Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Capsules
Patent
1998-05-08
2000-06-20
Webman, Edward J.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Capsules
424489, 424501, 514952, A61K 916, A61K 952, A61K 4730
Patent
active
060775327
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a process of preparing pharmaceutical ion exchange resin compositions.
European Patent Application Publication No. 368682 describes a process for the preparation of a pharmaceutical ion exchange resin composition that is readily dispersible in water comprising granulating an ion exchange resin having a pharmacologicaliy active ingredient bound thereto with a sugar or a sugar alcohol in the presence of sufficient water to facilitate granulation. Unit doses are prepared by filling e.g. capsules, sachets or other suitable containers with the granules. Although the product of EP 368682 is satisfactory when made at pilot scale of manufacture (ca. 10-12 kg), it has been found at production scale of manufacture (ca. 100 kg or more), that a variable level of pharmaceutically active ingredient is obtained in unit doses prepared from a single batch of granulate. For instance, in the case of an ion exchange resin composition containing morphine sulphate, unit doses prepared from one batch of granulate and with a desired morphine content of 20 mg may have morphine contents in the range of 18.5 to 23.5 mg and a mean content of 21 5 mg (coefficient of variations 8.3%).
One aim of the present invention is to provide a process for preparing a pharmaceutical ion exchange resin composition which can be used to prepare unit doses having a reduced inter-unit dose variability of the content of active ingredient This has, surprisingly, been achieved by using an aqueous solution of a sugar or sugar alcohol as a granulating medium instead of water.
According to the present invention there is provided a process for preparing a granular pharmaceutical ion exchange resin composition that is readily dispersible in water by granulating an ion exchange resin, having a pharmacologically active ingredient bound thereto, with a particulate sugar or sugar alcohol, characterised by the use of an aqueous solution of a sugar or sugar alcohol as a granulating medium.
The pharmaceutical ion exchange resin compositions prepared be the process of this invention disperse readily in water For example, dispersion readily occurs inside a minute upon stirring in sufficient water. Preferably a composition of this invention disperses with stirring with 60 seconds in at least 5, for instance 20 times its own weight in water.
The aqueous solution of sugar or sugar alcohol is conveniently added to a mixture of resin and particulate sugar or sugar alcohol during granulation.
Preferably the sugar or sugar alcohol in the granulating fluid is identical to the sugar or sugar alcohol with which the resin is granulated.
Preferably the sugar or the sugar alcohol present in the solution and present as solid has a molecular weight of from 90 to 550, especially from 150 to 370. The preferred sugars are mono- or di-saccharides and the preferred sugar alcohols are reduced mono- or di-saccharides. Suitable sugars/sugar alcohols are sucrose, dextrose, maltose, fructose, lactose, mannitol, sorbitol or, which is preferred, xylitol.
The particulate sugar/sugar alcohol granules is preferably finely divided, preferably having particle sizes of 600 microns or less. In a particularly preferred embodiment of the present process, at least 90% (by weight) of the particulate sugar/sugar alcohol granules will have particle sizes of 250 microns or less.
Preferably the sugar or sugar alcohol is present in the solution at a concentration of 40% w/w to 60% w/w, e.g. 45% w/w to 55% w/w most preferably about 50% w/w.
Preferably, the amount of granulating medium employed is from 1 to 20%, especially from 4 to 15%, by weight of the weight of the final dry weight of the complex/sugar, sugar alcohol mix. Once the drug-resin complex and the sugar/sugar alcohol have been granulated, the granules formed are then dried, preferably, until their water content is below 0.35% (by weight) (when measured by the Karl Fischer method of moisture analysis).
Any acidic or basic drug may be bound to the ion exchange resin. Preferably, however, active ingredients having a biol
REFERENCES:
patent: 3627583 (1971-12-01), Troy et al.
P.H. List et al.: "Hagers Handbuch Der Pharmazeutischon Praxis; 4th edition, vol. 7, part A" 1971, Springer Gerlog, Berlin Haldelberg, New York XPQO-2026431; p. 712.
Brown Adrian
Knott Trevor John
Leslie Stewart Thomas
Malkowska Sandra Therese Antoinette
Prater Derek Allan
Euro-Celtique S.A.
Webman Edward J.
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