Boost of solubility and supersaturation of celecoxib via synergistic interactions of methacrylic acid-ethyl acrylate copolymer (1:1) and hydroxypropyl cellulose in ternary amorphous solid dispersions

Abstract

A current trend in the development of amorphous solid dispersions (ASDs) is the combination of two polymers for synergistic enhancement in supersaturation of poorly soluble drugs. We investigated the supersaturation potential of celecoxib (CXB) using combinations of methacrylic acid-ethyl acrylate copolymer (1:1) (EL 100–55) and hydroxypropyl cellulose (HPC) SSL. Initially, the supersaturation potential of single polymers and combinations in various ratios was assessed. While EL 100–55 and HPC SSL alone showed limited potential in solubility enhancement of CXB the combination of both polymers led to a boost of CXB solubility, whereby most promising results were obtained using a 50:50 polymer ratio. Binary and ternary CXB ASDs (10% drug load) were prepared via vacuum compressing molding (VCM) and hot melt extrusion (HME). ASDs were studied by exploring the miscibility and intermolecular interactions and tested for their dissolution performance. HPC SSL was identified to be a suitable precipitation inhibitor when added to a fast dissolving CXB: EL 100–55 ASD. Ternary ASDs showed even further dissolution improvement, when processed by HME. The combination of heat and shear stress led to a homogeneous and intimate mixture of EL 100–55 and HPC SSL, resulting in formation of synergistic interactions with pronounced impact on CXB supersaturation.