{"title":"Preparation, optimization, and evaluation of midazolam nanosuspension: enhanced bioavailability for buccal administration.","authors":"Arezou Soroushnia, Fariba Ganji, Ebrahim Vasheghani-Farahani, Hamid Mobedi","doi":"10.1007/s40204-020-00148-x","DOIUrl":null,"url":null,"abstract":"<p><p>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 C<sub>max</sub> and the AUC<sub>0-</sub>5, and a major decrease in T<sub>max</sub>. The overall results indicate the nano-suspension of midazolam is a promising candidate for managing status epilepticus in children in emergency situation.</p>","PeriodicalId":20691,"journal":{"name":"Progress in Biomaterials","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40204-020-00148-x","citationCount":"6","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Progress in Biomaterials","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1007/s40204-020-00148-x","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/2/15 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
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.
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.