SOLID ORAL DOSAGE FORM HAVING EXCELLENT DISSOLUTION PROPERTIES
The present disclosure relates to a solid oral dosage form comprising: (i) (S)-4-amino-5-chloro-N-[{4-[(1-hydroxyacetyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide, a pharmaceutically acceptable salt thereof, or a hydrate or solvate of the same; (ii) a disintegrating agent; and (iii) a water-soluble polymer binder. The present disclosure also relates to a medicinal composition, a therapeutic agent and/or a preventive agent, which comprise the medicine according to the present disclosure, for treating and/or preventing digestive diseases, digestive symptoms, psychoneurological diseases or urinary diseases, a preferable example thereof being a solid oral dosage form.
1 . A solid oral formulation comprising:
(i) (S)-4-amino-5-chloro-N-[{4-[(1-hydroxyacetyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof;
(ii) a disintegrant; and
(iii) a water-soluble macromolecular binding agent.
2 . The solid oral formulation of claim 1 , wherein the disintegrant comprises a cellulose-based disintegrant.
3 . The solid oral formulation of claim 1 or 2 , wherein the disintegrant comprises croscarmellose sodium or a combination of low substituted hydroxypropyl cellulose and pregelatinized starch.
4 . The solid oral formulation of any one of claims 1 to 3 , wherein the disintegrant comprises croscarmellose sodium.
5 . The solid oral formulation of any one of claims 1 to 4 , wherein the disintegrant comprises pregelatinized starch.
6 . The solid oral formulation of any one of claims 1 to 5 , wherein the disintegrant comprises a combination of croscarmellose sodium and pregelatinized starch.
7 . The solid oral formulation of any one of claims 1 to 6 , wherein the disintegrant comprises a combination of low substituted hydroxypropyl cellulose and pregelatinized starch.
8 . The solid oral formulation of any one of claims 1 to 7 , wherein the water soluble macromolecular binding agent is selected from the group consisting of polyvinylpyrrolidone, copolyvidone, hydroxypropyl cellulose, and polyvinyl alcohol.
9 . The solid oral formulation of any one of claims 1 to 8 , wherein the water soluble macromolecular binding agent is selected from the group consisting of hydroxypropyl cellulose and polyvinyl alcohol.
10 . The solid oral formulation of any one of claims 3 to 9 , wherein a portion of the pregelatinized starch that is soluble in cold water is 40% by weight or less.
11 . The solid oral formulation of any one of claims 3 to 9 , wherein a portion of the pregelatinized starch that is soluble in water is 40% by weight or less.
12 . The solid oral formulation of any one of claims 1 to 11 , wherein content of the disintegrant is 1 to 50% by weight with respect to 100% by weight of the formulation.
13 . The solid oral formulation of any one of claims 1 to 12 , wherein content of the disintegrant other than the pregelatinized starch is 1 to 10% by weight with respect to 100% by weight of the formulation.
14 . The solid oral formulation of any one of claims 1 to 13 , wherein content of the disintegrant other than the pregelatinized starch is 1 to 5% by weight with respect to 100% by weight of the formulation.
15 . The solid oral formulation of any one of claims 3 to 14 , wherein content of the pregelatinized starch is 15 to 30% by weight with respect to 100% by weight of the formulation.
16 . The solid oral formulation of any one of claims 1 to 15 , wherein content of the (S)-4-amino-5-chloro-N-[{4-[(1-hydroxyacetyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is 1 to 30% by weight with respect to 100% by weight of the formulation.
17 . The solid oral formulation of any one of claims 1 to 16 , wherein content of the (S)-4-amino-5-chloro-N-[{4-[(1-hydroxyacetyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is 5 to 20% by weight with respect to 100% by weight of the formulation.
18 . The solid oral formulation of any one of claims 1 to 17 , wherein content of the (S)-4-amino-5-chloro-N-[{4-[(1-hydroxyacetyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is 5 to 15% by weight with respect to 100% by weight of the formulation.
