Modified Release of Compositions Containing a Combination of Carbidopa, Levodopa and Entacapone
The invention relates to a multiparticulate modified release composition that, upon administration to a patient, delivers a combination of carbidopa, levodopa and entacapone in a bimodal, multimodal or continuous manner. The multiparticulate modified release composition comprises a first component and at least one subsequent component, the first component comprising a first population of active ingredient containing particles and the at least one subsequent component comprising a second population of active ingredient containing particles. The invention also relates to a solid oral dosage form containing such a multiparticulate modified release composition, and to a method for the treatment of Parkinson's disease.
1 . A pharmaceutical composition comprising a first component of active ingredient-containing particles and at least one subsequent component of active ingredient-containing particles, wherein at least one of said components comprises a combination of carbidopa, levodopa and entacapone and at least one of said components further comprises a modified release coating, a modified release matrix material, or both, such that the composition, following oral delivery to a subject, delivers the active ingredient in a bimodal or multimodal manner.
2 . The composition of claim 1 wherein each component comprises a combination of carbidopa, levodopa and entacapone-containing particles.
3 . The composition of claim 1 wherein the composition comprises a first component of a combination of carbidopa, levodopa and entacapone-containing particles and one subsequent component of a combination of carbidopa, levodopa and entacapone-containing particles.
4 . The composition of claim 3 , wherein the first component comprises an immediate release component and the second component comprises a modified release component.
5 . The composition of claim 1 , wherein the active ingredient-containing particles are erodable.
6 . The composition of claim 1 , wherein at least one of said components further comprises a modified-release coating.
7 . The composition of claim 1 , wherein at least one of said components further comprises a modified-release matrix material.
8 . The composition of claim 7 , wherein said modified release matrix material is selected from the group consisting of hydrophilic polymers, hydrophobic polymers, natural polymers, synthetic polymers and mixtures thereof
9 . The composition of claim 8 wherein the combination of carbidopa, levodopa and entacapone is released to the surrounding environment by erosion.
10 . The composition of claim 9 wherein said composition further comprises an enhancer.
11 . The composition of claim 8 comprising from about 0.1 mg to about 1 g each of carbidopa, levodopa and entacapone.
12 . A pharmaceutical composition comprising a first component of active ingredient-containing particles and at least one subsequent component of active ingredient-containing particles, wherein at least one of said components comprises a combination of carbidopa, levodopa and entacapone and at least one of said components further comprises a modified release coating, a modified release matrix material, or both, such that the composition, following oral delivery to a subject, delivers the active ingredient in a continuous manner.
13 . The composition of claim 12 wherein each component comprises a combination of carbidopa, levodopa and entacapone-containing particles.
14 . The composition of claim 12 wherein the composition comprises a first component of a combination of carbidopa, levodopa and entacapone-containing particles and one subsequent component of a combination of carbidopa, levodopa and entacapone-containing particles.
15 . The composition of claim 14 , wherein the first component comprises an immediate release component and the second component comprises a modified release component.
16 . The composition of claim 12 , wherein the active ingredient-containing particles are erodable.
17 . The composition of claim 12 , wherein at least one of said components further comprises a modified-release coating.
18 . The composition of claim 12 , wherein at least one of said components further comprises a modified-release matrix material.
19 . The composition of claim 18 , wherein said modified release matrix material is selected from the group consisting of hydrophilic polymers, hydrophobic polymers, natural polymers, synthetic polymers and mixtures thereof
20 . The composition of claim 19 wherein the combination of carbidopa, levodopa and entacapone is released to the surrounding environment by erosion.
21 . The composition of claim 20 wherein said composition further comprises an enhancer.
22 . The composition of claim 19 comprising from about 0.1 mg to about 1 g each of carbidopa, levodopa and entacapone.
23 . A dosage form comprising the composition of claim 1 .
24 . The dosage form of claim 23 comprising a blend of active ingredient-containing particles contained within a hard gelatin or soft gelatin capsule.
25 . The dosage form of claim 24 , wherein the active ingredient-containing particles are in the form of mini-tablets and the capsule contains a mixture of said mini-tablets.
26 . The dosage form of claim 25 in the form of tablet.
27 . The dosage form of claim 26 wherein the combination of carbidopa, levodopa and entacapone-containing particles are provided in a rapidly dissolving dosage form.
28 . The dosage form of claim 26 wherein the tablet is a fast-melt tablet.
29 . A dosage form comprising the composition of claim 12 .
30 . The dosage form of claim 29 comprising a blend of active ingredient-containing particles contained within a hard gelatin or soft gelatin capsule.
31 . The dosage form of claim 30 , wherein the active ingredient-containing particles are in the form of mini-tablets and the capsule contains a mixture of said mini-tablets.
32 . The dosage form of claim 31 in the form of tablet.
33 . The dosage form of claim 32 wherein the combination of carbidopa, levodopa and entacapone-containing particles are provided in a rapidly dissolving dosage form.
34 . The dosage form of claim 32 wherein the tablet is a fast-melt tablet.
35 . A method for treating Parkinson's disease comprising the step of administering a therapeutically effective amount of the composition of claim 1 .
36 . The method of claim 35 , wherein said Parkinson's disease is associated with a condition selected from the group consisting of resting tremor, rigidity, and bradykinetic movements.
37 . A method for treating Parkinson's disease comprising the step of administering a therapeutically effective amount of the composition of claim 12 .
38 . The method of claim 37 , wherein said Parkinson's disease is associated with a condition selected from the group consisting of resting tremor, rigidity, and bradykinetic movements.
39 . The composition of claim 1 wherein the modified-release coating comprises a pH-dependent polymer coating for releasing a pulse of the active ingredient in said patient following a time delay of about 6 to about 12 hours after administration of said composition to said patient.
40 . The composition according to claim 39 , wherein said polymer coating comprises methacrylate copolymers.
41 . The composition according to claim 39 , wherein the polymer coating comprises a mixture of methacrylate and ammonio methacrylate copolymers in a ratio sufficient to achieve a pulse of the active ingredient following a time delay of at least about 6 hours.
42 . The composition according to claim 41 , wherein the ratio of methacrylate to ammonio methacrylate copolymers is approximately 1:1.