Comprehensive studies on physical and chemical stability in liquid and glassy states of Telmisartan (TEL): Solubility advantages given by cryomilled and quenched material

Karolina Adrjanowicz (1) , Marian Paluch (2) , Kamil Kaminski (2) , Lukasz Hawelek (2) , Katarzyna Grzybowska (2) , Daniel Zakowiecki (3)

1 Institute of Physics
2 Institute of Physics
3 Preformulation Department R&D

To make full use of the advantages given by amorphous pharmaceuticals it is necessary to understand the basic factors that determine their physical and chemical stability. Molecular mobility seems to be the most important one. Unfortunately, due to exceedingly long time scale required for molecular motion in the glassy state, direct monitoring of structural -relaxation time ( in this temperature regime is rather difficult. The aim of current studies was to provide complete information about the time scale of -mobility in glassy state of Telmisartan (TEL). For this drug a global molecular mobility seems to be the most dominant factor responsible for its long-term stability. Based on some estimation presented in our previous papers we concluded that at room temperature molecular mobility associated with the structural relaxation would exceed 3 years. Now, to characterize the temperature behavior of structural relaxation below glass temperature, Tg, we have used modified the Adam-Gibbs approach. Additionally, using results of dielectric measurements, we have performed a comparative analysis of molecular dynamics of amorphous TEL prepared by cryomilling as well as obtained by quench-cooling of the melt. The X-ray diffraction analysis was also carried out to confirm long-term stability of amorphous TEL, whereas solubility studies revealed its markedly better solubility profile than that for crystalline form. These findings have important implications for the further handling with this drug.

Mots clés: Physical Sciences

Karolina Adrjanowicz, Marian Paluch, Kamil Kaminski, Lukasz Hawelek, Katarzyna Grzybowska, et al.. Comprehensive studies on physical and chemical stability in liquid and glassy states of Telmisartan (TEL): Solubility advantages given by cryomilled and quenched material. Philosophical Magazine, 2011, pp.1. ⟨10.1080/14786435.2010.534742⟩. ⟨hal-00659045⟩