title: Ultrasonic emulsification of parenteral valproic acid-loaded nanoemulsion with response surface methodology and evaluation of its stability.
abstract: Response surface methodology (RSM) was used to optimize the formulation of a nanoemulsion for central delivery following parenteral administration. A mixture of medium-chain triglyceride (MCT) and safflower seed oil (SSO) was determined as a sole phase from the emulsification properties. Similarly, a natural surfactant (lecithin) and non-ionic surfactant (Tween 80) (ratio 1:2) were used in the formulation. A central composite design (CCD) with three-factor at five-levels was used to optimize the processing method of high energy ultrasonicator. Effects of pre-sonication ultrasonic intensity (A), sonication time (B), and temperature (C) were studied on the preparation of nanoemulsion loaded with valproic acid. Influence of the aforementioned specifically the effects of the ultrasonic processing parameters on droplet size and polydispersity index were investigated. From the analysis, it was found that the interaction between ultrasonic intensity and sonication time was the most influential factor on the droplet size of nanoemulsion formulated. Ultrasonic intensity (A) significantly affects the polydispersity index value. With this optimization method, a favorable droplet size of a nanoemulsion with reasonable polydispersity index was able to be formulated within a short sonication time. A valproic acid loaded nanoemulsion can be obtained with 60% power intensity for 15 min at 60 °C. Droplet size of 43.21±0.11 nm with polydispersity index of 0.211 were produced. The drug content was then increased to 1.5%. Stability study of nanoemulsion containing 1.5% of valproic acid had a good stability as there are no significant changes in physicochemical aspects such as droplet size and polydispersity index. With the characteristisation study of pH, viscosity, transmission electron microscope (TEM) and stability assessment study the formulated nanoemulsion has the potential to penetrate blood-brain barrier in the treatment of epilepsy.
authors.affiliation: Neuroscience Cluster, Department of Medicine, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors.forename: Suk Fei
authors.initials: SF
authors.lastname: Tan
authors.affiliation: Nanodelivery Group, Department of Chemistry, Faculty of Sciences, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors.forename: Hamid Reza Fard
authors.initials: HR
authors.lastname: Masoumi
authors.affiliation: Nanodelivery Group, Department of Chemistry, Faculty of Sciences, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors.forename: Roghayeh Abedi
authors.initials: RA
authors.lastname: Karjiban
authors.affiliation: Pharmacotherapeutic Unit, Department of Medicine, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors.forename: Johnson
authors.initials: J
authors.lastname: Stanslas
authors.affiliation: School of Pharmacy, Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin 2, Ireland.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Kirby
authors.affiliation: Nanodelivery Group, Department of Chemistry, Faculty of Sciences, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors.forename: Mahiran
authors.initials: M
authors.lastname: Basri
authors.affiliation: Neuroscience Cluster, Department of Medicine, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia. Electronic address: hamidon@upm.edu.my.
authors.forename: Hamidon Bin
authors.initials: HB
authors.lastname: Basri
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004333:Drug Administration Routes; D004355:Drug Stability; D004655:Emulsions; D036103:Nanotechnology / Q000379:methods*; D012450:Safflower Oil / Q000737:chemistry; D013223:Statistics as Topic; D014280:Triglycerides / Q000737:chemistry; D000069453:Ultrasonic Waves; D014635:Valproic Acid / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D004655:Emulsions; D014280:Triglycerides; D014635:Valproic Acid; D012450:Safflower Oil
keywords: Blood–brain barrier; Central composition design; Epilepsy; Nanoemulsion; Ultrasonication; Valproic acid