Optimization of Hot-Melt Granulation for High-Dose Tinidazole Tablets: Effects on Dissolution Enhancement and Taste Masking

Purpose:
This study aimed to optimize a high-shear hot-melt granulation process for the development of tinidazole 500 mg tablets while balancing dissolution enhancement and bitterness control.

Methods:
Polyethylene glycol (PEG) 4000 and crospovidone were incorporated as excipients to improve dissolution behavior and control bitterness. An I-optimal response surface design using Design-Expert software was applied to optimize formulation variables based on dissolution performance, Hausner ratio, and bitterness evaluated by a human sensory panel. The
influence of processing temperature on granule formation during hot-melt granulation was also investigated. Physicochemical characterization of the optimized system was performed using FT-IR, DSC, XRD, and SEM to elucidate the particle formation process and potential interactions between tinidazole and the excipients.

Results:
The optimized formulation containing 9% PEG 4000 and 6% crospovidone processed at 60 °C achieved over 95% drug dissolution within 30 min while maintaining bitterness within an acceptable range compared with raw tinidazole. PEG 4000 played a key role in improving dissolution behavior and modulating bitterness. Crospovidone demonstrated superior disintegration efficiency within the melt-derived matrix compared with sodium starch glycolate. The resulting granules exhibited good flowability (Hausner ratio 1.11) and appropriate particle size characteristics. Solid-state analyses confirmed that the crystalline structure of tinidazole was preserved after the hot-melt granulation process.

Conclusion:
High-dose tinidazole tablets were successfully developed using hot-melt granulation. The optimized formulation improved dissolution performance while maintaining acceptable bitterness levels, and solid-state analyses confirmed the structural stability of tinidazole within the melt-derived granule matrix.