(505c) Towards Continuous Manufacturing (CM) of Drug Loaded Strip Films: Continuous Mixing of Dry Micronized Drug Particles with Film Precursor Via Twin Screw Extruder (TSE)

Continuous manufacturing (CM) is an emerging technology in pharmaceutical industry. In this timely work, CM is being incorporated for strip film production where it is a natural addition for the current laborious mixing process. This strip films serve as a flexible dosage regimen for patient populations such as pediatrics and geriatrics, and those with dysphagia. Recent studies have explored the critical quality & material attributes of strip films produced via batch mixing. The novelty of the present study is continuous mixing via twin screw extruder at the room temperature, for the manufacturing of strip films containing BCS Class II drug particles. Fenofibrate and Hydroxyropyl Methyl cellulose (HPMC-E15LV) were used as the model BCS Class II drug and the polymeric matrix, respectively. Three different mixing speeds were used as critical processing parameters in TSE. Impeller mixer was also used as a batch mixer for the comparison purposes. Very fine micronized particles posed significant feeding challenge due to their highly cohesive nature. Current and future efforts involve improving powder feeding into TSE. Except for the lowest mixing speed, drug recovery upon dried film sample redispersion was excellent. In all cases, final products with very good content uniformity were successfully manufactured at the room temperature via TSE. However, uniformity of the final product reduced (express as RSD%) when such drug particles were used in the batch mixing process. The residence time in continuous mixing was remarkably low (~30 sec) compared to that of the batch mixing (3h). Overall, these results explore the introduction of micronized drug particles for TSE mixing, paving way to establishing continuous manufacturing for the strip films. Current efforts are directed towards integrating continuous film drying and overcoming cohesive drug powder feeding challenges.