Pharmaceutical compositions comprising Afatinib

{
  "publication_number": "US10525059B2",
  "country": "US",
  "kind": "B2",
  "title": "Pharmaceutical compositions comprising Afatinib",
  "abstract": "The present invention relates to a tablet comprising Afatinib or a pharmaceutically acceptable salt thereof, wherein the tablet is obtained by direct compression. The present invention further relates to a process for manufacturing a tablet of the invention as well as the use of the tablet of the invention.",
  "claims": [
    "1. A tablet comprising Afatinib dimaleate form L, wherein the tablet is obtained by direct compression, and the Afatinib dimaleate form L is characterized by (a) an X-ray powder diffractogram having peaks at 5.2, 10.3, 11.1, 15.5, 18.1±0.2 degrees two-theta, or (b) endothermic peaks at 125 and 171±2° C. as measured by differential scanning calorimetry (DSC).",
    "2. The tablet according to claim 1, further comprising one or more pharmaceutically acceptable excipients.",
    "3. The tablet according to claim 1, further comprising at least one filler, at least one binder, at least one disintegrant, at least one glidant and at least one lubricant.",
    "4. The tablet according to claim 1, further comprising a filler selected from sugars, starches, modified starches, sugar alcohols, cellulose derivatives, inorganic substances, and mixtures thereof.",
    "5. The tablet according to claim 1, further comprising a binder selected from celluloses, cellulose derivates, starch, modified starches, polyethyleneglycols, polyvinylpyrrolidones, polyvinylacetates, polyvinylalcohols, and mixtures thereof.",
    "6. The tablet according to claim 1, further comprising a disintegrant selected from sodium starch glycolate, crospovidone, crosscarmellose, sodium carboxymethylcellulose, dried corn starch, and mixtures thereof.",
    "7. The tablet according to claim 1, further comprising a glidant selected from colloidal silicon dioxide, light anhydrous silicic acid, and mixtures thereof.",
    "8. The tablet according to claim 1, further comprising a lubricant selected from stearic acid, magnesium stearate, sodium stearylfumarate, talcum, glycerol tribehenate, polyethylene glycol, and mixtures thereof.",
    "9. The tablet according to claim 1, further comprising a filler selected from lactose, mannitol, microcrystalline cellulose, pre-gelatinized starch, calcium phosphate, dibasic calcium phosphate, and mixtures thereof.",
    "10. The tablet according to claim 1, further comprising lactose, wherein the lactose has a D 90 of 100 to 600 μm.",
    "11. The tablet according to claim 1, comprising: (1) a core comprising 1-50% w/w Afatinib dimaleate form L, 20-90% w/w lactose monohydrate, 1-40% w/w microcrystalline cellulose, 0.5-15% w/w crospovidone, 0.1-5% w/w colloidal silicon dioxide, and 0.5-10% w/w magnesium stearate; and (2) a coating in an amount of 2-5 wt. % based on the core weight, wherein the coating comprises hydroxypropyl methylcellulose.",
    "12. A process for manufacturing a tablet according to claim 1, comprising: mixing Afatinib dimaleate form L or a blend of Afatinib dimaleate form L and one or more pharmaceutically acceptable excipients with at least one lubricant; and compressing the lubricated blend to form a tablet.",
    "13. A method of treating cancer, the method comprising administering the tablet of claim 1 to a subject in need thereof.",
    "14. The tablet according to claim 1, comprising lactose.",
    "15. The tablet according to claim 1, wherein the Afatinib dimaleate form L is characterized by an X-ray powder diffractogram having peaks at 5.2, 10.3, 11.1, 15.5, 18.1±0.2 degrees two-theta.",
    "16. The tablet according to claim 1, wherein the Afatinib dimaleate form L is characterized by endothermic peaks at 125 and 171±2° C. as measured by DSC.",
    "17. The tablet according to claim 15, wherein the Afatinib dimaleate form L is characterized by endothermic peaks at 125 and 171±2° C. as measured by DSC.",
    "18. The tablet according to claim 15, comprising: (1) a core comprising 1-50% w/w Afatinib dimaleate form L, 20-90% w/w lactose monohydrate, 1-40% w/w microcrystalline cellulose, 0.5-15% w/w crospovidone, 0.1-5% w/w colloidal silicon dioxide, and 0.5-10% w/w magnesium stearate; and (2) a coating in an amount of 2-5 wt. % based on the core weight, wherein the coating comprises hydroxypropyl methylcellulose.",
    "19. The tablet according to claim 16, comprising: (1) a core comprising 1-50% w/w Afatinib dimaleate form L, 20-90% w/w lactose monohydrate, 1-40% w/w microcrystalline cellulose, 0.5-15% w/w crospovidone, 0.1-5% w/w colloidal silicon dioxide, and 0.5-10% w/w magnesium stearate; and (2) a hydroxypropyl methylcellulose based coating in an amount of 2-5 wt. % based on the core weight.",
    "20. The tablet according to claim 17, comprising: (1) a core comprising 1-50% w/w Afatinib dimaleate form L, 20-90% w/w lactose monohydrate, 1-40% w/w microcrystalline cellulose, 0.5-15% w/w crospovidone, 0.1-5% w/w colloidal silicon dioxide, and 0.5-10% w/w magnesium stearate; and (2) a coating in an amount of 2-5 wt. % based on the core weight, wherein the coating comprises hydroxypropyl methylcellulose."
  ],
  "cpc": [
    "A61K 31/517",
    "A61K 9/2009",
    "A61K 9/2018",
    "A61K 9/2027",
    "A61K 9/2054",
    "A61K 9/2095",
    "A61P 35/00"
  ],
  "assignees": [
    "FRESENIUS KABI ONCOLOGY LTD"
  ],
  "filing_date": "2016-08-19",
  "publication_date": "2020-01-07",
  "grant_date": "2020-01-07",
  "priority_date": "2015-08-21",
  "application_number": "US-201615753525-A",
  "family_id": "56985646",
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}