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Development of sorafenib loaded nanoparticles to improve oral bioavailability using a quality by design approach
- Source :
- International Journal of Pharmaceutics. 566:229-238
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Sorafenib, a potent anticancer drug, has low absorption in the gastrointestinal tract due to its poor aqueous solubility. The main purpose of this investigation was to design sorafenib nanoparticle using a newly developed technique, nanoparticulation using fat and supercritical fluid (NUFS™) to improve the absorption of sorafenib. The quality by design (QbD) tool was adopted to define the optimal formulation variables: hydroxypropyl methyl cellulose (HPMC), polyvinyl pyrrolidone K30 (PVP), and poloxamer. The studied response variables were particle size of nanoparticle, dissolution (5, 60, and 180 min), drug concentration time profile of nanoparticle formulations, and maximum drug concentration. The result of particle size revealed that an increase in concentration of poloxamer and HPMC decreased the particle size of nanoparticles (p 0.05). Likewise, the concentration of drug release at different time point (5, 60, and 180 min) showed HPMC and poloxamer had positive effects on drug dissolution while PVP had negative effects on it. The design space was built in accordance with the particle size of nanoparticle (target 500 nm) and dissolution of sorafenib (target 7 µm/mL), following failure probability analysis using Monte Carlo simulations. In vivo pharmacokinetics studies in beagle dogs demonstrated that optimized formulation of sorafenib (F3 and F4 tablets) exhibited higher blood drug profiles indicating better absorption compared to the reference tablet (Nexavar
- Subjects :
- Male
Sorafenib
Administration, Oral
Biological Availability
Pharmaceutical Science
Antineoplastic Agents
Poloxamer
02 engineering and technology
Absorption (skin)
030226 pharmacology & pharmacy
03 medical and health sciences
chemistry.chemical_compound
Dogs
Hypromellose Derivatives
0302 clinical medicine
Pharmacokinetics
Blood drug
medicine
Animals
Particle Size
Protein Kinase Inhibitors
Chromatography
Povidone
021001 nanoscience & nanotechnology
Bioavailability
Drug Liberation
chemistry
Drug Design
Methyl cellulose
Nanoparticles
Particle size
0210 nano-technology
medicine.drug
Subjects
Details
- ISSN :
- 03785173
- Volume :
- 566
- Database :
- OpenAIRE
- Journal :
- International Journal of Pharmaceutics
- Accession number :
- edsair.doi.dedup.....870d5b3d6804b4a1a543e2dfeef5150c