or sugar substitutes, which do not cause caries, may seem like a simple solution at first instance, but in reality it is a major problem to meet all requirements at the same time. CH-A 64683 describes sweeteners that can substitute for sugar, which sweeteners comprise a mixture of kylitol, sorbitol and aspartame. It has been reported that sorbitol with synthetic sweeteners such as saccharin does not lead to a desired taste perception of a cyclamate. It is necessary that the unpleasant taste of the NAC be effectively masked and that the preparation have pleasant organoleptic properties. However, the preparation must also be stable enough to be stored; the various components must therefore be compatible with each other. Finally, it is also important that the preparation can be easily prepared on a technical scale.

It has now been found that it is indeed possible to meet all these requirements by a critical formulation of the preparation.

The present invention is characterized in that the preparation is a non-effervescent granulate consisting of: N-acetylcysteine 10-20 wt% sorbitol 67-78 wt% aspartame 2-3 wt% 40 flavoring 10 wt%, and optionally a pharmaceutically acceptable dye, the sum of the parts by weight of said components being 100%.

A preferred preparation according to the invention has the following composition: N-acetylcysteine 20% by weight 45 sorbitol 67.5% by weight aspartame 2.5% by weight flavoring 10% by weight

Comparison of a wide variety of formulations has made it clear that only formulations 50 within the above formulation meet the combined requirements of acceptability in taste perception, stability, and ease of technical preparation without the use of sucrose.

The term "flavoring" has the current meaning here, which encompasses a wide variety of artificial and natural flavors, but does not extend to simple sugars, sugar substitutes, 55 sweeteners and acids, such as xylitol, sorbitol and citric acid. Instead of "flavoring, also called the term "flavor substance". Of the flavor substances, lemon flavor is preferred, because the color of the solution suits the taste 194154 2

For better consumer acceptance, it may be necessary or desirable to use a colorant appropriate for the flavor. For example, with a peppermint flavor, a colorant can be used which gives the solution a green color. When using orange flavor, a colorant such as beta-carotene is preferably used. The dye is preferably used in an amount of 0.5-1.0% by weight.

The subject of the present invention is the preparation of the granulate in the usual pharmaceutical technical manner. The granulate can be packaged in suitable papers containing, for example, 1.1.5 or 2 g of the preparation. Preferably, each paper contains an amount of the preparation corresponding to 100,150, 200 or 300 mg of NAC.

The examples given below for a granulate according to the invention relate to a separate dose of 1 g: NAC 100 mg apartame 25 mg sorbitol 775 mg 15 lemon flavor 100 mg NAC 100 mg aspartame 25 mg sorbitol 774.2 mg 20 peppermint flavor 100 mg green food coloring 0.8 mg NAC 200 mg aspartame 25 mg 25 sorbitol 675 mg lemon flavor 100 mg NAC 200 mg aspartame 25 mg 30 sorbitol 674.2 mg orange flavor 100 mg orange food coloring (or β-carotene) 0 .8 mg NAC 150 mg 35 aspartame 30 mg sorbitol 720 mg citrus flavor 100 mg

The granules of the invention are easily soluble in water and provide an aqueous 40 NAC solution with a pleasant taste.

A number of examples are given below to further illustrate the invention without, however, limiting it.

Example I

45 A granulate consisting of NAC 10 kg aspartame 2.5 kg sorbitol 77.42 kg orange flavor 10 kg 50 color E110 (C.l. 15985) 0.08 kg is prepared in the following manner:

The powders, except for the colorant, are sieved on a 1.07 mm mesh sieve and mixed for 10 minutes. The mixture is then granulated in a fluidized bed granulator with an aqueous dye solution. The granulate is then packed into pressed 55 paper-aluminum-polyethylene papers into individual doses of 1 g (NAC dose per package is 100 mg).

Claims (2)

3 194154, Example II As described in example I, but with a mixture consisting of: NAC 20 kg aspartame 2.5 kg 5 sorbitol 67.42 kg orange flavor 10 kg β-carotene 0.08 kg preparations are prepared with a content of 1 g of the preparation (content of NAC = 200 mg). Example III In the manner mentioned in example I, but without the addition of a coloring agent, a granulate is prepared, consisting of: NAC 15 kg aspartame 3 kg 15 sorbitol 72 kg dtrusfruit flavor 10 kg The granulate is placed in papers of pressed paper. aluminum-polyethylene packaged in individual doses of 2 mg (300 mg NAC per individual dose) or alternatively in individual doses of 1 g (150 mg 20 NAC per separate dose). Example IV The composition described in Example I can also be prepared by the following alternative method. NAC, sorbitol and aspartame are sieved on a 1.08 mm mesh shaker and mixed. The mixture is placed in a granulator and granulated with an aqueous solution containing the dye E-110. The granulate thus formed is dried in a drier and granulated in a crank granulator equipped with a 1.0 mm screen. The flavoring substance is added to the granulate and the whole is mixed once more until a homogeneous mixture is formed. The mixture is packaged in pressed paper-aluminum-polyethylene papers in 1 g doses (100 mg NAC per separate dose). Example V The preparation described in Example II can also be prepared according to the following alternative method. NAC, sorbitol and aspartame are sieved on a shaker with a mesh size of 1.08 mm and mixed. The mixture is placed in a fluidized bed granulator and granulated with a water-alcohol solution (1: 1) containing β-carotene. The dried granulate is sieved with a 1.08 mm mesh sieve and the sieve fraction is mixed with the orange flavor. The mixture is then packed into pressed paper-aluminum-polyethylene papers into individual doses of 1 g (200 mg of NAC 40 per individual dose). Pharmaceutical water-soluble preparation containing N-acetylcysteine and aspartame, characterized in that the preparation is a non-effervescent granulate consisting of N-acetylcysteine 10-20 wt% sorbitol 67-78 wt% aspartame 2-3 wt. 50% flavor 10% by weight, and optionally a pharmaceutically acceptable colorant, the sum of the parts by weight of said components being 100%. 194154 4 < Pharmaceutical preparation according to claim 1, characterized in that it consists of N-acetylcysteine 20% by weight sorbitol 67.5% by weight aspartame 2.5% by weight 5 flavoring 10% by weight,