Development of HPMC-Based Hard Capsules with Rapid Disintegration Across Simulated Gastrointestinal pH Conditions: Formulation Design, Process Optimization, and Disintegration Mechanism of the HPMC/GG/ι-C Ternary System.

While hydroxypropyl methylcellulose (HPMC) is a promising plant-based alternative to gelatin, its industrial application is limited by poor mechanical properties and high production costs. In this study, high-performance HPMC-based hard capsules were developed using an HPMC/gellan gum/ι-carrageenan ternary system. The formulation and preparation process were optimized via single-factor experiments, response surface methodology, and low-field nuclear magnetic resonance analysis. Scanning electron microscopy was applied to characterize the microstructural evolution during disintegration. The optimized capsules exhibited rapid disintegration within 15 min across four pH media and satisfied the requirements of the Chinese Pharmacopoeia (2025). Drug dissolution profiles using cefradine and ranitidine hydrochloride showed over 85% cumulative release within 30 min, with similarity factors higher than 50 relative to commercial gelatin capsules under the tested conditions. This work provides a feasible and low-cost strategy for the industrial production of plant-based capsules and promotes the high-value utilization of polysaccharide-based capsule materials.