Inhibition of naproxen crystallization by polymers: The role of topology and chain length of polyvinylpyrrolidone macromolecules

This paper presents an innovative approach that utilizes self-synthesized homopolymers of polyvinylpyrrolidone (PVP) with different architectures as effective matrices for inhibiting the crystallization of naproxen (NAP). We have thoroughly investigated amorphous solid dispersions containing NAP and (i) self-synthesized linear PVP, (ii) self-synthesized three-armed star-shaped PVP, and (iii) self-synthesized linear PVP with a mass (M_n) corresponding to the length of one arm of the star polymer, as well as (iv) commercial linear PVP K30 as a reference. Differential scanning calorimetry, X-ray diffraction, and infrared spectroscopy studies, as well as molecular dynamics simulations were conducted to gain comprehensive insights into the thermal and structural properties, as well as intermolecular interactions in the NAP-PVP systems. The main purpose of all experiments was to assess the impact of macromolecule structure (topology, molecular weight) on the kinetics of the crystallization of NAP - a drug that is very difficult to vitrify. Our studies clearly showed that the most effective matrix in inhibiting the NAP crystallization is linear, self-synthesized PVP with higher molecular weight (M_n) similar to that of the commercial PVP K30, but lower, strictly controlled dispersity. We also found that crystallization of API proceeds at a similar pace for the binary mixture composed of a star-shaped PVP and linear polymer with M_n corresponding to M_n of one arm of the star-shaped macromolecule in the vicinity of the T_g. The obtained data highlight the key role of polymer structure in designing new pharmaceutical formulations.