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设计和优化载坎地沙坦自微乳给药系统以提高其溶出度和药效潜力。

Design and optimization of candesartan loaded self-nanoemulsifying drug delivery system for improving its dissolution rate and pharmacodynamic potential.

机构信息

Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, Haryana, India.

出版信息

Drug Deliv. 2020 Dec;27(1):756-771. doi: 10.1080/10717544.2020.1760961.

DOI:10.1080/10717544.2020.1760961
PMID:32397771
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7269045/
Abstract

During the last decades, much attention has been focused on SNEDDS approach to resolve concerns of BCS II class drugs with accentuation on upgrading the solubility and bioavailability. The present hypothesis confirms the theory that SNEDDS can reduce the impact of food on Candesartan solubilization, thereby offering the potential for improved oral delivery without co-administration with meals. The present studies describe quality-by-design-based development and characterization of Candesartan loaded SNEDDS for improving its pharmacodynamic potential. D-optimal mixture design was used for systematic optimization of SNEDDS, which showed globule size of 13.91 nm, more rapid drug release rate of >90% in 30 min and 16 s for self-emulsification. The optimized formulations were extensively evaluated, where an drug release study indicated up to 1.99- and 1.10-fold enhancement in dissolution rate from SNEDDS over pure drug and marketed tablet. pharmacodynamic investigation also showed superior antihypertensive potential of SNEDDS in normalizing serum lipid levels as compared to pure drug and marketed tablet that was executed on male Wistar rats. Overall, this paper reports successful systematic development of candesartan-loaded SNEDDS with distinctly improved biopharmaceutical performance. This research work interpreted a major role of SNEDDS for enhancing the rate of dissolution and bioavailability of poorly water soluble drugs.

摘要

在过去的几十年中,人们对 SNEDDS 方法给予了极大的关注,以解决 BCS II 类药物的问题,重点是提高溶解度和生物利用度。本假设证实了这样一种理论,即 SNEDDS 可以减少食物对坎地沙坦增溶的影响,从而有可能在不与餐同服的情况下改善口服递送。本研究描述了基于质量源于设计的坎地沙坦 SNEDDS 的开发和表征,以提高其药效潜力。采用 D-最优混合设计对 SNEDDS 进行了系统优化,结果显示,胶束粒径为 13.91nm,自乳化后 30min 内药物释放率超过 90%,达到 16s。对优化后的配方进行了广泛评估,药物释放研究表明,SNEDDS 相对于纯药物和市售片剂,药物溶解速率提高了 1.99 倍和 1.10 倍。药效学研究还表明,SNEDDS 在正常化血清脂质水平方面具有优越的降压潜力,优于纯药物和市售片剂,该研究在雄性 Wistar 大鼠上进行。总的来说,本文报道了成功开发了载有坎地沙坦的 SNEDDS,具有明显改善的生物药剂学性能。这项研究工作解释了 SNEDDS 在提高难溶性药物的溶解速率和生物利用度方面的重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecde/7269045/eb2086fc16a6/IDRD_A_1760961_F0011_C.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecde/7269045/fe26e3248933/IDRD_A_1760961_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecde/7269045/afc846ea677c/IDRD_A_1760961_F0003_C.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecde/7269045/0f492fe17d49/IDRD_A_1760961_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecde/7269045/b69f5a3c3c45/IDRD_A_1760961_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecde/7269045/003e26602509/IDRD_A_1760961_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecde/7269045/da349a2f14f6/IDRD_A_1760961_F0008_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecde/7269045/df10c382352b/IDRD_A_1760961_F0009_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecde/7269045/4516d3328ca9/IDRD_A_1760961_F0010_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecde/7269045/eb2086fc16a6/IDRD_A_1760961_F0011_C.jpg

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