Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1993-07-12
1995-02-28
Henley, III, Raymond J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
A61K 31405
Patent
active
053937732
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a pharmaceutical composition containing as active ingredient 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulphonamide, in particular a composition for intranasal administration.
3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulphonamide, which may be represented by the formula (I) ##STR1## and its physiologically acceptable salts and solvates are disclosed in UK Patent Specification No. 2162522. The compound of formula (I) exhibits selective vasoconstrictor activity and is useful in the treatment of migraine.
Oral compositions have certain disadvantages for the administration of anti-migraine agents. Thus, for example, one of the symptoms associated with migraine is nausea, and the presence of nausea may make it difficult for a patient to take an oral composition. Also, it is desirable that the anti-migraine drug should be rapidly absorbed into the bloodstream. Such rapid absorption can be achieved using intranasal or parenteral administration, but some patients dislike parenteral administration, particularly if the drug is to be self-administered. Intranasal administration therefore represents a preferred route for administration of the compound of formula (I).
We have now found a particularly advantageous formulation for the intranasal administration of the compound of formula (I) comprising an alkaline suspension of the compound of formula (I) or a physiologically acceptable salt or solvate thereof.
There is thus provided according to the invention a pharmaceutical composition in a form adapted for intranasal administration comprising a suspension of 3-[2-dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulphonamide or a suitable physiologically acceptable salt or solvate thereof as active ingredient wherein the pH is in the range of 8 to 12.
Suitable physiologically acceptable salts and solvates of 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulphonamide for use in the present invention are those which have relatively low aqueous solubility, e.g. the succinate and hydrochloride salts. Preferably the pharmaceutical compositions according to the invention contain 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulphonamide in the form of the free base.
For satisfactory intranasal administration, an active ingredient must be presented in a form which is readily absorbed through the nasal mucosa but which is unassociated with any adverse effects such as irritancy. Satisfactory intranasal formulations must also be sufficiently stable, chemically and physically, to be consistently dispensed in accurate metered doses, even after prolonged storage with potential temperature fluctuations of between 0.degree. and 400.degree. C. Accordingly, the active ingredient must be compatible with the excipients used in the formulation and should not aggregate in a manner which would result in a loss of accurate dose delivery.
Surprisingly, we have found that suspensions of 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulphonamide and suitable physiologically acceptable salts and solvates thereof having a pH in the range of 8 to 12 have excellent dispersion properties. In contrast, neutral and acidic formulations containing such active ingredients do not form readily dispersible suspensions and are unsuitable for use as suspensions for intranasal administration.
Preferably the pH of suspensions according to the invention will be in the range of 9 to 11; most preferably the pH of the suspensions according to the invention will be about 10.
Suspensions will generally be aqueous, for example prepared from water alone (for example sterile or pyrogen-free water) or water and a physiologically acceptable non-aqueous vehicle (for example ethanol, propylene glycol, polyethylene glycols such as PEG 400).
Such suspensions may additionally contain other excipients, for example preservatives (such as benzalkonium chloride and phenylethylalcohol), wetting agents/surfactants such as polysorbates (e.g. Tween 80) and sorbitan esters (e.g. Span 80), buffering a
REFERENCES:
patent: 5037845 (1991-08-01), Oxford
Craig Joanne
Saynor David A.
Crires T. J.
Glaxo Group Limited
Henley III Raymond J.
LandOfFree
Method for the intranasal administration of 3-[2-(dimethylamino) does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for the intranasal administration of 3-[2-(dimethylamino), we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for the intranasal administration of 3-[2-(dimethylamino) will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-848718