Celecoxib compositions

Abstract

Pharmaceutical compositions are provided comprising one or more orally deliverable dose units, each comprising particulate celecoxib in an amount of about 10 mg to about 1000 mg in intimate mixture with one or more pharmaceutically acceptable excipients. The compositions are useful in treatment or prophylaxis of cyclooxygenase-2 mediated conditions and disorders.

Description

[0001] This application claims the benefit of U.S. provisional application Ser. No. 60 / 110,333 filed Nov. 30, 1998 and to U.S. application Ser. No. 09 / 451,641 filed Nov. 30, 1999.FIELD OF THE INVENTION [0002] The present invention relates to orally deliverable pharmaceutical compositions containing celecoxib as an active ingredient, to processes for preparing such compositions, to methods of treatment of cyclooxygenase-2 mediated disorders comprising orally administering such compositions to a subject, and to the use of such compositions in the manufacture of medicaments. BACKGROUND OF THE INVENTION [0003] The compound 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (also referred to herein as celecoxib) was previously reported in Talley et al., U.S. Pat. No. 5,466,823 which describes and claims a class of 1,5-diaryl pyrazoles and their salts together with processes for the preparation of such compounds. Celecoxib has the structure: [0004] The 1,5-diary...

AI Technical Summary

Benefits of technology

[0036] (e) a maximum concentration (Cmax) not less than about 200 ng / ml.

[0037] In another embodiment, the composition has a relative bioavailability not less than about 50% by comparison with an orally delivered solution containing an equivalent amount of celecoxib.

[0038] In still another embodiment, the composition has a distribution of celecoxib primary particle sizes such that D90 is less than about 200 μm (90% of a sample of particles is smaller than the D90 value) in the longest dimension of the particles.

Problems solved by technology

The formulation of celecoxib for effective oral administration to a subject has hitherto been complicated by the unique physical and chemical properties of the compound, particularly its low solubility and factors associated with its crystal structure, including cohesiveness, low bulk density and low compressibility.

Even when blended with other substances, the celecoxib crystals tend to separate from the other substances and agglomerate together during mixing of the composition resulting in a non-uniformly blended composition containing undesirably large aggregates of celecoxib.

Therefore, it is difficult to prepare a pharmaceutical composition containing celecoxib that has the desired blend uniformity.

Further, handling problems are encountered during the preparation of pharmaceutical compositions comprising celecoxib.

For example, the low bulk density of celecoxib makes it difficult to process the small quantities required during formulation of the pharmaceutical compositions.

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