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In situ measurement of solvent-mediated phase transformations during dissolution testing
Jaakko Aaltonen1, Paula Heinänen, Leena Peltonen
1Division of Pharmaceutical Technology, P.O. Box 56, 00014 University of Helsinki, Finland. jaakko.aaltonen@helsinki.fi
Journal of Pharmaceutical Sciences
|August 8, 2006
Summary
This study investigated solvent-mediated phase transformations of theophylline (TP) and nitrofurantoin (NF) during dissolution. TP transformation significantly slowed dissolution, while NF’s effect was less clear, with TP transforming much faster.
Area of Science:
- Pharmaceutical Sciences
- Solid-State Chemistry
Background:
- Solvent-mediated phase transformations can impact drug dissolution rates.
- Understanding these transformations is crucial for drug formulation and performance.
Purpose of the Study:
- To investigate and quantify solvent-mediated phase transformations of theophylline (TP) and nitrofurantoin (NF) during dissolution.
- To correlate solid-state changes with dissolution behavior.
Main Methods:
- Utilized a channel flow intrinsic dissolution test system.
- Employed simultaneous UV-Vis spectrophotometry for drug concentration and in situ Raman spectroscopy for solid-state form analysis.
- Performed off-line scanning electron microscopy for solid phase investigation.
Main Results:
- Theophylline (TP) anhydrate transformed to TP monohydrate, decreasing dissolution rate.
- Nitrofurantoin (NF) anhydrate (form beta) transformed to NF monohydrate (form II), with less clear impact on dissolution rate.
- TP transformation was significantly faster than NF transformation.
- Microcrystalline cellulose delayed TP anhydrate transformation onset.
Conclusions:
- Simultaneous monitoring of dissolution and solid-state form provides enhanced understanding of phase transformations.
- Phase transformation kinetics and impact on dissolution vary significantly between TP and NF.
- Excipients can modulate the kinetics of solvent-mediated phase transformations.