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

Progress in Biomaterials (2021)Cite this article

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.

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Affiliations

  1. Department of Biomedical Engineering, Faculty of Chemical Engineering, Tarbiat Modares University, P.O. Box: 14115-114, Tehran, Islamic Republic of Iran

    Arezou Soroushnia, Fariba Ganji & Ebrahim Vasheghani-Farahani

  2. Department of Novel Drug Delivery Systems, Faculty of Polymer Science, Iran Polymer and Petrochemical Institute (IPPI), P.O. Box: 14965-115, Tehran, Iran

    Hamid Mobedi

Authors
  1. Arezou Soroushnia
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  2. Fariba Ganji
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Correspondence to Fariba Ganji.

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Conflict of interest

The authors would like to thank the Iran National Science Foundation (INSF) for the financial support of this work. Authors declare that have no conflict of interest. All in vivo experiments were performed in accordance with the international guide for the care and use of laboratory animals. The experimental procedures were evaluated and approved by the Committee for Ethics in Animal Research at Tarbiat Modares University (Approval No: IR.TMU.REC.1396.706).

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Soroushnia, A., Ganji, F., Vasheghani-Farahani, E. et al. Preparation, optimization, and evaluation of midazolam nanosuspension: enhanced bioavailability for buccal administration. Prog Biomater (2021). https://doi.org/10.1007/s40204-020-00148-x

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Keywords

  • Nano-suspension
  • Midazolam
  • Stabilizer
  • Buccal bioavailability
  • Pharmacokinetic