Experimental Design in Formulation of Diazepam Nanoemulsions: Physicochemical and Pharmacokinetic Performances
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2013
Authors
Dordevic, Sanela M.Radulovic, Tamara S.
Cekic, Nebojsa

Ranđelović, Danijela

Savić, Miroslav M.

Krajisnik, Danina R.
Milic, Jela R.
Savić, Snežana D.

Article (Published version)

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With the aid of experimental design, we developed and characterized nanoemulsions for parenteral drug delivery. Formulations containing a mixture of medium-chain triglycerides and soybean oil as oil phase, lecithin (soybean/egg) and polysorbate 80 as emulsifiers, and 0.1M phosphate buffer solution (pH 8) as aqueous phase were prepared by cold high-pressure homogenization. To study the effects of the oil content, lecithin type, and the presence of diazepam as a model drug and their interactions on physicochemical characteristics of nanoemulsions, a three factor two-level full factorial design was applied. The nanoemulsions were evaluated concerning droplet size and size distribution, surface charge, viscosity, morphology, drug-excipient interactions, and physical stability. The characterization revealed the small spherical droplets in the range 195-220nm with polydispersity index below 0.15 and zeta potential between -30 and -60mV. Interactions among the investigated factors, rather tha...n factors alone, were shown to more profoundly affect nanoemulsion characteristics. In vivo pharmacokinetic study of selected diazepam nanoemulsions with different oil content (20%, 30%, and 40%, w/w) demonstrated fast and intense initial distribution into rat brain of diazepam from nanoemulsions with 20% and 30% (w/w) oil content, suggesting their applicability in urgent situations.
Keywords:
nanoemulsion / diazepam / full factorial design / particle size / atomic force microscopy / FTIR / drug-excipient interaction / stability / pharmacokineticsSource:
Journal of Pharmaceutical Sciences, 2013, 102, 11, 4159-4172Publisher:
- Wiley-Blackwell, Hoboken
Projects:
- Development of micro- and nanosystems as carriers for drugs with anti-inflammatory effect and methods for their characterization (RS-34031)
- Behavioral ?ffects following repeated administration of newly synthesized ligands selective for distinct subtypes of GABAA receptor benzodiazepine binding site: comparison with standard psychopharmacologic drugs (RS-175076)
- Micro- Nanosystems and Sensors for Electric Power and Process Industry and Environmental Protection (RS-32008)
DOI: 10.1002/jps.23734
ISSN: 0022-3549
PubMed: 24114833