title: Part I: Development and optimization of solid-lipid nanoparticles using Box-Behnken statistical design for ocular delivery of gatifloxacin.
abstract: This study aims to improve gatifloxacin bioavailability to the eye using solid-lipid nanoparticles (SLN). Cationic SLNs were prepared by o/w-microemulsion method using stearylamine. The generated formulations were optimized by three-factor, three-level Box-Behnken statistical design. The independent variables were the lipid(mix) concentration (X1), poloxamers-188 (X2), and sodium-taurocholate (X3), while the dependent variables were drug release (Y1), encapsulation efficiency (EE) (Y2), and particle size (Y3 ) with applied constraints of maximizing drug release and EE and minimizing particle size. Response surface plots were drawn, statistical validity of the polynomials was established, optimized formulations were selected by feasibility and grid search, and the optimization process was validated. Particle size, polydispersity index, and zeta-potentials were measured by photon correlation spectroscopy. Particle's morphology was evaluated by transmission electron microscopy. Differential scanning calorimetry (DSC) and wide-angle X-ray diffraction (WXRD) studies were performed to characterize state of drug and lipid modification. SLN size was (250-305 nm) and zeta-potential (29-36 mV) after 3-month storage. Entrapment efficiencies were 46.58 and 78.55%, and loading efficiencies were 29.60 and 20.70 for SLN-C and SLN-D, respectively. DSC and WXRD analyses showed low-crystalline SLN and amorphous drug dispersion in SLN. In vitro release data were fitted to release kinetics equations, where the release pattern was found to follow Korsmeyer-Peppas model.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, KSA.
authors.forename: Mohd
authors.initials: M
authors.lastname: Abul Kalam
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Sultana
authors.forename: Asgar
authors.initials: A
authors.lastname: Ali
authors.forename: Mohd
authors.initials: M
authors.lastname: Aqil
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mishra
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Aljuffali
authors.forename: Aws
authors.initials: A
authors.lastname: Alshamsan
mesh_terms: D002152:Calorimetry, Differential Scanning; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D005123:Eye / Q000187:drug effects*; D024841:Fluoroquinolones / Q000008:administration & dosage* / Q000494:pharmacology*; D000077734:Gatifloxacin; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D012044:Regression Analysis; D015203:Reproducibility of Results; D012212:Rheology / Q000187:drug effects; D055672:Static Electricity; D013223:Statistics as Topic; D013535:Suspensions; D014961:X-Ray Diffraction
chemical_list: D024841:Fluoroquinolones; D008055:Lipids; D013535:Suspensions; D000077734:Gatifloxacin