Material-Sparing Approach using Differential Scanning Calorimeter and Response Surface Methodology for Process Optimization of Hot-Melt Extrusion

Abstract

The objective of the present investigations was to demonstrate the applicability of DSC combined with response surface methodology as a material-sparing tool for determination of the processing conditions for HME during initial stages of development. Mefenamic acid (MFA) and Eudragit EPO (EPO) were used as a model drug and the polymeric carrier, respectively. Initial screening was performed using film-casting, polarized light microscopy, and TGA analysis to determine the levels for the experimental design. A Box-Behnken design was used to study the effect of the independent parameters, viz. drug loading, heating rate, and processing temperature, on the dependent parameters, viz. residual crystallinity and drug degradation. The results showed a quadratic relationship between independent and dependent parameters. Based on the design space, MFA-EPO dispersions with 20% drug loading were prepared using HME and vacuum compression molding (VCM). Both the HME and VCM samples did not show any signs of residual crystallinity. However, degradation of MFA was observed in VCM sample and the HME filaments processed at 100 rpm, but not at 150 rpm. The results demonstrate that DSC has potential to be a material-sparing tool to optimize drug loading and processing temperature for HME and will help product development using HME cost-effective.

Keywords: Amorphous solid dispersions; Design of experiments (DoE); Differential scanning calorimeter; Hot-melt extrusion; Vacuum compression molding.