Development of celecoxib-UFL2®-dual polymer-chitosan solid dispersion using a tetra-system and evaluation of its solubility and permeability

Abstract

Drug solubilization is currently a major challenge. Therefore, the solid dispersion (SD) method has been used for over 60 years to solubilize and solidify drugs. This study aimed to investigate the solubilization and stabilization of celecoxib (CXB) using a tetra system with the SD method (solvent evaporation). The strategy was to improve CXB solubility by increasing the pH and dispersibility using UFL2®. Additionally, solubilization was promoted using a dual polymer, and stabilization was achieved using chitosan. The optimal SD1 formulation was confirmed based on physicochemical properties, dissolution, permeability, solubility, and stability tests. The dissolution (%) of the optimal SD1 formulation (CXB:UFL2®:IR®:K12®:chitosan = 200:150:100:100:50, weight ratio) was significantly improved, 1.81-, 2.56-, and 1.73-fold higher than that of Celebrex® in different dissolution media with sodium lauryl sulfate (SLS, 0.25 % w/v). In permeability evaluations of four types of membranes, it showed results superior to those of Celebrex®. In particular, CXB in the SD1 formulation changed from a crystalline to an amorphous form, with the accompanying thermal changes and hydrogen interactions. Moreover, the SD1 formulation remained stable for three months. In conclusion, the SD1 formulation has strong dissolution, solubility, and permeability and is considered worthy of industrial use. Animal testing with the improved formulations is also expected to yield encouraging results.