Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study

Abstract

Nanoparticles formulated from biodegradable polymers like poly(lactic-co-glycolic acid) (PLGA) are being extensively investigated as drug delivery systems due to their two important properties such as biocompatibility and controlled drug release characteristics. The aim of this work to formulated diazepam loaded PLGA nanoparticles by using emulsion solvent evaporation technique. Polyvinyl alcohol (PVA) is used as stabilizing agent. Diazepam is a benzodiazepine derivative drug, and widely used as an anticonvulsant in the treatment of various types of epilepsy, insomnia and anxiety. This work investigates the effects of some preparation variables on the size and shape of nanoparticles prepared by emulsion solvent evaporation method. These nanoparticles were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM). Zeta potential study was also performed to understand the surface charge of nanoparticles. The drug release from drug loaded nanoparticles was studied by dialysis bag method and the in vitro drug release data was also studied by various kinetic models. The results show that sonication time, polymer content, surfactant concentration, ratio of organic to aqueous phase volume, and the amount of drug have an important effect on the size of nanoparticles. Hopefully we produced spherical shape Diazepam loaded PLGA nanoparticles with a size range under 250 nm with zeta potential -23.3 mV. The in vitro drug release analysis shows sustained release of drug from nanoparticles and follow Korsmeyer-Peppas model.

Keywords: Biodegradable polymer; Diazepam; Emulsion solvent evaporation technique; Nanoparticles; Release kinetic models.

Fig. 1

Chemical structure of Diazepam

Fig. 2

Effect of a sonication time on the size of nanoparticles b PLGA content in organic phase in mg/ml on the size of nanoparticles c volume of organic phase in ml on the size of nanoparticles d volume of PVA content in  %w/V of aqueous phase and e diazepam content in mg/ml of organic phase

Fig. 3

TEM image for nanoparticles prepared by a 5 min sonication b 10 mg/ml PLGA of organic phase c 5 ml of organic solvent d 1 % (w/V) PVA of aqueous phase and e 1.5 mg/ml diazepam of organic phase (or optimization o different variables)

Fig. 4

a DLS image and b Zeta potential graph for nanoparticles prepared by optimization of different variables

Fig. 5

In-vitro drug release for nanoparticles prepared by optimization of different variables

Fig. 6

Drug release kinetics plots: a Zero order plot b First order plot c Higuchi plot and d Korsmeyer Peppas plot