The effect of formulation and processing parameters on processability and release from hot-melt extrusion (HME)-based matrices appears to be API and polymer dependent. Accordingly, the aim of this work was to design an extended-release formulation of diclofenac sodium by using HME technique and design of experiment (DoE). The extrudates were prepared using a vertical lab-scale single screw extruder. A D-optimal design with 16 formulations was employed to evaluate and model the effect of diclofenac sodium, ethyl cellulose and Natrosol L levels on the release profile. The percentage of drug release at 2, 4, 8 and 16 h were the dependent variables. The formulation factors that affect drug release were identified and satisfactorily modeled. The goodness of fit (R2) and goodness of prediction (Q2) parameters obtained for release responses were 0.913 and 0.682 at 2 h, 0.946 and 0.67 at 4 h, 0.942 and 0.658 at 8 h, and 0.892 and 0.673 at 16 h, respectively. The design space of optimal fractions of ethyl cellulose and Natrosol L at various drug levels was successfully constructed by response surface methodology. In conclusion, the DoE approach helped to identify and quantify formulation variables that affect the release of diclofenac sodium from HME-based formulation.
Keywords: Hot-melt extrusion; design of experiments; diclofenac sodium; ethyl cellulose; extended-release; hydroxyethyl cellulose.