Microwave-Assisted Wet Granulation for Engineering Rice Starch–Mannitol Co-Processed Excipients for Direct Compression of Orally Disintegrating Tablets

<b>Background/Objectives</b>: Enhancing excipient functionality through environmentally friendly and scalable processing methods is essential for improving the manufacturability and performance of orally disintegrating tablets (ODTs). Microwave-assisted wet granulation enables controlled microstructural modification without chemical alteration of excipient components. This study aimed to develop and evaluate a rice starch (RS)-mannitol co-processed excipient using microwave-assisted wet granulation for direct compression of ODTs. <b>Methods</b>: RS and mannitol were co-processed by wet granulation followed by microwave treatment under varying power levels and irradiation times. The effects of processing conditions on granule morphology, solid-state properties, porosity, powder flow, compressibility, wettability, and disintegration behavior were systematically investigated. The optimized excipient was further evaluated in ODT formulations containing chlorpheniramine maleate and piroxicam and benchmarked against a commercial co-processed excipient (Starlac^®). <b>Results</b>: Microwave treatment generated internal vapor pressure that promoted pore formation and particle agglomeration, resulting in enhanced powder flowability (compressibility index 8.4-10.8%). Partial crystallinity reduction and microstructural modification improved compressibility and surface wettability compared with non-microwave-treated materials. The optimized formulation (MW-RM-H-30) exhibited rapid wetting (25 s), high water absorption (90.5%), low contact angle (42°), and fast tablet disintegration (31 s). ODTs prepared with MW-RM-H-30 showed rapid disintegration (42 s for chlorpheniramine maleate and 32 s for piroxicam) and dissolution behavior comparable to Starlac^®. <b>Conclusions</b>: Microwave-assisted wet granulation provides an efficient, scalable, and environmentally friendly strategy for engineering starch-based co-processed excipients with enhanced functionality for direct compression ODT applications. The developed excipient demonstrates strong potential for solid dosage form manufacturing.