Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Patent
1992-07-07
1994-03-15
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
424475, 424479, 424480, 424482, 424493, 424495, A61K 932, A61K 936, A61K 958, A61K 962
Patent
active
052944484
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to delayed release formulations, especially those in which the delayed release characteristic is due to a coating. The term "coating" is used herein to encompass coatings for solid supports and also capsules enclosing fluids and/or solids and the term "coated" is used similarly.
In many situations it is desirable to coat an active substance in such a way that the active substance is released from the coating only after a predetermined interval or only after a change in environment. In a medical context, it is particularly advantageous to be able to administer orally a medicament which is coated so that it passes through the stomach and is released only when the coated material reaches the small intestine. Such coatings are called "enteric" coatings and are relatively easy to formulate taking advantage of the fact that the stomach contents are acid and the intestinal contents are neutral to slightly alkaline.
A harder task has been to provide a coated medicament which will survive both the stomach and the small intestine and will release the active ingredient only when the material reaches the large intestine or colon.
Many diseases of the colon, for example ulcerative colitis and Crohn's disease and potentially also cancer of the colon, could be better treated if site-specific delivery of the therapeutic agent could be effected. Therapeutic agents include corticosteroids, for example hydrocortisone and prednisolone, bisocodyl, phenolphthalein, rhein, sulphasalazine, cholestyramine, azathioprine, 5-aminosalicylic acid and various antibiotics and smooth muscle relaxants. Few effective oral therapies are available, and administration via the rectum is messy and relatively expensive. If drugs for the treatment of colonic disease are encapsulated in an enteric coating, absorption of the drug from the small intestine is very rapid, and only small amounts of the drug reach the required site of action. If site-specific release could be obtained, smaller doses would be required, with a reduction in undesirable side effects.
There are also situations other than the treatment of diseases of the colon where it is desirable to deliver a drug to the colon before it is released. Thus, in certain conditions such as arthritis the release of drugs in the ileum can cause problems and it is desirable for laxatives and anti-diarrhoeal drugs to be selectively released in the colon. Other drugs may also benefit from such a form of release depending upon their absorption characteristics.
A number of approaches have been suggested for site-specific release to the colon. Thus, glycoside derivatives of steroid drugs are reported to be poorly absorbed in the stomach and small intestine but to be released in the large intestine through microbial action (Friend, D. R. and Chang, G. W., J. Med. Chem., 1984, 27, 261). Moreover, coating of peptide drugs with polymers cross-linked with azoaromatic groups is reported to protect the drugs from digestion in the stomach and small intestine but allow their release in the large intestine by the action of the indigenous microflora to effect reduction of the azo bonds (Saffron, M. et al., Science, 1986, 233, 1081).
In U.K. Patent Application No. 8912048.9 (published as GB 2220350A) the use of glassy amylose is described for the purpose of effecting site-specific release in the colon. That application does refer to the possibility of further coating an amylose coated compound but only in the context of the use of "a conventional gelatin or enteric coating" for this purpose. It has now been found that especially advantageous results may be obtained using a particular form of additional coating material in conjunction with glassy amylose or even with the other predominantly amorphous form of amylose, rubbery amylose.
According to the present invention a delayed release composition comprises an active compound and amorphous amylose and has an outer coating comprising a film forming cellulose or acrylic polymer material.
The invention is based on the finding that providing
REFERENCES:
patent: 4642111 (1987-02-01), Sakamoto et al.
patent: 5108758 (1992-04-01), Allwood et al.
Chemical Abstracts vol. 112, No. 4, 1989 #25512n.
Chemical Abstracts vol. 109, No. 23, 1988 #206669c.
Allwood Michael C.
Archer David B.
Newton Johh M.
Ring Stephen G.
British Technology Group Limited
Page Thurman K.
Spear James M.
LandOfFree
Delayed release formulations does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Delayed release formulations, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Delayed release formulations will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1534749