Process for producing fenofibrate tablets
The invention provides processes using suspensions to produce fenofibrate compositions. The resulting fenofibrate compositions can be made in the form of a capsule.
1. A process for producing a capsule comprising fenofibrate, wherein the process comprises:
(i) preparing an aqueous suspension comprising at least one hydrophilic polymer and fenofibrate particles in micronized form having a particle size of less than 20 μm, wherein one hydrophilic polymer is a polyvinylpyrrolidone with a molecular weight between 20,000 and 100,000;
(ii) spraying the suspension onto inert carriers to form granulates; and
(iii) enclosing the granulates inside the capsule.
2. The process of claim 1 , wherein step (i) of preparing the suspension comprises (a) preparing a solution comprising at least one hydrophilic polymer and (b) adding the fenofibrate to the solution to produce the suspension.
3. The process of claim 1 , wherein step (i) of preparing the suspension comprises (a) preparing a solution comprising at least one hydrophilic polymer by dissolving the hydrophilic polymer and (b) adding the fenofibrate to the solution to produce the suspension.
4. The process of claim 1 , wherein step (i) of preparing the suspension comprises (a) adding the fenofibrate to a solution to form the suspension, and (b) dissolving at least one hydrophilic polymer in the suspension.
5. The process of claim 1 , wherein the suspension further comprises at least one surfactant.
6. The process of claim 1 , wherein the suspension comprises fenofibrate and hydrophilic polymer in a weight ratio of fenofibrate/hydrophilic polymer between 1/10 and 4/1.
7. The process of claim 1 , wherein the suspension comprises fenofibrate and hydrophilic polymer in a weight ratio of fenofibrate/hydrophilic polymer between 1/2 and 2/1.
8. The process of claim 1 , wherein the fenofibrate has a particle size less than 10 μm.
9. The process of claim 1 , wherein the suspension comprises fenofibrate in an amount from 1 to 40% by weight.
10. The process of claim 9 , wherein the suspension comprises fenofibrate in an amount from 10 to 25% by weight.
11. The process of claim 1 , wherein the suspension comprises the hydrophilic polymer in an amount from 5 to 40% by weight.
12. The process of claim 11 , wherein the suspension comprises the hydrophilic polymer in an amount from 10 to 25% by weight.
13. The process of claim 1 , wherein the at least one hydrophilic polymer further comprises; a poly(vinyl alcohol), a hydroxypropylcellulose, a hydroxy-methylcellulose, a hydroxypropylmethylcellulose, a gelatin, or a mixture of two or more thereof.
14. The process of claim 5 , wherein the suspension comprises the surfactant in an amount of up to 10% by weight.
15. The process of claim 14 , wherein the suspension comprises the surfactant in an amount of up to 5% by weight.
16. The process of claim 5 , wherein the suspension comprises surfactant and hydrophilic polymer in a weight ratio of surfactant/hydrophilic polymer between 1/500 and 1/10.
17. The process of claim 5 , wherein the suspension comprises surfactant and hydrophilic polymer in a weight ratio of surfactant/hydrophilic polymer between 1/100 and 5/100.
18. The process of claim 5 , wherein the surfactant is sodium lauryl sulfate, monooleate, monolaurate, monopalmitate, monostearate or another ester of polyoxyethylene sorbitane, sodium dioctylsulfosuccinate, lecithin, stearylic alcohol, cetostearylic alcohol, cholesterol, polyoxyethylene ricin oil, polyoxyethylene fatty acid glycerides, poloxamer, or a mixture of two or more thereof.
19. The process of claim 18 , wherein the surfactant is sodium lauryl sulfate.
20. The process of claim 1 , wherein the inert carriers are inert hydrosoluble carriers.
21. The process of claim 1 , which further comprises, between steps (ii) an (iii), mixing the granulates with at least one pharmaceutical excipient.
22. The process of claim 21 , wherein the pharmaceutical excipient is selected from the group consisting of at least one binder, at least one filler, at least one pigment, at least one disintegrating agent, at least one lubricant, at least one wetting agent, at least one buffer, and a mixture of two or more thereof.
23. The process of claim 21 , wherein the pharmaceutical excipient is selected from the group consisting of microcrystalline cellulose, lactose, starch, colloidal silica, talc, glycerol esters, sodium stearyl fumarate, titanium dioxide, magnesium stearate, stearic acid, cross-linked polyvinyl pyrrolidone, carboxymethyl starch, hydroxypropylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose, gelatin, and a mixture of two or more thereof.
24. The process of claim 1 , wherein the capsule comprises from 5 to 50% by weight fenofibrate, from 10 to 75% by weight carrier, and from 20 to 60% by weight hydrophilic polymer.
25. The process of claim 1 , wherein the capsule comprises from 20 to 45% by weight fenofibrate, from 20 to 50% by weight carrier, and from 25 to 45% by weight hydrophilic polymer.
