GB2192789A

GB2192789A - Acetylcysteine compositions

Info

Publication number: GB2192789A
Application number: GB08717581A
Authority: GB
Inventors: Annibale Gazzaniga; Valter Gianesello; Federico Stroppolo
Original assignee: Inpharzam International SA
Current assignee: Inpharzam International SA
Priority date: 1986-07-24
Filing date: 1987-07-24
Publication date: 1988-01-27
Anticipated expiration: 2007-07-24
Also published as: BE1000168A3; DE3723734C2; IT8721410A0; IT1222103B; FR2601875A1; GB8717581D0; SE500493C2; DE3723734A1; SE8702941L; NL8701744A; SE8702941D0; GB2192789B; CH666814A5; FR2601875B1; NL194154B; NL194154C

Description

1 GB2192789A 1

SPECIFICATION

Pharmaceutical compositions The invention relates to pharmaceutical compositions containing N- acetylcysteine. 5 N-acetylcysteine (hereinafter designated NAC) is a medicament with diverse favourable proper ties, one of which is mucolytic activity. For use in practice as a mucolytic agent, NAC can be taken orally in the form of an aqueous solution obtained by dissolving effervescent granules or an effervescent tablet. The organoleptic properties of the medicament can, however, be subjec tively unpleasant. It is therefore necessary to lessen the typical taste of NAC in the case of oral 10 administration.

In the pharmaceutical forms currently available commercially this is accomplished by an addi tion of sucrose. However, the use of sucrose can have disadvantages, especially for persons who suffer from diabetes. In addition, sucrose is a cariogenic sugar. It is therefore necessary to be able to provide, as an alternative to the already existing pharmaceutical forms, novel pharma- 15 ceutical preparations of NAC for oral use, which are indicated for subjects to whom sucrose can be harmful. The substitution of sucrose by an artificial sweetener or a non-cariogenic sweetening agent in a pharmaceutical form containing NAC is a problem which at first sight would appear easy to solve. In reality, there are manifold problems which are difficult to solve.

For example, it is necessary that the NAC and the sweetener are chemically compatible, that 20 the sweetener or sweetening agent is capable of effectively masking or lessening the typical flavour of NAC, that the resulting taste is pleasant anyhow, that the sweetener or sweetening agent is suitable for preparing the desired pharmaceutical form and is compatible with the associated operations.

The invention provides a pharmaceutical composition in the form of water soluble granules, the 25 composition comprising from 10 to 20% by weight of N-acetylcysteine, from 2 to 3% by weight of aspartame, from 67 to 75% by weight of sorbitol and about 10% by weight of a pharmaceu tically acceptable flavouring agent.

The flavouring agent is suitably present in an amount of from 5 to 15%, preferably 10% by weight. 30 Having regard to the acceptability by the consumer of the medicament, the use of a flavouring agent may demand the presence of acolourant which is normally associated with a particular taste. For example, the use of mint flavouring can demand the addition of a colourant which imparts a green colour to the solution. In such cases, it can be useful to combine the compo sition with a quantity of a pharmaceutically acceptable colourant, for example in a quantity 35 between 0.5 and 1 % by weight.

The granules according to the invention are prepared by procedures usual in pharmaceutical operations.

The granules can be distributed in suitable sachets containing, for example, 1, 1.5 or 2 g of the composition. 40 Preferably, each sachet contains a quantity of the composition corresponding to 100, 150, or 300 mg of NAC.

With reference to a dose of 1 g, representative examples of granules according to the invention are as follows:

2 GB2192789A 2 - NAC 100 mg Aspartame 25 mg Sorbitol 775 mg Lemon flavouring 100 _M91 5 k - NAC 100 mg Aspartame 25 mg 10 4 Sorbitol 774.2 mg Mint flavouring 100 mg Green colourant 0.8 mg 15 - NAC 200 mg Aspartame 25 mg Sorbitol 675 mg 20 Lemon flavouring 100 mg - NAC 200 mg Aspartame 25 mg 25 Sorbitol 674.2 mg orange flavouring 100 mg orange colourant 30 (or 13-carotene) 0.8 mg NAC 150 mg Aspartame 30 mg 35 Sorbitol 720 mg Citrus fruit flavouring 100 mg 40 The granules according to the invention disolve rapidly in water, giving an aqueous solution of NAC of pleasant palatability. The following Examples illustrate the invention.

Example 1 45

Granules composed of NAC 10 kg Aspartame 2.5 kg 50 Sorbitol 77.42 kg Orange flavouring 10 kg Colourant E110 0.08 kg 55 are prepared by the following procedure.

