目的 制备盐酸右美托咪定舌下片并评价其关键质量。方法 选择粉末直压法、泡腾法、升华法制备盐酸右美托咪定舌下片，通过休止角、卡尔系数评价中间体颗粒性能；以脆碎度、含量及含量均匀度、溶出度、崩解时限、润湿时间和吸水比等片剂关键质量属性以及离体口腔黏膜稳态渗透速率评价处方及工艺的合理性；比较盐酸右美托咪定舌下片与市售注射液在比格犬体内的药动学差异。结果 中间体混合粉末具有良好的流动性能；样品脆碎度、含量及含量均匀度均良好；采用升华法制备的样品释放最快，在同种工艺条件下，当处方中交联羧甲基纤维素钠与羧甲基淀粉钠比例为1∶3时，样品的释放速率最快；各处方均能在5 min内完全崩解，采用升华法制备的样品崩解最快，泡腾法次之；各处方样品完全润湿所需的时间与其完全崩解所消耗的时间呈正比，各样品吸水比无明显差异；采用升华法制备的样品体外稳态渗透速率较大，当处方中交联羧甲基纤维素钠与羧甲基淀粉钠比例为1∶3时，稳态渗透速率最大；舌下给药后比格犬体内t_max、C_max、AUC_0-t分别为（48.0±12.6）min、（5.6±0.5）ng·mL⁻¹、（8.7±0.9）ng·min·mL⁻¹，与iv给药相比，盐酸右美托咪定舌下片的生物利用度为85.29%，C_max降低约15%，但tmax明显延长。结论 采用升华法制备的盐酸右美托咪定舌下片处方和制备工艺合理，质量可控，体外稳态渗透速率最好，绝对生物利用度为85.29%，与注射液生物不等效，可以通过改变规格来解决。

Objective To prepare dexmedetomidine hydrochloride sublingual tablets and to evaluate its key quality. Methods Dexmedetomidine hydrochloride sublingual tablets was prepared by powder direct pressing method, effervescence method and sublimation method. The particle properties of the intermediate were evaluated by Angle of rerest and Karl coefficient. The rationality of prescription and process was evaluated by the key quality attributes of tablets, such as friability, content and content uniformity, dissolution, disintegrating time, wetting time and water absorption ratio, as well as the steady penetration rate of oral mucosa in vitro. The pharmacokinetic differences between sublingual tablets and injection of dexmedetomidine hydrochloride were compared in beagle dogs. Results The intermediate mixed powder had good flow performance. The friability, content and content uniformity of the samples were all good. The release rate of the sample prepared by sublimation method was the fastest. Under the same conditions, the release rate of the sample was the fastest when the ratio of sodium carboxymethyl cellulose and sodium carboxymethyl starch in the prescription was 1∶ 3. All the formulas could completely disintegrate within 5 min. The samples prepared by sublimation method had the fastest disintegration, followed by bubbling method. The time required for complete wetting of each prescription sample was proportional to the time consumed for complete disintegration, and there was no significant difference in water absorption ratio of each sample. The steady-state osmosis rate of the sample prepared by sublimation method was higher than that of the sample prepared by sublimation method. The steady-state osmosis rate was the highest when the ratio of sodium carboxymethyl cellulose and sodium carboxymethyl starch in the prescription was 1∶3. After sublingual administration, tmax, C_max and AUC_0-t in beagle dogs were (48.0±12.6) min, (5.6±0.5) ng·mL⁻¹ and (8.7±0.9) ng·min·mL⁻¹, respectively. Compared with iv administration, the bioavailability of dexmedetomidine hydrochloride sublingual tablet was 85.29%. C_max decreased by about 15%, but t_max increased significantly. Conclusion Dexmedetomidine hydrochloride sublingual tablet prepared by sublimation method has reasonable prescription and preparation process, controllable quality, best steady-state infiltration rate in vitro and absolute bioavailability of 85.29%, which is not equivalent to injection, and can be solved by changing specifications.

R944.4