Fabrication of amorphous solid dispersion of Entacapone for enhanced solubility and dissolution rate: Morphology, solid state characterization, In silico molecular docking studies

Formulation scientists face a significant challenge when dealing with APIs categorized as Biopharmaceutical Classification System (BCS) class II and IV, primarily because of their limited solubility. Entacapone (ENT), a BCS class IV drug, exhibits poor water solubility, resulting in limited oral bioavailability. The primary purpose of this research investigation was to utilize the Amorphous Solid Dispersion (ASD) approach to augment the solubility and dissolution rate of ENT. To achieve this objective, different polymers that were screened included Soluplus (R) (SOL), Copovidone (R) (COP), Hydroxypropyl methylcellulose (HPMC) E5, and Polyethylene glycol (PEG) 6000. Utilizing physical characterization techniques such as PXRD, DSC, PLM, and SEM, alterations in the solid state during dispersion formation were observed, confirming the reduced crystallinity of ENT within ASDs. In the ASD prepared with COP (20% ENT + 80 %COP ASD), the solubility increased by 10-fold and 50-fold compared to the crystalline ENT in enzyme-free SGF and enzyme-free SIF, respectively. In enzyme-free SIF media, 20 %ENT+80 %COP ASD exhibited a rapid dissolution rate and generated significant supersaturation levels compared to crystalline and amorphous ENT. In silico molecular docking experiments and ssNMR were used to investigate the binding interactions between ENT and COP. The XPS surface analysis of the optimized ASD revealed intermolecular interactions between the API and polymer. The results highlighted the significance of hydrogen bonding between ENT and COP. Furthermore, stability studies indicated that the formulation remained stable for up to 2 months at 40 degrees C/75 % RH, with no impact on amorphicity. Our study demonstrated that the ASD technique can overcome poor solubility and dissolution constraints of ENT.