Harnessing copovidone properties by hot melt extrusion with colloidal silicon dioxide for a novel co-processed pharmaceutical excipient development

Abstract

Vinylpyrrolidone-vinyl acetate copolymer (copovidone) is commonly used in oral solid dosage systems for its solubilizing and binding properties but suffers from native hygroscopicity and high mechanical fiber strength of its extruded strands, resulting in processing issues, compromised manufacturability, and formulation issues in long term storage. Herein, we report a co-processed excipient of copovidone (Plasdone™ S-630) with colloidal silicon dioxide (Aerosil® 200 Pharma) processed by a twin-screw HME setup. Aerosil® 200 was used to counteract moisture sensitivity and minimize extrude hardness by creating brittleness without changing the chemical composition. The optimized extrudes were extensively characterized by texture analysis, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), hot stage microscopy (HSM), contact angle and wettability study, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and X-ray micro-computed tomography. Ritonavir (RTV), a poorly water-soluble (BCS class II) antiretroviral agent, was used as a model drug to determine the functional performance of the fabricated excipients in direct compression tablet formulations. Tablets with co-processed excipient exhibited a 1.70-fold increase in % drug release at 2h (97% in 120 minutes). This work presents a facile method for designing a suitable co-processed excipient capable of modulating the release of poorly aqueous-soluble drugs.