Buccoadhesives have long been employed to improve the bioavailability of drugs undergoing significant hepatic first-pass metabolism. Diltiazem hydrochloride (DLZ) is also reported to have low oral bioavailability due to an extensive hepatic first-pass effect. Controlled-release buccoadhesive hydrophilic matrices containing DLZ were prepared using a 3(2) factorial design. Amounts of Carbopol 934P (CP) and Methocel K100LV (HPMC) were taken as the formulation variables (factors) for optimizing bioadhesion, and kinetics of dissolution and diffusion. A mathematical model was generated for each response parameter. Bioadhesive strength tended to vary quite linearly in increasing order with increasing amount of each polymer. The drug release pattern for all the formulation combinations was found to be non-fickian, approaching zero-order kinetics. The values of permeation coefficient tended to vary non-linearly with polymer amount, depicting the plausibility of interaction between the two polymers. Suitable combinations of the two polymers provided adequate bioadhesive strength and a fairly regulated release profile up to 10 hr. The response surfaces and contour plots for each response parameter are presented for further interpretation of the results. The optimum formulations were chosen and their predicted results found to be in close agreement with experimental findings.