Optimization of preparation method for ketoprofen-loaded microspheres consisting polymeric blends using simplex lattice mixture design

Abstract

In the present investigation, simplex lattice mixture design was applied for formulation development and optimization of a controlled release dosage form of ketoprofen microspheres consisting polymers like ethylcellulose and Eudragit®RL 100; when those were formed by oil-in-oil emulsion solvent evaporation method. The investigation was carried out to observe the effects of polymer amount, stirring speed and emulsifier concentration (% w/w) on percentage yield, average particle size, drug entrapment efficiency and in vitro drug release in 8h from the microspheres. Analysis of variance (ANOVA) was used to estimate the significance of the models. Based on the desirability function approach numerical optimization was carried out. Optimized formulation (KTF-O) showed close match between actual and predicted responses with desirability factor 0.811. No adverse reaction between drug and polymers were observed on the basis of Fourier transform infrared (FTIR) spectroscopy and Differential scanning calorimetric (DSC) analysis. Scanning electron microscopy (SEM) was carried out to show discreteness of microspheres (149.2±1.25μm) and their surface conditions during pre and post dissolution operations. The drug release pattern from KTF-O was best explained by Korsmeyer-Peppas and Higuchi models. The batch of optimized microspheres were found with maximum entrapment (~90%), minimum loss (~10%) and prolonged drug release for 8h (91.25%) which may be considered as favourable criteria of controlled release dosage form.