Successful factorial design for the optimization of methylprednisolone encapsulation in biodegradable nanoparticles

Abstract

Due to their crystalline nature, the encapsulation of hydrophobic corticosteroids within polymeric nanoparticles by o/w solvent evaporation method is often difficult to achieve. The aim of this study was to evaluate the effect of both process and formulation parameters on the encapsulation of a model corticosteroid: methylprednisolone (MP). For this purpose, a 3(2)factorial design was performed evaluating the effects of the concentration of emulsifiers and sonication time on the manufactured nanoparticles, followed by a multiresponse optimization. The study also included the evaluation of other parameters such as the type of organic solvent used, polymer characteristics and the initial mass of drug. The optimal nanoparticle formulation using 0.25% (w/v) of emulsifying agent (Polyvinyl-alcohol, PVA) and 5 min of sonication was then characterized. The highest encapsulation was obtained with an organic phase consisting of acetone: dichloromethane (1:1), polyD,L-lactide-co-glycolide (PLGA) 50:50 as polymer and an initial mass of 6.6 mg of methylprednisolone. Nanoparticles size and ζ potential of optimized formulation were respectively around 230 nm and -14 mV. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) demonstrated that the drug was molecularly dispersed within the nanoparticles. Release study showed that MP-loaded nanoparticles sustained drug release for up to 120 h. This study reflects the importance of factorial design to optimize the manufacture of nanoparticles encapsulating hydrophobic drugs.

Formulation and Optimization of Nonionic Surfactants Emulsified Nimesulide-Loaded PLGA-Based Nanoparticles by Design of Experiments

“…Linearity plots can reveal the relationship between the observed and the predicted responses. Graphs give similar information to the mathematical equations obtained from statistical analyses (26,30). In this research, four responses were evaluated, and each response was plotted in relation to the modified factor.…”

“…The focus of this study is to optimize and investigate the drug/polymer ratio, emulsifier type, and percentages used in the NP formulations on the physicochemical properties of the NMS-loaded PLGA NPs by using a 3 2 factorial design. Factorial experimental designs allow for the rapid and efficient screening of design variables with a limited number of planned experiments (25,26). The design of the experiments and the response surface methodology (RSM) approaches were implemented for optimal processing.…”

Investigation and optimization of formulation parameters on preparation of targeted anti-CD205 tailored PLGA nanoparticles

“…When the viscosity of the polymers increased, ZP value showed slightly more negative charge for uncapped NPs than the capped formulations. 50 When the polymer of higher viscosity is used it increases the concentration of the media resulting in semi-folded particles. 51 Increase in concentration of the organic phase also resulted in viscosity resistance against the net shear stress.…”

Oleic Acid Coated Gelatin Nanoparticles Impregnated Gel for Sustained Delivery of Zaltoprofen: Formulation and Textural Characterization

“…The application of factorial design in pharmaceutical formulation development has played a key role in understanding the relationship between the independent variables and the responses to them. 15 The objective of present study was to develop a nanogel with a strong capacity for controlled delivery of NSAID drug used in RA condition & its (TPA) i.e. texture profile analysis.…”