苏沃雷生口溶膜的制备及体内外评价  

Preparation and in vitro-in vivo evaluation of suvorexant orodispersible films

作　　者：赵朋 李聪慧 帅思祎 杨兵 张慧 刘楠 郑爱萍 王永军[1] 王增明 ZHAO Peng;LI Cong-hui;SHUAI Si-yi;YANG Bing;ZHANG Hui;LIU Nan;ZHENG Ai-ping;WANG Yong-jun;WANG Zeng-ming(Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang l10016,China;State Key Laboratory of National Security Specially Needed Medicines,Academy of Military Medical Sciences,Beijing 100850,China)

机构地区：[1]沈阳药科大学无涯创新学院,辽宁沈阳110016 [2]军事医学研究院国家安全特需药品全国重点实验室,北京100850

出　　处：《药学学报》2024年第9期2659-2664,共6页Acta Pharmaceutica Sinica

基　　金：国家重点研发计划资助项目(2023YFC2706100)。

摘　　要：口溶膜是一种新型的口服固体制剂,其在吞咽困难、自主行为不受控制等患者群体中广泛应用。本研究采用热熔挤出技术制备了苏沃雷生口溶膜,并通过崩解时限、机械性能、体外溶出及体内药代动力学等参数进行体内外评价,对比了已上市其他品种口溶膜及市售片剂Belsomra。所有动物实验经军事医学研究院实验动物管理与使用委员会批准(批准号:IACUC-DWZX-2024-504)。结果显示,苏沃雷生口溶膜崩解速度快,机械强度较市售其他品种口溶膜更优,可满足储存与运输需求。差示扫描量热法与X射线衍射法的结果表明,苏沃雷生以无定形状态分散在口溶膜中。其体外溶出较市售片剂快4倍,5min即完全溶出;比格犬体内药代动力学研究表明,自制口溶膜与Belsomra相比血药浓度时间曲线下面积无统计学差异,但起效更快,其达峰时间较Belsomra快1倍,最大血药浓度是Belsomra的2倍。基于热熔挤出技术制备的苏沃雷生口溶膜工艺简单、可连续化生产、质量稳定,可作为开发针对特殊患者的无溶剂薄膜制剂的平台。Orodispersible films(oral dispersible films),a novel form of oral solid dosage forms,are widely used for patients with dysphagia and those with uncontrollable autonomic behavior.In this study,suvorexant orodispersible film was prepared by hot melt extrusion technology,and the disintegration time,mechanical proper-ties,in vitro dissolution and pharmacokinetics were evaluated,compared with other orodispersible films and commercially available tablets Belsomra.All experiments were approved by the Committee on the Management and Use of Laboratory Animals of Academy of Military Medical Sciences(IACUC-DWZX-2024-504).The results showed that the dissolution rate of suvorexant orodispersible film was faster and the mechanical strength was better than that of other commercially available orodispersible film,which could meet the needs of storage and transporta-tion.Differential scanning calorimetry and X-ray diffraction results showed that suvorexant was dispersed within the orodispersible film in an amorphous state.The in vitro dissolution of the film was observed to be four times faster than that of the commercial tablets,achieving complete dissolution within five minutes.Pharmacokinetic evaluations in Beagle dogs revealed that the self-formulated orodispersible film exhibited no significant differences in the area under the blood concentration-time curve when compared with Belsomra.However,the film showed a faster onset of action,with a peak time that was twice as rapid,and a maximum blood concentration that was twice as high as that of Belsomra.Leveraging hot melt extrusion technology,the suvorexant orodispersible film offers a straightforward,continuous production process with consistent quality.It serves as an excellent platform for the development of solvent-free film preparations tailored for patients with special needs.

关 键 词：口溶膜 苏沃雷生 热熔挤出 机械强度 溶出 药代动力学 

分 类 号：R943[医药卫生—药剂学]