A multifaceted approach for grading of polymers for the development of stable amorphous solid dispersion of Riluzole

Abstract

The current work involves grading three widely used polymers for preparing a kinetically and thermodynamically stable amorphous solid dispersion (ASD) of a neuroprotective drug Riluzole (RLZ) by evaluating the drug-polymer interactions. Polymers were screened based on their chemical interaction with RLZ and their ability to inhibit the crystallization of the drug. Detailed computational studies were performed to quantify the non-covalent interactions between RLZ and the modelled structures of polymers; polyacrylic acid (PAA), polyvinylpyrrolidone vinyl acetate (PVP VA), and hydroxypropyl methyl cellulose acetate succinate (HPMC AS) for calculating the interaction energies of drug-polymer complexes. Experimental characterization of drug-polymer complexes through analytical techniques further validated the formation of the drug-polymer complexes. The results indicated that RLZ interacts with the polymers in the order PAA > PVP VA > HPMC AS, giving an insight into the stability of drug-polymer complexes. In vitro dissolution study also showed higher dissolution profile of RLZ with PAA. Further, the drug-polymer miscibility was determined by employing Flory-Huggins theory and stability in accordance with Gibbs free energy of mixing and phase diagram. This work presented a multi-technique approach for the grading of polymers in search of a stable ASD of the poorly water-soluble drug RLZ.