Corticosteroid compositions
Provided herein are methods for treating, preventing or alleviating the symptoms of and inflammation associated with inflammatory diseases and conditions of the gastrointestinal tract, for example, those involving the esophagus. Also provided herein are pharmaceutical compositions useful for the methods of the present invention.
1. An oral liquid pharmaceutical composition comprising a stable dispersion or suspension comprising:
a. budesonide in an amount of about 0.02 mg/mL to about 0.75 mg/mL of the composition,
b. disodium edetate in an amount of about 0.05 mg/mL to about 25 mg/mL of the composition,
c. a buffer, wherein the buffer is chosen from the group consisting of sodium citrate, citric acid, a carbonate buffer, a hydroxide buffer, a phosphate buffer, an acetate buffer, or combinations thereof,
d. polysorbate 80 in an amount of about 0.01 mg/mL to about 1 mg/mL of the composition,
e. a preservative, wherein the preservative is potassium sorbate present in an amount of about 0.2 mg/mL to about 10 mg/mL of the composition, sodium benzoate present in an amount of about 0.2 mg/mL to about 10 mg/mL of the composition, or a combination thereof,
f. a flavoring agent, a sweetener, or a combination thereof,
g. dextrose in an amount of 0-250 mg/mL of the composition,
h. at least one additional excipient comprising maltodextrin present in an amount of about 10 mg/mL to about 1 g/mL of the composition, and one or more of hydroxyethylcellulose (HEC), hydroxypropylmethyl-cellulose (HPMC), carboxymethyl-cellulose (CMC), microcrystalline cellulose (MCC), carbomer, and combinations thereof, present in an amount of about 5 mg/mL to about 100 mg/mL of the composition; and
i. water,
wherein the composition is physically and chemically stable, wherein during and after storage the particles of the dispersion or suspension do not cake or aggregate, wherein the composition remains substantially uniform for at least 1 day, and wherein the composition is suitable for single or multiple dose administration, the composition having a viscosity of at least 50 cP.
2. The pharmaceutical composition of claim 1 present in a multiple-unit container and comprising a plurality of unit doses.
3. The pharmaceutical composition of claim 1 , wherein the composition remains substantially uniform after storage.
4. The pharmaceutical composition of claim 1 , wherein the composition regains substantial uniformity upon mild or moderate agitation, swirling, gentle swirling or shaking.
5. The pharmaceutical composition of claim 1 , wherein after storage the composition regains substantial uniformity upon mild or moderate agitation, swirling, gentle swirling or shaking.
6. The pharmaceutical composition of claim 5 , wherein after mild or moderate agitation, swirling, gentle swirling or shaking, the composition remains substantially uniform for a convenient period of time.
7. The pharmaceutical composition of claim 2 , wherein the composition is a multiple dose formulation.
8. The pharmaceutical composition of claim 7 , wherein each dose from the container of the formulation is substantially uniform with regard to each other.
9. The pharmaceutical composition of claim 7 , wherein the first and final dose from the container are substantially uniform.
10. The pharmaceutical composition of claim 1 , wherein the budesonide is readily dispersed throughout the composition upon mild or moderate agitation.
11. The pharmaceutical composition of claim 1 , wherein the budesonide is readily dispersed throughout the composition upon mild or moderate agitation after storage.
12. The pharmaceutical composition of claim 1 , wherein the budesonide is easily resuspended in the composition upon mild or moderate agitation.
13. The pharmaceutical composition of claim 1 , wherein the budesonide is easily resuspended in the composition upon mild or moderate agitation after storage.
14. The pharmaceutical composition of claim 1 , wherein the budesonide is readily dispersed throughout the composition upon mild or moderate agitation after storage for one week.
15. The pharmaceutical composition of claim 1 , wherein the budesonide is readily dispersed throughout the composition upon mild or moderate agitation after storage for one month.
16. The pharmaceutical composition of claim 1 , wherein the budesonide does not cake after storage.
17. The pharmaceutical composition of claim 1 , wherein the composition is substantially free of non-budesonide particles.
18. The pharmaceutical composition of claim 1 , wherein the at least one excipient does not enhance the solubility of the budesonide in the water.
19. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is a non-Newtonian fluid.
20. The pharmaceutical composition of claim 19 , wherein the non-Newtonian fluid is selected from the group consisting of plastic, pseudo-plastic and dilatant.
21. The pharmaceutical composition of claim 20 , wherein the non-Newtonian fluid is pseudo-plastic.
22. The pharmaceutical composition of claim 21 , wherein the non-Newtonian fluid is thixotropic.
23. The pharmaceutical composition of claim 1 , wherein the budesonide comprises a plurality of microparticles.
24. The pharmaceutical composition of claim 1 , wherein the budesonide comprises a plurality of nanoparticles.
25. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises budesonide particles suspended in the composition.
26. The pharmaceutical composition of claim 25 , wherein the budesonide particles are microparticles having a mean diameter of about 0.1 microns to about 50 microns.
27. The pharmaceutical composition of claim 25 , wherein at least 95% of the budesonide particles are microparticles having a diameter of less than about 10 microns.
28. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition has a volume of about 1 mL to about 20 mL.
29. The pharmaceutical composition of claim 28 , wherein the pharmaceutical composition has a volume of about 3 mL to about 12 mL.
30. The pharmaceutical composition of claim 1 , wherein the at least one additional excipient comprises CMC, and wherein the CMC is present in an amount of about 5 mg/mL to about 30 mg/mL.
31. The pharmaceutical composition of claim 1 , wherein the at least one additional excipient comprises carbomer, and wherein the carbomer is present in an amount of about 5 mg/mL to about 100 mg/mL.
32. The pharmaceutical composition of claim 1 , wherein the at least one additional excipient comprises HPMC, and wherein the HPMC is present in an amount of about 5 mg/mL to about 30 mg/mL.
33. The pharmaceutical composition of claim 1 , wherein the at least one additional excipient comprises MCC, and wherein the MCC is present in an amount of about 5 mg/mL to about 30 mg/mL.
34. The pharmaceutical composition of claim 1 , wherein the at least one additional excipient comprises a combination of CMC and MCC, wherein the CMC-MCC combination is present in an amount of about 10 mg/mL to about 40 mg/mL, and wherein the CMC/MCC mixed weight ratio is about 11/89.
35. The pharmaceutical composition of claim 1 , wherein the maltodextrin has a dextrose equivalents of about 13 to about 18.
36. The pharmaceutical composition of claim 1 , wherein the buffer comprises sodium citrate present in an amount of about 0.1 mg/mL to about 30 mg/mL.
37. The pharmaceutical composition of claim 1 , wherein the buffer is sodium citrate present in an amount of about 0.1 mg/mL to about 30 mg/mL and citric acid present in an amount of about 0.1 mg/mL to about 10 mg/mL.
38. The pharmaceutical composition of claim 37 , wherein the additional excipient is selected from hydroxyethylcellulose (HEC), hydroxypropylmethyl-cellulose (HPMC), carboxymethyl-cellulose (CMC), microcrystalline cellulose (MCC), carbomer and combinations thereof, and wherein the additional excipient is present in an amount of about 5 mg/mL to about 100 mg/mL.
39. The pharmaceutical composition of claim 1 , wherein the additional excipient is maltodextrin present in an amount of about 1 mg/mL to about 1.5 g/mL.
40. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition has a total volume of about 1 mL to about 20 mL.
41. A kit comprising a multiple unit container and a plurality of doses of the stable oral pharmaceutical composition of claim 1 .
42. The kit of claim 41 , wherein the kit comprises about 2 to about 60 doses of the pharmaceutical composition.
43. The kit of claim 41 , wherein the kit comprises about 330 mL of the stable pharmaceutical composition.
44. The kit of claim 41 , wherein the kit comprises about 50 ml to about 600 mL of the stable pharmaceutical composition.
45. The kit of claim 41 , wherein the kit further comprises a metering device for administering the composition to an individual.
46. The kit of claim 45 , wherein the metering device is incorporated into the multiple unit container.
47. The pharmaceutical composition of claim 1 , wherein the maltodextrin has a dextrose equivalents of greater than 5.
48. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is chemically stable, comprising at least 90% of the initial amount of budesonide after being stored for 3 weeks.