The powders, excepting the colourant, are sieved through a screen of 1.07 mm mesh width and mixed for ten minutes. The mixture is then granulated in a fluid-bed granulator with an aqueous solution of the colourant. 60 The granules are then distributed over blisters in a laminated aluminiumpolyethylene sheet in a dose of 1 9 per blister (NAC dose per blister = 100 mg).

Example 2

Blisters containing 1 g of the composition(NAC content = 200 mg) are prepared in a manner 65 3 GB2192789A 3 analogous to that described in Example 1, but starting from NAC 20 kg Aspartame 2.5 kg 5 Sorbitol 67.42 kg orange flavouring 10 kg 13-carotene 0.08 kg 10 Example 3

Granules comprising 15 NAC 15 kg Aspartame 3 kg Sorbitol 72 kg 20 Citrus fruit flavouring 10 kg 25 are prepared in a manner analogous to that described in Example 1, but without the use of colourant.

The granules are distributed over blisters in a laminated aluminium/polyethylene sheet in a dose of 2 g per blister (300 mg of NAC per dose) or in an alternative dose of 1 9 per blister (150 mg of NAC per dose). 30 Example 4

The composition described in Example 1 may also be prepared by the following alternative procedure.

The NAC, the sorbitol and the aspartame are sieved on a vibrating screen of 1.08 mm mesh 35 width and mixed. The mixture is placed in an autogranulator and granulated with an aqueous solution containing colourant E. 110. The granules obtained are dried in the fixed bed (oven) and then homogenised by means of a vibrating granulator equipped with a screen of 1.0 mm mesh width. The flavouring is added during granulation and the whole is then mixed again until a homogeneous mixture is obtained. 40 The mixture is distributed over blisters in a laminated aluminium/polyethylene sheet in a dose of 1 9 per blister (100 mg of NAC per dose).

Example 5

The composition described in Example 2 may also be prepared by the following alternative 45 method.

The NAC, the sorbitol and the aspartame are sieved through a vibrating screen of 1.08 mm mesh width and mixed. The mixture is placed in a fluidbed autogranulator and granulated with an aqueous:alcoholic (1:1) solution containing the B-carotene. The dried granules are homogen- ised by means of a 1.08 mm screen and mixed with the orange flavouring. The mixture is then 50 distributed over blisters in a laminated aluminium /polyethylene sheet in a dose of 1 g per blister (200 mg of NAC per dose).

Claims

1. A pharmaceutical composition in the form of water soluble granules, the composition 55 comprising from 10 to 20% by weight of Wacetylcysteine, from 2 to 3% by weight of aspartame, from 67 to 78% by weight of sorbitol and about 10% by weight of a pharmaceuti cally acceptable flavouring agent.

2. A pharmaceutical composition according to Claim 1 containing a quantity selected from 100, 150, 200 and 300 mg of N-acetylcysteine per single dose. 60

3. A pharmaceutical composition according to Claim 1 or Claim 2 further comprising a pharma ceutically acceptable colourant.

4. A pharmaceutical composition according to Claim 1 or Claim 2 and comprising:

4 GB2192789A 4 N-Acetylcysteine 10% by weight Aspartame 2.5% by weight Sorbitol 77.5% by weight 5 Flavouring Agent 10% by weight I

5. A pharmaceutical composition according to Claim 1 or Claim 2 and comprising: 10 - Y N-Acetylcysteine 20% by weight Aspartame 2.5% by weight Sorbitol 67.5% by weight 15 Flavouring Agent 10% by weight

6. A pharmaceutical composition according to Claim 3 and comprising: 20 N-Acetylcysteine 10% by weight Aspartame 2.5% by weight Sorbitol 77.42% by weight 25 Flavouring Agent 10% by weight Colourant 0.08% by weight 30

7. A pharmaceutical composition according to Claim 3 and comprising:

N-Acetylcysteine 20% by weight Aspartame 2.5% by weight 35 Sorbitol 67.42% by weight Flavouring Agent 10% by weight Colourant 0.08% by weight 40

8. A pharmaceutical composition according to Claim 1 or Claim 2 and comprising:

N-Acetylcysteine 15% by weight 45 Aspartame 3% by weight Sorbitol 72% by weight Flavouring Agent 10% by weight 50 Published 1988 at The Patent Office, State House, 66/71 High Holborn, London WC 1 R 4TP. Further copies may be obtained from The Patent Office, Sales Branch, St Mary Cray, Orpington, Kent BR5 3RD. Printed by Burgess & Son (Abingdon) Ltd. Con. 1/87.