New perspectives of 19F MAS NMR in the characterization of amorphous forms of atorvastatin in dosage formulations
Language English Country Netherlands Media print-electronic
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
21356299
DOI
10.1016/j.ijpharm.2011.02.030
PII: S0378-5173(11)00165-7
Knihovny.cz E-resources
- MeSH
- Atorvastatin MeSH
- Time Factors MeSH
- Factor Analysis, Statistical MeSH
- Fluorine chemistry MeSH
- Crystallization MeSH
- Heptanoic Acids chemistry MeSH
- Magnetic Resonance Spectroscopy methods MeSH
- Powder Diffraction MeSH
- Pyrroles chemistry MeSH
- Reproducibility of Results MeSH
- Spectroscopy, Fourier Transform Infrared methods MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Atorvastatin MeSH
- Fluorine MeSH
- Heptanoic Acids MeSH
- Pyrroles MeSH
Despite recent advances in solid-state NMR spectroscopy, the structural characterization of amorphous active pharmaceutical ingredients (APIs) in solid dosage forms continues to be a monumental challenge. To circumvent complications following from low concentrations of APIs in tablet formulations, we propose a new time-saving procedure based on chemometric approach: factor analysis of (19)F MAS NMR spectra. Capability of the proposed method is demonstrated on atorvastatin--a typical representative of fluorinated pharmaceutical substances exhibiting extensive polymorphism. Applying the factor analysis on the recorded (19)F MAS NMR spectra, unique parameters for every sample were derived. In this way every solid form of atorvastatin was characterized and clearly distinguishable even among various amorphous and disordered forms. The proposed method was also found to be suitable for both qualitative and quantitative analysis of mixtures of various forms of atorvastatin. Reliability of the proposed method was extensively examined by comparing the obtained results with other experimental techniques such as (13)C CP/MAS NMR, FTIR and XRPD. As highly linear correlations between the sets of parameters obtained from different experimental data were found, the perspectives of the applied comparative factor analysis to obtain detail structural view on variability of amorphous forms of atorvastatin are also discussed. Although the reported method was tested on atorvastatin, authors expect wider application for any fluorinated compound to give the routine, fast and reliable characterization of amorphous forms of APIs in drug products even at low concentrations (1-5%). Bear in mind that 20-25% of currently developed pharmaceuticals contain at least one fluorine atom in the molecule.
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