A Systematic Approach to Design and Prepare Poly(meth)acrylate Based Solid Dispersions of Poorly Water-soluble Drug by Spray Drying

Abstract

Objective of present study was to develop formulation which improves solubility of furosemide and stability of spray dried solid dispersion. Various processing parameters were optimized by applying DoE. In first step, screening of poly(meth)acrylates were carried out using solvent casting methods to select appropriate polymer. In second step, solid dispersion was prepared using optimized poly(meth)acrylate via spray drying process and trials were conducted as per DoE. Characterization of spray dried microparticles was carried out using SEM, DSC, XRD, in-vitro dissolution, and stability study. EUDRAGIT® E PO was screened as a suitable polymeric carrier in solvent casting method. In-vitro dissolution showed 100% releases within 20 min for spray dried powder as compared to 9% release for pure drug after 60 min in 0.1 N HCl. SEM analysis revealed conversion of crystalline shape to spherical shape. DSC and XRD confirmed that crystalline form was converted into amorphous form which was stable even after 3 months of storage. Outcome of DoE revealed that, feed rate has significant effect on %LOD while solid content has major effect on the process yield. So, present work indicates that EUDRAGIT® E PO formed a stable spray dried solid dispersion and it has ability to enhance dissolution of furosemide.

Keywords:

• amorphous solid dispersion
• EUDRAGIT® E PO
• full factorial design
• furosemide
• microparticles
• poly(meth)acrylate
• solubility enhancement
• spray drying

Acknowledgments

Authors would like to thank Department of Condensed Matter Physics and Material Science, Tata Institute of Fundamental Research, Mumbai, India, for carrying out x-ray diffraction analysis and Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University, Varanasi, India, for carrying out FTIR study.