Molecular Dynamics, Physical Stability and Solubility Advantage from Amorphous Indapamide Drug

Abstract

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).

Transformation of an active pharmaceutical ingredient upon high-energy milling: A process-induced disorder in Biclotymol

“…Thus, the life expectancy of the amorphous state has to be addressed and optimized to secure protocols of formulation (Bhugra and Pikal, 2008). In recent years, a great effort has been dedicated to the study of "crystal to glass transformation" induced by milling (Wojnarowska et al, 2013) (Descamps et al, 2015). To date, a streamlining of transformations reached by milling has not been attained even if some empirical rules are emerging from current investigations (Dujardin et al, 2013).…”

Correlation between molecular dynamics and physical stability of two milled anhydrous sugars: Lactose and sucrose

“…Another important aspect to consider when milling crystalline materials is the fact that, the amorphous phase inevitably contains some quantity of moisture (either generated from within the material in case of crystalline hydrates or adsorbed from the environment). A recent study on ball milled indapamide (Wojnarowska et al, 2013) has suggested the presence of a water relaxation peak rather than the typical relaxation processes of amorphous phase. The distribution of this water affects the molecular dynamics of the amorphous phase and is therefore important in defining the stability of this phase.…”

Synthesis and amide imidic prototropic tautomerization in thiophene-2-carbohydrazide: XRD, DFT/HSA-computation, DNA-docking, TG and isoconversional kineticsviaFWO and KAS models

“…[5][6][7][8] Moreover, the carbohydrazide small molecule function as an essential pharmacophore in many therapeutically valuable materials, for example, the antiviral, antibacterial and antitubercular biological activities were dramatically increased by inserting the thiophene-carbohydrazide in the structure of big molecules. [5][6][7][8][9][10][11][12] Therefore, a huge number of heterocyclic carbohydrazide derivatives have been made available. [6][7][8][9][10][11][12][13][14][15] The prototropic tautomers are compounds that can be interconverted from molecule to another via single proton migration from group to the close neighbor atom.…”

“…[5][6][7][8][9][10][11][12] Therefore, a huge number of heterocyclic carbohydrazide derivatives have been made available. [6][7][8][9][10][11][12][13][14][15] The prototropic tautomers are compounds that can be interconverted from molecule to another via single proton migration from group to the close neighbor atom. 16 It's known that there is no pure separating line between such tautomers and isomers: tautomer is obviously isomer that transform with a comparatively depressed activation energy <20 kcal mol À1 .…”