Farideh Shiehzadeh, Daryosh Mohebi, Omid Chavoshian, Sara Daneshmand
{"title":"含有氨甲环酸的局部凝胶预防表面出血的配方、表征和优化:体内和体外评估。","authors":"Farideh Shiehzadeh, Daryosh Mohebi, Omid Chavoshian, Sara Daneshmand","doi":"10.4274/tjps.galenos.2022.60687","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Tranexamic acid (TXA) is used systemically to stop bleeding, but it can lead to thromboembolism. Trials have revealed the efficacy of topical TXA on local hemorrhages. However, there is a need for an efficient delivery system that can keep the drug at the site of action.</p><p><strong>Materials and methods: </strong>To develop a gel containing TXA (3%) optimized in terms of viscosity and dispersibility, the central composite design based on two factors-three levels [carbopol 940 and hydroxypropyl methylcellulose (HPMC), 1-1.5% and 1-2%, respectively] was applied. The spreadability and viscosity were assessed using glass slide and rheometer, respectively. To confirm the compatibility of TXA with the gel, fourier transform-infrared (FTIR) spectroscopy was performed. Drug content uniformity was analyzed by a spectroscopy method. An <i>ex vivo</i> mice model using Franz cells was applied to evaluate the permeation of TXA through the skin. To investigate the effect of topical TXA gel on bleeding time, IVY human method was performed.</p><p><strong>Results: </strong>HPMC/carbopol 940 (1:1, <i>w/w</i>) gel showed the highest quality in terms of viscosity and dispersibility (3.982 ± 17.6 and 6.052 ± 3.562, respectively). FTIR absorption spectrum showed that all the TXA index peaks appeared without displacement. The complete-encapsulated TXA content was uniformly dispersed throughout the gel. <i>In vitro</i> TXA cumulative release reached 90% in 4 h. The bleeding time determined <i>in vivo</i> for TXA gel was significantly lower than that for TXA solution and control.</p><p><strong>Conclusion: </strong>The results confirm the importance of further studies on this formulation as a potential medication to stop acute superficial bleeding.</p>","PeriodicalId":23378,"journal":{"name":"Turkish Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10445226/pdf/TJPS-20-261.pdf","citationCount":"2","resultStr":"{\"title\":\"Formulation, Characterization, and Optimization of a Topical Gel Containing Tranexamic Acid to Prevent Superficial Bleeding: <i>In Vivo</i> and <i>In Vitro</i> Evaluations.\",\"authors\":\"Farideh Shiehzadeh, Daryosh Mohebi, Omid Chavoshian, Sara Daneshmand\",\"doi\":\"10.4274/tjps.galenos.2022.60687\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>Tranexamic acid (TXA) is used systemically to stop bleeding, but it can lead to thromboembolism. Trials have revealed the efficacy of topical TXA on local hemorrhages. However, there is a need for an efficient delivery system that can keep the drug at the site of action.</p><p><strong>Materials and methods: </strong>To develop a gel containing TXA (3%) optimized in terms of viscosity and dispersibility, the central composite design based on two factors-three levels [carbopol 940 and hydroxypropyl methylcellulose (HPMC), 1-1.5% and 1-2%, respectively] was applied. The spreadability and viscosity were assessed using glass slide and rheometer, respectively. To confirm the compatibility of TXA with the gel, fourier transform-infrared (FTIR) spectroscopy was performed. Drug content uniformity was analyzed by a spectroscopy method. An <i>ex vivo</i> mice model using Franz cells was applied to evaluate the permeation of TXA through the skin. 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引用次数: 2
摘要
目的:氨甲环酸(TXA)用于全身止血,但它可导致血栓栓塞。试验表明局部使用TXA对局部出血有效。然而,需要一种有效的递送系统,使药物保持在作用部位。材料与方法:采用卡波醇940和羟丙基甲基纤维素(HPMC)分别为1-1.5%和1-2%的2因素- 3水平的中心复合设计,制备了一种粘度和分散性优化的含TXA(3%)凝胶。分别用玻片法和流变仪测定涂敷性和粘度。为了确定TXA与凝胶的相容性,傅里叶变换红外光谱(FTIR)进行了测试。用光谱学方法分析药物含量均匀性。采用体外小鼠Franz细胞模型评价TXA在皮肤中的渗透作用。采用IVY人用法研究外用TXA凝胶对出血时间的影响。结果:HPMC/carbopol 940凝胶(1:1,w/w)的粘度和分散性最高(分别为3.982±17.6和6.052±3.562)。FTIR吸收光谱显示,所有TXA指数峰均无位移。完全包封的TXA含量均匀地分散在凝胶中。体外4 h TXA累积释放量达到90%,体内测定的出血时间明显低于TXA溶液和对照组。结论:结果证实了进一步研究该制剂作为一种潜在的治疗急性浅表出血的药物的重要性。
Formulation, Characterization, and Optimization of a Topical Gel Containing Tranexamic Acid to Prevent Superficial Bleeding: In Vivo and In Vitro Evaluations.
Objectives: Tranexamic acid (TXA) is used systemically to stop bleeding, but it can lead to thromboembolism. Trials have revealed the efficacy of topical TXA on local hemorrhages. However, there is a need for an efficient delivery system that can keep the drug at the site of action.
Materials and methods: To develop a gel containing TXA (3%) optimized in terms of viscosity and dispersibility, the central composite design based on two factors-three levels [carbopol 940 and hydroxypropyl methylcellulose (HPMC), 1-1.5% and 1-2%, respectively] was applied. The spreadability and viscosity were assessed using glass slide and rheometer, respectively. To confirm the compatibility of TXA with the gel, fourier transform-infrared (FTIR) spectroscopy was performed. Drug content uniformity was analyzed by a spectroscopy method. An ex vivo mice model using Franz cells was applied to evaluate the permeation of TXA through the skin. To investigate the effect of topical TXA gel on bleeding time, IVY human method was performed.
Results: HPMC/carbopol 940 (1:1, w/w) gel showed the highest quality in terms of viscosity and dispersibility (3.982 ± 17.6 and 6.052 ± 3.562, respectively). FTIR absorption spectrum showed that all the TXA index peaks appeared without displacement. The complete-encapsulated TXA content was uniformly dispersed throughout the gel. In vitro TXA cumulative release reached 90% in 4 h. The bleeding time determined in vivo for TXA gel was significantly lower than that for TXA solution and control.
Conclusion: The results confirm the importance of further studies on this formulation as a potential medication to stop acute superficial bleeding.