Molecular dynamics, physical stability and solubility advantage from amorphous indapamide drug.

This study for the first time investigates physicochemical properties of amorphous indapamide drug (IND), which is a known diuretic agent commonly used in the treatment of hypertension. The solid-state properties of the vitrified, cryomilled and ball-milled IND samples were analyzed using X-ray powder diffraction (XRD), mass spectrometry, nuclear magnetic resonance (NMR), infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and broadband dielectric spectroscopy (BDS). These analytical techniques enabled us (i) to confirm the purity of obtained amorphous samples, (ii) to describe the molecular mobility of IND in the liquid and glassy state, (iii) to determine the parameters describing the liquid-glass transition i.e. Tg and dynamic fragility, (iv) to test the chemical stability of amorphous IND in various temperature conditions and finally (v) to confirm the long-term physical stability of the amorphous samples. These studies were supplemented by density functional theory (DFT) calculations and apparent solubility studies of the amorphous IND in 0.1 M HCl, phosphate buffer (pH=6.8), and water (25 and 37 °C).

Impact of water on molecular dynamics of amorphous α-, ß-, and γ-cyclodextrins studied by dielectric spectroscopy.

Dielectric, calorimetric, and x-ray diffraction measurements were carried out on α-, ß-, and γ-cyclodextrins, which are cyclic saccharides built by, respectively, six, seven, and eight glucose units connected via glycosidic linkage. Differential scanning calorimetry measurements indicated that each carbohydrate has a melting temperature located much above the temperature at which thermal decomposition begins. Moreover, calorimetric data revealed that it is possible to completely dehydrate each cyclodextrin by annealing them above 413 K. Unfortunately, it is impossible to obtain amorphous forms of cyclodextrin by simple cooling of the melt. Thus, a solid state amorphization method has been applied. X-ray diffraction studies demonstrated that by ball milling at room temperature we are able to obtain completely amorphous cyclodextrins. Finally, dielectric measurements were carried out to probe molecular dynamics in the amorphous state of cyclodextrins. It was found that there is only one relaxation process in amorphous hydrated cyclodextrins, while in dried samples two secondary relaxations are present. Moreover, we have shown that water has an enormous effect on the dynamics of both relaxation modes, i.e., with increasing content of water, the activation energy of the slow mode decreases, while that evaluated for the fast mode increases. We were not able to follow the dynamics of the structural relaxation process, because glass transition temperatures of amorphous cyclodextrins were found to lie above thermal degradation points.

Phase transition of displacive type in PbZr(0.94)Ti(0.06)O(3).

In this paper the electrostrictive properties above T(εmax), represented by the field-related M and polarization-related Q coefficients, have been reported for Pb(Zr(1-x)Ti(x))O(3) ceramics with x = 0.03-0.10. Among M(11)(T) and Q(11)(T) dependences, those found for Pb(Zr(0.94)Ti(0.06))O(3) have been clearly distinguished. In this case, the Q(11)(T) dependence is linear in the whole temperature range above T(εmax). Experimental and theoretical analysis of the M(11)(T) dependences has shown that the phase transition to the ferroelectric phase in Pb(Zr(0.94)Ti(0.06))O(3) ceramics seems to be of the displacive type.