Celecoxib and amlodipine formulation and method of making the same

• US 10,945,960 B2
• Filed: 05/31/2019
• Issued: 03/16/2021
• Est. Priority Date: 07/06/2017
• Status: Active Grant

• Current Assignee: Dexcel Limited
• Original Assignee: Dexcel Limited
• Inventors: Efrati, Yitshak Itsik
• Primary Examiner(s): Young, Micah Paul
• Application Number:
  US16/427,499
• Publication Number:
  US 20190282507A1
• Time in Patent Office: 655 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/4422 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077

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.

Claims

1. A pharmaceutical composition comprising:

(i) an admixture comprising

a dry granulate comprising celecoxib or a pharmaceutically acceptable salt, wherein the 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.

2. The pharmaceutical composition 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 pharmaceutical composition of claim 2, 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 pharmaceutical composition of claim 2, 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 pharmaceutical composition of claim 2, 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 pharmaceutical composition of claim 2, 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 pharmaceutical composition of claim 2, 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 pharmaceutical composition of claim 2, 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 pharmaceutical composition of claim 1 in the form of a tablet, a caplet, or a capsule.

10. The pharmaceutical composition of claim 1, wherein the dry granulate has LOD % in the range of from about 0.5% to about 2%.

11. The pharmaceutical composition of claim 10, wherein the dry granulate has LOD % in the range of from about 0.5% to about 1.5%.

12. The pharmaceutical composition of claim 1 comprising 200 mg celecoxib and 2.5, 5, or 10 mg amlodipine.

13. The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable salt of amlodipine is amlodipine besylate.

14. The pharmaceutical composition 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 pharmaceutical composition comprising:

an admixture comprising

a dry granulate comprising celecoxib or a pharmaceutically acceptable salt thereof and a diluent, a disintegrant, a binder, and a surfactant, wherein the 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 either amlodipine or amlodipine besylate admixed with the dry granulate, and a diluent, a disintegrant, a glidant, and a lubricant.