Novel Use of Similarity Factors f₂ and S_d for the Development of Diltiazem HCl Modified-Release Tablets Using a 3² Factorial Design

ABSTRACT

The objective of this study was to develop modified-release tablets of diltiazem HCl using a direct compression technique. A 3² factorial design was employed using the amount of alkali-treated guar gum and cetyl alcohol as independent variables. This article proposes the use of a novel approach—f₂and S_d values as dependent variables—to evaluate the effect of selected independent variables along with other dependent variables (i.e., percentage drug released in x min, Y_x; time required for z% drug release, t_z; and mean dissolution time (MDT)). It is concluded that when a decision is to be made for the selection of a best batch, it is perhaps more realistic to use the f₂ or S_d value which takes into account the dissolution profile as a whole, as opposed to Y_x and t_z values which use just one point from the dissolution plot. The batch showing the f₂ value nearest to 100 or the S_d value nearest to zero is ranked as the best batch (diltiazem HCl 90 mg, alkali-treated guar gum 80 mg and cetyl alcohol 15 mg). The gel strength and matrix erosion of the formulated tablets were dependent on the type and amount of the adjuvants. The drug release rate is well correlated with matrix erosion. The kinetics of drug release fitted best to the Korsmeyer and Peppas model. It is concluded that by using a proper combination of the hydrophilic polymer and cetyl alcohol one can achieve a desirable drug release pattern.