Physical Stability and Molecular Mobility of Resveratrol in a Polyvinylpyrrolidone Matrix

Abstract

The physical stability, molecular mobility, and appearance of nanocrystalline resveratrol in a polyvinylpyrrolidone (PVP) matrix were investigated. Two formulations with resveratrol loadings of 30% and 50% were prepared and characterized using powder X-ray diffraction (PXRD) and time-domain nuclear magnetic resonance (TD-NMR). Samples were studied over time (up to 300 days post-preparation), across temperatures (80-300 K), and under varying humidity conditions (0% and 75% relative humidity). The results demonstrate that the 30% resveratrol-PVP sample is a homogeneous amorphous solid dispersion (ASD), while the 50% resveratrol-PVP sample contained resveratrol nanocrystals measuring about 40 nm. NMR measurements and molecular dynamics (MD) simulations revealed that incorporation of resveratrol into the polymer matrix modifies the system's dynamics and mobility compared to the pure PVP polymer. Additionally, MD simulations analyzed the hydrogen bonding network within the system, providing insights for a better understanding of the physical stability of the ASD under different conditions.

Keywords: molecular mobility; physical stability; polyvinylpyrrolidone; relaxometry; resveratrol; time-domain NMR.

Figure 1

Sketches showing the chemical structures of (a) a resveratrol molecule and (b) a PVP monomer.

Figure 2

PXRD spectra for (a) bottom panel: PVP70/RSV30 in 0% RH just after preparation, top panel: PVP70/RSV30 stored in 75% RH for 300 days; (b) bottom panel: PVP50/RSV50 in 0% RH just after preparation, middle panel: PVP50/RSV50 stored in 75% RH for 300 days, top panel: crystalline resveratrol.

Figure 3

Spin–lattice T₁ relaxation times as a function of the time since the sample preparation for samples (a) stored in 0% RH and (b) in 75% RH; ● PVP70/RSV30, □ short component, ■ long component of PVP50/RSV50.

Figure 4

FID curves measured for the (a) PVP70/RSV30 and (b) PVP50/ASD50 samples on the first day since preparation (0% RH; bottom line), just after placing the samples in 75% RH (middle line), and after 300 days in 75% RH (top line).

Figure 5

¹H spin–lattice relaxation time T₁ values for (Δ) PVP, (●) PVP70/RSV30, and the (■) (□) PVP50/RSV50 shorter and longer components. The solid lines are the best fit to experimental points of Equation (1) including 3 relaxation processes.

Figure 6

Snapshot of a supercell of ASD (a) PVP70/RSV30 (b) and PVP70/RSV30/H₂O systems corresponding to the final configuration after the minimization procedure. PVP chains are represented in orange, RSV—blue, water: oxygen—red, hydrogen—white.

Figure 7

Intermolecular pair distribution functions (a) between oxygens for all atoms, (b) between oxygens in RSV, (c) between oxygens from –C=O groups of PVP chains and hydrogens in RSV, and (d) between oxygens from –C=O groups of PVP chains and hydrogens in water molecules. Blue lines—PVP70/RSV30, red lines—PVP70/RSV30/H₂O systems.

Figure 8

Fragment of (a) a PVP chain (orange) with RSV molecules linked to the chain via hydrogen bonding in PVP/RSV30 and (b) a PVP chain (orange) with RSV molecules and water molecules linked via hydrogen bonding. In RSV and water molecules: carbon atoms—grey, oxygen—red, hydrogen—white.

Figure 9

Orientational distribution function of P(Q) for the (a) C5-C7-C8-C9 and (b) C4-C5-C7-C8 torsional angles for the PVP70/RSV30 (blue points) and PVP70/RSV30/H₂O (red points) systems.

Figure 10

(a,b) Sketch of the resveratrol molecules showing selected torsional angles (marked in green) and (c,d) corresponding angular correlation functions for PVP70/RSV30 (blue points) and PVP70/RSV30/H₂O (red points).

Figure 10

(a,b) Sketch of the resveratrol molecules showing selected torsional angles (marked in green) and (c,d) corresponding angular correlation functions for PVP70/RSV30 (blue points) and PVP70/RSV30/H₂O (red points).