Diazepam-loaded parenteral nanoemulsions: Physicochemical characterization and in vitro release study

Abstract

The aim of the present study was to develop parenteral nanoemulsions containing increasing content of oil phase (20, 30 and 40%, w/w of medium-chain triglycerides-soybean oil mixture at 4:1 ratio), stabilized by lecithin-polysorbate 80 mixture, and to assess their feasibility as carriers for poorly water-soluble psychopharmacological drugs. To this purpose, nanoemulsions loaded with diazepam as a model drug were prepared through high pressure homogenization and characterized regarding droplet size, polydispersity, surface charge, viscosity, pH value, and electrical conductivity. Furthermore, the in vitro release of diazepam from developed nanoemulsions was examined using reverse dialysis bag technique, and drug release kinetics was evaluated through several mathematical models. After preparation, all formulations revealed small mean droplet size (206 ± 7 nm), with narrow size distribution (0.116 ± 0.012) and zeta potential around -50 mV, complying with pharmacopoeial requirements (USP 39-NF 34), wherein there were no significant changes in monitored parameters after one year of storage at 25 ± 2°C. In vitro drug release study demonstrated that 40-50% of diazepam was released from actual nanoemulsions within 1 h, while the kinetic release process could be described by Korsmeyer-Peppas model. The results obtained suggest that formulated parenteral nanoemulsions might be promising carriers for rapid delivery of lipophilic, poorly water-soluble psychopharmacological drugs.

Cilj ovog istraživanja bio je da se razviju parenteralne nanoemulzije sa rastućom koncentracijom uljane faze (20, 30 i 40% smeše triglicerida srednje dužine lanca i sojinog ulja u odnosu 4:1), stabilizovane kombinacijom lecitina i polisorbata 80, i da se proceni njihova pogodnost kao nosača za slabo rastvorljive psihofarmakološke lekovite supstance. U tu svrhu, homogenizacijom pod visokim pritiskom izrađene su nanoemulzije sa diazepamom kao model lekovitom supstancom i okarakterisane u pogledu veličine kapi, indeksa polidisperznosti, površinskog naelektrisanja, viskoziteta, pH vrednosti i električne provodljivosti. Takođe, primenom reverzne tehnike sa dijaliznim vrećicama procenjena je brzina oslobađanja diazepama iz razvijenih nanoemulzija, uz karakterizaciju dobijenih profila oslobađanja primenom različitih matematičkih modela. Nakon izrade, sve formulacije imale su malu prosečnu veličinu kapi (206 ± 7 nm), sa uskom raspodelom veličina (0,116 ± 0,012) i zeta potencijalom oko -50 mV, što je u skladu sa farmakopejskim zahtevima (USP 39-NF 34) pri čemu se vrednosti navedenih parametara nisu značajno promenile nakon godinu dana čuvanja na 25 ± 2°C. In vitro ispitivanje brzine oslobađanja pokazalo je da se 40-50% diazepama oslobodi iz ispitivanih nanoemulzija tokom 1 h, pri čemu se kinetika oslobađanja može opisati Korsmeyer-Peppas modelom. Dobijeni rezultati ukazuju da formulisane parenteralne nanoemulzije predstavljaju obećavajuće nosače za brzu isporuku slabo rastvorljivih psihofarmakoloških lekovitih supstanci.