Development of diclofenac sodium controlled release solid dispersion powders and capsules by freeze drying technique using ethylcellulose and chitosan as carriers

Controlled-release, solid dispersions of diclofenac sodium (DS) were prepared by freeze-drying technique, using ethylcellulose (EC) and chitosan (CS) as single and combined carriers. Factorial design was applied as an experimental design to study the main and interactive effects of EC and CS on drug dissolution from the controlled release solid dispersion. All DS solid dispersions showed slower drug dissolution than did DS powder. The equations of dissolution parameters as functions of EC and CS contents were established through multiple regression. The contour plots of the established equations were constructed. The 10:(2.4 + 0.05) DS:(EC + CS) solid dispersion was prepared and developed into a capsule dosage from, using lactose as diluent. The effect on capsule dissolution of a disintegrant, sodium starch glycolate (Explotab(R)), in concentrations of 2%, 5%, and 8% was studied. The solid-dispersion capsule containing 5% Explotab was found to provide the most similar dissolution profile to the one obtained with the 10:(2.4 + 0.05) DS:(EC + CS) solid-dispersion powder. The dissolutions of the 10:(2.4 + 0.05) solid-dispersion powder and capsules were closer to a first-order model than to a zero-order or diffusion control model.