Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken design

Jifu Hao¹, Xinsheng Fang², Yanfang Zhou³, Jianzhu Wang¹, Fengguang Guo¹, Fei Li¹, Xinsheng Peng^3
1College of Pharmacy, Taishan Medical University, Taian, PR China; ²Agronomy Department of Shandong Agriculture University, Taian, PR China; ³School of pharmaceutical Sciences, Guangdong Medical College, Dongguan, PR China

Abstract: The purpose of the present study was to optimize a solid lipid nanoparticle (SLN) of chloramphenicol by investigating the relationship between design factors and experimental data using response surface methodology. A Box-Behnken design was constructed using solid lipid (X₁), surfactant (X₂), and drug/lipid ratio (X₃) level as independent factors. SLN was successfully prepared by a modified method of melt-emulsion ultrasonication and low temperature-solidification technique using glyceryl monostearate as the solid lipid, and poloxamer 188 as the surfactant. The dependent variables were entrapment efficiency (EE), drug loading (DL), and turbidity. Properties of SLN such as the morphology, particle size, zeta potential, EE, DL, and drug release behavior were investigated, respectively. As a result, the nanoparticle designed showed nearly spherical particles with a mean particle size of 248 nm. The polydispersity index of particle size was 0.277 ± 0.058 and zeta potential was -8.74 mV. The EE (%) and DL (%) could reach up to 83.29% ± 1.23% and 10.11% ± 2.02%, respectively. In vitro release studies showed a burst release at the initial stage followed by a prolonged release of chloramphenicol from SLN up to 48 hours. The release kinetics of the optimized formulation best fitted the Peppas–Korsmeyer model. These results indicated that the chloramphenicol-loaded SLN could potentially be exploited as a delivery system with improved drug entrapment efficiency and controlled drug release.

Keywords: chloramphenicol, solid lipid nanoparticle, Box-Behnken design, melt-emulsion ultrasonication and low temperature-solidification technique