Comparative study of cilnidipine loaded PLGA nanoparticles: process optimization by DoE, physico-chemical...

Cilnidipine (CND) is known to have low oral bioavailability due to its poor aqueous solubility, low dissolution rate, and high gut wall metabolism. In the present study, CND-loaded PLGA nanoparticles (CND-PLGA-NPs) were prepared with two different grades of PLGA (50:50 and 75:25) by design of experiment. Critical factors affecting particle size and entrapment efficiency (EE%) were assessed by mixed design approach, comprising of Plackett-Burman design followed by rotatable central composite design. Particle size, PDI, zeta potential, and EE% of optimized formulations of CND-PLGA(50:50)-NPs and CND-PLGA(75:25)-NPs were 211.6 ± 1.8 nm, 0.21 ± 0.05, - 15.1 ± 1.6 mV, and 85.9 ± 1.5% and 243.5 ± 2.4 nm, 0.23 ± 0.06, -19.6 ± 1.3 mV, and 92.0 ± 1.2% respectively. No significant changes were observed in physical stability of NPs when stored at 25 °C/60% RH over a period of 3 months. Pharmacokinetic studies revealed that F_abs of CND-PLGA(50:50)-NPs (1.15) and CND-PLGA(75:25)-NPs (2.23) were significantly higher than the free CND (0.26). The C_max and AUC_0-∞ of CND-PLGA(50:50)-NPs (787.42 ± 27.38 ng/mL and 9339.37 ± 252.38 ng/ml × h) and CND-PLGA(75:25)-NPs (803.49 ± 19.63 ng/mL and 18,153.34 ± 543.05 ng/ml × h) were significantly higher (p ˂ 0.0001) compared with free CND (367.69 ± 47.22 ng/mL and 2107.95 ± 136.40 ng/ml × h). MRT_Oral of CND-PLGA(50:50)-NPs (33.36 ± 0.48 h) and CND-PLGA(75:25)-NPs (48.37 ± 0.61 h) were significantly higher (p ˂ 0.0001) compared with free CND (4.69 ± 0.58 h). CND-PLGA-NPs can provide higher and sustained plasma drug levels of CND and be effective in antihypertensive therapy. Graphical abstract.