Using Self-Nanoemulsifying System to Improve Oral Bioavailability of a Pediatric Antiepileptic Agent Stiripentol: Formulation and Pharmacokinetics Studies
| Autor: | Yong Chen, Yilan Jin, Peiyan Zhang, Shujun Xu, Mi Tang, Mengling Shen, Qiuyang Dai, Susu Huang |
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| Rok vydání: | 2020 |
| Předmět: |
Biodistribution
Central composite design Cmax Pharmaceutical Science Administration Oral Biological Availability 02 engineering and technology Aquatic Science 030226 pharmacology & pharmacy Polyethylene Glycols Excipients 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Delivery Systems Pulmonary surfactant Pharmacokinetics Drug Discovery Humans Ethyl oleate Tissue Distribution Particle Size Child Ecology Evolution Behavior and Systematics Chromatography Ecology Chemistry Dioxolanes General Medicine 021001 nanoscience & nanotechnology Bioavailability Solubility Drug delivery Nanoparticles Anticonvulsants Emulsions 0210 nano-technology Agronomy and Crop Science |
| Zdroj: | AAPS PharmSciTech. 21(5) |
| ISSN: | 1530-9932 |
| Popis: | This study aimed to develop a self-nanoemulsifying drug delivery system (SNEDDS) for poorly water-soluble drug stiripentol (STP) with enhanced oral bioavailability. Optimal excipients were selected by constructing pseudo-ternary phase diagrams using determined solubilities of STP, and then the proper composition of SNEDDS was investigated by employing a central composite design method. The optimized SNEDDS was composed of oil (ethyl oleate 39.61%), surfactant (Cremophor® RH 40 43.18%), co-surfactant (1,2-propanediol 17.21%), and STP of 50 mg/mL. The hydrodynamic size, zeta potential, and polydispersity index (PDI) were found to be 45.52 ± 1.99 nm, − 21.67 ± 0.24 mV, and 0.076 ± 0.011, respectively. The optimized STP-SNEDDS showed good stability in accelerated and dilution stability studies. It was also helpful to suppress STP degradation in acidic solution. Compared with STP suspension, STP-SNEDDS presented much faster dissolution rate. STP-SNEDDS successfully resulted in superior levels of Cmax and AUC0 → 6 h (4048.38 ± 704.54 μg/L and 7754.58 ± 1489.37 h μg/L, respectively) to STP suspension (1894.09 ± 1077.64 μg/L and 3556.93 ± 2470.01 h μg/L, respectively). The relative oral bioavailability of STP was 218.01%. The brain biodistribution studies showed that STP-SNEDDS presented significantly higher STP concentrations in the brain at 0.5 h and 1 h than that of STP suspension after administration. These findings indicated that a SNEDDS-based oral formulation of STP would be helpful for increasing its therapeutic potential. |
| Databáze: | OpenAIRE |
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