Simultaneous UV Imaging and Raman Spectroscopy for the Measurement of Solvent-Mediated Phase Transformations During Dissolution Testing

TY - JOUR

T1 - Simultaneous UV Imaging and Raman Spectroscopy for the Measurement of Solvent-Mediated Phase Transformations During Dissolution Testing

AU - Ostergaard, Jesper

AU - Wu, Jian

AU - Naelapää, Kaisa

AU - Boetker, Johan P

AU - Jensen, Henrik

AU - Rantanen, Jukka

N1 - © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

PY - 2014/4

Y1 - 2014/4

N2 - 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.

AB - 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.

U2 - 10.1002/jps.23883

DO - 10.1002/jps.23883

M3 - Journal article

C2 - 24496995

SN - 1520-6017

VL - 103

SP - 1149

EP - 1156

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

IS - 4

ER -