Composition comprising a benzimidazole and process for its manufacture
The invention provides new benzimidazole compositions, comprising: (a) a core containing said benzimidazole active ingredient; (b) an intermediate layer; and (c) an enteric layer; said core being substantially free of binder. The invention also provides a process for manufacturing the composition of the invention.
1 . A composition comprising a benzimidazole active ingredient, said composition comprising:
(a) a core containing said benzimidazole active ingredient;
(b) an intermediate layer; and
(c) an enteric layer;
said core being substantially free of binder.
2 . A composition comprising a benzimidazole active ingredient, said composition comprising:
(a) a core containing said benzimidazole active ingredient;
(b) an intermediate layer; and
(c) an enteric layer;
said core being substantially free of PVP and of HPMC.
3 . A composition comprising a benzimidazole active ingredient, said composition comprising:
(a) a core containing said benzimidazole active ingredient, where said core consists essentially of, by weight:
about 10 to about 80 parts of said benzimidazole active ingredient,
about 20 to about 85 parts of a first, water-soluble, diluent,
about 0 to about 80 parts of a second, water-insoluble, diluent,
about 10 to about 40 parts of a disintegrant; and
0 to about 5 parts of a lubricant;
(b) an intermediate layer; and
(c) an enteric layer.
4 . The composition of claim 3 , in which said core consists essentially of, by weight:
(a) a core containing said benzimidazole active ingredient, where said core consists essentially of, by weight:
about 15 to about 60 parts of said benzimidazole active ingredient,
about 40 to about 75 parts of a first, water-soluble, diluent,
about 0 to about 40 parts of a second, water-insoluble, diluent,
about 15 to about 30 parts of a disintegrant; and
about 0.5 to about 5 parts of a lubricant;
(b) an intermediate layer; and
(c) an enteric layer.
5 . The composition of claim 3 , comprising a first diluent and a second diluent and in which the weight ratio first diluent to second diluent is from about 1.5:1 to 1:1.5.
6 . The composition of claim 3 , in which said first, water-soluble, diluent is lactose and said second, water-insoluble, diluent if present is cellulose acetate.
7 . The composition of claim 3 , in which said disintegrant is cross-linked polyvinylpyrrolidone.
8 . The composition of claim 3 , in which said lubricant is selected from the group consisting of sodium stearylfumarate, magnesium stearate, talc, glyceryl behenate and their mixtures.
9 . A composition comprising a benzimidazole active ingredient, said composition comprising:
(a) a core containing said benzimidazole active ingredient, where said core consists essentially of, by weight:
about 15 to about 60 parts of said benzimidazole active ingredient,
about 40 to about 75 parts of lactose,
about 15 to about 30 parts of a disintegrant, and
about 0.5 to about 5 parts of a lubricant;
(b) an intermediate layer; and
(c) an enteric layer.
10 . The composition of claim 9 , in which said disintegrant is cross-linked polyvinylpyrrolidone.
11 . The composition of claim 9 , in which said lubricant is selected from the group consisting of sodium stearylfumarate, magnesium stearate, talc, glyceryl behenate and their mixtures.
12 . The composition of claim 3 , in which said core is substantially free of PVP and of HPMC.
13 . The composition of claim 9 , in which said core is substantially free of PVP and of HPMC.
14 . The composition of claim 1 , in which said benzimidazole active ingredient is selected from the group consisting of omeprazole, esomeprazole, pantoprazole, lansoprazole, leminoprazole, pariprazole, rabeprazole, timoprazole, aripiprazole and diapiprazole.
15 . The composition of claim 2 , in which said benzimidazole active ingredient is selected from the group consisting of omeprazole, esomeprazole, pantoprazole, lansoprazole, leminoprazole, pariprazole, rabeprazole, timoprazole, aripiprazole and diapiprazole.
16 . The composition of claim 3 , in which said benzimidazole active ingredient is selected from the group consisting of omeprazole, esomeprazole, pantoprazole, lansoprazole, leminoprazole, pariprazole, rabeprazole, timoprazole, aripiprazole and diapiprazole.
17 . The composition of claim 9 , in which said benzimidazole active ingredient is selected from the group consisting of omeprazole, esomeprazole, pantoprazole, lansoprazole, leminoprazole, pariprazole, rabeprazole, timoprazole, aripiprazole and diapiprazole.
18 . The composition of claim 1 , in which said benzimidazole active ingredient is not in the form of an alkaline salt, and said composition being exempt of alkaline-reacting compounds.
19 . The composition of claim 2 , in which said benzimidazole active ingredient is not in the form of an alkaline salt, and said composition being exempt of alkaline-reacting compounds.
20 . The composition of claim 3 , in which said benzimidazole active ingredient is not in the form of an alkaline salt, and said composition being exempt of alkaline-reacting compounds.
21 . The composition of claim 9 , in which said benzimidazole active ingredient is not in the form of an alkaline salt, and said composition being exempt of alkaline-reacting compounds.
22 . A composition comprising a benzimidazole active ingredient not being in the form of an alkaline salt, said composition being exempt of alkaline-reacting compounds, said composition comprising:
(a) a core containing said benzimidazole active ingredient, where said core consists essentially of, by weight:
about 15 to about 60 parts of said benzimidazole active ingredient,
about 40 to about 75 parts of a first, water-soluble, diluent,
about 0 to about 40 parts of a second, water-insoluble, diluent,
about 15 to about 30 parts of a disintegrant, and
about 0.5 to about 5 parts of a lubricant;
(b) an intermediate layer; and
(c) an enteric layer.
23 . The composition of claim 22 , in which said benzimidazole active ingredient is selected from the group consisting of omeprazole, esomeprazole, pantoprazole, lansoprazole, leminoprazole, pariprazole, rabeprazole, timoprazole, aripiprazole and diapiprazole.
