Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Patent
1992-06-05
1994-06-21
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
424474, 424475, 424482, 424682, 424686, 424687, 424696, 424697, 514781, 514788, 514960, 514961, 564238, A61K 936
Patent
active
053226984
DESCRIPTION:
BRIEF SUMMARY
The invention relates to a process for the preparation of a tablet or dragee composition containing a heat-, light- and moisture-sensitive active ingredient having monoclinic crystal structure.
The process according to the invention is particularly useful for preparing a pharmaceutical composition having antiarrhythmic activity and containing as active ingredient an aminoguanidine derivative of the general formula (I), ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 stand independently from each other, for hydrogen, halogen or C.sub.1-4 alkyl, nitro, C.sub.1-4 alkoxy or trifluormethyl group; alkyl group; C.sub.1-4 alkyl or C.sub.2-4 alkenyl group
It is very difficult to prepare an oral dosage form such as tablet or dragee from substance having monoclinic crystal structure since the adhesion between the crystal plates is weak and the aggregation of granules is difficult to compress.
According to a method well-proved in the practice for tabletting monoclinic crystalline substances and having weak adhesive properties (e.g. phenylbutazone, phenacetin, barbiturates), the powdered mixture containing the active ingredient is pressed after wet granulation [H. A. Lieberman, L. Lachman: Pharmaceutical Dosage Forms, Tablets, Volume 2, Marcel Dkker, Inc., N.Y. (1981)]. In this case, the binding force needed to the tablet formation is provided by the binding agent introduced during the kneading whereas the optimum compressibility is ensured by the optimum porosity and flowability developed in the preparing procedure carried out in a suitable way.
The wet granulation cannot be carried out and the table formation can be realized only by direct compression or briquetting when the active ingredient crystallizes in monoclinic system and is also sensitive to moisture (e.g. salycilic acid derivatives). In this case the necessary adhesion is ensured partly by the solid binding agent introduced as a powder mixture and partly by the binding forces developed at the so-called active sites of the granule surfaces [A. S. Rankel et al.: J. Pharm. Soc. 57, 574 (1968)].
In cases of moisture- and light-sensitive substances, the tablets should be provided with a protective coat to prevent any damage during the storage. A tablet prepared by direct compression should possess an appropriate hardness in order to be useful for a further processing, e.g. dragee formation.
The hardness can be enhanced by increasing the force of compression, however, the density of tablet is increased and the porosity thereof is decrased by enhancing the force of compression. The disintegration of the tablet is decisively influenced by the porosity since the higher the density of the tablet is, the slower is the penetration of the aqueous fluid thus, the dissolution of the active ingredient from a tablet of high density is very slow, the desired blood level of the acitve ingredient can be achieved only after a long period and the bioavailability of the active ingredient is also low.
During compression a heat effect is developed by the friction of the granules, whereby the heat-sensitive active ingredients are usually decomposed thus, a direct compression or briquetting cannot be employed in these cases.
As a consequence, it is a very difficult task to formulate monoclinic crystalline compounds simultaneously being sensitive to moisture, heat and light effects to tablet composition. No literature reference has been found for the solving of this problem.
The aim of the present invention is to work out a composition, which is useful for the preparation of a tablet or dragee core from monoclinic moisture-, heat- and light-sensitive compounds by compression. A further aim of the present invention is to prepare a tablet or dragee composition making possible the rapid absorption of the active ingredient as well as the development of high blood levels after taking the composition and resulting in a high bioavailability of the active ingredient.
Surprisingly, it has been found that the above aims can be achieved by adding 0.2 to 1.5 parts by weight of an anhydrous alkaline
REFERENCES:
patent: 3868463 (1975-02-01), Remy
patent: 3907999 (1975-09-01), Christy
patent: 4198402 (1980-04-01), Ezer et al.
Fonner, et al., "Pharmaceutical Dosage Forms", vol. 2, pp. 183-238 (1981).
Rankell et al., "Physics of Tablet Compression XV", vol. 57, No. 4 (1968) pp. 574-577.
Bacsa Gyorgy
Beke Katalin
Biblo Margit
Bobak Dorottya
Jancso Sandor
Biogal Gyogyszergyar Rt.
Page Thurman K.
Venkat Jyothsna A.
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