Quality by Design Approach for Preparation of Zolmitriptan/Chitosan Nanostructured Lipid Carrier Particles – Formulation and Pharmacodynamic Assessment
| Autor: | Awadeen, Randa Hanie, Boughdady, Mariza Fouad, Meshali, Mahasen Mohamed |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
Pectin Polysorbates Pharmaceutical Science Zolmitriptan 02 engineering and technology nanostructured lipid carrier 01 natural sciences Chitosan Mice chemistry.chemical_compound Drug Discovery Zeta potential Ultrasonics Original Research Drug Carriers zolmitriptan General Medicine Factorial experiment 021001 nanoscience & nanotechnology Lipids Tryptamines factorial design Pectins Emulsions 0210 nano-technology medicine.drug food.ingredient Sonication Biophysics Capsules Bioengineering 010402 general chemistry Biomaterials food pharmacodynamics medicine Animals Particle Size Oxazolidinones Chromatography Guar gum Organic Chemistry in situ gelling Nanostructures 0104 chemical sciences Solubility chemistry Gelatin Nanoparticles Particle size |
| Zdroj: | International Journal of Nanomedicine |
| ISSN: | 1178-2013 |
| DOI: | 10.2147/ijn.s274352 |
| Popis: | Purpose Zolmitriptan (ZT) is a selective serotonin agonist that is used for the treatment of migraine. It belongs to BCS class III with high solubility and low permeability. Besides, the drug is subjected to pre-systemic metabolism. Accordingly, new Zolmitriptan/chitosan nanostructured lipid carriers (ZT/CT NLCs) coated with Tween 80 (stealthy layer) have been developed to overcome such demerits. Methods The NLCs were developed by combining ultrasonication and double emulsion (w/o/w) techniques. The lipids were Gelucire and Labrasol. Herein, the quality by design (23 full factorial design) was scrupulously followed, where critical process parameters and critical quality attributes were predefined. The optimized formulation (F8) was fully characterized with respect to entrapment efficiency (%EE), percentage yield (% yield), particle size, size distribution (PDI), zeta potential (ZP), morphological appearance (TEM). In vitro release, stability study and pharmacodynamic evaluations were also assessed. The optimized freeze dried formula was dispensed in in situ gelling hard gelatin capsule encompassing pectin and guar gum for further in vitro and pharmacodynamic evaluations. Results The optimized spherical nanoparticles experienced high percentage EE and yield (78.14% and 60.19%, respectively), low particle size and PDI (343.87 nm and 0.209, respectively), as well as high negative ZP (−25.5 mV). It showed good physical stability at refrigerated conditions. The NLCs dispensed in in situ gelling hard gelatin capsule comprising pectin and guar gum experienced sustained release for 30 h and significantly maintained the pharmacological effect in mice up to 8 h (p < 0.001). Conclusion ZT, a BCS class III drug that suffers from poor permeability and pre-systemic metabolism, was successfully maneuvered as nanostructured lipid carrier particles (NLCs). The incorporation of the NLCs in in situ gelling hard gelatin capsules fulfilled a dual function in increasing permeability, as well as sustaining the pharmacodynamic effect. This result would open new vistas in improving the efficacy of other class III drugs. |
| Databáze: | OpenAIRE |
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