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Tuesday, August 9, 2011

Design and Optimization of NSAID Loaded Nanoparticles

The objective of the study was to design and evaluate NSAID loaded Nanoparticles drug delivery system,
where Flurbiprofen (model drug) Nanoparticles with suitable size range are envisaged to concentrate at
inflammation sites due to increase fragility of blood vessels at those sites and increased aggregation and
prostaglandin synthesis. Materials used were surfactant (pluronic F 68) and polymer (poly lactic co glycolic
acid; PLGA). The flurbiprofen loaded nanoparticles were prepared by solvent diffusion nano-precipitation
method. Experiment was carried out following 32 factorial designs, where drug-polymer ratio was varied to
optimize the formulation. From I.R studies no drug-polymer interaction was found. Particles size analysis was
done using Malvern Mastersizer. Two parameters, namely, drug-polymer ratio and solvent-nonsolvent ratio
were chosen for optimization following the factorial design. Amount of drug loading and surfactant were kept
constant, and only polymer load was varied. The in-vitro drug release profile from nanoparticles was found to
follow Higuchi square root kinetics implying a diffusion dependent release as is expected of an insoluble, nonswellable
nature of PLGA. It indicated that nanoparticles formed were matrix in nature, in which flurbiprofen
dispersed uniformly. Suitable polynomial models were generated and statistically validated using ANOVA for
the different responses, namely drug release (maximization) and particle size (minimization). Those models
were solved numerically and simultaneously to optimize the required formulation. Optimized formulation were
found to have a polymer-drug ratio of 18.89:1 and manufactured at a nonsolvent-solvent ratio of 4:1 to
maximized release after 8 hrs and minimized particle size. The methodology avoids the use of organic solvent
and thus provides a safe, reproducible and fast method of production of nanoparticles. The study collaborates on
the feasibility and suitability of aqueous polymeric drug delivery system, employing statistical design to
develop a clinically useful Nanoparticle system with targeting potential.
Keywords: Nanoparticles, NSAID, PLGA, pluronic F 68, optimization, factorial design.
Swati Sashmal, Swarupananda Mukherjee, Subhabrata Ray, Ram Sharnagat Thakur, Lakshmi K.Ghosh, Bijan K. Gupta
Pak. J. Pharm. Sci., 2007, Vol.20(2), 157-162


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