(M1130-08-48) Development of Buccal Miconazole Nitrate Tablets via Hot-Melt Extrusion for Enhanced Solubility and Mucosal Delivery

Purpose: Miconazole Nitrate (MCN) is a broad-spectrum antifungal agent classified as BCS Class II because it has poor water solubility and significant first-pass metabolism, which lead to limited oral bioavailability. This study aimed to develop buccal tablets of MCN using hot-melt extrusion (HME) combined with bioadhesive hydrophilic polymers, specifically hydroxypropyl methylcellulose (HPMC-E5) and polyethylene oxide (PEO-750). The amorphization of MCN through HME and its dispersion within polymer matrices were hypothesized to improve solubility, prolong mucosal residence time, and enhance drug release profiles suitable for buccal delivery.

Methods: Fixed load (25% w/w MCN) blends with binary ratios of HPMC-E5 and PEO-750 were processed via twin-screw extrusion (Process 11, Thermo Fisher Scientific) at 130 °C. The extrudates were milled and compressed into 240 mg, 8 mm tablets. The drug content was measured using UV spectrophotometry. The solid-state and thermal properties were characterized using TGA, DSC, PXRD, and FTIR. Dissolution studies were performed in 0.5% SDS (pH 6.7) at 37°C using USP Apparatus I to evaluate the effects of the polymer on MCN release kinetics.

Results: Thermal and solid-state characterization confirmed the successful amorphization of the drug and the compatibility of MCN with the selected polymer matrices. DSC analysis showed a sharp endothermic peak at ~178 °C in pure MCN, which was retained in the physical mixtures but completely absent in the extruded films, indicating a transition to the amorphous state. PXRD patterns further corroborated this finding, with intense crystalline peaks present in the physical mixtures and absent in the extruded formulations, confirming loss of crystallinity and molecular dispersion of MCN within the polymers. FTIR spectra revealed characteristic N–H stretching at ~3400 cm⁻¹ in pure MCN, with noticeable broadening and slight shifts in the extruded formulations, suggesting hydrogen bonding and polymer–drug interactions. TGA profiles confirmed the thermal stability of MCN and the polymer components up to ~280–290 °C, with no signs of degradation during processing. Together, these findings validate the effectiveness of hot-melt extrusion in producing stable, amorphous MCN-loaded buccal tablets with potential for enhanced solubility and mucosal performance.

Conclusion: Hot-melt extrusion using an HPMC‑E5/PEO‑750 matrix successfully amorphized and dispersed MCN into a mucoadhesive system without compromising stability. This technique offers a promising strategy for buccal delivery of poorly water-soluble antifungal agents and merits further in vivo performance evaluation

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DSC thermogram of Miconazole nitrate , HPMC-E5, PEO 750 , f1,f3,f5 physical mixtures and extruded films.

PXRD overlay of Micnoazole nitrate, polymers , f3 PM, and extruded film