Polyethylene oxides: protection potential against polymorphic transitions of drugs?

Abstract

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 wellknown 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.

An Investigation of Nifedipine Miscibility in Solid Dispersions Using Raman Spectroscopy

“…The strength of drug-polymer hydrogen bonding has also been studied by XPS (14) and ss-NMR (16) based on the shift in peak position. Recently, Raman spectroscopy has been widely utilized to reveal the occurrence of specific interaction (5,15,19,21,23). As with IR, changes in the chemical environment of the drug will affect the Raman spectral pattern in terms of peak position (15,(19)(20)(21)(22)(23)(24), peak shape (22) or new peaks (5,24).…”

“…The strength of intermolecular interaction is a key factor governing the physical stabilization of solid dispersions and it may be related to the miscibility of the drug in the polymer matrix (7). To date, there have been several attempts to apply analytical methods to characterize drug-polymer miscibility, e.g., differential scanning calorimetry (DSC) (3,(8)(9)(10)(11)(12)(13)(14)(15)(16), infrared spectroscopy (IR) (8)(9)(10)(11)(12)(13)(17)(18)(19), solid state-nuclear magnetic resonance (ss-NMR) (14,16), Xray powder diffractometry (XRD) (10), X-ray photoelectron spectroscopy (XPS) (14) and Raman spectroscopy (15,(19)(20)(21)(22)(23). The strength of intermolecular hydrogen bonding between drug and polymer in a solid dispersion has been investigated by IR based on the peak position (12,13,18) and peak height ratio (13,17).…”

The effects of tableting with potassium bromide on the infrared absorption spectra of indomethacin

“…This point is evidence for relaxation of the disordering of the crystal lattice which had started, along with recrystallization of indomethacin. It should be noted that this behavior of the system can only occur in the presence of the KBr matrix because, as demonstrated in [1], the presence of the excipient PEG should prevent the process of recrystallization of IM in powders and tablets.…”

“…Indomethacin is used in medicine as an anti-inflammatory. PEG, as demonstrated recently by Raman spectroscopy [1], can evidently prevent tableting-induced polymorphous transitions in indomethacin.…”

Application of Polyglycolized Glycerides in Protection of Amorphous Form of Etoricoxib during Compression

“…It was found to be superior to microcrystalline cellulose, the effect was attributed to the high elasticity of carrageenan during tableting. [5][6][7] Schmidt et al 8) have reported the potential of polyethylene oxides for protection of amorphous indomethacin due to tableting. Similarly, heterogeneous system containing lipids has been reported for enzyme stabilization in the tablet form.…”