용해도가 개선된 에피나코나졸 함유 고형 SNEDDS의 개발

초록

This study aimed to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) of efinaconazole (EFN) that enhances apparent solubility and dissolution while suppressing by stabilizing the solubilized state and mitigating microprecipitation. Based on solubility screening, Kollisolv® MCT 70, Solutol® HS 15, and Labrafil® M2125 CS were selected as oil, primary surfactant, and co-surfactant, and a 5:75:20 (w/w/w) ratio was finalized by composition scouting. For solidification, acetone was chosen as the spray-drying solvent based on EFN’s thermal behavior and solvent volatility, and free-flowing powders were obtained under mild conditions (inlet 60oC, outlet 45oC). SiO2 was used as a carrier, and Kollidon® VA 64 was adopted as a precipitation-inhibiting polymer. The solidified systems showed marked increases in EFN saturation solubility across various pH conditions. In particular, the VA64-containing formulation F3 (EFN : SiO2 : VA64=1 : 5 : 1, w/w/w) maintained high solubility of approximately 8,000 μg/mL over the tested pH range. In dissolution testing, release in purified water improved from approximately 10% for crystalline EFN to approximately 90% for F3, with consistent superiority at pH 6.8. Microstructural and solid-state analyses supported amorphization without evidence of new chemical interactions, aligning with the observed gains in solubility and dissolution. In summary, spray-dried EFN S-SNEDDS provides a handling- and storage-friendly platform that delivers pH-independent high apparent solubility with enhanced dissolution, offering a practical route for oral dosage development of EFN.

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