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

Abstract

The vinylpyrrolidone–vinyl acetate copolymer (copovidone) is commonly used in oral solid dosage systems for its solubilising and binding properties, but suffers from native hygroscopicity and the high mechanical fibre strength of its extruded strands, resulting in processing issues, compromised manufacturability, and formulation issues during long-term storage. Herein, we report a co-processed excipient, copovidone (CPS) (Plasdone™ S-630) with colloidal silicon dioxide (Aerosil® 200 Pharma) (AP), processed using a twin-screw HME setup. AP was used to counteract moisture sensitivity and minimise extrude hardness by creating brittleness without changing the chemical composition. The optimised extrudes were extensively characterised by texture analysis, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), hot stage microscopy (HSM), contact angle and wettability studies, 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 assess the functional performance of the fabricated excipients in direct-compression tablet formulations. Tablets with a co-processed excipient exhibited a 1.70-fold increase in % drug release at 2 h (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.