title: Multivariate Optimization of Rizatriptan Benzoate-Loaded Solid Lipid Nanoparticles for Brain Targeting and Migraine Management.
abstract: The present investigation aimed at development of brain-targeted rizatriptan benzoate-loaded solid lipid nanoparticles (RB-SLNs) by design of experiment, for improvement of its anti-migraine potential. Several formulation variables affecting the fabrication of RB-SLNs were screened using the Plackett-Burman design (PBD). The PBD results demonstrated lipid (Precirol® ATO 5) concentration, co-surfactant (Phospholipon® 90 H) concentration and temperature of lipid melt to be the critical variables, having a significant effect on the achievement of minimum particle size, maximum entrapment efficiency coupled with sustained drug release. The interactions between these formulation parameters and the variability between the batches were further explored employing the Box-Behnken design (BBD). The BBD results were validated by fabricating the suggested optimized solution, which yielded 220.4 ± 2.3 nm particle size with a sufficiently high entrapment efficiency of 71.8 ± 1.9% and 45.9 ± 2.7% cumulative drug release in 8 h. The optimized formulation was, thereafter, characterized by FTIR spectroscopy, wide angle XRD, thermal analysis and TEM imaging technique. The in vivo studies revealed the brain uptake potential of optimized RB-SLNs to be 18.43-folds higher with respect to the pure drug in its free form, post 2 h of oral drug administration. The significant anti-migraine efficacy of RB-SLNs was corroborated through the pharmacodynamic studies on adult male Swiss albino mice. The results hence explicate that RB-SLNs have distinctly improved brain target ability and offer an apt approach for the efficient therapeutic management of migraine.
authors.affiliation: Department of Pharmaceutical Sciences, G. J. University of Sci. & Tech., Hisar, 125001, India.
authors.forename: Priti
authors.initials: P
authors.lastname: Girotra
authors.affiliation: Department of Pharmaceutical Sciences, G. J. University of Sci. & Tech., Hisar, 125001, India. sksingh_gju@rediffmail.com.
authors.forename: Shailendra Kumar
authors.initials: SK
authors.lastname: Singh
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D008055:Lipids / Q000737:chemistry*; D008297:Male; D051379:Mice; D008881:Migraine Disorders / Q000188:drug therapy*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013501:Surface-Active Agents / Q000737:chemistry; D014230:Triazoles / Q000008:administration & dosage* / Q000737:chemistry*; D014363:Tryptamines / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008055:Lipids; D013501:Surface-Active Agents; D014230:Triazoles; D014363:Tryptamines; C093622:rizatriptan
keywords: Box-Behnken design; Plackett-Burman design; migraine; rizatriptan benzoate; solid lipid nanoparticles