Response Surface Methodology for Development and Optimization of Theophylline Pulmonary Delivery System

[摘要] The aim of the present study was to develop theophylline (TP) inhalable sustained delivery system by preparing solid lipid microparticles using glyceryl behenate (GB) and poloxamer 188 (PX) as a lipid carrier and a surfactant respectively. The method involves loading TP nanoparticles into the lipid using high shear homogenization – ultrasonication technique followed by lyophilization. The compositional variations and interactions were evaluated using response surface methodology, a Box – Behnken design of experiment (DOE). The DOE constructed using TP (X1), GB (X2) and PX (X3) levels as independent factors. Responses measured were the entrapment efficiency (% EE) (Y1), mass median aerodynamic diameter (MMAD, daer) (Y2), zeta potential (ZP, ξ) (Y3), fine particles fraction (% FPF) (Y4) and percentage of dissolution efficiency at 420 minutes (% DE420) (Y5). The optimized formula was characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X – ray powder diffraction (XRD) demonstrated that prolonged release physically due to the loaded TP exists mostly in its crystalline state . Analysis of dissolution data of the optimized formula indicated that the best fitting is with Higuchi model, whereas the mechanism of drug release pattern follows anomalous or non – Fickian diffusion.

[学科分类] 计算机网络和通讯

[关键词] Glyceryl behenate;solid lipid microparticles;theophylline nanoparticles