Identifying Optimized Parameters to Enhance the Productivity of Gas Generating Pellets Using a Dome Type Extruder.

Background: The extrusion-spheronization process continues to be utilized in pharmaceutical manufacturing, as evidenced by several recent patents and articles. The primary challenge in Pelletization via extrusion spheronization has been to optimize the production process to achieve high yields of spherical pellets ensuring they meet specific quality standards while keeping the production costs low.

Objective: Therefore, this study aimed to identify the ideal parameters for maximizing production rates using a dome extruder while maintaining the desired physical characteristics of the pellets.

Methods: By employing Design of Experiments (DoE) techniques and analyzing critical processing parameters, the research sought to delineate the optimal design space. The pellet formulation comprised Apixaban, microcrystalline cellulose, hypromellose, and sodium bicarbonate, intended to generate gas within the pellets. The study employed a Response Surface Methodology, specifically the Central Composite Face-Centered design, to systematically assess the impact of various process variables on both pellet properties and production rate. Key independent factors included Extruder speed (X1), Spheronization speed (X2), and Spheronization time (X3), which were determined based on the preliminary analyses. Characterization of pellets from each experiment encompassed measurements of sphericity via Aspect ratio (R1), Friability (R2), Bulk density (R3), and Percentage yield within a specific size range (R4).

Results: From the results, it was discerned that extrusion and spheronization speed emerged as critical process parameters within defined spheronization time for maximizing production rates while concurrently maintaining satisfactory pellet properties. Based on the design space analysis, extrusion speed spans from 23 to 27 rpm, while spheronization speed extends from 700 to 900 rpm at 5 min to 7 min of spheronization time, yielding more than 90% of the desired fraction of spherical pellets with good physical properties.

Conclusion: This study successfully optimized process parameters for pellet production using a dome-type extruder, employing a Quality by Design (QbD) approach. Key factors influencing pellet yield and quality-extrusion speed, spheronization speed, and spheronization time-were identified and systematically optimized. These optimized pellets may potentially undergo further coating with polymers to facilitate gastro-retentive or floating drug delivery systems, expanding their applicability in pharmaceutical formulations.