目的 将头孢克肟包合于β-环糊精（HP-β-CD）中掩盖其不良气味，采取直接压片将其制成口腔崩解片加快药物的溶出，提高生物利用度。方法 以物理混合法及研磨法，制备头孢克肟原料药和HP-β-CD比例为1∶1、1∶2、1∶3的包合物，HPLC法检测包合物中头孢克肟质量分数和溶出度，结合口味测试，筛选包合物的制备方法及比例；采用Box-Behnken设计（BBD）以崩解时限和硬度为考察指标优化头孢克肟口腔崩解片（简称自制片）的处方；通过粉末流动性评价、含量测定、体外药物溶出度验证等进行最佳处方工艺验证；考察自制片、参比制剂（头孢克肟片）在Beagle犬中的药动学；考察自制片在（40.0±2.0）℃、（75±5）%恒温恒湿箱中储存3个月的稳定性。结果 当采用研磨法、头孢克肟与β-环糊精比例为1∶3时，矫味作用、药物含量、体外药物溶出度结果最好。最优处方为：含头孢克肟200 mg的包合物、交联聚维酮38.81 mg、微晶纤维素75.77 mg、甘露醇63.57 mg、乳糖15.35 mg、滑石粉2 mg、硬脂酸镁2.5 mg、微粉硅胶1.5 mg、草莓香精0.5 mg。自制片的混粉流动性良好，崩解速度快，硬度为（52.37±0.51） N、机械强度良好；含量＞98.93%；不同介质中自制片与参比制剂溶出曲线具有相似性，且自制片的累积溶出率更高。自制片生物利用度为参比制剂的110.08%；自制片的达峰浓度（C_max）为3.158 mg·L^-1，参比制剂C_max为2.982 mg·L^-1；自制片的达峰时间（t_max）为2.5 h，参比制剂t_max为2.667 h；在6.0、8.0、10.0 h，自制片的血药浓度较参比制剂显著升高（P＜0.05）。在储存过程中，自制片外观性状、含量、体外药物溶出度无显著变化。结论 制备的头孢克肟掩味口腔崩解片工艺稳定、粉末流动性良好、机械强度良好、崩解速度快、口感好、服用方便、生物利用度高、能更快发挥药效，同时稳定性良好。

Objective Cefixime was enveloped in β -cyclodextrin (HP- β -CD) to cover up its bad smell, and directly pressed into orally disintegrating tablets to speed up the dissolution of the drug and improve the bioavailability. Methods The inclusion Methods were physical mixing and grinding Methods to prepare inclusion compounds in different proportions (cefixime API and HP- β- CD ratio was 1∶1, 1∶2, and 1∶3). HPLC method was used to detect the mass fraction and dissolution of cefixime in the inclusion complex, and combined with taste testing, the preparation method and proportion of the inclusion complex are screened. BoxBehnken design (BBD) was used to optimize the prescription of cefixime orally disintegrating tablets with the disintegration time and hardness as reference indicators. Verify the optimal prescription process through powder flowability evaluation, content determination, and in vitro drug dissolution validation. To investigate the pharmacokinetics of self-made cefixime orally disintegrating tablets and reference formulations in Beagle dogs. To investigate the stability of self-made cefixime orally disintegrating tablets stored at (40.0 ±2.0) ℃ and (75 ±5)% constant temperature and humidity chamber for three months. Results When the grinding method was adopted and the ratio of cefixime to β-cyclodextrin was 1∶3, the results of flavor correction, drug content, and drug dissolution in vitro were the best. The optimal prescription screened: Inclusion complex containing 200 mg of cefixime, crospovidone 38.81 mg, microcrystalline cellulose 75.77 mg, mannitol 63.57 mg, lactose 15.35 mg, talc 2 mg, magnesium stearate 2.5 mg, differential silica gel 1.5 mg, strawberry flavor 0.5 mg. The mixed powder of self-made oral disintegrating tablets had good flowability, fast disintegration speed, hardness of (52.37 ±0.51) N, and good mechanical strength. Content > 98.93%. The dissolution curves of self-made tablets and reference formulations in different media were similar, and the cumulative dissolution rate of self-made tablets was higher. The bioavailability of self-made tablets was 110.08% of the reference formulation. The C_max of self-made tablets and reference formulation were 3.158 and 2.982 mg·L^-1, and the t_max of self-made tablets and reference formulation were were 2.5 and 2.667 h. At 6.0, 8.0, and 10.0 h, the blood drug concentration of the self-made preparation significantly increased compared to the reference preparation (P < 0.05). During storage, there were no significant changes in the appearance, content, and in vitro drug dissolution of the tablets. Conclusion The prepared cefixime masking orally disintegrating tablets had stable process, good powder flowability, good mechanical strength, fast disintegration speed, good taste, easy to take, high bioavailability, and can exert efficacy faster, while maintaining good stability.

R943