Potential of carrageenans to protect drugs from polymorphic transformation

Abstract

Carrageenans were analysed in mixture with polymorphic drugs to test their potential for minimising polymorphic or pseudopolymorphic transitions, which are induced by the tableting process. The κ-carrageenans Gelcarin ® GP-812 NF and Gelcarin ® GP-911 NF and the ι-carrageenan Gelcarin ® GP-379 NF were tested in comparison to the well-known tableting excipients microcrystalline cellulose (MCC), hydroxypropyl methylcellulose (HPMC), and dicalcium phosphate dihydrate (DCPD). Amorphous indomethacin was chosen as model drug since its well-known recrystallisation behaviour can be mechanically stimulated. Further on, theophylline monohydrate was used. Its dehydration is induced by tableting. Pure materials and mixtures containing 20% (w/w) drug were compressed up to different maximum relative densities. The data obtained during tableting were analysed by three-dimensional (3D) modelling. Afterwards tablets were broken and examined by Fourier transform Raman spectroscopy in order to determine the degree of transformation inside the tablet. For quantitative interpretation, the intensities of representative bands were used. Thermal analysis was used additionally. Using 3D modelling a decrease of plastic deformation can be noticed in the order HPMC>MCC>carrageenans, whereas DCPD represents an exception because of brittle fracture. Best hindrance of polymorphic transformation showed the carrageenans, the hindrance was slightly worse for HPMC. MCC and DCPD could not hinder transformation. A complete protection of the amorphous form could not be achieved. For theophylline monohydrate, the results were similar.