SE443087B - COMPOSITION OF INHALATION COMPOSITION OF DISINODIUM CHROMOGLYCT AND LECITIN OR A SORBITAN OR SORBITOL ESTER IN A MIXTURE OF DICHLORDIFLUORMETHANE AND 1,2-DICHLOR-1,1,2,2-TETRAFLUORETHANE - Google Patents

Description

In preparing the suspension, the surfactant solidifies, but it is easily dispersed as small spaced particles in the mixture of propellant 12 and propellant 114. The resulting dispersions are usually stable for at least 30 minutes.

The dispersion of the surfactant in the mixture of the fuels 12 and 114 can be mixed with the finely divided disodium chromoglycate, which should be dried before use. The dispersion content of the atomized disodium cromoglycate is preferably 0, 1-10, 0% by weight and most preferably 1-5% by weight. Additional propellant 12 and / or propellant 114 (suitably cooled, eg to -50 ° C) may be added to the original dispersion or the original dispersion containing the atomized disodium cromoglycate.

The weight ratio of propellant 12 to propellant 114 in the final mixture is, as mentioned, between 2: 1 and 1: 1, preferably about 1.5: 1. Thus, an excess of propellant 12 relative to propellant 114 is preferred.

The dispersion or suspension of the surfactant in the final mixture of propellants 12 and 114 suitably contains 0.15-2.0% by weight of lecithin or sorbitan or sorbitol ester, preferably 0.2-1.2% by weight. In addition, such dispersions or suspensions suitably contain 0.05-2.0% by weight of disodium chromoglycate, preferably 0.2-2.0% by weight.

Dispersions of 0.2-2 parts by weight of sorbitan ester in a mixture of 50-70 parts by weight of propellant 12 and 50-30 parts by weight of 114 are stable for at least 16 hours at a temperature of -60 ° C.

Particularly preferred are such dispersions in which the surfactant is a sorbitan ester, e.g. sorbitan trioleate ("Span 8Û" b.

When lecithin is used, it is preferably vegetable, e.g. sojalecitin.

The compositions of the invention should contain less than 1.0% by weight of water, preferably less than 0.5% by weight of water and most preferably less than 0.2% by weight of water.

Certain compositions according to the invention are advantageous over corresponding compositions containing propellant 11 in that they either give a higher proportion of fine particles in the aerosol cloud formed or can be used for the preparation of such compositions. A suitable method for determining the proportion of fine particles in an aerosol cloud is described in J. Phar. Pharmac. 1973, 25, Suppl. 32? -36P. It has surprisingly been found that in inhalation compositions containing disodium cromoglycate a weight ratio of 12: 114 from 2: 1 to 1: 1 gives better results than a weight ratio lower than 1: 1. To show this, two disodium cromoglycate compositions have been compared, which differ only in the ratio 12: 114. Thus, two compositions A and B have been compared, where composition A is a composition according to the invention with a weight ratio propellant 12: propellant 114 of 3: 2, while composition B is a composition not covered by the invention (weight ratio 12: 114 is 2: 3, i.e. the preferred ratio according to GB 988 513).

The main differences between the two compositions are as follows: (1) Composition B tends to form aggregates, and the suspension has poor physical stability. (2) A dispersion test shows that composition A gives about twice as high a proportion of fine particles in the formed aerosol cloud as composition B. A high proportion of fine particles in the aerosol cloud is of great importance in the ability of an inhalation composition to penetrate deeply in the lungs.

The comparative test results show that composition B has deteriorated considerably after only 3.5 months under relatively mild conditions at room temperature. Composition A, on the other hand, shows only slightly degraded properties after 4 years of storage at room temperature.

The invention is illustrated by the following working examples.

Example. Spray packages were prepared as follows.

A sorbitan ester is dispersed in up to half the amount of propellant 12 at -40 ° C with stirring with a mixer which gives a high degree of dispersion. Dried finely ground disodium cromoglycate is added to the resulting dispersion, this substance being very easy to disperse. The remainder of propellant 12 is then added at -SOOC, after which propellant 114 is added, also cooled to -SOOC. The resulting mixture is filled into pressure vessels, on which valves, e.g. measuring valves, then fitted.

Compositions having the following composition were prepared:

Claims (6)

7807934-8 4 Weight% Weight% Dried, finely ground disodium chromoglycate 0, 3605 1.4420 Sorbitan trioleate 0.250D 1.0000 Fuel 114 39.7558 39.0232 Fuel 12 59.6337 58.5348 The stability was determined as follows. Pressure vessels equipped with measuring valves and containing the above compositions were stored at 5 ° C, 25 ° C and 37 ° C respectively for a period of 12 months. Other such spray containers were stored at (a) temperatures ranging from 15 ° C to 37 ° C and at (b) a temperature of 45 ° C for a period of 6 months. During all these test periods no change in (a) the amount of disodium chromoglycate discharged at each spraying, (b) the content of fine particles in the aerosol cloud or (c) the crystal size of the sodium cromoglycate could be observed. P a t e n t k r a v Inhalation composition, characterized in that it consists of a dispersion or suspension of 0.05-15% by weight of disodium cromoglycate with a mass median diameter of 0.01-10 μm and lecithin or a sorbitan or sorbitol ester in a mixture of dichlorodifluoromethane and 1 , 2-dichloro-1,1,2,2-tetrafluoroethane in a weight ratio of dichlorodifluoromethane: 1,2-dichloro-1,1,2,2-tetrafluoroethane from 2: 1 to 1: 1, and that it is free from trichloromonofluoromethane. Composition according to Claim 1, characterized in that it contains less than 4.0% by weight of lecithin or sorbitan or sorbitol ester. 3. A composition according to claim 2, characterized in that it contains 0.2-2.0% by weight of lecithin or sorbitan or serbitol ester. 4. A composition according to claim 3, characterized in that it contains 0.1-10% by weight of disodium cromoglycate. Composition according to any one of claims 1-4, characterized in that the ester is sorbitan sesvioleate, sorbitan monooleate, sorbitan monolaurate or sorbitan trioleate. Composition according to any one of claims 1-5, characterized in that it contains less than 1% by weight of water. Pooa QUALITY