Abstract
Molecular reorientations in rosuvastatin calcium, a drug that is widely used to prevent cardiovascular disease, were explored thoroughly by means of solid state nuclear magnetic resonance (1H and 13C NMR) combined with calculations of steric hindrances. The experimental results reveal rich internal reorientational dynamics. All relaxation processes were tested in a broad range of temperatures and described in terms of their type and the associated energy barriers. The internal molecular mobility of rosuvastatin calcium can be associated with the reorientational dynamics of four methyl groups, accompanied by reorientation of the isopropyl group. The energy barriers of methyl and isopropyl group reorientation depended on the type of E/Z isomers, while the water content also had a strong influence on the dynamics of the isopropyl group. In the paper, a consistent picture of the molecular dynamics is provided, facilitating our understanding of molecular mobility in this important pharmaceutical solid.
Highlights
A great number of active pharmaceutical ingredients (API) show low bioavailability due to their poor solubility
It is generally believed that knowledge of molecular dynamics, which is determined by intra- and intermolecular interactions, is of great importance in understanding the physicochemical properties of amorphous systems and for development of methods for enhancement of their physicochemical stability.[5,6]
We report our attempt to identify and describe molecular reorientation in amorphous RVCa, as well as to determine whether and how the water content of the sample in uences anion dynamics
Summary
A great number of active pharmaceutical ingredients (API) show low bioavailability due to their poor solubility. Their amorphous form is usually characterised by higher solubility. The use of amorphous substances is associated with problems due to their low physical stability.[1,2,3,4] It is generally believed that knowledge of molecular dynamics, which is determined by intra- and intermolecular interactions, is of great importance in understanding the physicochemical properties of amorphous systems and for development of methods for enhancement of their physicochemical stability.[5,6] In particular it has been found that the rate of global mobility (a-relaxation) close to the glass transition correlates with the tendency to crystallisation of APIs.[7,8,9] the molecular reorientations described by the so-called local mobility (b-relaxation)[7,9,10] can in uence on the recrystallization of amorphous systems. Molecular reorientations in amorphous systems are studied by nuclear magnetic resonance and quasielastic neutron scattering methods.[5,11,12,13,14,15,16,17,18] On the other hand, attempts
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