Compositions with reduced nitrosamine impurities

{
  "publication_number": "US2026102499A1",
  "country": "US",
  "kind": "A1",
  "title": "Compositions with reduced nitrosamine impurities",
  "abstract": "The present invention relates to storage-stable pharmaceutical compositions comprising a drug substance containing amine, and at least one excipient, wherein the nitrosamine impurities in the said compositions are within acceptable levels. The nitrite content of the storage-stable pharmaceutical compositions is not more than about 2 ppm. Further, the present invention also provides a process for the manufacture of the said compositions.",
  "claims": [
    "1. Storage-stable pharmaceutical compositions comprising drug substance containing amine and at least one excipient, wherein the nitrite content of the compositions is not more than about 2 ppm, and wherein the nitrosamine impurity content of the compositions is not more than about 18.5 ppm. 2. Storage-stable pharmaceutical compositions of claim 1, wherein the compositions are manufactured by a process that uses a solvent system containing about 0% to about 20% by weight of water. 3. (canceled) 4. The storage-stable compositions as claimed in claim 1, wherein the nitrate content of the compositions is not more than about 5 ppm. 5 - 6. (canceled) 7. The storage-stable compositions as claimed in claim 1, wherein the excipient has a nitrite content of not more than 2 ppm. 8. The storage-stable compositions as claimed in claim 1, wherein the excipient has a nitrate content of less than or equal to 5 ppm. 9 - 16. (canceled) 17. The storage-stable pharmaceutical compositions of claim 1 wherein the solvent system is a mixture of at least two non-aqueous solvents, in a weight ratio ranging from 20:1 to 1:20. 18 - 37. (canceled) 38. Storage stable pharmaceutical compositions comprising varenicline and at least one excipient, wherein the nitrite content of the compositions is not more than about 2 ppm, and wherein the nitrosamine impurity content of the compositions is not more than about 18.5 ppm, wherein the nitrite content of each of excipients used is not more than about 2 ppm; and wherein the compositions are manufactured by a process that uses a solvent system containing about 0% to about 20% by weight of water. 39. The storage-stable pharmaceutical compositions of claim 1, wherein the nitrate content of the said compositions is not more than about 5 ppm. 40. Storage-stable pharmaceutical compositions comprising varenicline and diluent from about 60% to about 95% by weight of the composition, disintegrant from about 1% to about 20% by weight of the composition, binder from about 0.1% to about 20% by weight of the composition, lubricant from about 0.25% to about 5% by weight of the composition, glidant from about 0.1% to about 10% by weight of the composition, optionally coating agent, wherein the nitrite content of the compositions is not more than about 2 ppm, and wherein the nitrosamine impurity content of the compositions is not more than about 18.5 ppm; and wherein the compositions are manufactured by a process that uses a solvent system containing mixture of at least one non-aqueous solvent and water, in a weight ratio ranging from 4:1 to 1:0. 41. The storage-stable pharmaceutical compositions of claim 8, wherein the diluent is selected from microcrystalline cellulose, starch, calcium phosphate, dibasic calcium phosphate, tribasic calcium phosphate, mannitol, sorbitol, lactose, and mixtures thereof, wherein the disintegrant is selected from sodium starch glycolate, starch, pregelatinized starch, crospovidone, croscarmellose sodium, and mixtures thereof, wherein the binder is selected from hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), methylcellulose, hydroxyethyl cellulose, starch, polyvinylpyrrolidone (PVP), polyvinyl alcohol, waxes, fatty alcohols, polyethylene glycol, carbomer, gums, alginates, polymethacrylates, and mixtures thereof, wherein the lubricant is selected from magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, sodium benzoate, palmitic acid, talc, and glyceryl behenate, and wherein the glidant is selected from colloidal silicon dioxide, hydrated silicon dioxide, light anhydrous silicic acid, aluminium silicate, titanium oxide, stearic acid, and talc. 42. Storage-stable pharmaceutical compositions comprising uncoated tablet comprising: a) 0.855% w/w of varenicline; b) 33.5% w/w of anhydrous dibasic calcium phosphate; c) 60.645% w/w of microcrystalline cellulose; d) 3.000% w/w of croscarmellose sodium; e) 1.000% w/w of colloidal silicon dioxide; and f) 1.000% w/w of magnesium stearate; wherein uncoated tablet is coated with opadry coating, wherein the nitrite content of the compositions is not more than about 2 ppm, and wherein the nitrosamine impurity content of the compositions is not more than about 18.5 ppm, and wherein the nitrite content of each of excipients used is not more than about 2 ppm; and wherein the compositions are manufactured by a process that uses a solvent system containing about 0% to about 20% by weight of water."
  ],
  "cpc": [
    "A61K 47/18",
    "A61K 45/06",
    "A61K 9/2095",
    "A61K 9/282",
    "A61K 9/2866",
    "A61K 9/2893"
  ],
  "filing_date": "2023-09-26",
  "publication_date": "2026-04-16",
  "priority_date": "2022-09-27",
  "application_number": "US-202319114030-A"
}