Using terahertz pulsed spectroscopy to quantify pharmaceutical polymorphism and crystallinity.
Terahertz pulsed spectroscopy (TPS) is a new technique that is capable of eliciting rich information when investigating pharmaceutical materials. In solids, it probes long-range crystalline lattice vibrations and low energy torsion and hydrogen bonding vibrations. These properties make TPS potentially an ideal tool to investigate crystallinity and polymorphism. In this study four drugs with different solid-state properties were analyzed using TPS and levels of polymorphism and crystallinity were quantified. Carbamazepine and enalapril maleate polymorphs, amorphous, and crystalline indomethacin, and thermotropic liquid crystalline and crystalline fenoprofen calcium mixtures were quantified using partial least-squares analysis. Root-mean-squared errors of cross validation as low as 0.349% and limits of detection as low as approximately 1% were obtained, demonstrating that TPS is an analytical technique of potential in quantifying solid-state properties of pharmaceutical compounds.
Strachan
Clare J
CJ
School of Pharmacy, University of Otago, P.O. Box 56, Dunedin, New Zealand.
Taday
Philip F
PF
Newnham
David A
DA
Gordon
Keith C
KC
Zeitler
J Axel
JA
Pepper
Michael
M
Rades
Thomas
T
D002220:Carbamazepine / Q000032:analysis; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D004338:Drug Combinations; D004656:Enalapril / Q000032:analysis; D005279:Fenoprofen / Q000032:analysis; D007213:Indomethacin / Q000032:analysis; D007536:Isomerism; D016018:Least-Squares Analysis; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011208:Powders; D015203:Reproducibility of Results; D013057:Spectrum Analysis / Q000379:methods*
D004338:Drug Combinations; D004364:Pharmaceutical Preparations; D011208:Powders; D002220:Carbamazepine; D004656:Enalapril; D005279:Fenoprofen; D007213:Indomethacin