19 . The solid oral formulation of any one of claims 1 to 18 , further comprising an excipient.
20 . The solid oral formulation of claim 19 , wherein the excipient is a water soluble excipient.
21 . The solid oral formulation of claim 20 , wherein the water soluble excipient is mannitol.
22 . The solid oral formulation of any one of claims 1 to 21 , further comprising a lubricant.
23 . The solid oral formulation of claim 22 , wherein the lubricant is sodium stearyl fumarate.
24 . The solid oral formulation of any one of claims 1 to 23 , wherein the solid oral formulation is prepared by granulating a mixed powder comprising the (S)-4-amino-5-chloro-N-[{4-[(1-hydroxyacetyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, the disintegrant, and the water soluble excipient by using a solution with the water soluble macromolecular binding agent dissolved therein.
25 . The solid oral formulation of any one of claims 1 to 24 , wherein a film coating is applied with a coating agent.
26 . The solid oral formulation of claim 25 , wherein the coating agent is selected from the group consisting of hypromellose, polyvinylpyrrolidone, and hydroxypropyl cellulose.
27 . The solid oral formulation of claim 25 or 26 , wherein the coating agent further comprises a plasticizer.
28 . The solid oral formulation of claim 27 , wherein the plasticizer is selected from the group consisting of polyethylene glycol, propylene glycol, triacetin, triethyl citrate, glycerin, glycerin fatty acid ester, and polyethylene glycol.
29 . The solid oral formulation of any one of claims 25 to 28 , wherein the coating agent further comprises a coloring agent.
30 . The solid oral formulation of claim 29 , wherein the coloring agent is titanium oxide and/or yellow iron sesquioxide.
31 . The solid oral formulation of any one of claims 1 to 30 for treating and/or preventing a digestive system disease, a digestive system symptom, a neuropsychiatric disease, or a urinary system disease.
32 . The solid oral formulation of claim 31 , wherein the digestive system disease is an irritable bowel syndrome (IBS) with constipation or chronic constipation.
33 . A composition for reducing or preventing the delay of drug dissolution, comprising a disintegrant.
34 . The composition of claim 33 , wherein the delay of drug dissolution is reduced or prevented after storage.
35 . The composition of claim 33 or 34 , wherein the delay of drug dissolution is reduced or prevented after an accelerated test (40° C./75% RH).
36 . The composition of any one of claims 33 to 35 , wherein the drug is (S)-4-amino-5-chloro-N-[{4-[(1-hydroxyacetyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof.
37 . The composition of any one of claims 33 to 36 , wherein the disintegrant comprises a cellulose-based disintegrant.
38 . The composition of any one of claims 33 to 37 , wherein the disintegrant comprises croscarmellose sodium or a combination of low substituted hydroxypropyl cellulose and pregelatinized starch.
39 . The composition of any one of claims 33 to 38 , wherein the disintegrant comprises croscarmellose sodium.
40 . The composition of any one of claims 33 to 39 , wherein the disintegrant comprises pregelatinized starch.
41 . The composition of any one of claims 33 to 40 , wherein the disintegrant comprises a combination of croscarmellose sodium and pregelatinized starch.
42 . The composition of any one of claims 33 to 41 , wherein the disintegrant comprises a combination of low substituted hydroxypropyl cellulose and pregelatinized starch.
43 . The composition of any one of claims 33 to 42 , which is used further in combination with a water soluble macromolecular binding agent.
44 . The composition of claim 43 , wherein the water soluble macromolecular binding agent is selected from the group consisting of polyvinylpyrrolidone, copolyvidone, hydroxypropyl cellulose, and polyvinyl alcohol.
45 . The composition of any one of claims 38 to 44 , wherein a portion of the pregelatinized starch that is soluble in cold water is 40% by weight or less.
46 . The composition of any one of claims 38 to 44 , wherein a portion of the pregelatinized starch that is soluble in water is 40% by weight or less.