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Polyethylene oxides: protection potential against polymorphic transitions of drugs?
Author(s) -
Schmidt Andrea G.,
Wartewig Siegfried,
Picker Katharina M.
Publication year - 2004
Publication title -
journal of raman spectroscopy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.748
H-Index - 110
eISSN - 1097-4555
pISSN - 0377-0486
DOI - 10.1002/jrs.1158
Subject(s) - tableting , amorphous solid , raman spectroscopy , microcrystalline , differential scanning calorimetry , recrystallization (geology) , theophylline , microcrystalline cellulose , materials science , polyethylene glycol , chemistry , chemical engineering , analytical chemistry (journal) , crystallography , organic chemistry , cellulose , thermodynamics , composite material , medicine , paleontology , physics , engineering , biology , optics , endocrinology
Polyethylene oxides (PEOs) were analysed in mixtures with polymorphic drugs to test their potential in order to prevent polymorphic or pseudopolymorphic transitions, which are induced by the tableting process. Five PEOs with different molecular weights were tested in comparison with the well‐known tableting excipients microcrystalline cellulose (MCC), hydroxypropylmethylcellulose (HPMC) and dicalcium phosphate dihydrate (DCPD). Amorphous indomethacin was chosen as the model drug. Its recrystallization behaviour is well known and can be mechanically stimulated. Theophylline monohydrate was also used; its dehydration is induced by tableting. Pure materials and mixtures containing 20% (w/w) of drug were compressed at different maximum relative densities. The tablets were broken in order to determine the degree of transformation inside by FT‐Raman spectroscopy. For quantitative interpretation, the intensities of representative Raman bands were used. Differential scanning calorimetry (DSC) was applied additionally. In tablets and mixtures of amorphous indomethacin and PEOs, recrystallization was dramatically lowered in comparison with the other excipients. The molecular weights of the various PEOs seem to have no influence. The Raman spectra indicate chemical interactions as the reason. Thus, PEO can stabilize amorphous indomethacin. DSC investigations verified these results. For theophylline monohydrate, no interactions could be detected and DCPD showed the best protection properties. Hence the results concerning indomethacin cannot be generalized, but blending with PEO could be a simple method to stabilize amorphous indomethacin. Copyright © 2004 John Wiley & Sons, Ltd.