Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Patent
1997-12-18
2000-05-16
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
424451, 424465, 424489, A61K 920, A61K 948
Patent
active
060634030
DESCRIPTION:
BRIEF SUMMARY
The invention concerns compressed dry-granulation tablets comprising desogestrel and a method of production thereof.
Desogestrel is a contraceptive steroid, widely used in preparations under various trade names among which Desogen.RTM., Marvelon.RTM., Mercilon.RTM., and Gracial.RTM..
It was observed that desogestrel shows a tendency to transfer out of tablets and granules. This is of particular concern when the tablet cores or granules comprise very low dosages of desogestrel. Tablets having desogestrel as active ingredient comprise usually 25-150 .mu.g, and typically 25, 50, 75, 100, or 150 .mu.g of desogestrel. For desogestrel, which has been used as active ingredient in contraceptive or HRT (hormone replacement therapy) drugs, this is not acceptable in view of its safety and reliability. For example a loss of 10% of the active substance within the shelf-life would have a dramatic effect on the amount of active ingredient in the tablet, and could lead to a tablet having less than the treshold amount of active ingredient to exert full activity.
It has now been found that compression of a dry-mix comprising desogestrel can be used for preventing the transfer of desogestrel from the tablet or granule to the environment. Apart from desogestrel the tablet or granule can further comprise an estrogen.
Examples of estrogens include ethinyl estradiol, .beta.-estradiol, mestranol (17.alpha.-ethinyl estradiol 3-methyl ether), estrone, estradiol, estradiol valerate, and other compounds with estrogenic activity. Ethinyl estradiol and .beta.-estradiol are the preferred estrogen.
As used herein "transfer" includes any process in which desogestrel prematurely leaves the dosage unit.
The term "dosage unit" generally refers to physically discrete units suitable as unitary dosages for humans or animals, each containing a predetermined quantity of active material (desogestrel and/or estrogen) calculated to produce the desired effect. Examples of such dosage units are tablets, granulates, powders, and pills.
Methods and compositions for making various dosage units are known to those skilled in the art. For example, methods and compositions for making, tablets and pills have been described in Remington's (18th edition, A. R. Gennaro Ed., Mack Publishing Co. Easton, Pa., 1990), at pages 1633 through 1665.
The concentration of steroid or steroids included in the tableting, mixture, and eventually the dosage unit, will of course depend on its intended use, and the eventual mass of the dosage unit. The amount of desogestrel used in a dosage unit will be well known to those skilled in the art.
A tablet core or granule according to the invention comprises typically a diluent and optionally a binder. Preferably the tablet core or granulate will also include a disintegrating agent.
Diluents or "filler excipients" are agents added to dosage units to increase the granules' and resulting dosage units' bulk, and to improve dry-binding characteristics. The preferred diluent for use in this regard is lactose. Other diluents include mannitol, sorbitol, (spray dried) lactose, (microcrystalline) cellulose, ethyl cellulose, xylitol, amylose, starch, starch-derivatives, dextrose, fructose, calcium carbonate, calcium phosphate, NaCaPO.sub.4, sucrose, and mixtures thereof. The diluent will typically make up from 70 to 95% by weight of the resulting steroid loaded granules.
Binders are agents used to impart cohesive properties to the granules and tablets, resulting in more physically stable dosage units, and include hydroxypropylcellulose, amylopectin, starch, povidone (polyvinylpyrrolidone), hydroxypropylmethylcellulose, gelatin, polyethyleneglycols, ethyl cellulose, acacia gum, gelatin, glycerol, and starch based binders. The preferred binder for use with the invention is polyvinylpyrrolidone. The binder will typically make up from 0.5 to 20% by weight of the resulting, steroid loaded tablet cores or granules, and preferably 0.5 to 5% by weight.
Disintegrating agents or "disintegrators" are substances or mixtures of substances added to a tablet
de Haan Pieter
Thys Carolus Paulus
Akzo Nobel N.V.
Blackstone William M.
Howard S.
Page Thurman K.
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