Ultrasonic emulsification of parenteral valproic acid-loaded nanoemulsion with response surface methodology and evaluation of its stability |
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| Affiliation: | 1. Neuroscience Cluster, Department of Medicine, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia;2. Nanodelivery Group, Department of Chemistry, Faculty of Sciences, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia;3. Pharmacotherapeutic Unit, Department of Medicine, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia;4. School of Pharmacy, Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin 2, Ireland;1. Key Laboratory of Food Colloids and Biotechnology, Ministry of Education, School of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China;2. Department of Food Technology, School of Food Science and Technology, National University of Rwanda, P.O. Box 4285, Kigali, Rwanda;3. Department of Human Ecology, Domasi College of Education, University of Malawi, P.O. Box 49, Domasi, Zomba, Malawi;4. Department of food science and technology, University of California, One Shields Avenue, Davis, CA 95616, United States;1. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;2. Department of Food Science and Technology, Faculty of Agriculture, University of Tabriz, P.O. Box 51666-16471 Tabriz, Iran;3. Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;4. Medicinal Plants and Drug Research Institute, Shahid Beheshti University, Tehran, Iran;5. Iranian Center of Excellence in Health Management, Tabriz University of Medical Sciences, Tabriz, Iran;1. Federal University of Lavras, Department of Food Science, Laboratory of Food Refrigeration, P.O. Box 3037, 37200-000 Lavras, Minas Gerais, Brazil;2. Federal University of Lavras, Department of Food Science, Packaging Laboratory, P.O. Box 3037, 37200-000 Lavras, Minas Gerais, Brazil;3. Federal University of Viçosa, Department of Food Technology, Av. Peter Henry Rolfs, s/n – Campus Universitário, Viçosa, MG 36570-900, Brazil;1. Department of Pharmaceutics, School of Pharmaceutical Education and Research, Hamdard University, New Delhi, India;2. Department of Pharmacology, School of Pharmaceutical Education and Research, Hamdard University, New Delhi, India;3. Department of Pharmaceutics, Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh, India |
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| 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. |
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| Keywords: | Ultrasonication Valproic acid Epilepsy Blood–brain barrier Central composition design Nanoemulsion |
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