Twin-screw melt granulation of Eudragit® FS100: optimization of coating-free delayed-release matrix tablets with HPMC...

This study aimed to develop a scalable, coating-free delayed-release matrix tablet via twin-screw melt granulation (TSMG) using Eudragit® FS100 and extra-granular hydroxypropyl methylcellulose K4M (HPMC). A Central Composite Design was employed to optimize three critical variables (drug load (10-30 %), screw speed (20-50 rpm), and HPMC concentration (5.6-13.1 % w/w)) to achieve <10 % drug release at 2 h in gastric conditions (pH 1.2) and >85 % in intestinal conditions (pH 7.4). The optimized formulation (30 % drug load, 20 rpm, 12.2 % HPMC) achieved 7.78 ± 0.15 % drug release at 2 h in acidic pH and complete release within 10 h in alkaline pH. Drug release kinetics showed excellent agreement with the Korsmeyer-Peppas model (R² = 0.9826; n = 1.132), indicating a Super Case II transport mechanism driven by polymer relaxation and erosion, approaching zero-order release. Gel thickness analysis confirmed formation and subsequent disintegration of a cohesive hydrogel barrier; while swelling and erosion studies supported the observed biphasic profile. Structural transitions generated by hydration were captured using microscopy. PXRD and DSC analyses indicated partial amorphization post-extrusion, with FTIR showing no chemical interaction between components. Accelerated stability testing confirmed formulation integrity. This work demonstrates a novel formulation strategy in which the interplay of pH-responsive and pH-independent polymers, along with controlled swelling-erosion behavior, achieves robust delayed-release profiles without the need for additive manufacturing or multi-step coating processes.