Pharmaceutical Compositions Of Carvedilol Salts And Process For Preparation Thereof
The present invention relates provides pharmaceutical compositions comprising an amorphous carvedilol salt and one or more pharmaceutically acceptable excipients, wherein the amorphous carvedilol salt is formed in situ during the preparation of the pharmaceutical composition. The amorphous carvedilol salt is preferably an amorphous carvedilol phosphate salt. The pharmaceutical compositions can be prepared by providing one or more inert cores; contacting the core or cores with a solution or a dispersion comprising carvedilol, an acid component and optionally a binder, in a solvent; removing the solvent; and optionally coating the core or cores with an extended release composition. Preferred pharmaceutical compositions contain both immediate-release pellets and at least one population of extended-release pellet.
1 . A core comprising a first coating of an amorphous carvedilol salt, wherein the amorphous carvedilol salt is formed in situ during coating of the core.
2 . A pharmaceutical composition comprising a plurality of cores of claim 1 and one or more pharmaceutically acceptable excipients.
3 . The pharmaceutical composition of claim 2 , wherein the carvedilol salt is carvedilol phosphate.
4 . The pharmaceutical composition of claim 3 , in capsule form.
5 . The pharmaceutical composition of claim 4 , wherein the capsule contains 10, 20, 40 or 80 mg total carvedilol phosphate.
6 . The pharmaceutical composition of claim 5 , wherein at least a portion of the cores comprise a second coating on the first coating comprising an extended-release polymer.
7 . The pharmaceutical composition of claim 6 , wherein the extended-release polymer is an ethyl acrylate-methyl methacrylate co-polymer.
8 . The pharmaceutical composition of claim 7 , wherein the second coating comprises a pore-forming agent.
9 . The pharmaceutical composition of claim 8 , wherein the pore-forming agent is amorphous silica.
10 . The pharmaceutical composition of claim 6 , wherein at least a portion of the cores lack an extended-release coating.
11 . The pharmaceutical composition of claim 10 , wherein the portion of the cores comprising a second coating consists of cores comprising different amounts of extended-release polymer and/or pore forming agent.
12 . A process for the preparation of a core comprising a first coating of an amorphous carvedilol salt, wherein the carvedilol salt is formed in situ during application of the coating, comprising:
a. providing one or more inert cores;
b. contacting the inert cores with a solution or a dispersion comprising carvedilol, an acid component and optionally a binder, in a solvent; and
c. removing the solvent.
13 . The process of claim 12 , wherein the acid component is phosphoric acid.
14 . The process of claim 13 , further comprising coating at least a portion of the cores with a second coating comprising an extended-release polymer.
15 . The process of claim 14 , wherein the second coating comprises a plasticizer and a pore-forming agent.
16 . The process of claim 15 , wherein the extended-release polymer is an ethyl acrylate-methyl methacrylate co-polymer and the pore-forming agent is amorphous silica.
17 . The process of claim 16 , further comprising filling the cores into a gelatin capsule.
18 . A core made by the process of claim 12 .
19 . A method of treating heart failure comprising administering the pharmaceutical composition of claim 10 to a patient in need thereof.
20 . A process for preparing an extended-release capsule comprising amorphous carvedilol phosphate, comprising:
a. providing one or more inert cores;
b. spraying a dispersion of carvedilol base, phosphoric acid, and a binder in a solvent over the cores;
c. removing the solvent such that amorphous carvedilol phosphate is formed;
d. coating the drug-coated cores with a dispersion comprising an extended-release polymer, plasticizer, and a pore-forming agent; and
e. filling the cores into a gelatin capsules.