Enhancement of Aqueous Solubility and Dissolution of Celecoxib through Phosphatidylcholine-Based Dispersion Systems Solidified with Adsorbent Carriers

Abstract

This study aimed to design phosphatidylcholine (PC)-based solid dispersion (SD) systems for enhancing the apparent aqueous solubility and dissolution of celecoxib (CLC), a selective cyclooxygenase-2 inhibitor with a highly hydrophobic property. Although PC-based dispersion formulations considerably increased solubilities of CLC, the lipidic texture of PC was not appropriate as a solid dosage form for oral administration of CLC. To mask the lipidic texture of PC-based matrices, Neusilin (R) US2, an adsorbent material with a porous structure and large surface area widely used in the pharmaceutical industry, was employed and thereby fully powderized PC-based dispersion formulations could be fabricated. However, PC matrices containing CLC strongly adsorbed to the pores of Neusilin (R) US2 was not able to be rapidly released. To address this problem, different hydrophilic materials were examined to promote the release of the CLC-dispersed PC matrices from Neusilin (R) US2. Among tested hydrophilic materials, croscarmellose sodium was the most suitable to facilitate fast drug dissolution from Neusilin (R) US2 particles, showing significantly enhanced apparent aqueous solubility and dissolution behavior of CLC. Through differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy (FT-IR) analysis, a considerably reduced crystallinity of CLC dispersed in the PC-based dispersion formulations was demonstrated. The PC-based SD formulations developed in this study would be useful for improving the oral bioavailability of poorly soluble drugs such as CLC.