Amorphous drug-PVP dispersions: application of theoretical, thermal and spectroscopic analytical techniques to the study of a molecule with intermolecular bonds in both the crystalline and pure amorphous state.
We report the case of BMS-488043-PVP solid dispersions which when analysed using modulated DSC showed compliance with the Gordon-Taylor model, confirming ideal mixing behaviour of the two components. The nature or presence of stabilising interactions between drug and PVP could not be confirmed using this technique. Use of FT-IR, Raman and solid-state NMR spectroscopy confirmed the presence of stabilising hydrogen bond interactions between the drug and PVP. Similar interactions are present as intermolecular bonds in the crystalline and pure amorphous drug system. The Gordon-Taylor equation, as it is not predictive of the presence of intermolecular bonds such as hydrogen bonding in an amorphous dispersion, may underestimate the likely physical stability of solid dispersions which are produced and stabilised by these interactions.
Tobyn
Michael
M
Biopharmaceutics R&D, Bristol-Myers Squibb, Reeds Lane, Moreton CH46 1QW, UK. mike.tobyn@bms.com
Brown
Jonathan
J
Dennis
Andrew B
AB
Fakes
Michael
M
Gao
Qi
Q
Gamble
John
J
Khimyak
Yaroslav Z
YZ
McGeorge
Gary
G
Patel
Chhaya
C
Sinclair
Wayne
W
Timmins
Peter
P
Yin
Shawn
S
D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004355:Drug Stability; D023581:HIV Fusion Inhibitors / Q000737:chemistry*; D007211:Indoles; D009682:Magnetic Resonance Spectroscopy; D044367:Phase Transition; D010879:Piperazines / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D019289:Pyruvic Acid; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman
D023581:HIV Fusion Inhibitors; D007211:Indoles; D010879:Piperazines; D019289:Pyruvic Acid; D011205:Povidone; C509651:BMS-488043