5 nm. The settled nanoparticles in centrifuge tube were redispersed in 5 ml fresh phosphate buffer saline (pH 7.4) and returned to the dissolution media.8 and 9 The dissolution data of each batch was fitted to various kinetic equations and mechanism of drug release investigated. Eqs (5), (6) and (7) are Zero order, First order, Higuchi

model and Korsmeyer–Peppas model respectively. equation(4) Qt=K0tQt=K0t equation(5) InQt=InQ0−K1t equation(6) Qt=Kht1/2Qt=Kht1/2 equation(7) Mt/Mα=KptnMt/Mα=Kptnwhere, Qt is the percentage of drug released at time t, Q0 is initial amount of drug present in the formulation and K0, K1, Kh are the constants of equations. Regression coefficient (R2) was determined from slope of the following plots: Cumulative Small molecule library % drug release vs Time (Zero order kinetic model), Log cumulative of % drug remaining vs Time (First order kinetic model), Cumulative % of drug release vs Square Staurosporine molecular weight root of Time (Higuchi model), Log cumulative % drug release vs Log time (Korsmeyer–Peppas model). 8 and 10 In Korsmeyer–Peppas model, first 60% of drug release was fitted and release exponent “n” was calculated

which is indicative of drug release mechanism. According to Korsmeyer theory, if ‘n’ is 0.45 then drug release will follows Fickian diffusion mechanism, for 0.45 < n < 0.89 follows Anomalous (non-Fickian) diffusion, for n = 0.89 case II transport and for n > 0.89 diffusion mechanism will super case II transport. 11 Results were evaluated by one-way analysis of variance (ANOVA) using Graphpad Instat® Version 3.06 software, where p < 0.05 was taken to represent a statistically significant difference. REPA-EC NPs were prepared by solvent diffusion technique using ethyl acetate as internal organic phase. Both REPA and EC are completely soluble in ethyl acetate therefore there was no possibility of drug loss from polymer due to homogenous matrix. In this study

we used EC of 300 cps viscosity range as drug carrying polymer. Due to high viscosity range it formed a saturated solution with ethyl acetate organic solvent. Both REPA and EC were hydrophobic in nature, thus hydrophobic polymer encapsulate larger amount of hydrophobic drug. When organic phase added in external water phase containing surfactant, REPA-EC matrix immediately Metalloexopeptidase start to precipitate because of insoluble in water and fast diffusion of ethyl acetate. Subsequently REPA-EC matrix was disrupted in nano size by high pressure homogenizer. Polyvinyl alcohol is a better surfactant in terms of encapsulation efficiency, drug content and particle size. PVA has greater propensity to migrate toward the surface of EC nanoparticles and stabilizes its surface more effectively and hence accomplish a lower particle size.9 Ethyl acetate is high soluble in water (8.7% w/v) and having less interfacial tension (6.78) with water due to which fast diffused out in external water phase at the time of solidification of nanoparticles.

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