Study on Preparation Process and in Vitro Release Behavior of Linagliptin Double-layer Sustained-release Tablets

OBJECTIVE To prepare novel linagliptin sustained-release tablets with double layers and to investigate the in vitro release behavior. METHODS The formulation was evaluated with a single factor design, hydroxyl propyl methyl cellulose(HPMC) were used as skeletal material and xanthan gum were used as adhesive, the dissolution curve in vitro was draw in pH 6.80 medium. The Ritger-Peppas, Higuchi, zero-order and first-order release equations were used to fit the dissolution curves and the principle of drug release was analyzed. RESULTS The optimized sample was composed of a drug-containing sustained-release layer and a drug-containing immediate-release layer. The sustained-release layer was composed of ligliptin(the main component) 3 mg, HPMC(the sustained-release matrix material, the models were K4M and K100M) 50 mg, microcrystalline cellulose(the filler) 100 mg, xanthan gum(gel sustained-release matrix) 15 mg, magnesium stearate(lubricant) 1 mg. The immediate release layer was composed of ligliptin(the main component) 2 mg, microcrystalline cellulose(filler) 10 mg, polyplasdone(disintegrating agent) 15 mg, magnesium stearate(lubricant) 1 mg. The final result had the highest matching degree with the zero-order release equation and was highly correlated. The fitting result r² was infinitely close to 1. CONCLUSION The linagliptin sustained-release tablets with double layers are successfully prepared and zero-order release is realized.