Penetration enhancer-containing spanlastics (PECSs) for transdermal delivery of haloperidol: in vitro characterization, ex vivo permeation and in vivo biodistribution studies.
Penetration enhancer-containing spanlastics (PECSs) for transdermal delivery of haloperidol: in vitro characterization, ex vivo permeation and in vivo biodistribution studies.
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DOI：
10.1080/10717544.2017.1410262
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发表时间：
2018-11
期刊：
影响因子：
6
通讯作者：
Bayoumi NA
中科院分区：
文献类型：
--
作者：
Fahmy AM;El-Setouhy DA;Ibrahim AB;Habib BA;Tayel SA;Bayoumi NA
氟哌啶醇(Hal)是一种应用广泛的抗精神病药物。口服时，由于肝脏首过代谢，其生物利用度较低。本研究旨在研制Hal经皮渗透促进剂缓释片(PECSS)，以促进Hal的透皮吸收和缓释。采用乙醇注射法制备了包封率、粒径、多分散指数和Zeta电位的微球。通过对体外渗透参数的统计分析，选择了F1L-由Span®60和吐温®80以4：1的重量比以及1%w/v Labrasol®制成-作为选定的配方(SF)。用2.5%w/v的HPMCK4M将SF制成水凝胶。该水凝胶具有良好的体外特性。此外，它在冰箱中保持了一个月的物理和化学稳定性。标记SF的最佳条件为：100MBq的L稀释液与50MBq的L生理盐水混合，其中99mTc200MBq，含有13.6MBq的还原剂(NaBH4)，反应时间为10 ，用生理盐水完成体积为300MBq的L，pH为10，反应时间为10 。生物分布研究表明，与口服99mTC-SF分散体相比，99mTC-SF透皮吸收水凝胶具有更好的缓释效果和更长的循环持续时间，在血液中具有脉动行为，在脑内的分布水平更高。因此，SF透皮水凝胶可能被认为是一种有前途的Hal维持治疗的缓释配方，其剂量较小，给药频率低于口服配方。
Haloperidol (Hal) is one of the widely used antipsychotic drugs. When orally administered, it suffers from low bioavailability due to hepatic first pass metabolism. This study aimed at developing Hal-loaded penetration enhancer-containing spanlastics (PECSs) to increase transdermal permeation of Hal with sustained release. PECSs were successfully prepared using ethanol injection method showing reasonable values of percentage entrapment efficiency, particle size, polydispersity index and zeta potential. The statistical analysis of the ex vivo permeation parameters led to the choice of F1L – made of Span® 60 and Tween® 80 at the weight ratio of 4:1 along with 1% w/v Labrasol® – as the selected formula (SF). SF was formulated into a hydrogel by using 2.5% w/v of HPMC K4M. The hydrogel exhibited good in vitro characteristics. Also, it retained its physical and chemical stability for one month in the refrigerator. The radiolabeling of SF showed a maximum yield by mixing of 100 µl of diluted formula with 50 µl saline having 200 MBq of 99mTc and containing 13.6 mg of reducing agent (NaBH4) and volume completed to 300 µl by saline at pH 10 for 10 min as reaction time. The biodistribution study showed that the transdermal 99mTc-SF hydrogel exhibited a more sustained release pattern and longer circulation duration with pulsatile behavior in the blood and higher brain levels than the oral 99mTc-SF dispersion. So, transdermal hydrogel of SF may be considered a promising sustained release formula for Hal maintenance therapy with reduced dose size and less frequent administration than oral formula.
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