Quality by Design Approach for Preparation of Zolmitriptan/Chitosan Nanostructured Lipid Carrier Particles - Formulation and Pharmacodynamic Assessment
INTERNATIONAL JOURNAL OF NANOMEDICINE
Authors: Awadeen, Randa Hanie; Boughdady, Mariza Fouad; Meshali, Mahasen Mohamed
Abstract
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 (2(3) 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.
Photometric and spectroscopic monitoring, radial velocities and evolutionary status of the chromospherically active, close eclipsing binaries ST Centauri and V0775 Centauri
ASTROPHYSICS AND SPACE SCIENCE
Authors: Moriarty, D. J. W.; Liakos, A.; Drinkwater, M. J.; Mohit, A.; Sweet, S. M.; West, J. F.
Abstract
We have combined photometric and spectroscopic observations of two very close eclipsing binary systems, ST Centauri and V775 Centauri, to determine their evolutionary state from calculations of masses and radii and other properties. Spectral types were determined and radial velocities calculated from spectra obtained with the Australian National University's 2.3 m telescope and Wide Field Spectrograph. The spectral type of the ST Cen primary component is F8 IV and the secondary is F8-8.5 IV. The ST Cen mean masses and radii of 1.40 +/- 0.05M circle dot for components 1 and 2 respectively. Our data show that V775 Cen is a close Algol binary system, with a secondary component that has evolved beyond terminal age Main Sequence, has filled its inner critical equipotential surface and is transferring mass to the primary star. The masses and radii of both components of V775 Cen are smaller than those of other Algol binary systems. Although the primary component of V775 Cen is on the Main Sequence, its spectral type is F0/F1 class IV. Both systems displayed episodes of photospheric and chromospheric activity. This was evident in the H alpha lines of ST Cen and the Na I D lines of the components in both systems. Narrow Na I D lines between those of the binary components suggest that circumbinary gas is present.