Sustained release tablet containing diclofenac-Na and methylhydr

Details Sustained release tablet containing diclofenac-Na and methylhydr Sustained release tablet containing diclofenac-Na and methylhydr

1996-09-11

1999-02-23

Page, Thurman K.

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Tablets, lozenges, or pills

424465, 424468, 424472, A61K 920, A61K 922

Patent

active

058741070

DESCRIPTION:

BRIEF SUMMARY
BACKGROUND OF THE INVENTION

1) Field of the Invention
The object of the present invention is to provide a tablet containing diclofenac-Na which provides sustained release of the active material.
2) Background Art
Tablets containing diclofenac-Na as the active material and hydroxypropylmethylcellulose as carrier and additive are known from WO-A-9 501 781. However, it is desirable to provide sustained release tablets which provide sustained release of the active material, so that an effective plasma concentration of diclofenac-Na is ensured even after a long interval of time (>12 hours).


SUMMARY OF THE INVENTION

This object is met according to the invention by a sustained release tablet containing diclofenac-Na as active material and methylhydroxypropylcellulose as sustained release agent, as well as customary additives, in which the ratio of methylhydroxypropylcellulose to diclofenac-Na amounts to .gtoreq.0.3.
It has been shown in in vitro experiments that tablets with a total content of 150.0 mg diclofenac-Na and 35.0 mg methylhydroxypropylcellulose per tablet release up to 100% sustained over approximately eight hours (Method: USP XXII, Paddle apparatus). However, it has unexpectedly been found that this sustained release effect is not present in vivo; rather a delay of only approximately 1 hour can be attained. Accordingly it was not to be expected that an alteration in the ratio of methylhydroxypropylcellulose to diclofenac-Na would allow a satisfactory sustained release in vivo to be obtained. Thus for example, with a two-layer sustained release tablet according to the invention with a total content of diclofenac-Na of 150.0 mg diclofenac-Na per tablet and a ratio of methylhydroxypropylcellulose to diclofenac-Na in the sustained release part of 122.5:125.0 and a ratio of methylhydroxypropylcellulose to diclofenac-Na in the initial part of 0:25 allowed a sustained release of approximately 15 hours to be attained in vivo.


DESCRIPTION OF THE PREFERRED EMBODIMENTS

According to a particular embodiment a sustained release tablet according to the invention comprises methylhydroxypropylcellulose with a ratio of methylhydroxypropylcellulose to diclofenac-Na.gtoreq.0.3 and methylhydroxypropylcellulose with a ratio of methylhydroxypropylcellulose to diclofenac-Na<0.3 or without methylhydroxypropylcellulose, tablet is obtainable in that the tablet portions (a) and (b) are made separately from one another and then brought together and the finished sustained release tablet obtained.
The portions (a) and (b) can be pressed together, especially to form a multi-layer tablet.
The invention will now be explained in more detail with reference to examples and figures, in which:
FIG. 1 shows release of diclofenac-Na in vitro from tablets according to example 2, example 3 or comparative example 1;
FIG. 2 shows release of diclofenac-Na in vivo of a tablet according to example 1 and a standard tablet in the trade; and
FIG. 3 shows the plasma level of a tablet according to example 2 and standard tablet in the trade;
FIG. 4 shows the plasma level (with standard deviation) of a tablet according to example 3 after as single oral administration.


EXAMPLES 1 AND 2



______________________________________ 1 2 ______________________________________ 1 diclofenac-sodium 125.0 100.0 2 lactose.1H.sub.2 O 70.4 50.0 3 methylhydroxypropylcellulose 122.5 50.0 4 colouring 0.1 0.0 5 water for granulation 6 magnesium stearate 3.5 2.0 7 highly dispersed silicon dioxide 3.5 0.0 325.0 202.0 ______________________________________
The colouring (4) was stirred into the water (5). Diclofenac-Na (1), lactose (2) and methylhydroxypropylcellulose (3) were added in a fluidised bed granulator and granulated with the aqueous colouring solution. The resultant granulate as well as magnesium stearate (6) and highly dispersed silicon dioxide (7) were passed through a forced sieve (1.25 mm) and homogenised in a container mixer. The resultant mixture was pressed into tablets on a rotating table tablet machine.
The release of diclofenac

REFERENCES:
patent: 5236713 (1993-08-01), Wato et al.
Vyas et al., Biological Abstracts, vol. 89, #29721, 1990.

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