In Silico and in Vitro Evaluation of Silk Fibroin Based Amorphous Ball-Milled Binary Solid Dispersion for Improved Solubility, Dissolution and Tablettability: The Case of Naproxen

Abstract

The present study aims to use a natural protein silk fibroin (SF) to enhance solubility, dissolution, tablettability, and subsequently, delivery of naproxen (NP) using a green technique  ball milling. The development of SF and NP solid dispersion (SF-NP-SD) for enhancing the solubility, dissolution, and compatibility of NP using ball milling. In silico molecular docking indicated a strong binding affinity of SF towards NP. Herein, SF-NP-SD (1:1) showed significant improvement (p 0.05) in saturation solubility (12 fold) and dissolution (1.46 fold) of NP. Along with reduced wetting time (p 0.05), optimum values of flowability, compressibility, and compatibility were noteworthy. The spectroscopic analysis confirmed favorable interactions, amorphization, and stabilization of NP. The tablet formulation of SF-NP-SD exhibited 1.38-fold enhanced dissolution. Molecular-level hydrophobic and hydrophilic interactions of SF favor molecular-level dispersion, enhance solubility and dissolution, and consecutively, improve drug delivery of NP.