Novel approach for overcoming the stability challenges of lipid-based excipients. Part 3: Application of polyglycerol esters of fatty acids for the next generation of solid lipid nanoparticles
| Autor: | Dirk Lochmann, Sebastian Reyer, Sharareh Salar-Behzadi, Claudia Meindl, Carolina Corzo |
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| Rok vydání: | 2019 |
| Předmět: |
Glycerol
Carrier system Polymers THP-1 Cells Chemistry Pharmaceutical Drug Storage Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Dosage form Dexamethasone law.invention Excipients 03 medical and health sciences 0302 clinical medicine Differential scanning calorimetry Drug Stability X-Ray Diffraction law Cell Line Tumor Solid lipid nanoparticle Zeta potential Humans Crystallization Particle Size Active ingredient Chromatography Calorimetry Differential Scanning Chemistry Fatty Acids Esters General Medicine 021001 nanoscience & nanotechnology Lipids Pharmaceutical Preparations A549 Cells Nanoparticles Particle size 0210 nano-technology Biotechnology |
| Zdroj: | European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 152 |
| ISSN: | 1873-3441 |
| Popis: | Solid lipid nanoparticles (SLN) are an advantageous carrier system for the delivery of lipophilic active pharmaceutical ingredients (APIs). The use of SLN has been limited due to stability issues attributed to the unstable solid state of the lipid matrix. A novel approach for overcoming this problem is the application of polyglycerol esters of fatty acids (PGFAs) as lipid matrices with stable solid state. PG2-C18 full, a PGFA molecule, was used to develop SLN loaded with dexamethasone as a model API. Dexamethasone-loaded SLN were manufactured via melt-emulsification and high pressure homogenization in the dosage form of a lipid nanosuspension. SLN with median particle size of 242.1 ± 12.4 nm, zeta potential of −28.5 ± 7.8 mV, entrapment efficiency of 90.2 ± 0.7% and API released after 24 h of 81.7 ± 0.7%, were produced. Differential Scanning Calorimetry (DSC) and Small and Wide Angle X-Ray Scattering (SWAXS) analysis of the lipid nanosuspension evidenced the crystallization of PG2-C18 full in a monophasic system in α-form and absence of polymorphism and crystallite growth up to 6 months storage at room temperature. This resulted in stable performance of the SLN after storage: absence of particle agglomeration, no API expulsion, and stable release profile. The potential pulmonary administration of SLN was tested by the nebulization capacity of the lipid nanosuspension. Cellular exposures to SLN did not induce cytotoxicity or immune effect on pulmonary cells. The application of PGFAs as safe and stable lipid matrices provide a promising approach for the development of the next generation of SLN. |
| Databáze: | OpenAIRE |
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