Claims for Patent: 10,925,835

Summary for Patent: 10,925,835

Title:	Celecoxib and amlodipine formulation and method of making the same
Abstract:	Provided herein is a celecoxib and amlodipine composition and method of making the same. The composition contains granules containing celecoxib. The amlodipine is incorporated into the composition as an extragranulate.
Inventor(s):	Efrati; Yitshak Itsik (Modiin, IL)
Assignee:	DEXCEL LTD. (Or-Akiva, IL) KITOV PHARMACEUTICALS (Tel Aviv, IL)
Application Number:	17/006,959
Patent Claims:	1. A method for treating pain and/or hypertension, and ameliorating celecoxib-induced elevation of blood pressure in a subject, comprising providing to the subject a pharmaceutical composition comprising (i) an admixture comprising a dry granulate comprising celecoxib or a pharmaceutically acceptable salt, wherein said dry granulate has a loss on drying (LOD) % of about 2.5% or less, wherein said dry granulate does not include amlodipine; and an extragranulate comprising amlodipine or a pharmaceutically acceptable salt thereof admixed with the dry granulate; and (ii) one or more excipients selected from the group consisting of a diluent, a disintegrant, a surfactant, a binder, a glidant, a lubricant, and combinations thereof, wherein the amount of celecoxib is sufficient to cause elevation in blood pressure, and wherein the amount of amlodipine is sufficient to ameliorate blood pressure elevation. 2. The method of claim 1, wherein each of the dry granulate and the extragranulate includes at least one of the one or more excipients, and wherein the at least one of the one or more excipients in the dry granulate and the at least one of the one or more excipients in the extragranulate are the same or different. 3. The method of claim 1, wherein the one or more excipients includes a diluent selected from the group consisting lactose, sucrose, mannitol, sorbitol, calcium phosphate, cellulose, kaolin, sodium chloride, and starch. 4. The method of claim 1, wherein the one or more excipients includes a disintegrant selected from the group consisting of cross-linked sodium carboxymethyl cellulose (croscarmellose sodium), cross-linked polyvinylpyrrolidone (crospovidone), sodium starch glycolate, pregelatinized starch, calcium carboxymethyl cellulose, low substituted hydroxypropyl cellulose, and magnesium aluminum silicate. 5. The method of claim 1, wherein the one or more excipients includes a surfactant selected from the group consisting of stearyl triethanolamine, sodium lauryl sulfate, sodium taurocholate, laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, glycerin monostearate, and polyvinyl alcohol. 6. The method of claim 1, wherein the one or more excipients includes a binder selected from the group consisting of polyvinylpyrrolidone (povidone; PVP), hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC), sodium alginate, alginic acid, guar gum, acacia gum, xanthan gum, carbopol, carboxymethyl cellulose, ethyl cellulose, maltodextrin, vinylpyrrolidone/vinyl acetate copolymer, microcrystalline cellulose, starch, and methyl cellulose. 7. The method of claim 1, wherein the one or more excipients includes a glidant selected from the group consisting of corn starch, colloidal silicon dioxide, silica anhydrous, and talc. 8. The method of claim 1, wherein the one or more excipients includes a lubricant selected from the group consisting of magnesium stearate, calcium stearate, oleic acid, caprylic acid, stearic acid, magnesium isovalerate, calcium laurate, magnesium palmitate, behenic acid, glyceryl behenate, glyceryl stearate, sodium stearyl fumarate, potassium stearyl fumarate, zinc stearate, sodium oleate, sodium stearate, sodium benzoate, sodium acetate, sodium chloride, talc, polyethylene glycol, and hydrogenated vegetable oil. 9. The method of claim 1, wherein the pharmaceutical composition is in the form of a tablet, a caplet, or a capsule. 10. The method of claim 1, wherein the dry granulate has LOD % in the range of from about 0.5% to about 2%. 11. The method of claim 1, wherein the dry granulate has LOD % in the range of from about 0.5% to about 1.5%. 12. The method of claim 1, wherein the pharmaceutical composition comprises 200 mg celecoxib and 2.5, 5, or 10 mg amlodipine. 13. The method of claim 1, wherein the pharmaceutically acceptable salt of amlodipine is amlodipine besylate. 14. The method of claim 1, wherein the dry granulate comprises celecoxib, a diluent, a disintegrant, a binder, and a surfactant; and wherein the extragranulate comprises amlodipine besylate, a diluent, a disintegrant, a glidant, and a lubricant. 15. A method for treating pain and/or hypertension, and ameliorating celecoxib-induced elevation of blood pressure in a subject, comprising providing to the subject a pharmaceutical composition comprising a combination of celecoxib and amlodipine, wherein the pharmaceutical composition is prepared from a wet granulation of celecoxib or a pharmaceutically acceptable salt thereof and one or more excipients to obtain a wet granulate, wherein said wet granulate does not include amlodipine, wherein the wet granulate was dried to obtain a dry granulate, wherein the dry granulate has a loss on drying (LOD) % of about 2.5% or less, wherein the dry granulate was admixed with an extragranulate comprising amlodipine or a pharmaceutically acceptable salt thereof and optionally one or more excipients, wherein the amount of celecoxib is sufficient to cause elevation in blood pressure, and wherein the amount of amlodipine is sufficient to ameliorate blood pressure elevation. 16. The method of claim 15, wherein the dry granulate has LOD % in the range of from about 0.5% to about 2%. 17. The method of claim 15, wherein the dry granulate has LOD % in the range of from about 0.5% to about 1.5%. 18. The method of claim 15, wherein the wet granulation was formed by dry mixing celecoxib or a pharmaceutically acceptable salt thereof and one or more excipients to obtain a dry mixture, and spraying the dry mixture with a granulation solution or suspension to obtain a wet granulate. 19. The method of claim 18, wherein the granulation solution or suspension comprises an aqueous medium. 20. The method of claim 18, wherein the granulation solution or suspension comprises an organic medium. 21. The method of claim 15, wherein the extragranulate comprises one or more excipients, and wherein the one or more excipients in the wet granulate and the one or more excipients in the extragranulate are the same or different selected from the group consisting of a diluent, a disintegrant, a surfactant, a binder, a glidant, a lubricant, and combinations thereof. 22. The method of claim 15, wherein the dry granulate was milled to produce a milled dry granulate prior to being admixed with the extragranulate. 23. The method of claim 15, wherein the pharmaceutical composition was compressed to obtain a tablet or a caplet. 24. The method of claim 15, wherein the subject has osteoarthritis.