Synergistic Effect of Synthetic Magnesium Aluminometasilicate and Dual Polymer in Celecoxib Solubilization by Solid Dispersion Method

Abstract

Purpose

The solid dispersion (SD) method has long been used to solubilize poorly soluble drugs in aqueous solutions. The aim of this study was to develop a celecoxib (CXB) dual polymer multisystem with CXB solubility characteristics, using the SD method. The hypothesis was: changing the pH environment of CXB in SD formulations using a Neusilin®UFL2 and maximizing solubilization through dual polymer.

Methods

The CXB SD formulations were prepared with carrier and dual polymer by solvent evaporation method. The optimal SD formulation were evaluated the physicochemical properties such as thermal change, crystallinity, and drug-excipient interaction.

Results

The optimal SD formulation (SD4, CXB:UFL2®:PVP/VA S630:K12®:chitosan = 1:1:0.5:0.5:0.5, weight ratio) significantly improved the dissolution (%) of CXB compared with the dissolution achieved using the commercial product (Celebrex®) in various dissolution media. The structure of CXB in the SD4 formulation changed from crystalline to amorphous, and intermolecular interactions between CXB and the excipients were confirmed. The SD4 formulation was shown to be stable for 12 months.

Conclusions

A novel CXB solubilization method using a dual polymer multisystem was tested and found to be effective; the results showed improved stabilization compared with the conventional method. These results are likely due to changes in the pH environment, drug crystallinity, and intermolecular interactions between CXB and the excipients. Further investigation of the SD4 formulation as well as animal studies are warranted, in order to test whether oral bioavailability is higher than that of Celebrex®.