26. The process of claim 24 , wherein the capsule further comprises up to 10% by weight surfactant.
27. The process of claim 26 , wherein the capsule comprises from 0.1 to 3% by weight surfactant.
28. A process for producing a capsule comprising fenofibrate, wherein the process comprises:
(i) preparing an aqueous suspension comprising at least one surfactant, at least one hydrophilic polymer, and fenofibrate particles in micronized form having a particle size of less than 20 μm, wherein one hydrophilic polymer is a poly vinylpyrrolidone with a molecular weight between 20,000 and 100,000;
(ii) spraying the aqueous suspension onto inert carriers to form granulates; and
(iii) enclosing the granulates inside a capsule.
29. The process of claim 28 , wherein step (i) of preparing the aqueous suspension comprises (a) preparing an aqueous solution comprising at least one surfactant and at least one hydrophilic polymer and (b) adding the fenofibrate to the aqueous solution to produce the aqueous suspension.
30. The process of claim 28 , wherein step (i) of preparing the aqueous suspension comprises (a) preparing an aqueous solution comprising at least one surfactant and at least one hydrophilic polymer by dissolving said surfactant and hydrophilic polymer and (b) adding the fenofibrate to the aqueous solution to produce the aqueous suspension.
31. The process of claim 28 , wherein step (i) of preparing the aqueous suspension comprises (a) dissolving at least one surfactant in an aqueous solution, (b) dissolving at least one hydrophilic polymer in an aqueous solution, and (c) adding the fenofibrate to the aqueous solution to produce the aqueous suspension.
32. The process of claim 28 , wherein step (i) of preparing an aqueous suspension comprises (a) dissolving at least one hydrophilic polymer in an aqueous solution, (b) dissolving at least one surfactant in an aqueous solution, and (c) adding the micronized fenofibrate to the aqueous solution to form the aqueous suspension.
33. The process of claim 28 , wherein step (i) of preparing the aqueous suspension comprises (a) dissolving at least one surfactant in an aqueous solution, (b) adding the fenofibrate to the aqueous solution to form the aqueous suspension, and (c) dissolving at least one hydrophilic polymer in the aqueous suspension.
34. The process of claim 28 , wherein step (i) of preparing the aqueous suspension comprises (a) dissolving at least one hydrophilic polymer in an aqueous solution, (b) adding the fenofibrate to the aqueous solution to form the aqueous suspension, and (c) dissolving at least one surfactant in the aqueous suspension.
35. The process of claim 28 , wherein the suspension comprises fenofibrate and hydrophilic polymer in a weight ratio of fenofibrate/hydrophilic polymer between 1/10 and 4/1.
36. The process of claim 28 , wherein the suspension comprises fenofibrate and hydrophilic polymer in a weight ratio of fenofibrate/hydrophilic polymer between 1/2 and 2/1.
37. The process of claim 28 , wherein the fenofibrate has a particle size less than 10 μm.
38. The process of claim 28 , wherein the suspension comprises fenofibrate in an amount from 1 to 40% by weight.
39. The process of claim 38 , wherein the suspension comprises fenofibrate in an amount from 10 to 25% by weight.
40. The process of claim 28 , wherein the suspension comprises the hydrophilic polymer in an amount from 5 to 40% by weight.
41. The process of claim 40 , wherein the suspension comprises the hydrophilic polymer in an amount from 10 to 25% by weight.
42. The process of claim 28 , wherein the at least one hydrophilic polymer further comprises; a poly(vinyl alcohol), a hydroxypropylcellulose, a hydroxy-methylcellulose, a hydroxypropylmethylcellulose, a gelatin, or a mixture of two or more thereof.
43. The process of claim 28 , wherein the suspension comprises the surfactant in an amount of up to 10% by weight.
44. The process of claim 43 , wherein the suspension comprises the surfactant in an amount of up to 5% by weight.
45. The process of claim 28 , wherein the suspension comprises surfactant and hydrophilic polymer in a weight ratio of surfactant/hydrophilic polymer between 1/500 and 1/10.
46. The process of claim 28 , wherein the suspension comprises surfactant and hydrophilic polymer in a weight ratio of surfactant/hydrophilic polymer between 1/100 and 5/100.
47. The process of claim 28 , wherein the surfactant is sodium lauryl sulfate, monooleate, monolaurate, monopalmitate, monostearate or another ester of polyoxyethylene sorbitane, sodium dioctylsulfosuccinate, lecithin, stearylic alcohol, cetostearylic alcohol, cholesterol, polyoxyethylene ricin oil, polyoxyethylene fatty acid glycerides, poloxamer, or a mixture of two or more thereof.
48. The process of claim 47 , wherein the surfactant is sodium lauryl sulfate.
49. The process of claim 28 , wherein the inert carriers are inert hydrosoluble carriers.
50. The process of claim 28 , which further comprises, between steps (ii) and (iii), mixing the granulates with at least one pharmaceutical excipient.
51. The process of claim 50 , wherein the pharmaceutical excipient is selected from the group consisting of at least one binder, at least one filler, at least one pigment, at least one disintegrating agent, at least one lubricant, at least one wetting agent, at least one buffer, and a mixture of two or more thereof.
