Crystallization Kinetics of an Amorphous Pharmaceutical Compound Using Fluorescence-Lifetime-Imaging Microscopy

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http://hdl.handle.net/10138/301179

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Rautaniemi , K , Vuorimaa-Laukkanen , E , Strachan , C J & Laaksonen , T 2018 , ' Crystallization Kinetics of an Amorphous Pharmaceutical Compound Using Fluorescence-Lifetime-Imaging Microscopy ' , Molecular Pharmaceutics , vol. 15 , no. 5 , pp. 1964-1971 . https://doi.org/10.1021/acs.molpharmaceut.8b00117

Title: Crystallization Kinetics of an Amorphous Pharmaceutical Compound Using Fluorescence-Lifetime-Imaging Microscopy
Author: Rautaniemi, Kaisa; Vuorimaa-Laukkanen, Elina; Strachan, Clare J.; Laaksonen, Timo
Contributor: University of Helsinki, Faculty of Pharmacy
University of Helsinki, Tampere University of Technology (TUT)
Date: 2018-05
Language: eng
Number of pages: 8
Belongs to series: Molecular Pharmaceutics
ISSN: 1543-8384
URI: http://hdl.handle.net/10138/301179
Abstract: Pharmaceutical scientists are increasingly interested in amorphous drug formulations especially because of their higher dissolution rates. Consequently, the thorough characterization and analysis of these formulations are becoming more and more important for the pharmaceutical industry. Here, fluorescence lifetime-imaging microscopy (FLIM) was used to monitor the crystallization of an amorphous pharmaceutical compound, indomethacin. Initially, we identified different solid indomethacin forms, amorphous and gamma- and alpha-crystalline, on the basis of their time-resolved fluorescence. All of the studied indomethacin forms showed biexponential decays with characteristic fluorescence lifetimes and amplitudes. Using this information, the crystallization of amorphous indomethacin upon storage in 60 degrees C was monitored for 10 days with FLIM. The progress of crystallization was detected as lifetime changes both in the FLIM images and in the fluorescence-decay curves extracted from the images. The fluorescence-lifetime amplitudes were used for quantitative analysis of the crystallization process. We also demonstrated that the fluorescence-lifetime distribution of the sample changed during crystallization, and when the sample was not moved between measuring times, the lifetime distribution could also be used for the analysis of the reaction kinetics. Our results clearly show that FLIM is a sensitive and nondestructive method for monitoring solid-state transformations on the surfaces of fluorescent samples.
Subject: fluorescence
fluorescence lifetime
amorphous materials
crystal growth
kinetics
SOLID-STATE FLUORESCENCE
INDOMETHACIN POLYMORPHS
RAMAN-SPECTROSCOPY
SURFACE CRYSTALLIZATION
ACETYLSALICYLIC-ACID
DISSOLUTION BEHAVIOR
PHYSICAL STABILITY
DOSAGE FORMS
T-G
DRUG
116 Chemical sciences
317 Pharmacy
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