Oral antimicrobial pharmaceutical compositions
View Patent ↗The present invention relates to oral pharmaceutical compositions with controlled and/or programmed release containing at least one active ingredient having antimicrobial and/or anti-infectious activity for the treatment of infections of the large intestine, in particular the colon.
1. A controlled release oral pharmaceutical composition comprising:
(1) a tablet core comprising a homogeneous structure comprising
(a) rifamycin SV,
(b) a hydrophilic substance,
(c) a lipophilic substance, and
(d) an amphiphilic substance; and
(2) a coating on said tablet core, said coating comprising a gastro-resistant substance,
wherein said controlled release oral pharmaceutical composition comprises from about 10% to about 90% by weight of rifamycin SV, and
wherein said controlled release oral pharmaceutical composition provides an in vitro release rate of said rifamycin SV in a buffer at pH 7.2 such that less than about 20% of said rifamycin SV is released after about 1 hour and more than about 70% of said rifamycin SV is released after about 8 hours.
2. A controlled release oral pharmaceutical composition according to claim 1 , wherein said controlled release oral pharmaceutical composition provides an in vitro release rate of said rifamycin SV in a buffer at pH 7.2 such that less than about 50% of said rifamycin SV is released after about 3 hours.
3. A controlled release oral pharmaceutical composition according to claim 1 , wherein said controlled release oral pharmaceutical composition is resistant to dissolution in an acidic environment.
4. A controlled release oral pharmaceutical composition according to claim 1 , wherein said controlled release oral pharmaceutical composition is resistant to dissolution for 2 hours in an environment at pH 1.
5. A controlled release oral pharmaceutical composition according to claim 1 , wherein said controlled release oral pharmaceutical composition is resistant to dissolution for 1 hour in an environment at pH 6.4.
6. A controlled release oral pharmaceutical composition according to claim 1 , wherein said controlled release oral pharmaceutical composition comprises from about 20% to about 60% by weight of rifamycin SV.
7. A controlled release oral pharmaceutical composition according to claim 1 , wherein said rifamycin SV is in the form of a sodium salt.
8. A controlled release oral pharmaceutical composition according to claim 1 , wherein said lipophilic substance is a lipophilic substance having a melting point less than about 90° C.
9. A controlled release oral pharmaceutical composition according to claim 1 , wherein said amphiphilic substance comprises lecithin.
10. A controlled release oral pharmaceutical composition according to claim 1 , wherein said hydrophilic substance is chosen from at least one of carboxyvinyl polymers, carboxyvinyl copolymers, hydroxyalkyl celluloses, alkyl celluloses, carboxyalkyl celluloses, polysaccharides, pectins, hyaluronic acid, glucuronic acid and glucosamines.
11. A controlled release oral pharmaceutical composition according to claim 10 , wherein said hydrophilic substance is chosen from at least one of carboxyvinyl polymers and carboxyvinyl copolymers.
12. A controlled release oral pharmaceutical composition according to claim 1 , wherein said gastro-resistant substance comprises at least one methacrylic acid polymer.
13. A method of treating an infection of the large intestine comprising administering to a patient in need thereof a therapeutically effective amount of a controlled release oral pharmaceutical composition comprising:
(1) a tablet core comprising a homogeneous structure comprising
(a) rifamycin SV,
(b) a hydrophilic substance,
(c) a lipophilic substance, and
(d) an amphiphilic substance; and
(2) a coating on said tablet core, said coating comprising a gastro-resistant substance,
wherein said controlled release oral pharmaceutical composition comprises from about 10% to about 90% by weight of rifamycin SV, and
wherein said controlled release oral pharmaceutical composition provides an in vitro release rate of said rifamycin SV in a buffer at pH 7.2 such that less than about 20% of said rifamycin SV is released after about 1 hour and more than about 70% of said rifamycin SV is released after about 8 hours.
14. A method of treating an infection of the large intestine according to claim 13 , wherein said controlled release oral pharmaceutical composition provides an in vitro release rate of said rifamycin SV in a buffer at pH 7.2 such that less than about 50% of said rifamycin SV is released after about 3 hours.
15. A method of treating an infection of the large intestine according to claim 13 , wherein said controlled release oral pharmaceutical composition is resistant to dissolution in an acidic environment.
16. A method of treating an infection of the large intestine according to claim 13 , wherein said controlled release oral pharmaceutical composition is resistant to dissolution for 2 hours in an environment at pH 1.
17. A method of treating an infection of the large intestine according to claim 13 , wherein said controlled release oral pharmaceutical composition is resistant to dissolution for 1 hour in an environment at pH 6.4.
18. A method of treating an infection of the large intestine according to claim 13 , wherein said controlled release oral pharmaceutical composition comprises from about 20% to about 60% by weight of rifamycin SV.
19. A method of treating an infection of the large intestine according to claim 13 , wherein said rifamycin SV is in the form of a sodium salt.
20. A method of treating an infection of the large intestine according to claim 13 , wherein said lipophilic substance is a lipophilic substance having a melting point less than about 90° C.
21. A method of treating an infection of the large intestine according to claim 13 , wherein said amphiphilic substance comprises lecithin.
22. A method of treating an infection of the large intestine according to claim 13 , wherein said hydrophilic substance is chosen from at least one of carboxyvinyl polymers, carboxyvinyl copolymers, hydroxyalkyl celluloses, alkyl celluloses, carboxyalkyl celluloses, polysaccharides, pectins, hyaluronic acid, glucuronic acid and glucosamines.
23. A method of treating an infection of the large intestine according to claim 21 , wherein said hydrophilic substance is chosen from at least one of carboxyvinyl polymers and carboxyvinyl copolymers.
24. A method of treating an infection of the large intestine according to claim 13 , wherein said gastro-resistant substance comprises at least one methacrylic acid polymer.
25. A method of treating an infection of the large intestine according to claim 13 , wherein the infection of the large intestine is infectious colitis, bacillary dysentery, pseudomembranous colitis, traveller's diarhoea, diverticular disease or diverticulitis.
26. A method of treating an infection of the large intestine according to claim 13 , wherein the infection of the large intestine is traveller's diarhoea.