Preparation of 10-hydroxycamptothecin proliposomes by the supercritical CO2 anti-solvent process

• 10-hydroxycamptothecin proliposomes (HCPT-PL) were prepared via SAS process.
• The process variables were optimized by an OA25 (55) orthogonal design.
• TEM images show that spherical and clavate morphologies were obtained.
• Part of the encapsulated HCPT still maintains its crystalline state.
• The drug release follows the first order kinetics, the drug diffusion mainly corresponds to a Fickian diffusion mechanism.

For this study, 10-Hydroxycamptothecin proliposomes (HCPT-PL) were prepared using the supercritical CO2 anti-solvent process. The mixture of soy lecithin and cholesterol were chosen as liposomal components. The effects of different variables, i.e., the mass ratio of soy lecithin to cholesterol, the mass ratio of HCPT to liposomal components, temperature, pressure and HCPT solution flow rate on HCPT-PL formation were investigated using an OA25 (55) orthogonal experimental design. The formulations were evaluated quantitatively using an overall desirability function, which was calculated based on four assessment indices, i.e., particle size, particle size distribution, drug loading and encapsulation efficiency. SEM and TEM images showed that spherical or clavate HCPT-PL were obtained under different processing conditions, and the drug loading has a significant effect on the morphologies. Under the optimized conditions, clavate HCPT-PL with a mass median diameter of 209.8 ± 38.4 nm, a drug loading of 5.33% and an encapsulation efficiency of 85.28% were obtained. For the optimized HCPT-PL, the residual DCM meets the ICH requirement, and part of the encapsulated HCPT still maintains its crystalline state. And the result of in vitro release rate study showed that HCPT-PL sustained the HCPT release rate successfully, where the drug release of the optimized HCPT-PL followed the first order kinetics, and the drug diffusion mainly corresponded to a Fickian diffusion mechanism during the first 10 h.

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