Simultaneous UV imaging and raman spectroscopy for the measurement of solvent-mediated phase transformations during dissolution testing.
The current work reports the simultaneous use of UV imaging and Raman spectroscopy for detailed characterization of drug dissolution behavior including solid-state phase transformations during dissolution. The dissolution of drug substances from compacts of sodium naproxen in 0.1 HCl as well as theophylline anhydrate and monohydrate in water was studied utilizing a flow-through setup. The decreases in dissolution rates with time observed by UV imaging were associated with concomitant solid form changes detected by Raman spectroscopy. Sodium naproxen and theophylline anhydrate were observed to convert to the more stable forms (naproxen, and theophylline monohydrate) within approximately 5 min. Interestingly, the new approach revealed that three intermediate forms are involved in the dissolution process prior to the appearance of the neutral naproxen during dissolution in an acidic medium. The combination of UV imaging and Raman spectroscopy offers a detailed characterization of drug dissolution behavior in a time-effective and sample-sparing manner.
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen, DK-2100, Denmark.
Jesper
J
Østergaard
Jian X
JX
Wu
Kaisa
K
Naelapää
Johan P
JP
Boetker
Henrik
H
Jensen
Jukka
J
Rantanen
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D009288:Naproxen / Q000737:chemistry*; D044367:Phase Transition; D012995:Solubility; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet; D013059:Spectrum Analysis, Raman; D013806:Theophylline / Q000737:chemistry*; D014665:Vasodilator Agents / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012997:Solvents; D014665:Vasodilator Agents; D014867:Water; D009288:Naproxen; D013806:Theophylline
Raman spectroscopy; UV imaging; UV/Vis spectroscopy; dissolution; dissolution rate; hydrates/solvates; imaging methods; solid form transformation