Molecular Dynamics and Diffusion in Amorphous Solid Dispersions Containing Imidacloprid

Abstract

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 (T g ), 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 m 2 s −1 , while the viscosity values of the dispersions at T g varied between 10 8 Pa s and 10 10 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.

Modified Free Volume Theory for Self-Diffusion of Small Molecules in Amorphous Polymers

“…Note that the reverse proportionality between D R and η has been experimentally shown to remain practically unchanged close to T g . This process was followed by inserting the obtained viscosities at each temperature into the F-SE relation according to the procedure elaborated in a previous work Figure draws a comparison between the predictions of the original and modified FVT with the experimental data.…”

“…Diffusion of small species within polymeric matrices represents a field of growing technical importance to various industrial applications. Particularly in formulation technologies, diffusion of active ingredients in polymers gains practical relevance for ensuring the physical stability of pharmaceutical amorphous solid dispersions, controlled pesticide release from polymers, , design of intravaginal drug delivery systems, , and development of insecticide-impregnated mosquito nets . The free volume theory (FVT) of Vrentas and Duda , offers an efficient predictive approach for estimating the self-diffusivity of small molecules in amorphous non-cross-linked polymers, proven to be consistent with experimental data on multiple occasions. , However, shortcomings such as appearance of negative values of specific hole free volume and the need for at least two measured diffusivity values leave room for improving this model.…”

Relaxation and diffusion of an ionic plasticizer in amorphous poly(vinylpyrrolidone)

“…35–46 PVP-based amorphous solid dispersions featuring pharmaceuticals such as nifedipine, 47,48 indomethacin, 49–51 and others were also investigated. 52…”

“…[35][36][37][38][39][40][41][42][43][44][45][46] PVP-based amorphous solid dispersions featuring pharmaceuticals such as nifedipine, 47,48 indomethacin, [49][50][51] and others were also investigated. 52 Another area of research, which is particularly relevant for energy storage technologies, is the transport of penetrants that act as electric charge carriers in polymer matrices. 23,[53][54][55] The workhorse material here is polyethylene oxide, 56 a semicrystalline polar polymer doped with various salts in a rather reduced concentration range.…”