目的 將頭孢克肟包合于β-環(huán)糊精（HP-β-CD）中掩蓋其不良?xì)馕叮扇≈苯訅浩瑢⑵渲瞥煽谇槐澜馄涌焖幬锏娜艹?，提高生物利用度?b>方法 以物理混合法及研磨法，制備頭孢克肟原料藥和HP-β-CD比例為1∶1、1∶2、1∶3的包合物，HPLC法檢測(cè)包合物中頭孢克肟質(zhì)量分?jǐn)?shù)和溶出度，結(jié)合口味測(cè)試，篩選包合物的制備方法及比例；采用Box-Behnken設(shè)計(jì)（BBD）以崩解時(shí)限和硬度為考察指標(biāo)優(yōu)化頭孢克肟口腔崩解片（簡(jiǎn)稱自制片）的處方；通過粉末流動(dòng)性評(píng)價(jià)、含量測(cè)定、體外藥物溶出度驗(yàn)證等進(jìn)行最佳處方工藝驗(yàn)證；考察自制片、參比制劑（頭孢克肟片）在Beagle犬中的藥動(dòng)學(xué)；考察自制片在（40.0±2.0）℃、（75±5）%恒溫恒濕箱中儲(chǔ)存3個(gè)月的穩(wěn)定性。結(jié)果 當(dāng)采用研磨法、頭孢克肟與β-環(huán)糊精比例為1∶3時(shí)，矯味作用、藥物含量、體外藥物溶出度結(jié)果最好。最優(yōu)處方為：含頭孢克肟200 mg的包合物、交聯(lián)聚維酮38.81 mg、微晶纖維素75.77 mg、甘露醇63.57 mg、乳糖15.35 mg、滑石粉2 mg、硬脂酸鎂2.5 mg、微粉硅膠1.5 mg、草莓香精0.5 mg。自制片的混粉流動(dòng)性良好，崩解速度快，硬度為（52.37±0.51） N、機(jī)械強(qiáng)度良好；含量＞98.93%；不同介質(zhì)中自制片與參比制劑溶出曲線具有相似性，且自制片的累積溶出率更高。自制片生物利用度為參比制劑的110.08%；自制片的達(dá)峰濃度（C_max）為3.158 mg·L^-1，參比制劑C_max為2.982 mg·L^-1；自制片的達(dá)峰時(shí)間（t_max）為2.5 h，參比制劑t_max為2.667 h；在6.0、8.0、10.0 h，自制片的血藥濃度較參比制劑顯著升高（P＜0.05）。在儲(chǔ)存過程中，自制片外觀性狀、含量、體外藥物溶出度無顯著變化。結(jié)論 制備的頭孢克肟掩味口腔崩解片工藝穩(wěn)定、粉末流動(dòng)性良好、機(jī)械強(qiáng)度良好、崩解速度快、口感好、服用方便、生物利用度高、能更快發(fā)揮藥效，同時(shí)穩(wěn)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