Abstract Emulsification/internal gelation has been suggested as an alternative to extrusion/external
gelation in the encapsulation of several compounds including non-steroidal anti-inflammatory
drugs such as diclofenac sodium. The objective of the present study was a trial to formulate diclofenac
sodium as controlled release microparticles that might be administered once or twice daily. This
could be achieved via emulsification/internal gelation technique applying Box-Behnken design to
choose these formulae. Box-Behnken design determined fifteen formulae containing specified
amounts of the independent variables, which included stirring speed in rpm (X1), drug:polymer
ratio (X2) and the surfactant span 80% (X3). The dependent variables studied were cumulative percent
release after two hours (Y1), four hours (Y2) and eight hours (Y3). The prepared microparticles
were characterized for their production yield, sizes, shapes and morphology, entrapment efficiency
and Diclofenac sodium in vitro release as well. The results showed that the production yield of the
prepared diclofenac sodium microparticles was found to be between 79.55% and 97.41%. The formulated
microparticles exhibited acceptable drug content values that lie in the range 66.20–96.36%.
Also, the data obtained revealed that increasing the mixing speed (X1) generally resulted in
decreased microparticle size. In addition, scanning electron microscope images of the microparticles
illustrated that the formula contains lower span concentration (1%) in combination with lower stirring
speed (200 rpm) which showed wrinkled, but smooth surfaces. However, by increasing surfactant
concentration, microspheres’ surfaces become smoother and slightly porous. Kinetic treatment
of the in vitro release from drug-loaded microparticles indicated that the zero order is the drug
release mechanism for the most formulae.