Preparation, optimization, and evaluation of midazolam nanosuspension: enhanced bioavailability for buccal administration.

IF 4.4 3区 医学 Q2 ENGINEERING, BIOMEDICAL
Progress in Biomaterials Pub Date : 2021-03-01 Epub Date: 2021-02-15 DOI:10.1007/s40204-020-00148-x
Arezou Soroushnia, Fariba Ganji, Ebrahim Vasheghani-Farahani, Hamid Mobedi
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引用次数: 6

Abstract

Midazolam is considered as one of the best first-line drugs in managing status epilepticus in children who require emergency drug treatment. Due to poor water solubility, oral bioavailability of midazolam is relatively low. To improve its dissolution and absorption, midazolam nano-suspensions were formulated with different stabilizers using the ultrasonic technique. A combination of Tween 80 and Poloxamer (TP) was considered as one stabilizer and 3-methyl chitosan (TMC) as another stabilizer. The ratio of the stabilizers was selected as an independent variable, and their effects on the particle size and the zeta potential were evaluated by the simplex lattice mixture method. The freeze-dried optimized midazolam nano-suspension powder was characterized by particle-size analysis, SEM, the stability test, and the dissolution test. The optimized midazolam nano-suspension (containing 76% TMC and 24% TP) had a mean particle size of 197 ± 7 nm and a zeta potential of 31 ± 4 (mV). The stability test showed that the midazolam nano-suspension is stable for 12 months. In the in vitro dissolution test, the midazolam nano-suspension showed a marked increase in the drug dissolution percentage versus coarse midazolam. In the in vivo evaluation, the midazolam nano-suspension exhibited a significant increase in the Cmax and the AUC0-5, and a major decrease in Tmax. The overall results indicate the nano-suspension of midazolam is a promising candidate for managing status epilepticus in children in emergency situation.

咪达唑仑纳米混悬液的制备、优化和评价:提高口腔给药的生物利用度。
咪达唑仑被认为是治疗需要紧急药物治疗的儿童癫痫持续状态的最佳一线药物之一。由于咪达唑仑水溶性较差,口服生物利用度较低。为提高咪达唑仑纳米混悬液的溶出性和吸附性,采用超声法制备了咪达唑仑纳米混悬液。研究了Tween 80与Poloxamer (TP)的复合稳定剂和3-甲基壳聚糖(TMC)的复合稳定剂。以稳定剂的配比为自变量,采用单纯形晶格混合法评价了稳定剂对颗粒尺寸和zeta电位的影响。采用粒度分析、扫描电镜(SEM)、稳定性测试和溶出度测试等方法对优化后的咪唑安定纳米悬浮粉进行了表征。优化后的咪达唑仑纳米悬浮液(含76% TMC和24% TP)的平均粒径为197±7 nm, zeta电位为31±4 (mV)。稳定性试验表明,该咪达唑仑纳米悬浮液在12个月内稳定。在体外溶出度试验中,纳米咪达唑仑悬浮液的药物溶出率明显高于粗粒咪达唑仑。在体内评价中,咪达唑仑纳米混悬液Cmax和AUC0-5显著升高,Tmax显著降低。综上所述,纳米咪达唑仑悬浮液是治疗紧急情况下儿童癫痫持续状态的有希望的候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Progress in Biomaterials
Progress in Biomaterials MATERIALS SCIENCE, BIOMATERIALS-
CiteScore
9.60
自引率
4.10%
发文量
35
期刊介绍: Progress in Biomaterials is a multidisciplinary, English-language publication of original contributions and reviews concerning studies of the preparation, performance and evaluation of biomaterials; the chemical, physical, biological and mechanical behavior of materials both in vitro and in vivo in areas such as tissue engineering and regenerative medicine, drug delivery and implants where biomaterials play a significant role. Including all areas of: design; preparation; performance and evaluation of nano- and biomaterials in tissue engineering; drug delivery systems; regenerative medicine; implantable medical devices; interaction of cells/stem cells on biomaterials and related applications.
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