24 . A composition comprising omeprazole, said composition comprising:
(a) a core containing said omeprazole, where said core consists essentially of, by weight:
about 15 to about 60 parts of said omeprazole,
about 40 to about 75 parts of lactose,
about 15 to about 30 parts of a disintegrant, and
about 0.5 to about 5 parts of a lubricant;
(b) an intermediate layer; and
(c) an enteric layer.
25 . A composition comprising esomeprazole, said composition comprising:
(a) a core containing said esomeprazole, where said core consists essentially of, by weight:
about 15 to about 60 parts of said esomeprazole,
about 40 to about 75 parts of lactose,
about 15 to about 30 parts of a disintegrant, and
about 0.5 to about 5 parts of a lubricant;
(b) an intermediate layer; and
(c) an enteric layer.
26 . A composition comprising pantoprazole, said composition comprising:
(a) a core containing said pantoprazole, where said core consists essentially of, by weight:
about 15 to about 60 parts of said pantoprazole,
about 40 to about 75 parts of lactose,
about 15 to about 30 parts of a disintegrant, and
about 0.5 to about 5 parts of a lubricant;
(b) an intermediate layer; and
(c) an enteric layer.
27 . A composition comprising lansoprazole, said composition comprising:
(a) a core containing said lansoprazole, where said core consists essentially of, by weight:
about 15 to about 60 parts of said lansoprazole,
about 40 to about 75 parts of lactose,
about 15 to about 30 parts of a disintegrant, and
about 0.5 to about 5 parts of a lubricant;
(b) an intermediate layer; and
(c) an enteric layer.
28 . A composition comprising rabeprazole, said composition comprising:
(a) a core containing said rabeprazole, where said core consists essentially of, by weight:
about 15 to about 60 parts of said rabeprazole,
about 40 to about 75 parts of lactose,
about 15 to about 30 parts of a disintegrant, and
about 0.5 to about 5 parts of a lubricant;
(b) an intermediate layer; and
(c) an enteric layer.
29 . The composition according to claim 1 , provided either in a single tablet form or in the form of micro-tablets enclosed inside a capsule.
30 . The composition according to claim 2 , provided either in a single tablet form or in the form of micro-tablets enclosed inside a capsule.
31 . The composition according to claim 3 , provided either in a single tablet form or in the form of micro-tablets enclosed inside a capsule.
32 . The composition according to claim 9 , provided either in a single tablet form or in the form of micro-tablets enclosed inside a capsule.
33 . The composition according to claim 22 , provided either in a single tablet form or in the form of micro-tablets enclosed inside a capsule.
34 . The composition according to claim 24 , provided either in a single tablet form or in the form of micro-tablets enclosed inside a capsule.
35 . The composition according to claim 25 , provided either in a single tablet form or in the form of micro-tablets enclosed inside a capsule.
36 . The composition according to claim 26 , provided either in a single tablet form or in the form of micro-tablets enclosed inside a capsule.
37 . The composition according to claim 27 , provided either in a single tablet form or in the form of micro-tablets enclosed inside a capsule.
38 . The composition according to claim 28 , provided either in a single tablet form or in the form of micro-tablets enclosed inside a capsule.
39 . A process for preparing a composition comprising a benzimidazole active ingredient, said composition comprising:
(a) a core containing said benzimidazole active ingredient, where said core consists essentially of, by weight:
about 10 to about 80 parts of said benzimidazole active ingredient,
about 20 to about 85 parts of a first, water-soluble, diluent,
about 0 to about 80 parts of a second, water-insoluble, diluent,
about 10 to about 40 parts of a disintegrant; and
0 to about 5 parts of a lubricant;
(b) an intermediate layer; and
(c) an enteric layer;
said process comprising the steps of
(i) granulating said active ingredient with said diluents, said disintegrant and said lubricant if any;
(ii) compressing the product of step (i) to form a tablet core containing an active ingredient;
(iii) coating said core with said intermediate layer; and
(iv) coating a product from step (iii) with said enteric layer.
40 . The process according to claim 39 , in which step (i) is wet granulation.
41 . The process according to claim 39 , in which step (i) comprises the following sub-steps:
(a) dry mixing said benzimidazole active ingredient, said first diluent and optionally said second diluent and optionally part of said disintegrant;
(b) granulating the product of sub-step (a) with water;
(c) drying the granulates of sub-step (b);
(d) dry mixing the dried granulates of sub-step (c) with said disintegrant or the remainder thereof and said lubricant, if any.
42 . A process for preparing a composition comprising a benzimidazole active ingredient, said composition comprising:
(a) a core containing said benzimidazole active ingredient, where said core consists essentially of, by weight:
about 15 to about 60 parts of said benzimidazole active ingredient,
about 40 to about 75 parts of lactose,
about 15 to about 30 parts of a disintegrant, and
about 0.5 to about 5 parts of a lubricant;
(b) an intermediate layer; and
(c) an enteric layer;
said process comprising the steps of
(i) granulating said active ingredient with said lactose, said cellulose acetate, said disintegrant and said lubricant;
(ii) compressing the product of step (i) to form a tablet core containing an active ingredient;
(iii) coating said core with said intermediate layer; and
(iv) coating a product from step (iii) with said enteric layer.
43 . The process according to claim 42 , in which step (i) is wet granulation.
44 . The process according to claim 42 , in which step (i) comprises the following sub-steps:
(a) dry mixing said benzimidazole active ingredient, said lactose and optionally part of said disintegrant;
(b) granulating the product of sub-step (a) with water;
(c) drying the granulates of sub-step (b);
(d) dry mixing the dried granulates of sub-step (c) with said disintegrant or the remainder thereof and said lubricant.