Wang Yueli, Li Dongbo, Li Xiaojuan, Ren Dandan, Zhang Wei, Shu Gang, Lin Juchun, Li Haohuan, Xu Funeng, Peng Guangneng, Fu Hualin
Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, China.
Drug Deliv Transl Res. 2025 Mar;15(3):968-977. doi: 10.1007/s13346-024-01651-5. Epub 2024 Jun 19.
Metamizole easily decomposes in the body and has a short action time and low bioavailability. Hence, frequent injection administrations are needed to maintain its plasma concentration. This study aimed to design and develop an in-situ gel based on poloxamer 407 and 188 to assess its long-acting antipyretic effects. The in-situ gel-forming systep00m with optimum sol-gel transition temperature of 35.9 °C to 36.3 °C could be formed using a combination of P407 at a ratio of 21-23% (w/v) and P188 at a ratio of 2-4% (w/v). In vitro erosion test showed that the in-situ gel's erosion curve and the metamizole release rate both reached about 90% at 6 h, revealing a good linear relationship between the in-situ gel erosion and the drug release. In vitro release test with dialysis tube showed that the release of metamizole from the in-situ gel was remarkably slower than that from the metamizole solution. Approximately 85% of metamizole was released in the dialysis tube within 7 h, implying a good sustained release effect. Pharmacodynamic study showed that the in-situ gel injection extended the action time of metamizole relative to that when using the metamizole solution. Pharmacokinetic study revealed that the in-situ gel significantly increased the blood serum half-life and area under the curve), contributing to a sustained release and improved bioavailability. This study demonstrated that in-situ gel injection could prolong the action of metamizole in the body to reduce the number of administration times and has good clinical application.
安乃近在体内易分解，作用时间短且生物利用度低。因此，需要频繁注射以维持其血浆浓度。本研究旨在设计并开发一种基于泊洛沙姆407和188的原位凝胶，以评估其长效解热作用。使用比例为21 - 23%（w/v）的P407和比例为2 - 4%（w/v）的P188组合，可形成溶胶 - 凝胶转变温度最佳为35.9℃至36.3℃的原位凝胶形成系统。体外溶蚀试验表明，原位凝胶的溶蚀曲线和安乃近释放率在6小时时均达到约90%，表明原位凝胶溶蚀与药物释放之间存在良好的线性关系。用透析管进行的体外释放试验表明，安乃近从原位凝胶中的释放明显慢于从安乃近溶液中的释放。约85%的安乃近在7小时内在透析管中释放，意味着具有良好的缓释效果。药效学研究表明，与使用安乃近溶液相比，原位凝胶注射延长了安乃近的作用时间。药代动力学研究表明，原位凝胶显著增加了血清半衰期和曲线下面积，有助于实现缓释并提高生物利用度。本研究表明，原位凝胶注射可延长安乃近在体内的作用时间，减少给药次数，具有良好的临床应用价值。
