Formulation performance window for manufacturing cellulose-based sustained-release mini-matrices of highly water-soluble drug via hot-melt extrusion technology

The aim of the proposed work was to develop robust hot-melt extrusion (HME) process for fabricating sustained-release mini-matrices (pellets) of a highly water-soluble drug, tramadol hydrochloride. The current work was designed to identify a formulation window with target functional performances such as streamlined processability and sustained-release profile with alcohol-resistant properties. HME was used to perform screening tests of various drug loadings and excipients to determine the acceptable limit of each independent component (critical material attributes, CMAs) in the Design of Experiment (DoE). It was observed that the ratio of hydrophobic (ethyl cellulose, EC; Compritol ATO 888, C888) to hydrophilic (hydroxypropyl cellulose, HPC) components were critical factors evaluated using DoE. The processing temperature (105–175 °C) was identified as a critical process parameter. FTIR chemical imaging was used to assess the drug-matrix interaction, confirming a homogeneous drug distribution inside the polymer-lipid matrix system. SEM analysis and FTIR results were also in close agreement. Finally, a feasible formulation window containing EC, C888, and HPC in the ratios of 40:20:10 with the desired quality target product profile was successfully developed. Hydroalcoholic dissolution studies revealed safe and sustained-release of tramadol that resisted drug release variations for the first few hours in alcohol. The developed mini-matrices followed the Peppas–Sahlin model indicating a combination of Fickian diffusion and swelling mechanisms. Herein we conclude, a successful blueprint technology for the development of alcohol-resistant mini-matrices of tramadol hydrochloride via HME to provide once-a-day therapy for pain management, consequently reducing the dosing frequency. Graphical abstract: [Figure not available: see fulltext.]