Uses of milrinone controlled-release formulation
AssigneeCardiora Pty Ltd.
InventorsDavid Martin Kaye, Guy Krippner, Geetha Thanga Mariappan
Life of this patent
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Abstract
The present invention relates to oral controlled-release formulations of 5-(pyridinyl)-2(1H)-pyridinone compounds and their use in the treatment of a subject with heart failure, a stage, class or manifestation of heart failure, or at risk of developing or exhibiting symptoms of heart failure. The formulations of the invention release the compounds in the range of between 0.1 μg/kg body weight/minute and 20 μg/kg body weight/minute.
Claims21
A method of treating a subject with heart failure, said method comprising administering to the subject an oral controlled-release formulation comprising:
- (i) a core comprising:
- (a) milrinone, or a pharmaceutically acceptable salt thereof;
- (b) hydroxypropylmethylcellulose having a viscosity of 80,000 to 120,000 cps:
- hydroxypropylmethylcellulose having a viscosity of about 50 cps;
- and at least one pharmaceutically acceptable excipient;
- (ii) a sustained release coating;
- and
- (iii) an enteric coating;
- wherein the hydroxypropylmethylcellulose (80,000 to 120,000 cps) and the hydroxypropylmethylcellulose (about 50 cps) are in a ratio of about 1.5:1 to 1:1.5, and the ratio of milrinone, or a pharmaceutically acceptable salt thereof, to total hydroxypropylmethylcellulose is about 1:3 to 1:5, and
- wherein the formulation exhibits zero order release of about 100% of milrinone, or a pharmaceutically acceptable salt thereof, over about 12 hours at pH 6.8.
A method of treating a subject with a stage, class or manifestation of heart failure, said method comprising administering to the subject an oral controlled-release formulation comprising:
- (i) a core comprising:
- (a) milrinone, or a pharmaceutically acceptable salt thereof;
- (b) hydroxypropylmethylcellulose having a viscosity of 80,000 to 120,000 cps:
- hydroxypropylmethylcellulose having a viscosity of about 50 cps;
- and at least one pharmaceutically acceptable excipient;
- (ii) a sustained release coating;
- and
- (iii) an enteric coating;
- wherein the hydroxypropylmethylcellulose (80,000 to 120,000 cps) and the hydroxypropylmethylcellulose (about 50 cps) are in a ratio of about 1.5:1 to 1:1.5, and the ratio of milrinone, or a pharmaceutically acceptable salt thereof, to total hydroxypropylmethylcellulose is about 1:3 to 1:5, and
- wherein the formulation exhibits zero order release of about 100% of milrinone, or a pharmaceutically acceptable salt thereof, over about 12 hours at pH 6.8.
A method of treatment that permits the release of milrinone, or a pharmaceutically acceptable salt thereof, effective to ameliorate symptoms of heart failure in a subject for a period of at least 6 hours, said method comprising administering to the subject an oral controlled-release formulation comprising:
- (i) a core comprising:
- (a) milrinone, or a pharmaceutically acceptable salt thereof;
- (b) hydroxypropylmethylcellulose having a viscosity of 80,000 to 120,000 cps:
- hydroxypropylmethylcellulose having a viscosity of about 50 cps;
- and at least one pharmaceutically acceptable excipient;
- (ii) a sustained release coating;
- and
- (iii) an enteric coating;
- wherein the hydroxypropylmethylcellulose (80,000 to 120,000 cps) and the hydroxypropylmethylcellulose (about 50 cps) are in a ratio of about 1.5:1 to 1:1.5, and the ratio of milrinone, or a pharmaceutically acceptable salt thereof, to total hydroxypropylmethylcellulose is about 1:3 to 1:5, and
- wherein the formulation exhibits zero order release of about 100% of milrinone, or a pharmaceutically acceptable salt thereof, over about 12 hours at pH 6.8.
Dependencies are inferred from the claim text.