Characterization of factors affecting the release of low-solubility drug from prolonged release tablets

Diclofenac sodium (2-[(2,6-dichlorophenyl)amino]benzeneacetic acid monosodium salt) was investigated as a low-solubility drug and Naklofen® retard prolonged release tablets, containing 100 mg of diclofenac sodium as a prolonged release lipophilic matrix system using factorial design approach. First, the solubility characteristics of diclofenac sodium in aqueous media with various ionic strengths, ionic compositions and pH in the range of 1–8 were determined. The obtained results showed that the solubility of diclofenac sodium depends mainly on pH of the aqueous medium and less on the composition and ionic strength of the medium. Next, the estimation of the effects of six different factors (type of the dissolution apparatus, rotation speeds of the stirring elements, pH, ionic strengths of dissolution medium, the applied salt, and the producer of the on-line connected dissolution apparatus and UV spectrophotometer) on the release of diclofenac sodium, using the two-level six-factorial design was investigated. It was found that rotation speeds of the stirring elements, pH, and ionic strengths of the dissolution medium have a significant impact on the drug release and should be further followed in future drug release analyses. The advantages of the factorial design approach are obvious in this work. It is a very economic way of obtaining the maximum amount of information in a short period of time, especially in the case of prolonged release formulations where each experiment requires at least 24 h.