Biomaterial Database

Molecular Dynamics and Diffusion in Amorphous Solid Dispersions Containing Imidacloprid. 2023

Ali Mansuri, and Philipp Münzner, and Anrika Heermant, and Fabian Patzina, and Tim Feuerbach, and Judith Winck, and Arnoldus W P Vermeer, and Werner Hoheisel, and Roland Böhmer, and Catalin Gainaru, and Markus Thommes

Department of Biochemical and Chemical Engineering, TU Dortmund University, 44227 Dortmund, Germany.

The main goal of this study is to develop an experimental toolbox to estimate the self-diffusion coefficient of active ingredients (AI) in single-phase amorphous solid dispersions (ASD) close to the glass transition of the mixture using dielectric spectroscopy (DS) and oscillatory rheology. The proposed methodology is tested for a model system containing the insecticide imidacloprid (IMI) and the copolymer copovidone (PVP/VA) prepared via hot-melt extrusion. For this purpose, reorientational and the viscoelastic structural (α-)relaxation time constants of hot-melt-extruded ASDs were obtained via DS and shear rheology, respectively. These were then utilized to extract the viscosity as well as the fragility index of the dispersions as input parameters to the fractional Stokes-Einstein (F-SE) relation. Furthermore, a modified version of Almond-West (AW) formalism, originally developed to describe charge diffusion in ionic conductors, was exercised on the present model system for the estimation of the AI diffusion coefficients based on shear modulus relaxation times. Our results revealed that, at the calorimetric glass-transition temperature (Tg), the self-diffusion coefficients of the AI in the compositional range from infinite dilution up to 60 wt % IMI content lied in the narrow range of 10-18-10-20 m2 s-1, while the viscosity values of the dispersions at Tg varied between 108 Pa s and 1010 Pa s. In addition, the phase diagram of the IMI-PVP/VA system was determined using the melting point depression method via differential scanning calorimetry (DSC), while mid-infrared (IR) spectroscopy was employed to investigate the intermolecular interactions within the solid dispersions. In this respect, the findings of a modest variation in melting point at different compositions stayed in agreement with the observations of weak hydrogen bonding interactions between the AI and the polymer. Moreover, IR spectroscopy showed the intermolecular IMI-IMI hydrogen bonding to have been considerably suppressed, as a result of the spatial separation of the AI molecules within the ASDs. In summary, this study provides experimental approaches to study diffusivity in ASDs using DS and oscillatory rheology, in addition to contributing to an enhanced understanding of the interactions and phase behavior in these systems.

UI	MeSH Term	Description	Entries
D011108	Polymers	Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., BIOPOLYMERS; PLASTICS).	Polymer
D002152	Calorimetry, Differential Scanning	Differential thermal analysis in which the sample compartment of the apparatus is a differential calorimeter, allowing an exact measure of the heat of transition independent of the specific heat, thermal conductivity, and other variables of the sample.	Differential Thermal Analysis, Calorimetric,Calorimetric Differential Thermal Analysis,Differential Scanning Calorimetry,Scanning Calorimetry, Differential
D004339	Drug Compounding	The preparation, mixing, and assembly of a drug. (From Remington, The Science and Practice of Pharmacy, 19th ed, p1814).	Drug Formulation,Drug Preparation,Drug Microencapsulation,Pharmaceutical Formulation,Compounding, Drug,Formulation, Drug,Formulation, Pharmaceutical,Microencapsulation, Drug,Preparation, Drug
D000073943	Neonicotinoids	A class of insecticides that are structurally similar to NICOTINE and have physiologically similar effects as agonists of NICOTINIC ACETYLCHOLINE RECEPTORS, but are less toxic to vertebrates. They are widely used in agriculture.	Neonicotinoid
D012995	Solubility	The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)	Solubilities
D013696	Temperature	The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.	Temperatures
D056004	Molecular Dynamics Simulation	A computer simulation developed to study the motion of molecules over a period of time.	Molecular Dynamics Simulations,Molecular Dynamics,Dynamic, Molecular,Dynamics Simulation, Molecular,Dynamics Simulations, Molecular,Dynamics, Molecular,Molecular Dynamic,Simulation, Molecular Dynamics,Simulations, Molecular Dynamics