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Characterization and quantitation of clarithromycin polymorphs by powder X-ray diffractometry and solid-state NMR
Yuichi Tozuka1, Atsutoshi Ito, Hiroko Seki
1Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan. ytozuka@p.chiba-u.ac.jp
Chemical & Pharmaceutical Bulletin
|August 23, 2002
Summary
Solid-state NMR effectively characterizes clarithromycin polymorphs. This technique accurately quantifies polymorphic fractions, crucial for drug quality control and development.
Area of Science:
- Pharmaceutical Sciences
- Solid-State Chemistry
- Analytical Chemistry
Background:
- Clarithromycin exists in multiple crystalline forms (polymorphs).
- Polymorphism significantly impacts drug properties like solubility and bioavailability.
- Accurate characterization and quantification of polymorphs are essential for pharmaceutical development.
Purpose of the Study:
- To characterize different forms of clarithromycin.
- To establish a quantitative method for determining polymorphic fractions.
- To evaluate the utility of solid-state NMR for polymorph analysis.
Main Methods:
- Solid-state cross-polarization magic-angle spinning (CP/MAS) 13C-NMR spectroscopy.
- Analysis of characteristic resonances of the C1 carbonyl carbon.
- Quantitative analysis based on peak area integration.
Main Results:
- Two distinct polymorphs (form I and form II) were identified.
- Characteristic C1 carbonyl carbon resonances were observed at 176.2 ppm (form II) and 175.2 ppm (form I).
- A linear correlation (R² > 0.99) was established between peak area and the content of form I, enabling accurate quantification.
Conclusions:
- Solid-state NMR is a powerful and reliable technique for characterizing clarithromycin polymorphs.
- The method allows for precise quantitative analysis of polymorphic mixtures.
- This approach is valuable for ensuring drug quality and consistency.