Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Patent
1998-06-19
2000-03-14
Spear, James M.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
424464, 424470, 514778, 514779, 514781, 514951, A61K 920
Patent
active
060369752
DESCRIPTION:
BRIEF SUMMARY
This invention relates to to a tablet comprising an active ingredient selected from tolfenamic acid and pharmaceutically acceptable salts thereof which is capable of rapid release of the active ingredient. In addition the invention relates to a method of preparing such tablet.
Tolfenamic acid, N-(2-methyl-3-chlorophenyl)-anthranilic acid, and salts thereof are known compounds having antiinflammatory and analgesic activity. The compounds and their aforementioned activities as well as a method of preparing the compounds have been described in DK patent no. 116 061.
During the treatment of patients suffering from rheumatic diseases with tolfenamic acid preparations some patients noticed a reduced occurrence of migraine attacks, and tolfenamic acid is now being marketed both as antiinflammatory and analgesic agent, particularly for the treatment of rheumatic diseases and dysmenorrhoea, and as anti-migraine agent (prophylactic as well as curative).
The tolfenamic acid preparations were originally formulated as capsules consisting of a hard gelatine capsule shell containing a loose powder of the tolfenamic acid in admixture with usual tablet and capsule fillers, the powder being made available for dissolution in the gastro-intestinal tract, when the gelatine capsule has been dissolved.
The capsule formulation was chosen because of difficulties in preparing a tablet containing a therapeutic dose and still being of a reasonable size, as a tablet of a size which could be easily swallowed by a patient, turned out to be very difficult to disintegrate.
Later efforts resulted in the development of tablets being capable of providing a bioavailability of the tolfenamic acid corresponding to that obtained by the tolfenamic acid capsules. Furthermore the maximum plasma concentration was found to be somewhat higher for the tablet formulation than for the capsule formulation. However, T.sub.max, the time at which the maximum plasma concentration is obtained, was essentially unchanged.
The potential of zolfenamic acid of curing a migraine attack has accentuated the desire of obtaining a small tablet which is capable of providing a high plasma concentration of tolfenamic acid within a short time.
As a result of extensive research aiming at attaining this object, a tablet having these characteristics has now been developed. Thus a tablet has been provided, which is capable of providing a maximum plasma concentration of tolfenamic acid being almost twofold of that obtained with the capsule formulation (mean values of 5.60 .mu.g/ml and 2.95 .mu.g/ml, respectively, in a cross-over test carried out on 12 test persons), and furthermore within about half the time after administration (T.sub.max median values of 1.0 hours and 1.8 hours, respectively). As a further essential point, the mean plasma concentration reached half an hour after administration of the tablet according to the invention has been found to be more than twofold of that obtained by the known tablet, 2.60 .mu.g/ml and 1.18 .mu.g/ml, respectively. Thus a therapeutic level of tolfenamic acid is reached much faster by administration of the tablet according to the invention than by administration of the known tablet, among other things making the tablet according to the invention particularly suited for acute treatment of a migraine attack.
These surprising results are based on a selection of a particular combination of tablet formulation aids and a particular particle size of the active ingredient.
Accordingly the invention provides a tablet comprising an active ingredient selected from tolfenamic acid and pharmaceutically acceptable salts thereof, said active ingredient having a mean particle size of .ltoreq.10 .mu.m, and said tablet furthermore comprising alginic acid or a pharmaceutically acceptable salt thereof in an amount of 1.5-6.0% by weight and a superdisintegrant in an amount of at least 6% by weight.
The designation superdisintegrant refers to a group of disintegration agents being well-known to a person skilled in the art. Generally speaking, superdisintegran
REFERENCES:
patent: B14753801 (1992-07-01), Oren et al.
Bj.o slashed.rnsdottir Karen
Christensen Lars Hedevang
Gebhard-Hansen Knud Erik
Pedersen S.o slashed.ren Bols
A/S Gea Farmaceutisk Fabrik
Spear James M.
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