Experimental Design in Formulation of Diazepam Nanoemulsions: Physicochemical and Pharmacokinetic Performances
Само за регистроване кориснике
2013
Аутори
Dordevic, Sanela M.Radulovic, Tamara S.
Cekic, Nebojsa
Randjelović, Danijela
Savić, Miroslav M.
Krajisnik, Danina R.
Milic, Jela R.
Savić, Snežana D.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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.
Кључне речи:
nanoemulsion / diazepam / full factorial design / particle size / atomic force microscopy / FTIR / drug-excipient interaction / stability / pharmacokineticsИзвор:
Journal of Pharmaceutical Sciences, 2013, 102, 11, 4159-4172Издавач:
- Wiley-Blackwell, Hoboken
Финансирање / пројекти:
- Развој микро- и наносистема као носача за лекове са антиинфламаторним деловањем и метода за њихову карактеризацију (RS-MESTD-Technological Development (TD or TR)-34031)
- Бихејвиорални ефекти понављане примене новосинтетисаних супстанци селективних за поједине подтипове бензодиазепинског места везивања ГАБА А рецептора: поређење са стандардним психофармаколошким лековима (RS-MESTD-Basic Research (BR or ON)-175076)
- Микро, нано-системи и сензори за примену у електропривреди, процесној индустрији и заштити животне средине (RS-MESTD-Technological Development (TD or TR)-32008)
DOI: 10.1002/jps.23734
ISSN: 0022-3549
PubMed: 24114833
WoS: 000325550400032
Scopus: 2-s2.0-84885846550
Институција/група
IHTMTY - JOUR AU - Dordevic, Sanela M. AU - Radulovic, Tamara S. AU - Cekic, Nebojsa AU - Randjelović, Danijela AU - Savić, Miroslav M. AU - Krajisnik, Danina R. AU - Milic, Jela R. AU - Savić, Snežana D. PY - 2013 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/1194 AB - 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 than 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. PB - Wiley-Blackwell, Hoboken T2 - Journal of Pharmaceutical Sciences T1 - Experimental Design in Formulation of Diazepam Nanoemulsions: Physicochemical and Pharmacokinetic Performances VL - 102 IS - 11 SP - 4159 EP - 4172 DO - 10.1002/jps.23734 ER -
@article{ author = "Dordevic, Sanela M. and Radulovic, Tamara S. and Cekic, Nebojsa and Randjelović, Danijela and Savić, Miroslav M. and Krajisnik, Danina R. and Milic, Jela R. and Savić, Snežana D.", year = "2013", abstract = "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 than 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.", publisher = "Wiley-Blackwell, Hoboken", journal = "Journal of Pharmaceutical Sciences", title = "Experimental Design in Formulation of Diazepam Nanoemulsions: Physicochemical and Pharmacokinetic Performances", volume = "102", number = "11", pages = "4159-4172", doi = "10.1002/jps.23734" }
Dordevic, S. M., Radulovic, T. S., Cekic, N., Randjelović, D., Savić, M. M., Krajisnik, D. R., Milic, J. R.,& Savić, S. D.. (2013). Experimental Design in Formulation of Diazepam Nanoemulsions: Physicochemical and Pharmacokinetic Performances. in Journal of Pharmaceutical Sciences Wiley-Blackwell, Hoboken., 102(11), 4159-4172. https://doi.org/10.1002/jps.23734
Dordevic SM, Radulovic TS, Cekic N, Randjelović D, Savić MM, Krajisnik DR, Milic JR, Savić SD. Experimental Design in Formulation of Diazepam Nanoemulsions: Physicochemical and Pharmacokinetic Performances. in Journal of Pharmaceutical Sciences. 2013;102(11):4159-4172. doi:10.1002/jps.23734 .
Dordevic, Sanela M., Radulovic, Tamara S., Cekic, Nebojsa, Randjelović, Danijela, Savić, Miroslav M., Krajisnik, Danina R., Milic, Jela R., Savić, Snežana D., "Experimental Design in Formulation of Diazepam Nanoemulsions: Physicochemical and Pharmacokinetic Performances" in Journal of Pharmaceutical Sciences, 102, no. 11 (2013):4159-4172, https://doi.org/10.1002/jps.23734 . .