Preparation of highly stable diclofenac potassium pellet with microcrystalline cellulose by extrusion–spheronization

摘要

Abstract The main purpose of this study is to prepare highly stable diclofenac potassium (DP) pellet with microcrystalline cellulose (MCC) by extrusion–spheronization. Using MCC, {DP} pellets were prepared and the stability was investigated. Related compounds of {DP} pellets were analyzed by High Pressure Liquid Chromatography (HPLC). After stability test of 60?°C/75% {RH} for 10?d, the values of two main related compounds were 0.94% and 2.17%, respectively. Compatibility tests show that instability of {DP} was mainly caused by MCC. To improve the stability of {DP} in presence of MCC, different kinds of stabilizers were investigated. Upon addition of 1.5% (w/w) sodium hydroxide, the primary related compound of pellets was reduced to be 0.159% after stability test of 60?°C/75% {RH} for 50?d. This study demonstrated that {MCC} induced decomposition of {DP} upon exposure to moisture could be prohibited by addition of sodium hydroxide. The mechanisms were discussed and residual hydroxyl free radicals in excipients were responsible for decomposition of DP. Finally, this formulation of {DP} is highly stable with sustained-release behavior.