Comparative study of cilnidipine loaded PLGA nanoparticles: process optimization by DoE, physico-chemical characterizati
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ORIGINAL ARTICLE
Comparative study of cilnidipine loaded PLGA nanoparticles: process optimization by DoE, physico-chemical characterization and in vivo evaluation Rimpy Diwan 1 & Shareef Khan 1 & Punna Rao Ravi 1
# Controlled Release Society 2020
Abstract 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 CNDPLGA(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 Fabs 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 Cmax and AUC0-∞ of CNDPLGA(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). MRTOral 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. Keywords Cilnidipine . PLGA . Polymeric nanoparticles . Plackett-Burman design . Rotatable central composite design . Pharmacokinetic study
Introduction The World Health Organization considers cardiovascular diseases (among them high blood pressure or hypertension) as the most important global public health problem which are associated with increased risk for mortality and disability, affecting over 40% of adults over the age of 25 and causing an
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13346-020-00732-5) contains supplementary material, which is available to authorized users. * Punna Rao Ravi [email protected] 1
Department of Pharmacy, BITS-Pilani Hyderabad Campus, Jawaharnagar, Shameerpet (M), Hyderabad 500078, Telangana, India
estimated 9.4 million deaths every year [1, 2]. Hypertension treatment is an everyday challenge faced by both patient and primary care physicians [3]. Global epidemiological reports reveal that only 45–50% population is getting treated with antihypertensive drugs. Approximately 29.8% of Indian population is suffering from hypertension [4]. Most of the antihypertensive
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