Search

EP-3938094-B1 - PROCESS FOR SPRAY DRYING A GLP-1 PEPTIDE

EP3938094B1EP 3938094 B1EP3938094 B1EP 3938094B1EP-3938094-B1

Inventors

  • VANGSGAARD, Ole
  • HANSEN, Marlene, Hørslev

Dates

Publication Date
20260506
Application Date
20200313

Claims (15)

  1. A process for spray drying of a feed solution comprising semaglutide, said process comprising introducing the feed solution comprising semaglutide in a solvent into a spray dryer and introducing an atomising gas and a drying gas, characterised in that the spray dryer comprises a gas heater for the drying gas with an inner surface comprising iron and less than 18.5% chromium.
  2. The process according to claim 1, characterised in that the inner surface comprises 10 to less than 18.5% chromium.
  3. The process according to claim 1, characterised in that the inner surface comprises 14 to less than 18.5% chromium.
  4. The process according to claim 1, characterised in that the inner surface comprises 16-18% chromium.
  5. The process according to any of the preceding claims, characterised in that the inner surface comprises 8-16% nickel.
  6. The process according to any of the preceding claims, characterised in that the inner surface comprises 10-14% nickel.
  7. The process according to any one of the preceding claims, characterised in that the inner surface has a depth of 0.001 cm to 10 cm.
  8. The process according to any one of the preceding claims, characterised in that the feed solution solvent comprises an organic alcoholic solvent.
  9. The process according to any one of the preceding claims, characterised in that the feed solution solvent comprises ethanol.
  10. The process according to any one of the preceding claims, characterised in that the feed solution comprises 0.1-10% (w/w) semaglutide in 40-75% (w/w) aqueous ethanol.
  11. The process according to any one of the preceding claims, characterised in that the feed solution comprises 0.5-2.5% (w/w) semaglutide in 49-60% (w/w) aqueous ethanol.
  12. The process according to any one of the preceding claims, characterised in that the drying gas is nitrogen.
  13. The process according to any one of the preceding claims, characterised in that the drying gas is recirculated.
  14. The process according to any one of the preceding claims further comprising a step of formulating semaglutide obtained by said process into a pharmaceutical composition.
  15. The process according to claim 14, wherein said pharmaceutical composition is a tablet.

Description

The present invention relates to the field of spray drying of a feed solution comprising a GLP-1 peptide, such as semaglutide. More specifically, the invention pertains to processes for spray drying of a feed solution comprising semaglutide wherein an improved purity is obtained. BACKGROUND Protein and peptide stability during processing and upon storage is of the utmost importance when manufacturing drug substances and drug products. During spray drying of drug substances, impurities may arise due to reactions between solvents and the drug substance. It is highly desirable to obtain processes for spray drying of drug substances, wherein as little impurities as possible are generated during the drying process and wherein the highest possible drug stability and drug purity are obtained. It is known from the prior art that amino groups and certain amino acids can be used for binding of acetaldehydes and that acetaldehyde is capable of reacting with a variety of proteins to form both stable and unstable products. Unstable products are readily reversible, whereas stable products are essentially irreversible products that are characterized by their resistance to various treatments. It is furthermore known from the prior art that there exist instances of non-oxidative ethanol dehydrogenation to acetaldehyde catalysed by metal species. A process for spray-drying a feed solution comprising semaglutide is described in WO2010/072621 A2. SUMMARY In some aspects the present invention relates to a process for spray drying of a feed solution comprising semaglutide, said process comprising introducing the feed solution comprising semaglutide in a solvent into a spray dryer and introducing an atomising gas and a drying gas, characterised in that the spray dryer comprises a gas heater for the drying gas with an inner surface comprising iron and less than 18.5% chromium. The present inventors have observed an increased amount of impurity generation upon moving a process for spray drying of a feed solution comprising semaglutide from a first unit to a second unit. The change in unit was facilitated by a need for increasing the production and both units are standard units for spray drying. The impurity was characterised as having an increased molar weight, corresponding to a product reacted with acetaldehyde. It was not apparent what the cause of impurities was but after extensive investigations and considerations it was evident that there was a significant correlation between the gas inlet temperature and the level of free acetaldehyde in the spray dried product, which then could react with the product. It furthermore appeared that the increased amount of impurity generation was caused by the gas heater material, since passing ethanol spiked nitrogen over material identical to the gas heater material showed ethanol dehydrogenation, dependent on the gas temperature. The present inventors have observed that a lower amount of impurities is generated when applying a gas heater made of stainless steel 316 in the spray drying process compared to when applying a gas heater made of Incoloy 800 in such processes. The present invention appears to be independent of production scale. BRIEF DESCRIPTION OF DRAWINGS Fig. 1 shows acetaldehyde content (ppm) when using a gas heater made of Incoloy 800 or stainless steel 316 in the spray drying process.Fig. 2 shows the amount of impurities (%) generated during spray drying as function of acetaldehyde content (ppm) when using a gas heater made of Incoloy 800 or stainless steel 316 in the spray drying process. DESCRIPTION In some embodiments the present invention relates to a process for spray drying of a feed solution comprising semaglutide, said process comprising introducing the feed solution comprising semaglutide in a solvent into a spray dryer and introducing an atomising gas and a drying gas, characterised in that the spray dryer comprises a gas heater for the drying gas with an inner surface comprising iron and less than 18.5% chromium. Spray drying is often used as a step in the manufacture of drug substances and drug products. The purity of the obtained products is important for the overall product costs as well as the safety for subjects subsequently receiving the final drug product. Gas heater material Different material can be used for gas heaters. Different materials have different properties and are useful for different purposes. Incoloy 800 is an iron-nickel-chromium alloy with moderate strength and good resistance to oxidation, carburization and sulfidation at elevated temperatures, such as above 800 °C. It is particularly useful and widely used for high-temperature equipment, such as heat-treating equipment and heat exchangers in chemical processes. Incoloy 800 comprises iron, 30-35% nickel and 19-23% chromium along with other components (Special Metals Corporation, 2004 (Sept 04), publication number SMC-046). Stainless steel is a term used to describe an extremely versatile fam