A novel formulation of zolpidem for direct nose-to-brain delivery: synthesis, encapsulation and intranasal administration to mice

J Pharm Pharmacol. 2018 Sep;70(9):1164-1173. doi: 10.1111/jphp.12958. Epub 2018 Jun 28.

Abstract

Objectives: Anxiolytic drug zolpidem was incorporated into the microcontainers based on mesoporous calcium carbonate particles modified by diethylaminoethyl-dextran/hyaluronic acid shell. The release of zolpidem in saline solution and in polymer film modelling nasal mucosa was investigated. The anxiolytic effect of zolpidem upon intranasal administration of microcontainers and free medicine was determined by in vivo experiments on mice.

Methods: The structures of all compounds during zolpidem synthesis were established using nuclear magnetic resonance spectroscopy. The loading efficacy and release kinetics of zolpidem were analysed by spectrophotometry. Surface morphology of formulation was investigated by scanning electron microscopy. To determine the effect of zolpidem-loaded containers administration by the intranasal route in vivo experiments was carried out applying the open field test.

Key findings: Nasal administration of zolpidem in the form of the microcontainers based on mesoporous calcium carbonate particles modified by diethylaminoethyl-dextran/hyaluronic acid shell has a pronounced anxiolytic effect on the behaviour of the animals in the open field test.

Conclusions: The polyelectrolyte shell deposited together with zolpidem enhances the loading efficacy of the microcontainers. In vivo experiments on mice demonstrate increase in anxiolytic effect of zolpidem in microcontainers compared with upon intranasal administration of free medicine.

Keywords: anxiolytic effect; intranasal delivery; microcontainers; zolpidem.

MeSH terms

  • Administration, Intranasal
  • Animals
  • Brain / drug effects*
  • Drug Compounding
  • Drug Delivery Systems / methods*
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / chemical synthesis
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nasal Mucosa / drug effects*
  • Zolpidem / administration & dosage*
  • Zolpidem / chemical synthesis*

Substances

  • Hypnotics and Sedatives
  • Zolpidem