Quality by Design (QbD) approach to optimize the formulation of a bilayer combination tablet (Telmiduo) manufactured via high shear wet granulation.

A bilayer tablet, which consisted of telmisartan and amlodipine besylate, was formulated based on a Quality by Design (QbD) approach. The control and response factors were determined based on primary knowledge and the target values of the control tablet (Twynsta). A D-optimal mixture design was used to obtain the optimal formulations in terms of D-mannitol, crospovidone, and MCC for the telmisartan layer, and CCM-Na, PVP K25, and Prosolv for the amlodipine layer. The quantitative effects of the different formulation factors on the response factors were accurately predicted using the equations of best fit and a strong linearity was observed between the predicted and actual values of the response factors. The optimized bilayer tablet was obtained using a numeric optimization technique and was characterized compared with a control (Twynsta) by using various physical evaluations and in vivo pharmacokinetic parameters. The physical stability of Telmiduo was greater than that of Twynsta owing to the improvement of formulation factors. The in vivo pharmacokinetic parameters suggested that Telmiduo might have pharmaceutical equivalence and bioequivalence with Twynsta. Therefore, the bilayer tablet that consisted of telmisartan and amlodipine besylate could be produced using a more economical and simpler method than that used to produce Twynsta. Moreover, the suitability of QbD for effective product development in the pharmaceutical industry was shown.