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

Abstract

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.

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Do, HH., Nguyen, NQ., Tran, V.T. et al. Optimization of Hot-Melt Granulation for High-Dose Tinidazole Tablets: Effects on Dissolution Enhancement and Taste Masking. J Pharm Innov 21, 592 (2026). https://doi.org/10.1007/s12247-026-10843-0