52. The process of claim 50 , wherein the pharmaceutical excipient is selected from the group consisting of microcrystalline cellulose, lactose, starch, colloidal silica, talc, glycerol esters, sodium stearyl fumarate, titanium dioxide, magnesium stearate, stearic acid, cross-linked polyvinyl pyrrolidone, carboxymethyl starch, hydroxypropylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose, gelatin, and a mixture of two or more thereof.
53. The process of claim 28 , wherein the capsule comprises from 5 to 50% by weight of fenofibrate, from 10 to 75% by weight of carrier, from 20 to 60% by weight of hydrophilic polymer, and up to 10% by weight of surfactant.
54. The process of claim 53 , wherein the capsule comprises from 20 to 45% by weight of fenofibrate, from 20 to 50% by weight of carrier, from 25 to 45% by weight of hydrophilic polymer, and from 0.1 to 3% by weight of surfactant.
55. A process for producing a capsule comprising fenofibrate, wherein the process comprises:
(i) preparing an aqueous suspension comprising at least one surfactant, at least one hydrophilic polymer, and fenofibrate particles in micronized form having a particle size of less than 20 μm, wherein one hydrophilic polymer is a polyvinylpyrrolidone with a molecular weight between 20,000 and 100,000; by (a) preparing an aqueous solution comprising at least one surfactant and at least one hydrophilic polymer by dissolving the surfactant and the hydrophilic polymer and (b) adding the fenofibrate particles to the solution to produce the aqueous suspension;
(ii) spraying the aqueous suspension onto inert carriers to form granulates and
(iii) enclosing the granulates inside a capsule.
56. The process of claim 55 , wherein the suspension comprises fenofibrate and hydrophilic polymer in a weight ratio of fenofibrate/hydrophilic polymer between 1/10 and 4/1.
57. The process of claim 55 , wherein the suspension comprises fenofibrate and hydrophilic polymer in a weight ratio of fenofibrate/hydrophilic polymer between 1/2 and 2/1.
58. The process of claim 55 , wherein the fenofibrate has a particle size less than 10 μm.
59. The process of claim 55 , wherein the suspension comprises fenofibrate in an amount from 1 to 40% by weight.
60. The process of claim 59 , wherein the suspension comprises fenofibrate in an amount from 10 to 25% by weight.
61. The process of claim 55 , wherein the suspension comprises the hydrophilic polymer in an amount from 5 to 40% by weight.
62. The process of claim 61 , wherein the suspension comprises the hydrophilic polymer in an amount from 10 to 25% by weight.
63. The process of claim 55 , wherein the at least one hydrophilic polymer further comprises; and a poly(vinyl alcohol), a hydroxypropylcellulose, a hydroxy-methylcellulose, a hydroxypropylmethylcellulose, a gelatin, or a mixture of two or more thereof.
64. The process of claim 55 , wherein the suspension comprises the surfactant in an amount of up to 10% by weight.
65. The process of claim 64 , wherein the suspension comprises the surfactant in an amount of up to 5% by weight.
66. The process of claim 55 , wherein the suspension comprises surfactant and hydrophilic polymer in a weight ratio of surfactant/hydrophilic polymer between 1/500 and 1/10.
67. The process of claim 55 , wherein the suspension comprises surfactant and hydrophilic polymer in a weight ratio of surfactant/hydrophilic polymer between 1/100 and 5/100.
68. The process of claim 55 , wherein the surfactant is sodium lauryl sulfate, monooleate, monolaurate, monopalmitate, monostearate or another ester of polyoxyethylene sorbitane, sodium dioctylsulfosuccinate, lecithin, stearylic alcohol, cetostearylic alcohol, cholesterol, polyoxyethylene ricin oil, polyoxyethylene fatty acid glycerides, poloxamer, or a mixture of two or more thereof.
69. The process of claim 68 , wherein the surfactant is sodium lauryl sulfate.
70. The process of claim 55 , wherein the inert carriers are inert hydrosoluble carriers.
71. The process of claim 55 , which further comprises, between steps (ii) and (iii), mixing the granulates with at least one pharmaceutical excipient.
72. The process of claim 71 , wherein said pharmaceutical excipient is selected from the group consisting of at least one binder, at least one filler, at least one pigment, at least one disintegrating agent, at least one lubricant, at least one wetting agent, at least one buffer, and a mixture of two or more thereof.
73. The process of claim 71 , wherein said pharmaceutical excipient is selected from the group consisting of microcrystalline cellulose, lactose, starch, colloidal silica, talc, glycerol esters, sodium stearyl fumarate, titanium dioxide, magnesium stearate, stearic acid, cross-linked polyvinyl pyrrolidone, carboxymethyl starch, hydroxypropylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose, gelatin, and a mixture of two or more thereof.
74. The process of claim 55 , wherein the capsule comprises from 5 to 50% by weight of fenofibrate, from 10 to 75% by weight of carrier, from 20 to 60% by weight of hydrophilic polymer, and up to 10% by weight of surfactant.
75. The process of claim 55 , wherein the capsule comprises from 20 to 45% by weight of fenofibrate, from 20 to 50% by weight of carrier, from 25 to 45% by weight of hydrophilic polymer, and from 0.1 to 3% by weight of surfactant.