Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Capsules
Patent
1993-08-20
1995-03-28
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Capsules
424461, 424462, 424463, A61K 958
Patent
active
054015120
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to the administration of drugs to the intestine and has particular, but not exclusive, application to the treatment of colonic disorders by administration to the ileum and/or colon of drugs such as 5-amino-salicylic acid (hereinafter referred to as 5-ASA).
Treatment of diseases of the intestine usually requires the delivery of a drug to the affected site. When the disease is essentially confined to a specific part of the intestine, such as the colon in ulcerative colitis or Crohn's colitis, it is desirable to target administration of the drug to that part in order to provide and control optimum local concentration of the drug. In this connection, some drugs such as 5-ASA are absorbed or inactivated in the small intestine.
The formulation of a drug in a conventional enteric coated capsule or tablet merely prevents release of the drug until the alkaline environment of the small intestine is reached. The problem of targeting the drug to the colon in an effective and viable manner was not solved until the proposal by the present inventors to coat solid oral dosage forms with a thick coating of an anionic polymer of defined pH dissolution profile (see EP-A-0097651).
Several "delayed release" forms of orally administrable drugs have been proposed. The delayed release may result from the physical properties of the formulation or from the chemical and physical properties of a derivative of the drug. It is known to provide capsules and tablets with a coating which will disintegrate to release the drug gradually when the capsule or tablet has reached the acid environment of the stomach or the alkaline environment of the small intestine. Similarly, it is known to provide capsules and tablets with a coating permeable to the drug contained and through which the drug is gradually released.
It was proposed in GB-A-1219026 (published January 1971) to embed individual particles of a drug in a slowly disintegrating or slowly dissolving resin matrix having a particular dissolution profile to provide an orally administrable formulation for selectively administering the drug to the large intestine. The resin is selected such that the drug remains substantially protected within the resin matrix while the particles travel through the stomach and small intestine of a patient and that the drug is substantially completely exposed at the time the particles reach the large intestine. In particular, the nature and amount of the resin is selected so that when a quantity of the embedded drug is introduced into a Stoll-Gershberg disintegration apparatus, submerged in a simulated intestinal fluid (made in accordance with the U.S. Pharmacopoeia, Volume XVII, 1965 at page 919 but modified by containing no pancreatin), and operated as described in the patent specification, 2% to 12% of the drug dissolves within an hour of the introduction of the formulation into the fluid and 18% to 88% of the drug dissolves within three hours of said introduction. It is specifically stated that the resin is selected so that the dissolution rate of the drug is not pH dependent but is time dependent. The preferred resin is a high-viscosity grade modified vinyl acetate resin (available under the Registered Trade Mark "Gelva" C3-V30) and other specified resins are carboxylated polyvinyl acetates, polyvinyl/maleic anhydride copolymers, poly(methacrylic acid), ethylene/maleic anhydride copolymers, ethyl cellulose, methylacrylic acid/methyl methacrylate copolymers, waxes and mixtures thereof including mixtures with shellac. Tablets of the embedded particles coated with a standard coating solution containing cellulose-acetate-phthalate are reported.
It will be appreciated that the carrier system disclosed in GB-A-1219026 relies upon the rate of disintegration or dissolution of the resin as the preparation passes through the gastro-intestinal tract. The time dependency makes it impossible to limit administration of the drug to the colon because of large variations in the transit time in the gastro-intestinal tract, especially in the sto
REFERENCES:
patent: 4250166 (1981-02-01), Maekawa et al.
patent: 5260071 (1993-11-01), Lemelson
patent: 5283064 (1994-02-01), Suzuki et al.
Roth et al `hagers handbuch der pharmazeutischen praxis` 1971, Springer-verlag, Berlin Heidelbeerg New-York pp. 494-495, Nachbehandlungen von Gelatinkapseln.
Evans Brian K.
Rhodes John
Hulina Amy
Page Thurman K.
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