Pharmaceutical compositions having good dissolution properties

• US 5,506,248 A
• Filed: 05/22/1995
• Issued: 04/09/1996
• Est. Priority Date: 08/02/1993
• Status: Expired due to Fees

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Nikfar, Faranak, Jerzewski, Robert L., Serajuddin, Abu T. M., Jain, Nemichand B.
• Primary Examiner(s): HENLEY III, RAYMOND J
• Application Number:
  US08/445,623
• Time in Patent Office: 323 Days
• Field of Search: 514/374
• US Class Current: 514/374
• CPC Class Codes: A61K 31/42 Oxazoles
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/485 Inorganic compounds

Abstract

An ifetroban composition is provided which has good dissolution properties even on aging, when dispersed in water has a pH of at least 7 and includes a salt of ifetroban, one or more basifying agents, such as magnesium oxide or calcium carbonate, and where in tablet form includes one or more fillers such as mannitol and/or microcrystalline cellulose, one or more disintegrating agents such as crospovidone, one or more lubricants such as magnesium stearate, optionally one or more glidants such as colloidal silicon dioxide, one or more binders such as pregelatinized starch (dry binder) or polyvinyl-pyrrolidone (wet binder) and optionally a film coating containing a film former such as hydroxypropyl cellulose and a plasticizer such as 1,2,3-propanetriol triacetate.

Claims

1. A pharmaceutical composition which has good dissolution properties even after aging, comprising a medicament which is a salt of ifetroban and one or more basifying agents to impart a desired pH of at least 7 to an aqueous dispersion of said composition.

2. The pharmaceutical composition as defined in claim 1 wherein the ifetroban salt is the sodium salt, potassium salt, calcium salt or magnesium salt.

3. The pharmaceutical composition as defined in claim 1 wherein said ifetroban salt is present in an amount within the range of from about 1 to about 60% by weight of the composition.

4. The pharmaceutical composition as defined in claim 1 wherein the medicament is ifetroban sodium salt.

5. The pharmaceutical composition as defined in claim 1 wherein the basifying agent is present in an amount within the range of from about 0.2 to about 75% by weight of the composition.

6. The pharmaceutical composition as defined in claim 1 wherein the basifying agent is an alkali metal hydroxide or salt, an alkaline earth metal hydroxide or salt or ammonium hydroxide.

7. The pharmaceutical composition as defined in claim 6 wherein the basifying agent is MgO, Mg(OH)₂, Ca(OH)₂, NaOH, KOH, LiOH, NH₄ OH, Al(OH)₃, magaldrate, CaCO₃ or NaHCO₃.

8. The pharmaceutical composition as defined in claim 1 in the form of a tablet further including a filler present in an amount within the range of from about 5 to about 95% by weight.

9. The pharmaceutical composition as defined in claim 8 wherein the filler is lactose, sugar, corn starch, modified corn starch, mannitol, dicalcium phosphate dihydrate, maltodextrin, calcium sulfate, sorbitol, wood cellulose, microcrystalline cellulose, calcium carbonate or mixtures thereof.

10. The pharmaceutical composition as defined in claim 1 wherein a binder is optionally present in an amount within the range of from about 1 to about 35% by weight.

11. The pharmaceutical composition as defined in claim 10 wherein the binder is microcrystalline cellulose, povidone, corn starch, modified corn starch, hydroxypropyl-methylcellulose, sugars, gum acacia, carnauba wax, paraffin, spermaceti, polyethylenes or microcrystalline wax.

12. The pharmaceutical composition as defined in claim 8 further including a disintegrant present in an amount within the range of from about 0.5 to about 10% by weight.

13. The pharmaceutical composition as defined in claim 12 wherein the disintegrant is croscarmellose sodium, crospovidone, sodium starch glycolate, pregelatinized starch, corn starch or microcrystalline cellulose.

14. The pharmaceutical composition as defined in claim 1 in the form of a tablet having the following formulation:

from about 5 to about 70% by weight ifetroban sodium salt;

from about 1 to about 10% by weight of basifying agent which is magnesium oxide, calcium carbonate, sodium bicarbonate or aluminum hydroxide, to impart a pH of at least 7;

further including from about 10 to about 90% by weight of a filler which is mannitol, microcrystalline cellulose, lactose, and/or dicalcium phosphate dihydrate;

optionally including from about 2 to about 20% by weight microcrystalline cellulose, starch and/or polyvinylpyrrolidone as a binder;

optionally including from about 2 to about 8% by weight of croscarmellose sodium or crospovidone as a disintegrant; and

further including from about 0.5 to about 2% by weight magnesium stearate as a lubricant.

15. The pharmaceutical composition as defined in claim 1 having a pH in water of from 8 to 11.

16. The pharmaceutical composition as defined in claim 1 in the form of a tablet or capsule.

17. The pharmaceutical composition as defined in claim 1 in the form of a coated tablet which includes a film coating.

18. The pharmaceutical composition as defined in claim 1 wherein the film coating comprises up to about 15% by weight of the coated tablet and is formed of one or more film-formers or binders and a plasticizer.

19. The pharmaceutical composition as defined in claim 18 wherein the film-former is a hydrophilic polymer which is hydroxypropylmethyl cellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose or methylcellulose, and/or a hydrophobic polymer which is ethyl cellulose, cellulose acetate, polyvinyl-maleic anhydride polymer, acrylic acid polymer and the plasticizer is 1,2,3-propanetriol triacetate, triethyl citrate, tributyl citrate, diethyl phthalate, castor oil and/or polyethylene glycol.

20. A method of maintaining or improving dissolution properties of a salt of ifetroban on aging, which comprises including with an ifetroban salt composition one or more basifying agents, compatible with ifetroban salt, to impart a desired pH of a least 7 to an aqueous dispersion of the composition.

21. The method as claimed in claim 20 wherein said ifetroban salt is present in an amount within the range of from about 1 to about 60% by weight of the composition and the basifying agent is present in an amount within the range of from about 1 to about 75% by weight of the composition.

22. The method as defined in claim 20 wherein the basifying agent is an alkali metal hydroxide or salt, an alkaline earth metal hydroxide or salt or ammonium hydroxide.