Humidity induced phase transformation of poloxamer 188 and its effect on physical stability of amorphous solid dispersion of AMG 579, a PDE10A inhibitor.
Poloxamer 188, a commonly used emulsifying and solubilizing agent, was found to be the cause of crystallization of an investigational drug, AMG 579, from its amorphous solid dispersion at accelerated storage conditions. Investigation of this physical stability issue included thorough characterization of poloxamer 188 at non-ambient conditions. At 40°C, poloxamer 188 becomes deliquescent above relative humidity of 75%. Upon returning to ambient conditions, the deliquescent poloxamer 188 loses water and re-solidifies. The reversible phase transformation of poloxamer 188 may cause physical and chemical stability issues and this risk should be assessed when selecting it as an excipient for formulation development.
Process Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, United States.
Qiong
Q
Wu
Process Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, United States.
Michael T
MT
Kennedy
Process Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, United States.
Karthik
K
Nagapudi
Process Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, United States. Electronic address: ykiang@amgen.com.
Y-H
YH
Kiang
D001562:Benzimidazoles / Q000032:analysis / Q000737:chemistry*; D004355:Drug Stability; D006813:Humidity / Q000009:adverse effects; D044367:Phase Transition; D010726:Phosphodiesterase Inhibitors / Q000032:analysis / Q000737:chemistry*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D020442:Poloxamer / Q000032:analysis / Q000737:chemistry*; D011719:Pyrazines / Q000032:analysis / Q000737:chemistry*
D001562:Benzimidazoles; D010726:Phosphodiesterase Inhibitors; D011719:Pyrazines; D020442:Poloxamer; C119843:PDE10A protein, human; D010727:Phosphoric Diester Hydrolases; C000594998:1-(4-(3-(4-(1H-benzo(d)imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone
Amorphous solid dispersion; Hygroscopicity; Physical stability; Poloxamer