Modified release formulations and methods of treating inflammatory bowel disease
First Claim
1. A pharmaceutical composition for administration to a subject in need thereof comprising a dose of an aminosalicylate active agent chosen from 4-amino salicylic acid, 5-amino salicylic acid, and pharmaceutically acceptable salts, esters and pro-drugs thereof, and at least one pharmaceutically acceptable excipient, wherein the composition exhibits:
- (a) a drug-release profile that is independent of surrounding pH and (b) a dissolution profile, when tested in a U.S.P. Type II apparatus (paddles) at 37°
C. and 50 rpm, in pH 6.8 buffer for the test;
1 hour;
less than or equal to about 20% drug released;
2 hours;
less than or equal to about 35% drug released;
3 hours;
less than or equal to about 50% drug released;
4 hours;
less than or equal to about 60% drug released;
6 hours;
less than or equal to about 75% drug released; and
12 hours;
from about 25% to about 100% drug released; and
wherein upon administration, the composition exhibits;
(c) at least one ratio chosen from a total urine recovery or total plasma (AUC) ratio of metabolite of the active agent to the active agent greater than or equal to 10;
1, and a Cmax ratio of metabolite of the active agent to the active agent greater than or equal to 5;
1; and
(d) from greater than 30% to about 100% of the dose of the active agent excreted in the urine as metabolite of the active agent and the active agent.
4 Assignments
0 Petitions
Accused Products
Abstract
Methods and formulations for treating inflammatory bowel disease are disclosed. The methods and formulations include, but are not limited to, methods and formulations for delivering effective concentrations of 4-aminosalicylic acid and/or 5-aminosalicylic acid, and pharmaceutically acceptable salts and pro-drugs thereof, to affected areas of the intestine, i.e., distal gut. The methods and formulations comprise modified-release elements, providing for drug delivery to the affected or desired area. Diseases and conditions treatable with the present invention include Crohn'"'"'s disease and ulcerative colitis.
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Citations
19 Claims
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1. A pharmaceutical composition for administration to a subject in need thereof comprising a dose of an aminosalicylate active agent chosen from 4-amino salicylic acid, 5-amino salicylic acid, and pharmaceutically acceptable salts, esters and pro-drugs thereof, and at least one pharmaceutically acceptable excipient, wherein the composition exhibits:
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(a) a drug-release profile that is independent of surrounding pH and (b) a dissolution profile, when tested in a U.S.P. Type II apparatus (paddles) at 37°
C. and 50 rpm, in pH 6.8 buffer for the test;
1 hour;
less than or equal to about 20% drug released;
2 hours;
less than or equal to about 35% drug released;
3 hours;
less than or equal to about 50% drug released;
4 hours;
less than or equal to about 60% drug released;
6 hours;
less than or equal to about 75% drug released; and
12 hours;
from about 25% to about 100% drug released; and
wherein upon administration, the composition exhibits;
(c) at least one ratio chosen from a total urine recovery or total plasma (AUC) ratio of metabolite of the active agent to the active agent greater than or equal to 10;
1, and a Cmax ratio of metabolite of the active agent to the active agent greater than or equal to 5;
1; and
(d) from greater than 30% to about 100% of the dose of the active agent excreted in the urine as metabolite of the active agent and the active agent. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
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15. A method of treating inflammatory bowel disease comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising a dose of an aminosalicylate active agent chosen from 4-amino salicylic acid, 5-amino salicylic acid, and pharmaceutically acceptable salts, esters and pro-drugs thereof, and at least one pharmaceutically acceptable excipient, wherein the composition exhibits:
-
(a) a drug-release profile that is independent of surrounding pH and (b) a dissolution profile, when tested in a U.S.P. Type II apparatus (paddles) at 37°
C. and 50 rpm, in pH 6.8 buffer for the test;
1 hour;
less than or equal to about 20% drug released;
2 hours;
less than or equal to about 35% drug released;
3 hours;
less than or equal to about 50% drug released;
4 hours;
less than or equal to about 60% drug released;
6 hours;
less than or equal to about 75% drug released; and
12 hours;
from about 25% to about 100% drug released; and
wherein upon administration, the composition exhibits;
(c) at least one ratio chosen from a total urine recovery or total plasma (AUC) ratio of metabolite of the active agent to the active agent greater than or equal to 10;
1, and a Cmax ratio of metabolite of the active agent to the active agent greater than or equal to 5;
1; and
(d) from greater than 30% to about 100% of the dose of the active agent excreted in the urine as metabolite of the active agent and the active agent. - View Dependent Claims (16, 17, 18, 19)
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Specification