正交实验优化盐酸左米那普仑缓释微丸胶囊处方工艺及其体内外评价

Objective: To optimize the formula and manufacturing technology of levomilnacipran hydrochloride sustained release pellets capsules and investigate the drug release in vitro and the absorption in Beagles. Methods: Levomilnacipran hydrochloride sustained release pellets were prepared using ethyl cellulose as sustained-release coating material by fluidized bed. The factors such as inlet air temperature, feeding rate and pray pressure were optimized by orthogonal tests. The orthogonal tests were also used to screen the major influencing factors (coating weight, curing time, and the content of talc) on the release of levomilnacipran hydrochloride. The coating formula and coating weight were optimized taking the cumulative release rate of levomilnacipran hydrochloride at 2, 6, 12 h as the evaluation index. The drug release in vitro and the pharmacokinetic parameters after single oral doses of the test and reference preparations in Beagles were also studied. Results: The optimum preparation parameters of the pellets were as follows: the inlet air temperature of 40 ℃, the spray pressure of 0.2 Mpa, and the feeding rate of 6 r•min^-1. The best sustained release coating formula was as follows: the weight gain of sustained release layer of 16%, the curing time of 24 h, and the content of talc of 30%. The levomilnacipran hydrochloride sustained release pellets had notable sustained release effect. The 95% confidence intervals of AUC_0-t, AUC_0-∞ and C_max for the test preparation after single oral doses were all within the bioequivalence criteria. Conclusion: The orthogonal test method can be used to optimize the formulation process of levonatelli hydrochloride sustained-release pellets. The cumulative release rate of delayed release pellets capsules prepared by the fluidized bed coating technique can meet the release requirement, and it has an ideal sustained release effect which is equivalent to the branded products in vitro and in vivo.