氟比洛芬固体分散体口腔贴剂的研制与评价

M. Sadik, Abdullah Khan
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摘要

氟比洛芬是一种抗炎药物,用于治疗类风湿关节炎和强直性脊柱炎。本文旨在利用固体分散(SD)技术解决氟比洛芬溶解度不足的问题。本论文是在已发表的固体分散体的基础上,以1:5:2的比例考虑含氟比洛芬药物:AQOAT AS: SLS为药物:聚合物:表面活性剂的最终最佳优化配方,并将其加入口腔贴剂中,以克服胃部副作用,实现药物的持续释放。本研究以聚乙烯醇羟乙基纤维素(HEC)、羟丙基甲基纤维素E15 (HPMC E15)、聚乙烯醇吡罗烷酮(PVP)、卡波醇等聚合物为原料,采用溶剂铸造技术配制了15个口腔贴片,并对其进行了药物含量、药物扩散、体内溶出度和稳定性研究。其中,BP14缓释片在12 h内的释药效果较好,释药率为99.96%,而上市缓释片在6 h内的释药率为96.86%。释药动力学结果表明,口腔贴片符合零级释药动力学,相关系数(R2)在0.905 ~ 0.971之间,其中BP14制剂的R2值最佳。所有制剂均符合Higuchi模型,R2范围为0.9911 ~ 0.9962,表明药物通过扩散释放。结果表明,口腔贴片是氟比洛芬的较好替代方案,有利于延长药物释放时间,有效治疗类风湿关节炎。
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Formulation and Evaluation of Flurbiprofen Solid Dispersions Incorporated Buccal Patches
Flurbiprofen is an anti-inflammatory drug used in treating rheumatoid arthritis and ankylosing spondylitis. The present work is aimed at overcoming the deprived solubility of flurbiprofen by solid dispersion (SD) technique. The current paper is  the continuance of the published solid dispersion by considering the best final optimized formulation containing flurbiprofen drug: AQOAT AS: SLS as drug: polymer: surfactant in 1:5:2 ratios, and incorporating it into buccal patches to overcome the gastric side effect and attaining  sustained drug release. In this study 15 buccal patches  were formulated  by adopting  solvent casting technique  using polymers like polyvinyl hydroxyethylcellulose (HEC), hydroxypropryl methyl cellulose E15 (HPMC E15), polyvinyl pyrrolidone (PVP), carbopol and analyzed  for the drug content, drug  diffusion, in-vivo dissolution  and stability studies. All SD loaded patches displayed superior drug release (95% to 99.96%) over 12 h. The formulation BP14 showed excellent drug release extended over 12 h with drug release of 99.96% whereas marketed formulation which is sustained release Tablet showed 96.86% drug release within 6 h. The drug release kinetics show that the buccal patches follow zero order release kinetics with correlation coefficient (R2) ranging between 0.905-0.971 and BP14 formulation shown best R2 value. All the formulations exhibited best fit to Higuchi model with R2 ranging between 0.9911 – 0.9962 indicating drug release by diffusion process. The results conclude that buccal patches are superior alternatives for flurbiprofen that facilitates enhanced drug release for prolonged period of time in the effective management of rheumatoid arthritis.
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