Sustained Release Solid Dispersions of Pentoxyfylline: Formulation and Optimization

Abstract

Objective: The purpose of the study is to formulate and optimize sustained release solid dispersions of pentoxyfylline using a combination of eudragit polymers and ethyl cellulose. Methods: Solid dispersions were formulated by solvent evaporation method.Preliminary batches were formulated using various drug to polymer ratio; with eudragit S100 and L100 (1:1 to 1:5 ratio), and with ethyl cellulose(1:1 to 1:3 ratio) and evaluated for solubility analysis. Based on results of preliminary batches, Box Behnken design was further applied and three factors (X1- concentration of Eudragit S100, X2- concentration of Eudragit L100, X3- concentration of Ethyl Cellulose) were selected with three levels (+1, 0, -1). Multiple linear regression was applied to generate polynomial equations and statistical evaluation. Prepared solid dispersions were investigated for sustained release properties via in vitro dissolution studies. Fourier transform infrared spectroscopic analysis (FTIR), X-ray diffraction analysis (X-RD), Differential scanning calorimetry (DSC) studies were carried out to evaluate drug polymer interactions. Scanning Electron Microscopy (SEM) analysis of optimized solid dispersion was carried out to evaluate surface morphology of the particles. Results: Batch F5 showed maximum sustained release (65.46% in 24 h) characteristics out of all solid dispersions. DSC studies indicated drug integrity when mixed with the polymeric carriers. FTIR and X-RD studies also ruled out any drug polymer interaction. A change in crystalline habit was observed in solid dispersion particles (F5 batch) as seen in SEM micrographs. Polynomial mathematical model generated using multiple regression analysis was found to be statistically significant (p<0.05). Conclusion: Release retarding effect was found to be dependent on polymer concentration. Therefore, an optimized combination may lead to better sustaining effect.