Formulation and Optimization of Diclofenac Sodium Loaded Ethylcellulose Nanoparticles

Design of experiment (DoE) is a useful time and cost-effective tool for analyzing the effect of independent variables on the formulation characteristics. The aim of this study is to evaluate the effect of the process variables on the characteristics involved in the preparation of Diclofenac Sodium (DC) loaded ethylcellulose (EC) nanoparticles (NP) using Central Composite Design (CCD). NP were prepared by W/O/W emulsion solvent evaporation method. Three factors were investigated (DC/EC mass ratio, PVA concentration, homogenization speed) in order to optimize the entrapment efficiency (EE) and the particle size of NP. The optimal formulation was characterized by Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and in vitro release. Optimized formulation showed an EE of 49.09 % and an average particle size of 226.83 nm with a polydispersity index of 0.271. No drug-polymer interaction was observed in FTIR and DSC analysis. SEM images showed that the particles are spherical and uniform. The in vitro release study showed a sustained release nature, 53.98 % of the encapsulated drug has been released over 24hours period. This study demonstrated that statistical experimental design methodology can optimize the formulation and the process variables to achieve favorable responses.

Introduction

Nanoparticles are one of the promising drug delivery systems for controlling particle size, surface properties and release of therapeutic ingredients in order to reach the target at the therapeutic desirable proportion and rate regimen (Mohanraj, Chen, 2006). Biocompatible, biodegradable and non-biodegradable polymers as Chitosan derivatives, PLA, PLGA, EC, are used for the preparation of polymeric nanoparticles by dissolution, entrapment, encapsulation or attachment of a drug to a nanoparticle matrix (Nagavarmaet al, 2012). NP matrix carriers can improve the encapsulation efficiency and stability of the drugs inside the NPs and provide effective drug levels over longer periods of time compared to traditional therapy (Cooper, Harirforoosh, 2014). Different methods are used for the preparation of nanoparticles.One of the most used is the solvent evaporation method. Uniform concentration of drug at the site of absorption, maintaining of stable plasma concentration and reducing toxic effects can be achieved by developing controlled-release drug delivery systems (Barzegar-Jalaliet al, 2012).

Diclofenac sodium (DC) is a non-steroidal anti- inflammatory drug used for treatment of inflammatory diseases. DC has a short half-life of 1-2h and should be administered frequently at a high dose, which leads to severe undesirable effects and rises the possibility for missing a dose (Arias et al, 2009). The development of sustained dosage release forms was needed to ovoid theses inconveniences (Krishna Sailaja, Nandini, 2016). The design of experiment (DoE) is a valuable tool used for optimization. It allows the finding of the optimal conditions for the best responses of experiments and understand the relationship between the dependent and independent variables in the formulation or process development (Vera Candiotiet al, 2014). The response surface methodology (RSM) is the combination of statistical and mathematical techniques based on the recapitulation of experimental data from experimental design (Trivedi et al, 2015). One of the promising RMS used in DoE is central composite design (Yang et al, 2014).

The objective of this study was to formulate and characterize DC-loaded EC-NP with the aim to evaluate the effect of the process variables on the characteristics involved using Central Composite Design.

Materials

Diclofenac sodium was purchased from CAYMAN chemical company. Ethylcellulose (viscosity 22cP, 48% ethoxyl), Polyvinylalcohol (87-90% hydrolyzed, average mol wt. 30.000-70.000) and dialysis bags (cut-off 12 kDa) were procured from Sigma Aldrich USA. All other solvents and ingredients used were of analytical grade.

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BADAOUI, Fatima Zohra and BOUZID, DjallelFormulation and Optimization of Diclofenac Sodium Loaded Ethylcellulose Nanoparticles. Brazilian Journal of Pharmaceutical Sciences [online]. 2022, v. 58, e19586. Available from: https://doi.org/10.1590/s2175-97902022e19586. Epub 24 June 2022. ISSN 2175-9790. https://doi.org/10.1590/s2175-97902022e19586.