Development of cyclosporine A nanosuspension using experimental design by response surface methodology: In vitro evaluations

INTRODUCTION: This study aims to develop nanosuspensions of cyclosporine A (CycA) using a top-down technology (high pressure homogenization - HPH) for oral admistration.
METHODS: The formulations were prepared using different ratios of hydroxypropyl methylcellulose (HPMC) (1% and 0.5%) and sodium dodecyl sulfate (SDS) (1%) to improve the solubility of CycA. The HPH method was optimized by investigating the effects of critical formulation parameters (stabilizer ratio) and critical process parameters (number of homogenization cycles) on the particle size (PS), polydispersity index (PDI), and zeta potential (ZP) of nanosuspension using Design of Experiment (DoE). After lyophilization, differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transformed infrared (FTIR) spectroscopy, and morphological evaluation with scanning electron microscopy (SEM) were performed. The stability studies were performed at 4oC and 25oC storage conditions. The solubility of optimum CycA nanosuspension was investigated by comparing with coarse CycA powder and physical mixture (PM). In vitro dissolution studies were conducted in four media by using dissolution testing USP apparatus I.
RESULTS: PS, PDI, and ZP values for nanosuspension were found about 250 nm, 0.6, -35 mV, respectively. Under storage conditions, CycA nanosuspension demonstrated significant physical stability at both 4oC and 25oC for 9 months. The solubility of CycA was improved 1.9- and 1.4-times by nanosuspension in accordance with CycA powder and PM, respectively. CycA nanosuspension exhibited higher dissolution than CycA coarse powder in 0.1 N HCl, FaSSIF, and FeSSIF medium.
DISCUSSION AND CONCLUSION: CycA nanosuspension was successfully developed using the DoE approach with HPH method with HPMC: SDS combination in 1: 0.5 ratio and solubility and dissolution of CycA was improved in nanosuspension.