Formulations and methods of treating inflammatory bowel disease
View Patent ↗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 to affected areas of the intestine. 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.
1. A pharmaceutical composition comprising: a salicylate and/or salicylic acid chosen from 5-amino salicylic acid, pharmaceutically acceptable salts and esters thereof, and pro-drugs thereof; at least one pharmaceutically acceptable excipient; and a polymer system chosen from (a) at least one of methyl cellulose and hydroxypropylmethylcellulose in combination with ethyl cellulose, and (b) at least two ammonio methacrylate co-polymers; wherein the composition is formulated as a modified-release pharmaceutical composition with a modified-release matrix core, wherein the composition exhibits a drug-release profile that is independent of surrounding pH and wherein the composition exhibits the following 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 10% drug released;
2 hours: from about 0 to about 35% drug released;
3 hours: from about 10 to about 60% drug released;
4 hours: from about 20 to about 60% drug released;
6 hours: from about 40 to about 80% drug released; and
12 hours: from about 75 to about 100% drug released.
2. The pharmaceutical composition according to claim 1 , wherein the composition exhibits the following 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 5% drug released;
2 hours: from about 0 to about 25% drug released;
3 hours: from about 15 to about 30% drug released;
4 hours: from about 40 to about 50% drug released;
6 hours: from about 60 to about 75% drug released; and
12 hours: from about 90 to about 100% drug released.
3. The composition according to claim 1 , wherein the salicylate and/or salicylic acid is chosen from 5-amino salicylic acid and pharmaceutically acceptable salts of 5-amino salicylic acid.
4. The composition according to claim 1 , wherein the salicylate and/or salicylic acid is chosen from 5,5″-azo-bis salicylic acid and pharmaceutically acceptable salts thereof.
5. The composition according to claim 1 , wherein the polymer system comprises hydroxypropylmethylcellulose and ethylcellulose.
6. The composition according to claim 5 , wherein the at least one pharmaceutically acceptable excipient comprises hydroxypropylmethylcellulose.
7. The composition according to claim 1 , wherein the polymer system comprises at least two ammonio methacrylate co-polymers.
8. The composition according to claim 1 , wherein the polymer system comprises a functional coating and a sealant.
9. The composition according to claim 8 , wherein the functional coating comprises ethylcellulose and the sealant comprises hydroxypropylmethylcellulose.