Synergistic co-processing of heat-moisture treated resistant rice starch with HPMC and Eudragit® S100: A novel multifunctional excipient for direct compression and colon-targeted delivery.

A novel multifunctional excipient was developed based on co-processed resistant rice starch (RRS) for direct compression (DC) tablet and targeted colonic drug delivery. While rice starch (RS) is biodegradable and exhibits good compressibility for DC, its poor flowability and low resistant starch content limit its applicability in both DC and controlled-release formulations. To address these limitations, RS was modified using heat-moisture treatment (HMT) with optimal process parameters (moisture content, temperature, and treatment time) were determined through a design of experiments (DoE) approach. The optimized HMT conditions successfully increased resistant starch content by approximately fourfold compared with native RS, and enhanced the plastic deformation properties of RRS, improving its compressibility. To achieve targeted colonic release, a pH-sensitive and enzyme-degradable polymer system was incorporated. The optimized RRS was co-processed with high-viscosity HPMC and Eudragit® S100 through wet granulation to obtain a co-processed excipient (CRRS). The resulting CRRS demonstrated enhanced flowability, packing efficiency, and plastic deformation characteristics, meeting all SeDeM expert system criteria for DC suitability. The corrective excipient proportion (CP, %) indicated a high dilution capacity, supporting drug loading of up to 55 %. Tablets containing 30 % w/w 5-aminosalicylic acid (5-ASA) as a model drug, prepared by DC using CRRS, exhibited acceptable uniformity of dosage units, friability, and drug content. In vitro dissolution studies revealed a controlled-release pattern, achieving approximately 80 % cumulative release within 12 h. The dense matrix formed by resistant starch and functional polymers effectively restricted water penetration and enzymatic access, promoting gradual and site-specific release under colonic conditions compared with tablets lacking RRS. Release kinetics followed the Higuchi model, with n values suggesting an anomalous transport mechanism involving both diffusion and erosion. Overall, CRRS represents a promising multifunctional excipient combining excellent DC performance with controlled, site-specific colonic drug delivery potential, supporting the development of advanced oral dosage forms.