Objectives: Preparation and evaluation of novel fast disintegrating strips of lomerizine hydrochloride.Methods: Physicochemical properties of the lomerizine hydrochloride were determined such as solubility and oil/water partition coefficient.The effect of different permeation enhancers on the penetration of model drug through porcine buccal mucosa was investigated.The mechanisms of permeation enhancement were clarified by the biophysical changes of mucosal tissues using FT-IR spectroscopy, and hematoxylin-eosin (HE) staining methods.After that, an oral fast disintegrating strip (OFDS) was prepared by solvent casting method.The optimized formulation of lomerizine-OFDS was obtained based on the measurement of pharmaceutical parameters by orthogonal design.The quality control and stability test of lomerizine-OFDS were conducted.Finally, pharmacokinetic study was performed after attaching lomerizine-OFDS to oral cavity of rabbits.Results: The solubility of lomerizine hydrochloride is 6.50mg.mL-1 in pure water and 31.55mg/mL in ethanol, respectively.The result of in vitro penetration test showed that the penetration effect of penetration enhancers was as following: 5%PG > I%PG > 3%PG > 0.3%HA+3%PG > 3%SDGC+3%PG > l%Azone > 0.3%HA+3%SDGC > 0.3%HA.The result of FT-IR revealed the mechanism of penetration enhancer.The epithelial lipids were extracted by using PG as penetration enhancer.HA results in increasing molecular motion as the gel to liquid crystalline transition occur.The mechanism of SDGC was the growth in translational movement or mobility of lipid acyl chains.Histological evaluation showed that no penetration enhancers caused cytological or structural changes in the buccal epithelium.The optimal formulation of lomerizine-OFDS (drug content 15%) is as follows: film-forming material=HPMC (5cp) ∶ HA (40∶1); plasticizer 0.45g PEG400, disintegrant 0.10g pregelatinized starch, permeation enhancer 0.45g PG.The prepared lomerizine-OFDS were accord with the criteria of films provided in CP (2010) including appearance, weight variation and microbial limit.Stability test indicated that lomerizine-OFDS should be preserved in dark and dry condition.The preliminary pharmacokinetic study showed that lomerizine-OFDS had faster absorption and shorter peak time compared with marketed tablet.Conclusions: A novel fast disintegrating strips of lomerizine hydrochloride was prepared.In vitro physicochemical characterization preliminary pharmacokinetic study further confirmed its practical feasibility.