Preparation and in vitro-in vivo evaluation of lasmiditan tablets

JIA Jun-wei; HAN Jian-cheng; WANG Hui; WANG Chun; FENG Zhong

doi:10.20251/j.cnki.1003-3734.2026.14.011

Abstract：Objective:To prepare lasmiditan tablets and study the in vitro dissolution and pharmacokinetics.Methods:Literature and patents were investigated for designing and optimizing the formulation composition and preparation process.Based on the wet granulation preparation process,taking Reyow® as the reference preparation,the optimal excipient ratios of pregelatinized starch,croscarmellose sodium and magnesium stearate were screened out by Box-Behnken experiment.The particle size and tableting hardness of the API before granulation were determined by single factor experiment.The relevant permeation parameters and pharmacokinetic characteristics of the self-developed tablets and reference preparation in the PAMPA(parallel artificial membrane permeability assay)and the pharmacokinetic characteristics in Beagle dogs were further studied.Results:The particle size of the API was determined to be 220 μm,and the hardness of the tablet was 80 N.The content of pregelatinized starch was 8.77%,and the content of croscarmelase sodium was 4.58%.The magnesium stearate content was 2.67%.The membrane permeability of the self-developed tablets and the reference preparation were1.125×10-4 and1.117×10-4 cm·s-1,respectively,and the permeability rates were 0.846 804 and 0.847 113 μg·min-1·cm-2,respectively.The in vivo experiments showed that the Cmax of the self-made tablets and Reyow® were 189 and 188 ng·L-1,the Tmax was 3 h.The oral relative bioavailability of homemade tablets was 93.32%.Conclusion:The PAMPA permeation and release behavior in Beagle dogs were basically the same between the self-developed tablets and the reference tablets.The self-developed preparation is preliminary bioequivalent to the original product.The process is suitable for the preparation of lasmiditan tablets.