Zero‐order release three‐layered tablet with an acemetacin solid dispersion core and a hydroxypropyl methylcellulose capped matrix

Abstract

The purpose of this study was to prepare a three-layered tablet with hydroxypropyl methylcellulose (HPMC) polymers as a capped matrix to achieve a zero-order release for acemetacin. As the middle active core, a solid dispersion in poly(vinyl pyrrolidone)-K30 polymers was manufactured via a solvent method to improve the solubility of acemetacin. A Box-Behnken design was used to optimize the formula, when the amounts of HPMC in the middle layer, HPMC in the external layer, and mannitol in the middle layer were chosen as the influencing factors. The dissolution profiles of the optimized formula exhibited superior fitting to the zero-order release in 24 h. A bioavailability experiment was carried out by the administration of those three-layered tablets to rabbits and their comparison with market Gaoshunsong controlled release capsules. The delayed time to reach the maximum plasma concentration, decreased the maximum plasma concentration, area under the plasma concentration-time curve (0-48 h) AUC 0-48 , and area under the plasma concentration-time curve (0-1) AUC 0-1 were 9.33 6 2.51 h, 8.59 6 0.94 mg/mL, 200.81 6 11.36 mg h/mL, and 212.902 6 31.66 mg h/mL, respectively.